Abstract
Background. The omega-3 index (eicosapentaenoic acid + docosahexaenoic acid) content in red blood cell membranes has been suggested as a novel risk marker for cardiac death. Objective. To ...assess the ability of the omega-3 index to predict all-cause mortality, cardiac death and sudden cardiac death following hospitalization with an acute coronary syndrome (ACS), and to include arachidonic acid (AA) in risk assessment. Material and methods. The omega-3 index was measured in 572 consecutive patients (median 63 years and 59% males) admitted with chest pain and suspected ACS in an inland Northern Argentinean city with a dietary habit that was essentially based on red meat and a low intake of fish. Clinical endpoints were collected during a 5-year follow-up period, median 3.6 years, range 1 day to 5.5 years. Stepwise Cox regression analysis was employed to compare the rate of new events in the quartiles of the omega-3 index measured at inclusion. Multivariable analysis was performed. Results. No statistical significant differences in baseline characteristics were noted between quartiles of the omega-3 index. The median of the adjusted omega-3 index was 3.6%. During the follow-up period, 100 (17.5%) patients died. Event rates were similar in all quartiles of the omega-3 index, with no statistical significant differences. AA added no prognostic information. Conclusion. In a population with a low intake of fish and fish oils, the adjusted omega-3 index did not predict fatal events following hospitalization in patients with acute chest pain and suspected ACS.
Regulatory machinery for gene expression, replication, and repair are architecturally organized in nuclear microenvironments. This compartmentalization provides threshold concentrations of ...macromolecules for the organization and assembly of regulatory complexes for combinatorial control. A mechanistic under standing of biological control requires the combined application of molecular, cellular, biochemical, and in vivo genetic approaches. This chapter provides methodologies to characterize nuclear organization of regulatory machinery by in situ immunofluorescence microscopy.
Chromatin remodeling at eukaryotic gene promoter sequences accompanies transcriptional activation. Both molecular events rely on specific protein−DNA interactions that occur within these promoter ...sequences. Binding of CBFα/AML/PEBP2α (core binding factor α/acute myelogenous leukemia/polyoma enhancer binding protein 2α) proteins is a key event in both tissue-specific and developmentally regulated osteocalcin (OC) promoter activity. To address linkage between chromatin organization and transcription factor binding, we reconstituted segments of the rat OC gene proximal promoter into mononucleosomes and studied binding of CBFα proteins. We analyzed binding of bacterially produced Cbfα2Α and Cbfα2B, two splice variants of the human CBFα2 gene, and determined the effect of heterodimerization with the Cbfβ subunit on binding activity. Our results indicate that binding of the truncated Cbfα2A protein to naked DNA is independent of Cbfβ whereas Cbfα2A binding to nucleosomal DNA was enhanced by Cbfβ. In contrast, the Cbfα2B interaction with either naked or nucleosomal DNA was strongly dependent on heterodimerization with the Cbfβ subunit. Additionally, our results demonstrate that both Cbfα2A alone and Cbfα2B complexed with Cbfβ can interact with nucleosomal DNA only if there is a degree of flexibility in the positioning of the histone octamer on the DNA fragment and exposure of the CBFα site. This situation was achieved with a DNA segment of 182 bp from the rat OC promoter that preferentially positions mononucleosomes upstream of the CBFα binding site and leaves this element partially exposed. Taken together, these results suggest that nucleosomal translational positioning is a major determinant of the binding of CBFα factors to nucleosomal DNA.
Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of ...80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.
Background: INTERBIO-21st is Phase II of the INTERGROWTH-21st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University ...and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.
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