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The insulin/IGF1signaling pathway (ISP) plays an essential role in long-term health. Some perturbations in this pathway are associated with diseases such as type 2 diabetes; other perturbations extend lifespan in worms, flies, and mice. The ISP regulates many biological processes, including energy storage, apoptosis, transcription, and cellular homeostasis. Such regulation involves precise rewiring of temporal events in protein phosphorylation networks. For an animated version of this Enhanced SnapShot, please visit http://www.cell.com/cell/enhanced/odonoghue.
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Fator de Crescimento Insulin-Like I/metabolismo , Insulina/metabolismo , Transdução de Sinais , Animais , Humanos , Fosforilação , Proteínas/metabolismoRESUMO
BACKGROUND: Deep learning-based methods have been successfully applied to MRI image registration. However, there is a lack of deep learning-based registration methods for magnetic resonance spectroscopy (MRS) spectral registration (SR). PURPOSE: To investigate a convolutional neural network-based SR (CNN-SR) approach for simultaneous frequency-and-phase correction (FPC) of single-voxel Meshcher-Garwood point-resolved spectroscopy (MEGA-PRESS) MRS data. STUDY TYPE: Retrospective. SUBJECTS: Forty thousand simulated MEGA-PRESS datasets generated from FID Appliance (FID-A) were used and split into the following: 32,000/4000/4000 for training/validation/testing. A 101 MEGA-PRESS medial parietal lobe data retrieved from the Big GABA were used as the in vivo datasets. FIELD STRENGTH/SEQUENCE: 3T, MEGA-PRESS. ASSESSMENT: Evaluation of frequency and phase offsets mean absolute errors were performed for the simulation dataset. Evaluation of the choline interval variance was performed for the in vivo dataset. The magnitudes of the offsets introduced were -20 to 20 Hz and -90° to 90° and were uniformly distributed for the simulation dataset at different signal-to-noise ratio (SNR) levels. For the in vivo dataset, different additional magnitudes of offsets were introduced: small offsets (0-5 Hz; 0-20°), medium offsets (5-10 Hz; 20-45°), and large offsets (10-20 Hz; 45-90°). STATISTICAL TESTS: Two-tailed paired t-tests for model performances in the simulation and in vivo datasets were used and a P-value <0.05 was considered statistically significant. RESULTS: CNN-SR model was capable of correcting frequency offsets (0.014 ± 0.010 Hz at SNR 20 and 0.058 ± 0.050 Hz at SNR 2.5 with line broadening) and phase offsets (0.104 ± 0.076° at SNR 20 and 0.416 ± 0.317° at SNR 2.5 with line broadening). Using in vivo datasets, CNN-SR achieved the best performance without (0.000055 ± 0.000054) and with different magnitudes of additional frequency and phase offsets (i.e., 0.000062 ± 0.000068 at small, -0.000033 ± 0.000023 at medium, 0.000067 ± 0.000102 at large) applied. DATA CONCLUSION: The proposed CNN-SR method is an efficient and accurate approach for simultaneous FPC of single-voxel MEGA-PRESS MRS data. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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Aprendizado Profundo , Humanos , Estudos Retrospectivos , Ácido gama-Aminobutírico/química , Espectroscopia de Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
Any conflict in countries that process nuclear power plants raises concerns of the potential radiation injuries to the people in that region and beyond such as the current conflict in Ukraine. International healthcare organizations and societies should prepare for the potential scenarios of nuclear incidents. The Worldwide Network for Blood and Marrow Transplantation (WBMT) and its members, have recent experience preparing for this type of events such as the Fukushima incident in 2011. In this article, we discuss the risks of radiation exposure, current guidelines, and scientific evidence on hematopoietic support, including the role of hematopoietic stem cell transplant (HCT) for those exposed to nuclear radiation, and the role that the WBMT and other global BMT societies can play in triaging and managing people suffering from radiation injuries.
