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The identification of the active sites for the electrochemical reduction of CO2 (CO2 RR) to specific chemical products is elusive, owing in part to insufficient data gathered on clean and atomically well-ordered electrode surfaces. Here, ultrahigh vacuum based preparation methods and surface science characterization techniques are used with gas chromatography to demonstrate that subtle changes in the preparation of well-oriented Cu(100) and Cu(111) single-crystal surfaces drastically affect their CO2 RR selectivity. Copper single crystals with clean, flat, and atomically ordered surfaces are predicted to yield hydrocarbons; however, these were found experimentally to favor the production of H2 . Only when roughness and defects are introduced, for example by electrochemical etching or a plasma treatment, are significant amounts of hydrocarbons generated. These results show that structural and morphological effects are the key factors determining the catalytic selectivity of CO2 RR.
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BACKGROUND AND PURPOSE: AV-1451 (18 F-AV-1451, flortaucipir) positron emission tomography was performed in C9orf72 expansion carriers to assess tau accumulation and disease manifestation. METHODS: Nine clinically characterized C9orf72 expansion carriers and 18 age- and gender- matched cognitively normal individuals were psychometrically evaluated and underwent tau positron emission tomography imaging. The regional AV-1451 standard uptake value ratios from multiple brain regions were analyzed. Spearman correlation was performed to relate the AV-1451 standard uptake value ratio to clinical, psychometric and cerebrospinal fluid measures. RESULTS: C9orf72 expansion carriers had increased AV-1451 binding in the entorhinal cortex compared to controls. Primary age-related tauopathy was observed postmortem in one patient. AV-1451 uptake did not correlate with clinical severity, disease duration, psychometric performance or cerebrospinal fluid markers. CONCLUSION: C9orf72 expansion carriers exhibited increased AV-1451 uptake in entorhinal cortex compared to cognitively normal controls, suggesting a propensity for primary age-related tauopathy. However, AV-1451 accumulation was not associated with psychometric performance in our cohort.
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Proteína C9orf72/genética , Disfunção Cognitiva/metabolismo , Córtex Entorrinal/metabolismo , Tomografia por Emissão de Pósitrons , Tauopatias/metabolismo , Proteínas tau/metabolismo , Idoso , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Estudos de Coortes , Expansão das Repetições de DNA , Córtex Entorrinal/diagnóstico por imagem , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Tauopatias/complicações , Tauopatias/diagnóstico por imagemRESUMO
The key role of morphological defects (e.g., irregular steps and dislocations) on the selectivity of model Cu catalysts for the electrocatalytic reduction of CO2 (CO2RR) is illustrated here. Cu(111) single-crystal surfaces prepared under ultrahigh vacuum (UHV) conditions and presenting similar chemical and local microscopic surface features were found to display different product selectivity during the CO2RR. In particular, changes in selectivity from hydrogen-dominant to hydrocarbon-dominant product distributions were observed based on the number of CO2RR electrolysis pretreatment cycles performed prior to a subsequent UHV surface regeneration treatment, which lead to surfaces with seemingly identical chemical composition and local crystallographic structure. However, significant mesostructural changes were observed through a micron-scale microscopic analysis, including a higher density of irregular steps on the samples producing hydrocarbons. Thus, our findings highlight that step edges are key for C-C coupling in the CO2RR and that not only atomistic but also mesoscale characterization of electrocatalytic materials is needed in order to comprehend complex selectivity trends.
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This work presents the results of the behavioural and serologic survey on HIV/AIDS conducted from December 2007 to December 2008 among the group of STD (sexually transmitted disease) patients, supposed to be at HIV infection risk. In Mauritania, the last survey of HIV seroprevalence among the STD patients goes up to the year 1995 (the prevalence was estimated then to be 0.9%). The goal was to determine the seroprevalence of HIV and syphilis and to gather information on the knowledge, the sexual behaviours on a risk concerning the HIV/AIDS, and the sexually transmitted disease among these patients. The census has been made on over 224 STD patients during the period of the study, without predominance of sex and with a majority of young adults. The prevalence for HIV is 9% and for the syphilis it is 10%. Actually, the condom is widely underused by this group, even in occasional intercourse. The STD patients are a group of risk towards HIV, because of their risk behaviours and low level of knowledge.
