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171.
Vitantonio Di Bello Iacopo Fabiani Lorenzo Conte Valentina Barletta Maria Grazia Delle Donne Cucco Cuono Laura Anna Leo Frank Lloyd Dini Mario Marzilli Aldo Pinchera Ferruccio Santini 《Obesity (Silver Spring, Md.)》2013,21(5):881-892
Objective:
Obesity has reached global epidemic proportions and is associated with numerous comorbidities, including major cardiovascular (CV) diseases.Design and Methods:
It has many adverse effects on hemodynamics and CV structure and function: it increases total blood volume and cardiac output, and the cardiac workload is greater. Typically, obese patients have a higher cardiac output but a lower level of total peripheral resistance at any given level of arterial pressure. Most of the increase in cardiac output in obesity is caused by stroke volume, although heart rate typically mildly increases also due to enhanced sympathetic activation.Results:
Over the last few years, experimental investigations have unraveled some important pathogenetic mechanisms that may underlie a specific form of “obesity cardiomyopathy.” Bariatric surgery represents an effective alternative to treat obesity when nonsurgical weight loss programs (diet + behavior modifications + regular exercise) have failed. A great numbers of questions are still open in the global comprehension of the pathophysiological interactions between obesity and heart.Conclusion:
Conventional two‐dimensional Doppler echocardiography, integrated by relative new technological ultrasonic approaches, represents the reference technique to study and possibly clarify both the very complex hemodynamic changes induced by obesity and those relative to obesity treatment. 相似文献172.
Elena Riccitelli Paola Giussani Clara Di Vito Giuseppe Condomitti Cristina Tringali Manuela Caroli Rossella Galli Paola Viani Laura Riboni 《PloS one》2013,8(6)
Glioblastomas are the most frequent and aggressive intracranial neoplasms in humans, and despite advances and the introduction of the alkylating agent temozolomide in therapy have improved patient survival, resistance mechanisms limit benefits. Recent studies support that glioblastoma stem-like cells (GSCs), a cell subpopulation within the tumour, are involved in the aberrant expansion and therapy resistance properties of glioblastomas, through still unclear mechanisms. Emerging evidence suggests that sphingosine-1-phosphate (S1P) a potent onco-promoter able to act as extracellular signal, favours malignant and chemoresistance properties in GSCs. Notwithstanding, the origin of S1P in the GSC environment remains unknown. We investigated S1P metabolism, release, and role in cell survival properties of GSCs isolated from either U87-MG cell line or a primary culture of human glioblastoma. We show that both GSC models, grown as neurospheres and expressing GSC markers, are resistant to temozolomide, despite not expressing the DNA repair protein MGMT, a major contributor to temozolomide-resistance. Pulse experiments with labelled sphingosine revealed that both GSC types are able to rapidly phosphorylate the long-chain base, and that the newly produced S1P is efficiently degraded. Of relevance, we found that S1P was present in GSC extracellular medium, its level being significantly higher than in U87-MG cells, and that the extracellular/intracellular ratio of S1P was about ten-fold higher in GSCs. The activity of sphingosine kinases was undetectable in GSC media, suggesting that mechanisms of S1P transport to the extracellular environment are constitutive in GSCs. In addition we found that an inhibitor of S1P biosynthesis made GSCs sensitive to temozolomide (TMZ), and that exogenous S1P reverted this effect, thus involving extracellular S1P as a GSC survival signal in TMZ resistance. Altogether our data implicate for the first time GSCs as a pivotal source of extracellular S1P, which might act as an autocrine/paracrine signal contributing to their malignant properties. 相似文献
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177.