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Transplante de Células-Tronco Hematopoéticas , Lesões por Radiação , Humanos , Centrais Nucleares , Medula Óssea , Ucrânia/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Transplante de Células-TroncoRESUMO
BACKGROUND: Autologous haemopoietic stem cell transplantation (AHSCT) is an effective treatment for systemic sclerosis (SSc); however, treatment-related toxicity remains a key issue. AIMS: To investigate the perceptions of rheumatologists on the use of AHSCT for SSc. METHODS: Australian rheumatologists were asked for their opinion on the role of AHSCT, the indications for treatment and the barriers to the use of AHSCT for SSc. A secondary analysis assessed what factors influenced the perception of AHSCT. RESULTS: A total of 77.8% rheumatologists agreed or strongly agreed with the statement that AHSCT is an accepted treatment for SSc. While 65.1% agreed or strongly agreed that treatment-associated mortality was a significant barrier to referral for AHSCT, only 15.2% agreed or strongly agreed that this risk was unacceptable. Progressive lung or skin disease, or lack of response to other therapies, were considered the main referral criteria. A total of 92.0% of respondents agreed or strongly agreed that reduction of treatment toxicity would increase their likelihood to refer patients for AHSCT. Rheumatologists who were aware of the correct evidence base were more likely to consider AHSCT an acceptable treatment for SSc (4.21 ± 0.7 vs 3.64 ± 0.9, P = 0.007). Rheumatologists desire improved patient selection criteria and access to treatment. CONCLUSION: In this national survey of rheumatologists, AHSCT is considered an accepted therapy. However, concern about toxicity remains a potential barrier to patient referral. Access, studies to refine patient selection and development of AHSCT protocols that improve safety were identified as key areas of need.
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Over 85% of parents use social media; however, limited research has investigated the associations between parental social media use and food parenting practices. The objectives of this study were to: 1) describe how mothers and fathers use social media focused on topics related to child feeding and family meals; and 2) examine associations between parental social media use focused on child feeding and family meals and mothers' and fathers' food parenting practices. Data were obtained from 179 mothers and 116 fathers of children aged 3-8 years enrolled in a family-based obesity prevention intervention. We used descriptive statistics to describe parents' social media use in relation to child feeding and family meals and linear regressions with generalized estimating equations to explore associations between parents' social media use and food parenting practices. Models were stratified by parent gender and adjusted for household income, parent ethnicity, parent age, child sex, and intervention status. A higher percent of mothers than fathers reported using social media to seek information related to child feeding and family meals (64.8% mothers; 25.0% fathers) and to share and compare family meals and food choices (41.9% mothers; 19.8% fathers). While social media use was not associated with food parenting practices in mothers, fathers' social media use to share and compare family meals and food choices was associated with negative food parenting practices, i.e., greater use of food for emotional regulation (ß = 0.37, p = 0.02) and greater use of food for reward (ß = 0.34, p = 0.02). Study results can inform strategies to promote healthy social media use among parents of young children.
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Poder Familiar , Mídias Sociais , Feminino , Criança , Humanos , Pré-Escolar , Poder Familiar/psicologia , Comparação Social , Mães/psicologia , RefeiçõesRESUMO
Purpose: Fish and seafood consumption by North American children is low. This is concerning, given the critical role of n-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid), found in fish and seafood, in early development. This study aimed to determine whether parental factors related to fish and seafood consumption are associated with frequency of fish and seafood consumption in Canadian children.Methods: A subgroup of parents (n = 28) participating in the Guelph Family Health Study Pilot reported their perceptions and history of fish and seafood consumption, confidence in preparing fish and seafood dishes, and the frequency of intake for their children (n = 40).Results: This study found that 20% of children consumed one serving of saltwater fish, freshwater fish, or shellfish weekly and 63% consumed at least one type of fish or seafood monthly. Parental cooking confidence preparing fish and seafood was positively associated with at least monthly fish and seafood intake in children.Conclusions: These findings suggest that some children may have low intakes of fish and seafood due to a lack of parental cooking confidence when preparing fish and seafood dishes. Therefore, future research and interventions focused on addressing this barrier may aid in improving fish and seafood intake.