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Infecções por HIV/epidemiologia , Soroprevalência de HIV , HIV-1 , Infecções Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Cidades/epidemiologia , Preservativos/estatística & dados numéricos , Feminino , Infecções por HIV/sangue , HIV-1/fisiologia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Mauritânia/epidemiologia , Comportamento Sexual/fisiologia , Comportamento Sexual/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/sangue , Adulto JovemRESUMO
Electrocatalyst surfaces prepared under ultrahigh vacuum (UHV) conditions can create model surfaces to better connect theoretical calculations with experimental studies. The development of a single crystal sample holder and inert electrochemical cells prepared with modularity and chemical stability in mind would allow for expensive single crystals to be reused indefinitely in both UHV and electrochemical settings. This sample holder shows reproducible surface preparations for single crystal samples and consistent electrochemical experiments without the introduction of impurities into the surface. The presented setup has been used as a critical piece for the characterization of Cu(111) surfaces under CO2 electrochemical reduction reaction conditions as a test case.
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While metabolism was initially thought to play a passive role in cell biology by generating ATP to meet bioenergetic demands, recent studies have identified critical roles for metabolism in the generation of new biomass and provision of obligate substrates for the epigenetic modification of histones and DNA. This review details how metabolites generated through glycolysis and the tricarboxylic acid cycle are utilized by somatic stem cells to support cell proliferation and lineage commitment. Importantly, we also discuss the evolving hypothesis that histones can act as an energy reservoir during times of energy stress. Finally, we discuss how cells integrate both extrinsic metabolic cues and intrinsic metabolic machinery to regulate cell fate.
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Células-Tronco Adultas/metabolismo , Células-Tronco Adultas/citologia , Animais , Proliferação de Células , Ciclo do Ácido Cítrico , Glicólise , HumanosRESUMO
gamma-Sarcoglycan is a transmembrane, dystrophin-associated protein expressed in skeletal and cardiac muscle. The murine gamma-sarcoglycan gene was disrupted using homologous recombination. Mice lacking gamma-sarcoglycan showed pronounced dystrophic muscle changes in early life. By 20 wk of age, these mice developed cardiomyopathy and died prematurely. The loss of gamma-sarcoglycan produced secondary reduction of beta- and delta-sarcoglycan with partial retention of alpha- and epsilon-sarcoglycan, suggesting that beta-, gamma-, and delta-sarcoglycan function as a unit. Importantly, mice lacking gamma-sarco- glycan showed normal dystrophin content and local- ization, demonstrating that myofiber degeneration occurred independently of dystrophin alteration. Furthermore, beta-dystroglycan and laminin were left intact, implying that the dystrophin-dystroglycan-laminin mechanical link was unaffected by sarcoglycan deficiency. Apoptotic myonuclei were abundant in skeletal muscle lacking gamma-sarcoglycan, suggesting that programmed cell death contributes to myofiber degeneration. Vital staining with Evans blue dye revealed that muscle lacking gamma-sarcoglycan developed membrane disruptions like those seen in dystrophin-deficient muscle. Our data demonstrate that sarcoglycan loss was sufficient, and that dystrophin loss was not necessary to cause membrane defects and apoptosis. As a common molecular feature in a variety of muscular dystrophies, sarcoglycan loss is a likely mediator of pathology.
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Apoptose/genética , Distrofina/metabolismo , Glicoproteínas de Membrana/deficiência , Proteínas Musculares/fisiologia , Animais , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Distroglicanas , Histocitoquímica , Imuno-Histoquímica , Laminina/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Microscopia Eletrônica , Músculo Esquelético/patologia , Distrofias Musculares/genética , Miocárdio/patologiaRESUMO
Although synaptic AMPA receptors have been shown to rapidly internalize, synaptic NMDA receptors are reported to be static. It is not certain whether NMDA receptor stability at synaptic sites is an inherent property of the receptor, or is due to stabilization by scaffolding proteins. In this study, we demonstrate that NMDA receptors are internalized in both heterologous cells and neurons, and we define an internalization motif, YEKL, on the distal C-terminus of NR2B. In addition, we show that the synaptic protein PSD-95 inhibits NR2B-mediated internalization, and that deletion of the PDZ-binding domain of NR2B increases internalization in neurons. This suggests an involvement for PSD-95 in NMDA receptor regulation and an explanation for NMDA receptor stability at synaptic sites.
