149 research outputs found

    Low availability of carnitine precursors as a possible reason for the diminished plasma carnitine concentrations in pregnant women

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    <p>Abstract</p> <p>Background</p> <p>It has been shown that plasma carnitine concentrations decrease markedly during gestation. A recent study performed with a low number of subjects suggested that this effect could be due to a low iron status which leads to an impairment of carnitine synthesis. The present study aimed to confirm this finding in a greater number of subjects. It was moreover intended to find out whether low carnitine concentrations during pregnancy could be due to a reduced availability of precursors of carnitine synthesis, namely trimethyllysine (TML) and γ-butyrobetaine (BB).</p> <p>Methods</p> <p>Blood samples of 79 healthy pregnant women collected at delivery were used for this study.</p> <p>Results</p> <p>There was only a weak, non-significant (P > 0.05), correlation between plasma concentration of ferritin and those of free and total carnitine. There was no correlation between other parameters of iron status (plasma iron concentration, hemoglobin, MCV, MCH) and plasma concentration of free and total carnitine. There were, however, significant (P < 0.05) positive correlations between concentrations of TML and BB and those of free and total carnitine in plasma.</p> <p>Conclusions</p> <p>The results of this study suggest that an insufficient iron status is not the reason for low plasma carnitine concentrations observed in pregnant women. It is rather indicated that low plasma carnitine concentrations are caused by a low availability of precursors for carnitine synthesis during gestation.</p

    To be or not to be a pseudogene: a molecular epidemiological approach to the mclx genes and its impact in tuberculosis

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    Tuberculosis presents a myriad of symptoms, progression routes and propagation patterns not yet fully understood. Whereas for a long time research has focused solely on the patient immunity and overall susceptibility, it is nowadays widely accepted that the genetic diversity of its causative agent, Mycobacterium tuberculosis, plays a key role in this dynamic. This study focuses on a particular family of genes, the mclxs (Mycobacterium cyclase/LuxR-like genes), which codify for a particular and nearly mycobacterial-exclusive combination of protein domains. mclxs genes were found to be pseudogenized by frameshift-causing insertion(s)/deletion(s) in a considerable number of M. tuberculosis complex strains and clinical isolates. To discern the functional implications of the pseudogenization, we have analysed the pattern of frameshift-causing mutations in a group of M. tuberculosis isolates while taking into account their microbial-, patient- and disease-related traits. Our logistic regression-based analyses have revealed disparate effects associated with the transcriptional inactivation of two mclx genes. In fact, mclx2 (Rv1358) pseudogenization appears to be primarily driven by the microbial phylogenetic background, being mainly related to the Euro-American (EAm) lineage; on the other hand, mclx3 (Rv2488c) presents a higher tendency for pseudogenization among isolates from patients born on the Western Pacific area, and from isolates causing extra-pulmonary infections. These results contribute to the overall knowledge on the biology of M. tuberculosis infection, whereas at the same time launch the necessary basis for the functional assessment of these so far overlooked genes.This work was supported by Fundacao para a Ciencia e Tecnologia (FCT), Portugal, and cofunded by Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER), and from Projeto Estrategico - LA 26 - 2013-2014 (PEst-C/SAU/LA0026/2013). H.N.-G. received a personal FCT Grant (SFRH/BD/33902/2209). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Mother-to-child transmission of human immunodeficiency virus in aten years period

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    <p>Abstract</p> <p>Objectives</p> <p>to evaluate mother-to-child transmission (MTCT) rates and related factors in HIV-infected pregnant women from a tertiary hospital between 2000 and 2009.</p> <p>Subjects and method</p> <p>cohort of 452 HIV-infected pregnant women and their newborns. Data was collected from recorded files and undiagnosed children were enrolled for investigation. Statistical analysis: qui-square test, Fisher exact test, Student <it>t </it>test, Mann-Whitney test, ANOVA, risk ratio and confidence intervals.</p> <p>Results</p> <p>MTCT occurred in 3.74%. The study population displayed a mean age of 27 years; 86.5% were found to have acquired HIV through sexual contact; 55% were aware of the diagnosis prior to the pregnancy; 62% were not using HAART. Mean CD4 cell-count was 474 cells/ml and 70.3% had undetectable viral loads in the third trimester. HAART included nevirapine in 35% of cases and protease inhibitors in 55%; Zidovudine monotherapy was used in 7.3%. Mean gestational age at delivery was 37.2 weeks and in 92% by caesarian section; 97.2% received intravenous zidovudine. Use of AZT to newborn occurred in 100% of them. Factors identified as associated to MTCT were: low CD4 cell counts, elevated viral loads, maternal AIDS, shorter periods receiving HAART, other conditions (anemia, IUGR (intra uterine growth restriction), oligohydramnium), coinfecctions (CMV and toxoplasmosis) and the occurrence of labor. Use of HAART for longer periods, caesarian and oral zidovudine for the newborns were associated with a decreased risk. Poor adhesion to treatment was present in 13 of the 15 cases of transmission; in 7, coinfecctions were diagnosed (CMV and toxoplasmosis).</p> <p>Conclusion</p> <p>Use of HAART and caesarian delivery are protective factors for mother-to-child transmission of HIV. Maternal coinfecctions and other conditions were risk factors for MTCT.</p

    Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

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    A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

    Intrinsic Mitochondrial Membrane Potential and Associated Tumor Phenotype Are Independent of MUC1 Over-Expression

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    We have established previously that minor subpopulations of cells with stable differences in their intrinsic mitochondrial membrane potential (Δψm) exist within populations of mammary and colonic carcinoma cells and that these differences in Δψm are linked to tumorigenic phenotypes consistent with increased probability of participating in tumor progression. However, the mechanism(s) involved in generating and maintaining stable differences in intrinsic Δψm and how they are linked to phenotype are unclear. Because the mucin 1 (MUC1) oncoprotein is over-expressed in many cancers, with the cytoplasmic C-terminal fragment (MUC1 C-ter) and its integration into the outer mitochondrial membrane linked to tumorigenic phenotypes similar to those of cells with elevated intrinsic Δψm, we investigated whether endogenous differences in MUC1 levels were linked to stable differences in intrinsic Δψm and/or to the tumor phenotypes associated with the intrinsic Δψm. We report that levels of MUC1 are significantly higher in subpopulations of cells with elevated intrinsic Δψm derived from both mammary and colonic carcinoma cell lines. However, using siRNA we found that down-regulation of MUC1 failed to significantly affect either the intrinsic Δψm or the tumor phenotypes associated with increased intrinsic Δψm. Moreover, whereas pharmacologically mediated disruption of the Δψm was accompanied by attenuation of tumor phenotype, it had no impact on MUC1 levels. Therefore, while MUC1 over-expression is associated with subpopulations of cells with elevated intrinsic Δψm, it is not directly linked to the generation or maintenance of stable alterations in intrinsic Δψm, or to intrinsic Δψm associated tumor phenotypes. Since the Δψm is the focus of chemotherapeutic strategies, these data have important clinical implications in regard to effectively targeting those cells within a tumor cell population that exhibit stable elevations in intrinsic Δψm and are most likely to contribute to tumor progression

    Morphological and Functional Changes in the Retina after Chronic Oxygen-Induced Retinopathy

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    The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment

    Physiotherapists' experiences of physiotherapy interventions in scientific physiotherapy publications focusing on interventions for children with cerebral palsy: a qualitative phenomenographic approach

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    Background: Physiotherapy research concerning interventions for children with CP is often focused on collecting evidence of the superiority of particular therapeutic methods or treatment modalities. Articulating and documenting the use of theory, instrumentation and research design and the assumptions underlying physiotherapy research interventions are important. Physiotherapy interventions focusing on children with Cerebral Palsy should, according to the literature, be based on a functional and environmental perspective with task-specific functional activity, motor learning processes and Family-Centred Service i.e. to enhance motor ability and improve capacity so that the child can perform the tasks necessary to participate actively in everyday life. Thus, it is important to coordinate the norms and values of the physiotherapist with those of the family and child. The aim of this study was to describe how physiotherapists' experiences physiotherapy interventions for children with CP in scientific physiotherapy publications written by physiotherapists. Methods: A qualitative phenomenographic approach was used. Twenty-one scientific articles, found in PubMed, strategically chosen according to year of publication (2001-2009), modality, journals and country, were investigated. Results: Three qualitatively different descriptive categories were identified: A: Making it possible a functional-based intervention based on the biopsychosocial health paradigm, and the role of the physiotherapist as collaborative, interacting with the child and family in goal setting, intervention planning and evaluation, B: Making it work an impairment-based intervention built on a mixed health paradigm (biomedical and biopsychosocial), and the role of the physiotherapist as a coach, leading the goal setting, intervention planning and evaluation and instructing family members to carry out physiotherapist directed orders, and; C: Making it normal an impairment-based intervention built on a biomedical health paradigm, and the role of the physiotherapist as an authoritative expert who determine goals, intervention planning and evaluation. Conclusions: Different paradigms of health and disability lead to different approaches to physiotherapy which influence the whole intervention process regarding strategies for the assessment and treatment, all of which influence Family-Centred Service and the child's motor learning strategies. The results may deepen physiotherapists' understanding of how different paradigms of health influence the way in which various physiotherapy approaches in research seek to solve the challenge of CP
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