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Ácidos Graxos Ômega-3 , Criança , Animais , Humanos , Canadá , Ácidos Docosa-Hexaenoicos , Alimentos Marinhos/análise , Culinária , Peixes , DietaRESUMO
Purpose: Our understanding of the influence of sugar intake on anthropometrics among young children is limited. Most existing research is cross-sectional and has focused on sugar-sweetened beverages. The study objective was to investigate longitudinal associations between young children's total, free, and added sugar intake from all food sources at baseline with anthropometric measures at baseline and 18 months.Methods: The Guelph Family Health Study (GFHS) is an ongoing randomized controlled trial and a family-based health promotion study. Food records and anthropometric data were collected at baseline (n = 109, 55 males; 3.7 ± 1.1 y, mean ± SD) and 18 months (n = 109, 55 males; 5.1 ± 1.1 y) of the GFHS pilots. Associations between sugar intakes and anthropometrics were estimated using linear regression models with generalized estimating equations adjusted for age, sex, household income, and intervention status.Results: Total sugar intake was inversely associated with body weight at 18 months (P = 0.01). There was no effect of time on any other associations between total, free, and added sugar intakes and anthropometrics.Conclusions: Early life dietary sugar intakes may not relate to anthropometric measures in the short term. Further investigation into potential associations between dietary sugar intakes and anthropometric variables over longer time periods is warranted.
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Both genetic susceptibility and environmental exposures are thought to be involved in multiple sclerosis (MS) pathogenesis. Of all viruses potentially relevant to MS aetiology, Epstein-Barr virus (EBV) is the best-studied. EBV is a B cell lymphotropic virus which is able to evade the immune system by establishing latent infection in memory B cells, and EBV reactivation is restricted by CD8 cytotoxic T cell (CTL) responses in immune competent individuals. Autologous haematopoietic stem cell transplantation (AHSCT) is considered to be the most effective therapy in the treatment of relapsing MS even though chemotherapy-induced lymphopenia can associate with the re-emergence of latent viruses. Despite the increasing interest in EBV and MS pathogenesis the relationship between AHSCT, EBV and viral immunity in people with MS has not been investigated to date. This study analysed immune responses to EBV in a well characterised cohort of 13 individuals with MS by utilising pre-AHSCT, and 6-, 12- and 24-month post AHSCT bio-banked peripheral blood mononuclear cells and plasma samples. It is demonstrated that the infused stem cell product contains latently EBV-infected memory B cells, and that EBV viremia occurs in the immune-compromised recipient post-transplant. High throughput TCR analysis detected expansion and diversification of the CD8 CTL responses reactive with EBV lytic and latent antigens from 6 to 24 months following AHSCT. Increased levels of latent EBV infection found within the B cell pool following treatment, as measured by EBV genomic detection, did not associate with disease relapse. This is the first study of EBV immunity following application of AHSCT in the treatment of MS and not only raises important questions about the role of EBV infection in MS pathogenesis, but is of clinical importance given the expanding clinical trials of adoptive EBV-specific CTLs in MS.
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Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Humanos , Herpesvirus Humano 4 , Linfócitos T Citotóxicos , Esclerose Múltipla/terapia , Leucócitos Mononucleares , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Excess dietary sugar intake increases the risk of unhealthy weight gain, an important cardiometabolic risk factor in children. To further our understanding of this relationship, we performed a narrative review using two approaches. First, research examining dietary sugar intake, its associations with cardiometabolic health, impact of genetics on sweet taste perception and intake, and how genetics moderates the association of dietary sugar intake and cardiometabolic risk factors in preschool-aged children 1.5-5 years old is reviewed. Second, methodological considerations for collecting and analyzing dietary intake of sugar, genetic information, and markers of cardiometabolic health among young children are provided. Our key recommendations include the following for researchers: (1) Further longitudinal research on sugar intake and cardiometabolic risk factors is warranted to inform policy decisions and guidelines for healthy eating in preschool-aged children. (2) Consistency in sugar definitions is needed across research studies to aid with comparisons of results. (3) Select dietary collection tools specific to each study's aim and sugar definition(s). (4) Limit subjectivity of dietary assessment tools as this impacts interpretation of study results. (5) Choose non-invasive biomarkers of cardiometabolic disease until the strengths and limitations of available biomarkers in preschool-aged children are clarified. (6) Select approaches that account for the polygenic nature of cardiometabolic disease such as genome risk scores and genome wide association studies to assess how genetics moderates the relationship between dietary sugar intake and cardiometabolic risk. This review highlights potential recommendations that will support a research environment to help inform policy decisions and healthy eating policies to reduce cardiometabolic risk in young children.