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Sistema Nervoso Central/metabolismo , Endocitose/fisiologia , Neurônios/metabolismo , Transporte Proteico/fisiologia , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismo , Membranas Sinápticas/metabolismo , Motivos de Aminoácidos/fisiologia , Animais , Sítios de Ligação/fisiologia , Sistema Nervoso Central/ultraestrutura , Clatrina/metabolismo , Proteína 4 Homóloga a Disks-Large , Feto , Células HeLa/citologia , Células HeLa/metabolismo , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Proteínas do Tecido Nervoso/metabolismo , Neurônios/ultraestrutura , Estrutura Terciária de Proteína/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/ultraestrutura , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Membranas Sinápticas/ultraestruturaRESUMO
INTRODUCTION: Infiltration and extravasation account for 23-78 % of the complications stemming from peripheral venous perfusions in neonatal intensive care units. Their consequences, sometimes dramatic, can be pain, infections, or even loss of skin, which can lead to nerve and/or muscle damage, particularly severe for preterm neonates. Today there are no recommendations on the care of these lesions, which can lead to an erroneous choice or to a delay in the possible treatments. OBJECTIVE: This review of the literature aims to explore and propose elements of therapeutic care collected in the scientific literature. It focuses on skin lesions due to extravasation of peripheral venous perfusions in neonatal intensive care units. METHODS: The PubMed database and the publishers' platform ScienceDirect were used. The bibliographies of the selected articles were also run. All types of studies examining one or several treatments for the care of postextravasation skin lesions in neonatal intensive care units were included in the search, without any limit on the date, except for case reports. To estimate the quality of the studies, the tool proposed by the French National Authority for Health, which classifies the various types of studies according to their proof level, was used. RESULTS/DISCUSSION: Thirteen publications were analyzed, including four case series, five retrospective studies, and four interventional studies. The vast majority of these studies have been published since 2005. No comparative, controlled, and randomized trials appear in the literature. Chronologically, we observed a growing interest in the premature infant population, in parallel with the increasing number of publications. Among the significant number of treatments proposed, five main categories were identified: topical treatment, surgery, the Gault method, no specific treatment, and others. All the skin lesions of the babies studied healed, without important aftereffects. These publications also show that most of the time a combination of different types of treatment is used depending on the lesions' progress and doctor's assessment. Few differences are made between term neonates and premature neonates in the choice of treatment. All these types of care can be applied to both populations. In spite of the lack of consensus on the care to be adopted, all the authors emphasize the important role of prevention according to the official regulations. CONCLUSION: The total absence of studies with a sufficient level of proof does not allow, at this time, the elaboration of guidelines for the care of these lesions. However, the proposals made in the literature seem promising. Therefore, it would be wise to conduct randomized trials on relatively large samples to compare these various types of treatment.
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Extravasamento de Materiais Terapêuticos e Diagnósticos/complicações , Dermatopatias/etiologia , Dermatopatias/terapia , Humanos , Recém-Nascido , Infusões Intravenosas , Unidades de Terapia Intensiva Neonatal , PerfusãoRESUMO
Skeletal muscle stem cells (MuSCs) derived from the somatic mesoderm play a critical role in successful muscle regeneration following injury and trauma. MuSCs have been found to undergo rapid changes in metabolism following a change in cell state, such as that which occurs during the transition from quiescence to an actively proliferating state. There is mounting evidence that metabolism is critically important in the regulation of quiescence, activation, and differentiation and thus the development of new techniques that aim to further probe the metabolism of MuSCs is essential. The Seahorse XF Bioanalyzer is a powerful tool that simultaneously measures the extracellular rate of change in oxygen partial pressure and pH, providing a method to measure mitochondrial respiration and lactate production. In this chapter, we describe the use of key metabolic inhibitors that allow for the investigation of mitochondrial substrate utilization in primary MuSCs.