Vicente Más Laura Rodriguez Eduardo Olmedillas Olga Cano Concepción Palomo María C. Terrón Daniel Luque José A. Melero Jason S. McLellan 《PLoS pathogens》2016,12(9)
Human metapneumovirus (hMPV) is a paramyxovirus that is a common cause of bronchiolitis and pneumonia in children less than five years of age. The hMPV fusion (F) glycoprotein is the primary target of neutralizing antibodies and is thus a critical vaccine antigen. To facilitate structure-based vaccine design, we stabilized the ectodomain of the hMPV F protein in the postfusion conformation and determined its structure to a resolution of 3.3 Å by X-ray crystallography. The structure resembles an elongated cone and is very similar to the postfusion F protein from the related human respiratory syncytial virus (hRSV). In contrast, significant differences were apparent with the postfusion F proteins from other paramyxoviruses, such as human parainfluenza type 3 (hPIV3) and Newcastle disease virus (NDV). The high similarity of hMPV and hRSV postfusion F in two antigenic sites targeted by neutralizing antibodies prompted us to test for antibody cross-reactivity. The widely used monoclonal antibody 101F, which binds to antigenic site IV of hRSV F, was found to cross-react with hMPV postfusion F and neutralize both hRSV and hMPV. Despite the cross-reactivity of 101F and the reported cross-reactivity of two other antibodies, 54G10 and MPE8, we found no detectable cross-reactivity in the polyclonal antibody responses raised in mice against the postfusion forms of either hMPV or hRSV F. The postfusion-stabilized hMPV F protein did, however, elicit high titers of hMPV-neutralizing activity, suggesting that it could serve as an effective subunit vaccine. Structural insights from these studies should be useful for designing novel immunogens able to induce wider cross-reactive antibody responses. 相似文献
178.
William Whittaker Laura Anselmi S?ren Rud Kristensen Yiu-Shing Lau Simon Bailey Peter Bower Katherine Checkland Rebecca Elvey Katy Rothwell Jonathan Stokes Damian Hodgson 《PLoS medicine》2016,13(9)
BackgroundHealth services across the world increasingly face pressures on the use of expensive hospital services. Better organisation and delivery of primary care has the potential to manage demand and reduce costs for hospital services, but routine primary care services are not open during evenings and weekends.Extended access (evening and weekend opening) is hypothesized to reduce pressure on hospital services from emergency department visits. However, the existing evidence-base is weak, largely focused on emergency out-of-hours services, and analysed using a before-and after-methodology without effective comparators.ConclusionsThe study found that extending access was associated with a reduction in emergency department visits in the first 12 months. The results of the research have already informed the decision by National Health Service England to extend primary care access across Greater Manchester from 2016. However, further evidence is needed to understand whether extending primary care access is cost-effective and sustainable. 相似文献
179.
Matthew A. Christensen Laura Bettencourt Leanne Kaye Sai T. Moturu Kaylin T. Nguyen Jeffrey E. Olgin Mark J. Pletcher Gregory M. Marcus 《PloS one》2016,11(11)
BackgroundSmartphones are increasingly integrated into everyday life, but frequency of use has not yet been objectively measured and compared to demographics, health information, and in particular, sleep quality.AimsThe aim of this study was to characterize smartphone use by measuring screen-time directly, determine factors that are associated with increased screen-time, and to test the hypothesis that increased screen-time is associated with poor sleep.MethodsWe performed a cross-sectional analysis in a subset of 653 participants enrolled in the Health eHeart Study, an internet-based longitudinal cohort study open to any interested adult (≥ 18 years). Smartphone screen-time (the number of minutes in each hour the screen was on) was measured continuously via smartphone application. For each participant, total and average screen-time were computed over 30-day windows. Average screen-time specifically during self-reported bedtime hours and sleeping period was also computed. Demographics, medical information, and sleep habits (Pittsburgh Sleep Quality Index–PSQI) were obtained by survey. Linear regression was used to obtain effect estimates.ResultsTotal screen-time over 30 days was a median 38.4 hours (IQR 21.4 to 61.3) and average screen-time over 30 days was a median 3.7 minutes per hour (IQR 2.2 to 5.5). Younger age, self-reported race/ethnicity of Black and "Other" were associated with longer average screen-time after adjustment for potential confounders. Longer average screen-time was associated with shorter sleep duration and worse sleep-efficiency. Longer average screen-times during bedtime and the sleeping period were associated with poor sleep quality, decreased sleep efficiency, and longer sleep onset latency.ConclusionsThese findings on actual smartphone screen-time build upon prior work based on self-report and confirm that adults spend a substantial amount of time using their smartphones. Screen-time differs across age and race, but is similar across socio-economic strata suggesting that cultural factors may drive smartphone use. Screen-time is associated with poor sleep. These findings cannot support conclusions on causation. Effect-cause remains a possibility: poor sleep may lead to increased screen-time. However, exposure to smartphone screens, particularly around bedtime, may negatively impact sleep. 相似文献
180.
Teresa Aldámiz-Echevarría Juan Berenguer Pilar Miralles María A. Jiménez-Sousa Ana Carrero Daniel Pineda-Tenor Cristina Díez Francisco Tejerina Leire Pérez-Latorre José M. Bellón Salvador Resino 《PloS one》2016,11(2)