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BACKGROUND AIMS: Autologous hematopoietic stem cell transplantation (AHSCT) is a highly effective therapy for relapsing multiple sclerosis. Re-infused stem cells provide "rescue" from the pancytopenia induced by immuno-chemotherapy. To date, no study has analyzed the non-stem cell content of the leukapheresis product (graft) in regards to its influence on disease remission in AHSCT for multiple sclerosis (MS). METHODS: Detailed immunophenotyping of the stem cell graft was performed in a cohort of highly active patients with MS (n = 22) followed for a median of 6 years' post-AHSCT. RESULTS: Effector memory populations thought to house pathogenic clones including Th17 cells and central nervous system homing T cells were detected in the graft at similar proportions to pre-AHSCT. There was no association between absolute counts of these populations in the graft and treatment response. Only in responder patients was there evidence of a significant decrease in these putative pro-inflammatory populations by 3 months' post-transplant. Although there was no statistical difference in the number of T regulatory cells (Tregs) in the graft between responders and relapsing patients, the absolute count of Tregs in the graft correlated with circulating Tregs in the first 6 months post-AHSCT in responders alone. CONCLUSIONS: Our results collectively suggest that the early establishment of immune tolerance post-AHSCT appears to relate to a decrease in putative pathogenic cell populations following reinfusion, and that Treg load in the leukapheresis product is less relevant to treatment response than the early expansion of graft-derived Tregs. It therefore remains unclear whether employment of CD34 selection to manipulate the graft may offer additional benefit in remission rates post-AHSCT for MS. Cellular therapy targeted toward early Treg expansion may provide recourse for long-term remission rates in MS.
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Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Humanos , Esclerose Múltipla/terapia , Imunofenotipagem , Transplante Autólogo , Transplante de Células-TroncoRESUMO
BACKGROUND: Corticosteroids (CSs) have previously been incorporated into graft versus host disease (GVHD) prophylaxis regimens for bone marrow (BM) and haemopoietic stem cell transplant (HSCT). AIMS: To assess the impact of prophylactic CS in HSCT using peripheral blood (PB) stem cells. METHODS: Patients were identified from three HSCT centres receiving a first PB-HSCT between January 2011 and December 2015 from a fully human leukocyte antigen (HLA)-matched sibling or unrelated donor for acute myeloid leukaemia or acute lymphoblastic leukaemia. To enable meaningful comparison, patients were divided into two cohorts. RESULTS: Cohort 1 included only myeloablative-matched sibling HSCT, where the only variation in GVHD prophylaxis was the addition of CS. In these 48 patients, there were no differences in GVHD, relapse, non-relapse mortality, overall survival or GVHD-relapse-free-survival (GRFS) at 4 years after transplant. Cohort 2 included the remaining HSCT recipients, where one group received CS-prophylaxis and the non-CS group received an antimetabolite, ciclosporin and anti-T-lymphocyte globulin. In these 147 patients, those receiving CS-prophylaxis experienced higher rates of chronic GVHD (71% vs 18.1%, P < 0.001) and lower rates of relapse (14.9% vs 33.9%, P = 0.02). Those receiving CS-prophylaxis had a lower 4-year GRFS (15.7% vs 40.3%, P = 0.002). CONCLUSIONS: There does not appear to be a role for adding CS to standard GVHD prophylaxis regimens in PB-HSCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Recidiva Local de Neoplasia , Doença Enxerto-Hospedeiro/prevenção & controle , Corticosteroides/uso terapêutico , Estudos de Coortes , Recidiva , Estudos RetrospectivosRESUMO
Unhealthy diets are detrimental to health, but home meal preparation is associated with better diet quality. Among a sample of parents of children aged 2-12, this study aimed to 1) explore perceived challenges and strategies to meeting the 2019 Canada's Food Guide recommendation of "Cook more often". From October 2019 to January 2020, 8 focus groups were conducted with 40 parents (73% mothers; 78% white) from Southwestern Ontario, Canada. Sessions were audio-recorded and transcribed verbatim. A hybrid thematic approach with inductive and deductive data analysis was used. Reported challenges included time constraints, picky eating, lacking cooking skills, high price of some fresh ingredients, school restrictions on meals at school, and the influence of children's peers on food choices, mainly unhealthy snacks. Reported strategies to mitigate some challenges included planning and preparing meals ahead of time, using technology or services to make meal planning and grocery shopping more convenient, using devices and kitchen instruments, such as Crockpot®, to make cooking faster, receiving help from spouse or child(ren), and acknowledging that foods perceived as less healthful in moderation can be included in meal preparation. These findings can help inform interventions and educational campaigns to support cooking among families with young children.