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Mitocôndrias Musculares/metabolismo , Mioblastos Esqueléticos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Compostos de Epóxi/farmacologia , Ácidos Graxos/metabolismo , Glucose/metabolismo , Ácido Glutâmico/metabolismo , Concentração de Íons de Hidrogênio , Hipoglicemiantes/farmacologia , Mitocôndrias Musculares/efeitos dos fármacos , Mioblastos Esqueléticos/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Smegmamorpha , Sulfetos/farmacologia , Tiadiazóis/farmacologiaRESUMO
Preeclampsia (PE) is a complex disorder that affects 3-5% of all pregnancies and is a leading cause of maternal and fetal morbidity and mortality. To date, the heterogeneity of clinical presentation, disease severity and outcomes have limited significant advances in early prediction, diagnosis, and therapeutic intervention of PE. The rapidly expanding field of metabolomics, which has the capacity to quantitatively detect low molecular weight compounds (metabolites) in tissue and biological fluids, shows tremendous promise in gaining a better understanding of PE. This review will discuss this emerging field and its contribution to recent advances in the understanding of PE pathophysiology, and identification of early predictive metabolic biomarkers for this complex disorder.
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Metabolômica/métodos , Modelos Biológicos , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/terapia , Medicina de Precisão , Animais , Biomarcadores/metabolismo , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Feminino , Humanos , Metabolômica/tendências , Placenta/fisiopatologia , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/fisiopatologia , Gravidez , Projetos de Pesquisa/tendências , Útero/metabolismo , Útero/fisiopatologiaRESUMO
OBJECTIVE: Early supplementation of breastfed infants may have consequences both for the mother and the child. We hypothesised that it would result in decreased maternal weight loss and in shorter durations of breastfeeding and birth intervals. DESIGN: Controlled randomised population-based trial. SETTING: Six villages in the Sine area of Senegal, West Africa. SUBJECTS: Healthy breastfed infants and their mothers, 68 controls and 66 supplemented infants at randomization. INTERVENTION: Supplementation with high-energy, nutrient dense food from 4 to 7 months of age, twice daily under supervision of field workers. Both controls and supplemented infants were free to eat other complementary foods. Maternal weight was measured monthly. Dates of breastfeeding cessation and of subsequent births were collected prospectively through weekly demographic surveillance, and were analysed using Cox's regression models and 'intent-to-supplement' approach. RESULTS: Mean maternal weight gain from 4 to 7 months postpartum tended to be greater in the supplemented group (+0.25 kg/months, 95% confidence interval (CI): -0.07, +0.57). Supplemented infants were breastfed for significantly longer durations than controls (medians: 24.9 and 23.7 months, respectively, P: 0.034). Their adjusted hazard ratio (HR) for breastfeeding cessation was 0.59 (95% CI: 0.40, 0.89). Their mothers had a lower risk of a new birth than mothers of controls (adjusted HR: 0.57, 95% CI: 0.36, 0.92). CONCLUSIONS: Early short-term infant supplementation tended to decrease maternal postpartum weight loss, but it increased, rather than shortened, the duration of breastfeeding and birth interval. SPONSORSHIP: This study was supported by a grant from the French Ministry of Research (Grant 92L0623).
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Aleitamento Materno/estatística & dados numéricos , Lactação/fisiologia , Bem-Estar Materno , Desmame , Redução de Peso/fisiologia , Adulto , Alimentação com Mamadeira , Feminino , Humanos , Lactente , Alimentos Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Taxa de Gravidez , Modelos de Riscos Proporcionais , Senegal , Fatores de TempoRESUMO
In recent years, Cambodia has demonstrated significant success in specific aspects of immunization with gains through campaign efforts in measles control and polio eradication. In contrast, routine immunization rates have failed to improve over the last five years. In response, the National Immunization Program of the Ministry of Health developed a coverage improvement planning (CIP) process. This paper describes the CIP process in Cambodia, including identified barriers to and strategies for improving coverage. Immunization coverage rose in 8 of 10 pilot districts in the year following the introduction of CIP in 2003. The mean increase in DPT3 coverage across pilot districts on an annual basis was 16%, which provides encouraging early evidence for the effectiveness of the intervention. Factors associated with success in coverage improvement included: (1) development of a needs-based micro-plan, (2) application of performance-based contracting between levels of management, (3) investment in social mobilization, (4) securing finance for health outreach programs and (5) strengthened monitoring systems. Lessons learned will guide program expansion to improve immunization coverage nationally.
