56 research outputs found

    Dietary patterns and changes in frailty status: the Rotterdam study

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    Purpose: To determine the associations between a priori and a posteriori derived dietary patterns and a general state of health, measured as the accumulation of deficits in a frailty index. Methods: Cross-sectional and longitudinal analysis embedded in the population-based Rotterdam Study (n = 2632) aged 45 years. Diet was assessed at baseline (year 2006) using food frequency questionnaires. Dietary patterns were defined a priori using an existing index reflecting adherence to national dietary guidelines and a posteriori using principal component analysis. A frailty index was composed of 38 health deficits and measured at baseline and follow-up (4 years later). Linear regression analyses were performed using adherence to each of the dietary patterns as exposure and the frailty index as outcome (all in Z-scores). Results: Adherence to the national dietary guidelines was associated with lower frailty at baseline (β −0.05, 95% CI −0.08, −0.02). Additionally, high adherence was associated with lower frailty scores over time (β −0.08, 95% CI −0.12, −0.04). The PCA revealed three dietary patterns that we named a “Traditional” pattern, high in legumes, eggs and savory snacks; a “Carnivore” pattern, high in meat and poultry; and a “Health Conscious” pattern, high in whole grain products, vegetables and fruit. In the cross-sectional analyses adherence to these patterns was not associated with frailty. However, adherence to the “Traditional” pattern was associated with less frailty over time (β −0.09, 95% CI −0.14, −0.05). Conclusion: No associations were found for adherence to a “healthy” pattern or “Carnivore” pattern. However, Even in a population that is relatively young and healthy, adherence to dietary guidelines or adherence to the Traditional pattern could help to prevent, delay or reverse frailty levels

    Flow cytometric minimal residual disease assessment in B-cell precursor acute lymphoblastic leukaemia patients treated with CD19-targeted therapies — a EuroFlow study

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    The standardized EuroFlow protocol, including CD19 as primary B-cell marker, enables highly sensitive and reliable minimal residual disease (MRD) assessment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients treated with chemotherapy. We developed and validated an alternative gating strategy allowing reliable MRD analysis in BCP-ALL patients treated with CD19-targeting therapies. Concordant data were obtained in 92% of targeted therapy patients who remained CD19-positive, whereas this was 81% in patients that became (partially) CD19-negative. Nevertheless, in both groups median MRD values showed excellent correlation with the original MRD data, indicating that, despite higher interlaboratory variation, the overall MRD analysis was correct.The EuroFlow Consortium received support from the FP6-2004-LIFESCIHEALTH-5 programme of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP). The EuroFlow Consortium is part of the European Scientific Foundation for Hemato-Oncology (ESLHO), a Scientific Working Group (SWG) of the European Hematology Association (EHA). TS and LS were supported by a Scientific Grant from the Medical University of Silesia Nr. PCN-1-050/K/0/K

    Reactivation of ancestral strains of HIV-1 in the gp120 V3 env region in patients failing antiretroviral therapy and subjected to structured treatment interruption

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    We analyzed gp120V3 HIV-1 env region genetic diversity of 27 patients failing antiretrovirals and subjected to 12-week structured treatment interruption (STI). Based on heteroduplex mobility assays, eight patients presented low pre- and post-STI genetic diversity (G1); five presented high pre-STI but low post-STI diversity (G2); five presented low pre-STI and high post-STI diversity (G3); and nine, high pre- and post-STI diversity (G4). One patient from G1, two from G2 and two from G3 were subjected to proviral DNA end-point PCR and sequencing. in three patients, the dramatic disturbance caused by STI resulted in ancestral viral progeny activation, which repopulated the cell reservoir. in two patients presenting highly homogeneous sequences and low immune selective pressure (dN/dS ratio < 1), this phenomenon was not observed. the mechanisms involved in viral evolution, in which antiretroviral therapy also applies selective pressure, sometimes affects coreceptor usage of circulating viruses, leading to the suppression of x4 strains. (c) 2006 Published by Elsevier Inc.Universidade Federal de São Paulo, Escola Paulista Med, Lab Retrovirol, BR-04039032 São Paulo, BrazilFundacao Pro Sangue, BR-05403000 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Lab Retrovirol, BR-04039032 São Paulo, BrazilWeb of Scienc

    Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

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    Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors

    Dietary patterns and changes in frailty status: the Rotterdam study

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    Purpose: To determine the associations between a priori and a posteriori derived dietary patterns and a general state of health, measured as the accumulation of deficits in a frailty index. Methods: Cross-sectional and longitudinal analysis embedded in the population-based Rotterdam Study (n = 2632) aged 45 years. Diet was assessed at baseline (year 2006) using food frequency questionnaires. Dietary patterns were defined a priori using an existing index reflecting adherence to national dietary guidelines and a posteriori using principal component analysis. A frailty index was composed of 38 health deficits and measured at baseline and follow-up (4 years later). Linear regression analyses were performed using adherence to each of the dietary patterns as exposure and the frailty index as outcome (all in Z-scores). Results: Adherence to the national dietary guidelines was associated with lower frailty at baseline (β −0.05, 95% CI −0.08, −0.02). Additionally, high adherence was associated with lower frailty scores over time (β −0.08, 95% CI −0.12, −0.04). The PCA revealed three dietary patterns that we named a “Traditional” pattern, high in legumes, eggs and savory snacks; a “Carnivore” pattern, high in meat and poultry; and a “Health Conscious” pattern, high in whole grain products, vegetables and fruit. In the cross-sectional analyses adherence to these patterns was not associated with frailty. However, adherence to the “Traditional” pattern was associated with less frailty over time (β −0.09, 95% CI −0.14, −0.05). Conclusion: No associations were found for adherence to a “healthy” pattern or “Carnivore” pattern. However, Even in a population that is relatively young and healthy, adherence to dietary guidelines or adherence to the Traditional pattern could help to prevent, delay or reverse frailty levels

    Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model

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    Background Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. Methods and principal findings S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. Conclusion S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice

    The distribution of congenital anomalies within the VACTERL association among tumor necrosis factor antagonist-exposed pregnancies is similar to the general population

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    Objective. To compare the distribution of congenital anomalies within the VACTERL association (vertebral defects, anal atresia, cardiac, tracheoesophageal, renal, and limb abnormalities) between patients exposed to tumor necrosis factor-alpha (TNF-alpha) antagonist and the general population. Methods. Analysis for comparison of proportional differences to a previous publication between anomaly subgroups, according to subgroup definitions of the European Surveillance of Congenital Anomalies (EUROCAT), a population-based database. Results. Most EUROCAT subgroups belonging to the VACTERL association contained only one or 2 records of TNF-a antagonist exposure, so comparison of proportions was imprecise. Only the category "limb abnormalities" showed a significantly higher proportion in the general population. Conclusion. The high number of congenital anomalies belonging to the VACTERL association from a report of pregnancies exposed to TNF-alpha antagonists could not be confirmed using a population-based congenital anomaly database. (First Release July 1 2011; J Rheumatol 2011;38:1871-4; doi:10.3899/jrheum.101316)
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