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Culinária , Comportamento Alimentar , Feminino , Criança , Humanos , Pré-Escolar , Pais , Refeições , OntárioRESUMO
Purpose: To investigate the breakfast quality of preschool-aged children through a comparison of their energy and nutrient intakes at breakfast to published benchmarks for a balanced breakfast.Methods: Dietary data were collected for 163 children aged 3-5 years enrolled in the Guelph Family Health Study using one parent-reported online 24-hour recall and analyzed for energy and nutrient intakes. Breakfast quality was assessed by tallying the frequency of participants whose nutrient and energy intakes at their breakfast meal met the recommendations for a balanced breakfast established by the International Breakfast Research Initiative (IRBI).Results: Almost all participants (98%) consumed breakfast, and most participants (82.5%) met the energy IRBI recommendation. However, the majority of participants did not meet the IRBI recommendations for breakfast intakes of most macronutrients and micronutrients. In particular, fewer than 25% of participants met the IRBI recommendations for breakfast intakes of dietary fibre, niacin, folate, vitamin C, calcium, potassium and zinc.Conclusions: Almost all preschool-aged children in this study consumed breakfast, but the nutritional quality of their breakfast did not meet recommendations for most nutrients. These results can inform nutrition education and intervention programs for children that aim to improve the nutritional quality of breakfast.
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Desjejum , Dieta , Humanos , Pré-Escolar , Criança , Canadá , Ingestão de Energia , Ingestão de AlimentosRESUMO
Porcine cells devoid of three major carbohydrate xenoantigens, αGal, Neu5GC, and SDa (TKO) exhibit markedly reduced binding of human natural antibodies. Therefore, it is anticipated that TKO pigs will be better donors for human xenotransplantation. However, previous studies on TKO pigs using old world monkeys (OWMs) have been disappointing because of higher anti-TKO pig antibodies in OWMs than humans. Here, we show that long-term survival of renal xenografts from TKO pigs that express additional human transgenes (hTGs) can be achieved in cynomolgus monkeys. Kidney xenografts from TKO-hTG pigs were transplanted into eight cynomolgus recipients without pre-screening for low anti-pig antibody titers. Two recipients of TKO-hTG xenografts with low expression of human complement regulatory proteins (CRPs) (TKO-A) survived for 2 and 61 days, whereas six recipients of TKO-hTG xenografts with high CRP expression (TKO-B) survived for 15, 20, 71, 135, 265, and 316 days. Prolonged CD4+ T cell depletion and low anti-pig antibody titers, which were previously reported important for long-term survival of αGal knock-out (GTKO) xenografts, were not always required for long-term survival of TKO-hTG renal xenografts. This study indicates that OWMs such as cynomolgus monkeys can be used as a relevant model for clinical application of xenotransplantation using TKO pigs.