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Acessibilidade aos Serviços de Saúde/organização & administração , Programas de Imunização/métodos , Programas de Imunização/organização & administração , Programas Nacionais de Saúde/organização & administração , Camboja , Pesquisas sobre Atenção à Saúde , Política de Saúde , Humanos , Relações Interinstitucionais , Desenvolvimento de ProgramasRESUMO
The glutamate receptor subunit delta2 has a unique distribution at the parallel fiber-Purkinje cell synapse of the cerebellum, which is developmentally regulated such that delta2 occurs at both parallel fiber synapses and climbing fiber synapses early in development but is restricted to parallel fiber synapses in adult animals. To identify proteins that might be involved in the trafficking or docking of delta2 receptors, we screened a yeast two-hybrid library with the cytosolic C terminus of delta2 and isolated a member of the postsynaptic density (PSD)-95 family of proteins, which are known to interact with the extreme C termini of NMDA receptors. We find that delta2 binds specifically to PSD-93, which is enriched in Purkinje cells. In addition, PSD-93 clusters delta2 when they are coexpressed in heterologous cells, and clustering is disrupted by point mutations of delta2 that disrupt the delta2-PSD-93 interaction. Ultrastructural localization of PSD-93 and delta2 shows they are colocalized at parallel fiber synapses; however, PSD-93 also is present at climbing fiber synapses of the adult rat, where delta2 is not found, indicating that the presence of PSD-93 alone is not sufficient for determining the synaptic expression of delta2.
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Fibras Nervosas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Glutamato/metabolismo , Sinapses/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Linhagem Celular , Proteína 4 Homóloga a Disks-Large , Biblioteca Gênica , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , RatosRESUMO
BACKGROUND: Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. Because these activities underlie restenosis, inhibition of the PDGF-receptor tyrosine kinase (PDGFr-TK) is postulated to decrease restenosis. METHODS AND RESULTS: RPR101511A is a novel compound which selectively and potently inhibits the cell-free and in situ PDGFr-TK and PDGFr-dependent proliferation and chemotaxis in vascular smooth muscle cells (VSMC). To evaluate the effect of RPR101511A (30 mg. kg-1. d-1 BID for 28 days following PTCA) on coronary restenosis, PTCA was performed in hypercholesterolemic minipigs whose left anterior descending (LAD) coronary artery had been injured by overdilation and denudation, yielding a previously existing lesion. Angiographically determined prePTCA minimal lumen diameters (MLD) were similar in vehicle and RPR101511A-treated pigs (1.98+/-0.09 versus 2.01+/-0.08 mm) and increased to the same extent in the 2 groups following successful PTCA (2.30+/-0.06 versus 2.52+/-0.13). At termination, there was an average 50% loss of gain in the vehicle-treated group but no loss of gain with RPR101511A (2.16+/-0. 05 versus 2.59+/-0.11, P<0.001). Morphometric analysis of the LAD showed that RPR101511A caused a significant decrease in total intimal/medial ratio (0.96+/-0.58 versus 0.67+/-0.09, P<0.05). CONCLUSIONS: RPR101511A, which acts by inhibition of the PDGFr-TK, completely prevented angiographic loss of gain following PTCA and significantly reduced histological intimal hyperplasia.
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Angioplastia Coronária com Balão , Doença das Coronárias/prevenção & controle , Inibidores Enzimáticos/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinoxalinas/farmacologia , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Tiofenos/farmacologia , Administração Oral , Animais , Doença das Coronárias/terapia , Recidiva , Suínos , Fatores de Tempo , Túnica Íntima/metabolismo , Túnica Média/metabolismoRESUMO
Blood pressure (BP) variability is associated with several cardiovascular (CV) risk factors. Is BP variability measurement of any additive value, in terms of CV risk assessment strategies? To answer this question, we analyzed data from the SU.FOL.OM3 secondary prevention trial that included 2501 patients with background of CV disease history (coronary or cerebrovascular disease). BP was measured every year allowing calculation of variability of BP, expressed as s.d. and coefficient of variability (s.d./mean systolic BP) in 2157 patients. We found that systolic BP variability was associated with several CV risk factors: principally hypertension, age, and diabetes. Furthermore, all antihypertensives were positively associated with variability. Logistic regression analysis revealed that three factors were independent predictors of major CV event: coefficient of variability of systolic BP (OR=1.23 per s.d., 95% CI: 1.04-1.46, P=0.016), current smoking (OR=1.94, 95% CI: 1.03-3.66, P=0.039), and inclusion for cerebrovascular disease (OR=1.92, 95% CI: 1.29-2.87, P=0.001). Finally, when comparing logistic regression models characteristics without, and then with, inclusion of BP variability, there was a modest but statistically significant improvement (P=0.04). In conclusion, age, BP and diabetes were the major determinants of BP variability. Furthermore, BP variability has an independent prognostic value in the prediction of major CV events; but improvement in the prediction model was quite modest. This last finding is more in favor of BP variability acting as an integrator of CV risk than acting as a robust independent CV risk factor in this high-risk population.
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Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Idoso , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Regressão , Fatores de RiscoRESUMO
The dystrophin-glycoprotein complex (DGC) is critical for muscle membrane stability. The sarcoglycans are transmembrane proteins within the DGC, and the function of the sarcoglycans is unknown. Mutations in sarcoglycan genes cause autosomal recessive muscular dystrophy. We have identified a new sarcoglycan gene with high homology to alpha-sarcoglycan highlighting the redundancy of the DGC. This gene, named epsilon-sarcoglycan, has an identical intron-exon structure to alpha-sarcoglycan, and is more broadly expressed. The characterization of epsilon-sarcoglycan should make it possible to determine if it, like the other sarcoglycan genes, is mutated in muscular dystrophy.
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Proteínas do Citoesqueleto/química , Glicoproteínas de Membrana/química , Proteínas Musculares/química , Alelos , Sequência de Aminoácidos , Mapeamento Cromossômico , Clonagem Molecular , Distrofina/genética , Éxons/genética , Humanos , Íntrons/genética , Dados de Sequência Molecular , Distrofias Musculares/genética , Sarcoglicanas , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
The effect of supplementation on growth was tested by means of four similar controlled randomized trials in the Congo (n = 120), Senegal (n = 110), Bolivia (n = 127), and New Caledonia (n = 90). Four-month-old infants were randomly allocated to supplement or control groups. A cereal-based precooked porridge was offered twice daily for 3 mo and consumption was monitored. Both groups were free to eat local food. At 7 mo of age, all infants were still breast-fed in the Congo, Senegal, and Bolivia compared with 47% in New Caledonia. Mean daily consumption of the supplement varied among countries (558-790 kJ/d). Mean length at 4 mo was lowest in Bolivia, higher in Senegal and the Congo, and near the National Center for Health Statistics reference in New Caledonia. The mean 4-7 mo length increment was 0.48 cm higher for supplemented than for control infants in Senegal (P < 0.05), whereas weight increments did not differ. No significant effect was found in the other countries.
PIP: Findings from this study of the link between nutritional supplementation during breast feeding and infant growth disagree with earlier studies. The effect of nutritional supplementation on growth in length was only modest, but significant only in Senegal and not significant in the Congo, Bolivia, and New Caledonia. It is hypothesized that food supplementation during the 4-7 month period would have a positive effect on linear growth. This study included four controlled randomized trials among 120 infants in the Congo, 110 infants in Senegal, 127 infants in Bolivia, and 90 infants in New Caledonia. The infants were 4 months old when placed in the supplement or control groups. Supplementation included the addition of a cereal-based precooked porridge twice daily for 3 months. Both groups continued to eat local foods. Breast feeding patterns were different in New Caledonia, where only 47% of infants were still breast fed at 7 months of age. Mean daily supplementation varied among countries, from 558 to 790 kJ/day. Mean length was lowest in Bolivia, higher in Senegal and the Congo, and close to the US National Center for Health Statistics reference measures in New Caledonia. The study was conducted in rural parts of Senegal and New Caledonia and periurban parts of Bolivia and the Congo. Supplementation was supervised by field workers. The samples included infants with a length-for-age score of -2.5 or higher and a weight-for-length Z score of -2 or higher at 4 months. Anthropometric measurements were taken at 4 months and 4, 8, and 13 weeks later (at 4.9, 5.8, and 7.0 months of age). 24-hour food recalls were collected monthly for consumption of breast milk, special local infant food, commercial "western" baby food, milk substitutes, family food, water, and other than milk liquids.