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Transplante de Rim , Animais , Animais Geneticamente Modificados , Rejeição de Enxerto/genética , Humanos , Macaca fascicularis , Suínos , Transplante HeterólogoRESUMO
PURPOSE: To introduce a novel convolutional neural network (CNN)-based approach for frequency-and-phase correction (FPC) of MR spectroscopy (MRS) spectra to achieve fast and accurate FPC of single-voxel MEGA-PRESS MRS data. METHODS: Two neural networks (one for frequency and one for phase) were trained and validated using published simulated and in vivo MEGA-PRESS MRS dataset with wide-range artificial frequency and phase offsets applied. The CNN-based approach was subsequently tested and compared to the current deep learning solution: multilayer perceptrons (MLP). Furthermore, random noise was added to the original simulated dataset to further investigate the model performance at varied signal-to-noise ratio (SNR) levels (i.e., 10, 5, and 2.5). Additional frequency and phase offsets (i.e., small, moderate, large) were also applied to the in vivo dataset, and the CNN model was compared to the conventional approach SR and model-based SR implementation (mSR). RESULTS: The CNN model is more robust to noise compared to the MLP-based approach due to having smaller mean absolute errors in both frequency (0.01 ± 0.01 Hz at SNR = 10 and 0.01 ± 0.02 Hz at SNR = 2.5) and phase (0.12 ± 0.09° at SNR = 10 and -0.07 ± 0.44° at SNR = 2.5) offset prediction. Furthermore, better performance was demonstrated for FPC when compared to the MLP-based approach, and SR when applied to the in vivo dataset for both with and without additional offsets. CONCLUSION: A CNN-based approach provides a solution to the automated preprocessing of MRS data, and the experimental results demonstrate the quantitatively improved spectra quality compared to the state-of-the-art approach.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Espectroscopia de Ressonância Magnética , Razão Sinal-RuídoRESUMO
BACKGROUND: The COVID-19 pandemic has forced a fundamental change in the global procurement of allogeneic hematopoietic progenitor cells (HPCs) for transplantation. To better meet the emergent challenges of transporting cryopreserved allogeneic HPC during pandemics, there is an urgent need for External Quality Assurance (EQA) programs to evaluate reproducibility and harmonization of viable CD34+ cell (vCD34+) HPC enumeration, as the current EQA programs are unsuitable for analysis of vCD34+. The cost-effective distribution of HPC cryopreserved reference samples (CRSs) with acceptable reproducibility and specificity is key to the success of a vCD34+ EQA program. METHODS: Cryopreserved HPC samples (n = 11) were either stored on dry ice for 1 to 4 days or for 1 day followed by liquid nitrogen (LN) storage for 1 to 3 days to assess optimal conditions for vCD34+ EQA. Flow cytometric enumeration of vCD34+ HPCs was performed using a single platform assay combined with 7-AAD viability dye exclusion. The optimum transportation condition was validated in pilot and multicenter national studies (n = 12). RESULTS: A combination of 1 day on dry ice followed by LN storage stabilized viability compared with continuous storage on dry ice. This study demonstrates that dispatch of CRSs on dry ice to recipient centers across a distance of ≤4000 km within 26 h, followed by LN storage, resulted in reproducible intercenter vCD34+ enumeration. The estimated cost of safer and more convenient dry ice delivery is >20-fold lower than that of LN. CONCLUSION: This approach can form the basis for economically and scientifically acceptable distribution of CRSs for external vCD34+ EQA.
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COVID-19 , Pandemias , Antígenos CD34 , COVID-19/epidemiologia , Criopreservação/métodos , Células-Tronco Hematopoéticas , Humanos , Pandemias/prevenção & controle , Reprodutibilidade dos TestesRESUMO
Cardiac light chain (AL) amyloidosis is a condition with a very poor prognosis. We report a retrospective analysis comparing the traditional melphalan and dexamethasone protocol with cyclophosphamide, bortezomib and dexamethasone in late-stage cardiac AL amyloidosis. The primary end points were overall survival and haematological response. Both regimens provided meaningful responses in this difficult to treat patient group.