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Países em Desenvolvimento , Grão Comestível , Crescimento , Alimentos Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Estatura/fisiologia , Bolívia , Aleitamento Materno , Congo , Feminino , Alimentos Fortificados , Humanos , Lactente , Masculino , Nova Caledônia , Senegal , Aumento de Peso/fisiologiaRESUMO
Mutations in dysferlin were recently described in patients with Miyoshi myopathy, a disorder that preferentially affects the distal musculature, and in patients with Limb-Girdle Muscular Dystrophy 2B, a disorder that affects the proximal musculature. Despite the phenotypic differences, the types of mutations associated with Miyoshi myopathy and Limb-Girdle Muscular Dystrophy 2B do not differ significantly. Thus, the etiology of the phenotypic variability associated with dysferlin mutations remains unknown. Using genetic linkage and mutation analysis, we identified a large inbred pedigree of Yemenite Jewish descent with limb-girdle muscular dystrophy. The phenotype in these patients included slowly progressive, proximal, and distal muscular weakness in the lower limbs with markedly elevated serum creatine kinase (CK) levels. These patients had normal development and muscle strength and function in early life. Muscle biopsies from 4 affected patients showed a typical dystrophic pattern but interestingly, in 2, an inflammatory process was seen. The inflammatory infiltrates included primarily CD3 positive lymphocytes. Associated with this phenotype, we identified a previously undescribed frameshift mutation at nucleotide 5711 of dysferlin. This mutation produced an absence of normal dysferlin mRNA synthesis by affecting an acceptor site and cryptic splicing. Thus, splice site mutations that disrupt dysferlin may produce a phenotype associated with inflammation.
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Processamento Alternativo/genética , Proteínas de Membrana , Proteínas Musculares/genética , Distrofias Musculares/genética , Mutação/genética , Análise Mutacional de DNA , Disferlina , Feminino , Ligação Genética , Humanos , Imuno-Histoquímica , Inflamação/genética , Inflamação/patologia , Masculino , Distrofias Musculares/classificação , Distrofias Musculares/patologia , Linhagem , FenótipoRESUMO
In the present studies, ligand competition experiments were conducted to examine the ability of angiotensin II peptide agonists and nonpeptide AT1- and AT2-selective receptor antagonists to inhibit the binding of [125I]angiotensin II to bovine adrenal cortical membranes. Angiotensin II, angiotensin III, the All-(3-8) hexapeptide fragment of angiotensin II, and the AT1-selective receptor antagonist L-158,809, inhibited [125I]angiotensin II binding in a biphasic fashion indicative of a ligand interaction at more than one recognition site. Approximately 20% of low affinity [125I]angiotensin II binding was inhibited only by high micromolar concentrations of L-158,809. RG 13647 (1(-1,4-benzodioxan-2-methyl)-5-diphenylacetyl-4,5,6,7-tetra hydro-1H-imidazo- [4,5,c]-pyridine-6-carboxylic acid) represents a potent and AT2-selective analog of PD 123177 and showed weak activity in competing for [125I]angiotensin II binding with an IC50 value of 100 microM. When subsequent competition studies were conducted in the presence of 1 microM L-158,809 to block [125I]angiotensin II to the AT1 receptor subtype, the angiotensin II agonists produced monophasic inhibition curves with AII-(3-8) showing the greatest activity (IC50 = 6 nM) followed by angiotensin III (IC50 = 15 nM) much greater than angiotensin II (IC50 = 110 nM). RG 13647 was not found to significantly inhibit this portion of [125I]angiotensin II binding. These data demonstrate that bovine adrenal cortex contains both the AT1 receptor subtype, as well as, a novel class of [125I]angiotensin II recognition sites which may be analogous to the recently described angiotensin IV (AT4) receptor.