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Amiloidose , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Bortezomib , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Melfalan , Estudos Retrospectivos , Dexametasona , Amiloidose/tratamento farmacológico , CiclofosfamidaRESUMO
BACKGROUND: Results have been varied regarding the effect of donor age on the outcome of unrelated donor haemopoietic cell transplantation (HCT). AIMS: To determine the influence of donor age on adult unrelated donor HCT outcome in Australia. METHODS: Patients were included in the study if they were aged 16 years or above and underwent first allogeneic unrelated donor HCT in Australia for the indications of acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML), chronic myelogenous leukaemia (CML) or myelodysplastic syndromes (MDS) between the years of 2001 and 2014 inclusive. The main outcome measure was overall survival (OS), which was tested against independent variables using univariate Kaplan-Meier methods and multivariate Cox regression. RESULTS: A total of 1158 unrelated donor HCT were represented in the data. Cumulative incidences of engraftment, transplant related mortality (TRM), acute graft-versus-host disease (GvHD), chronic GvHD and relapse were not significantly affected by donor age. OS probability at 5 years post-transplant was 48.3%. In multivariate analysis of OS, year of transplant 2001-2007, recipient age 40 years or greater, poor risk disease, human leukocyte antigen (HLA) match less than 6/6 and poor performance status at transplant (Karnofsky scale) were independently significant adverse OS risk factors. Donor age was not a significant risk factor for OS in univariate or multivariate analysis. CONCLUSIONS: The conclusion from this study was that donor age (up to 59 years) did not influence post-transplant outcome among adult unrelated donor HCT performed in Australia for haematologic malignancies.
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Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Adolescente , Adulto , Austrália/epidemiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Recidiva Local de Neoplasia , Resultado do TratamentoRESUMO
Staphylococcus aureus is an important pathogen for keratitis, a vision-threatening disease. We aimed to investigate the genotyping, antibiotic susceptibility, and clinical features of S. aureus keratitis, and to explore the possible role of Panton-Valentine leucocidin (PVL), a major virulence factor of S. aureus. We recruited 49 patients with culture-proven S. aureus keratitis between 2013 and 2017 at Chang Gung Memorial Hospital, Taiwan. PVL gene, multilocus sequence type (MLST), staphylococcal cassette chromosome mec (SCCmec), and pulsed-field gel electrophoresis (PFGE) were performed. Antibiotic susceptibility was verified using disk diffusion/E test. There were 49 patients with S. aureus keratitis; 17 (34.7%) were caused by methicillin-resistant S. aureus (MRSA) and 9 (18.4%) isolates had PVL genes. The predominant genotyping of MRSA isolates was CC59/PFGE type D/SCCmec VT/PVL (+). All methicillin-sensitive S. aureus (MSSA) and approximately 60% MRSA were susceptible to fluoroquinolones. No significant differences in clinical features, treatments, and visual outcomes were observed between MRSA/MSSA or PVL(+)/PVL(-) groups. In Taiwan, approximately one third of S. aureus keratitis was caused by MRSA, mainly community-associated MRSA. Although MRSA isolates were more resistant than MSSA, clinical characteristics were similar between two groups. Fluoroquinolones could be good empiric antibiotics for S. aureus keratitis.
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Infecções Comunitárias Adquiridas , Ceratite , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Genótipo , Humanos , Ceratite/tratamento farmacológico , Ceratite/epidemiologia , Leucocidinas/genética , Meticilina , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/genética , Staphylococcus aureus/genética , Taiwan/epidemiologia , Fatores de Virulência/genéticaRESUMO
Purpose: To determine if intake (servings/day) of total dairy and/or dairy subtypes (milk, cheese, and yogurt) were associated with biomarkers related to dyslipidemia, insulin sensitivity and inflammation in a sample of cardio-metabolically healthy young children from the Guelph Family Health Study at the University of Guelph, Guelph, Ontario, Canada.Methods: Baseline data from 42 children (aged 2.0-6.2 years) from 33 families who provided a dietary assessment and a fasted blood sample were included in this cross-sectional analysis. Linear and logistic regressions using generalized estimating equations were used for analysis and models were adjusted for age, gender, and household income.Results: In total, 42 children (3.74 ± 1.23 years old; mean (± SD)) consumed median (25th percentile, 75th percentile) servings/day of 1.70 (1.16, 2.81) for total dairy, 0.74 (0.50, 1.70) for milk, 0.63 (0.00, 1.16) for cheese, and 0.00 (0.00, 0.38) for yogurt. Cheese intake was significantly inversely associated with LDL cholesterol (-0.16 (95% CI: -0.29, -0.03) mmol/L per serving; P = 0.02)). No other associations between dairy intake and biomarkers were significant.Conclusions: Cheese intake was inversely associated with LDL cholesterol in this preliminary study of cardio-metabolically healthy young children, thereby warranting further research on dairy intake and cardiometabolic risk factors.