Prevalence of Cardiovascular Risk Factors among Cancer Patients in the United States

Background: Cancer and cardiovascular diseases (CVDs) are leading causes of morbidity and mortality. We analyzed national data to examine the prevalence of CVD risk factors among adult cancer survivors in the United States. Methods: Participants included adults ≥18 years of age from the National Health and Nutrition Examination Survey 2001-2002 to 2013-2014. CVD risk factors included hypertension, diabetes, dyslipidemia, obesity, smoking, and physical activity. Prevalence of 1, 2, or ≥3 CVD risk factors was compared between cancer and noncancer participants. All CVD risk factors were adjusted for age and smoking and additionally for sex. Differences in CVD risk factors among cancer and noncancer participants were identified using logistic regression analysis. Results: Among 35,379 eligible participants, 2906 (8.4%) had a history of cancer. The proportion of participants having a single CVD risk factor was lower among cancer survivors compared with noncancer participants (25.8% vs. 33.9%, P \u3c 0.001). The proportions of participants having two CVD risk factors (33.5% vs. 24.6%, P \u3c 0.001) and ≥3 CVD risk factors (27.4% vs. 16.4%, P \u3c 0.001) were higher among cancer survivors. However, these associations lost significance upon adjusting for age. The odds of total hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI]: 1.11-1.40) and total diabetes (OR 1.33, 95% CI: 1.08-1.65) were significantly higher among cancer survivors. Conclusions: Our study showed that adult cancer survivors in the United States had higher levels of CVD risk factors primarily due to age-related factors, in addition to cancer complications. There is a significant need for improved CVD risk assessment and prevention services for cancer survivors

Adenosine A2A receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice

© 2009 Nature Publishing Group All rights reservedPrevious in vitro studies have characterized the electrophysiological and molecular signaling pathways of adenosine tonic modulation on long-lasting synaptic plasticity events, particularly for hippocampal long-term potentiation(LTP). However, it remains to be elucidated whether the long-term changes produced by endogenous adenosine in the efficiency of synapses are related to those required for learning and memory formation. Our goal was to understand how endogenous activation of adenosine excitatory A2A receptors modulates the associative learning evolution in conscious behaving mice. We have studied here the effects of the application of a highly selective A2A receptor antagonist, SCH58261, upon a well-known associative learning paradigm - classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus(US). A single electrical pulse was presented to the Schaffer collateral–commissural pathway to evoke field EPSPs (fEPSPs) in the pyramidal CA1 area during the CS–US interval. In vehicle-injected animals, there was a progressive increase in the percentage of conditioning responses (CRs) and in the slope of fEPSPs through conditioning sessions, an effect that was completely prevented (and lost) in SCH58261 (0.5 mg/kg, i.p.)-injected animals. Moreover, experimentally evoked LTP was impaired in SCH58261- injected mice. In conclusion, the endogenous activation of adenosine A2A receptors plays a pivotal effect on the associative learning process and its relevant hippocampal circuits, including activity-dependent changes at the CA3-CA1 synapse.This study was supported by grants from the Spanish Ministry of Education and Research (BFU2005-01024 and BFU2005-02512), Spanish Junta de Andalucía (BIO-122 and CVI-02487), and the Fundación Conocimiento y Cultura of the Pablo de Olavide University (Seville, Spain).B. Fontinha was in receipt of a studentship from a project grant (POCI/SAU-NEU/56332/2004) supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), and of an STSM from Cost B30 concerted action of the EU

Comparison of multi-year Ka-band propagation characteristics at four sites in North America and Europe

Tropospheric phenomena such as clouds and mainly rain cause higher attenuation at Ka-band than at lower frequencies. In this collaborative paper, the main results of four long-term Ka-band propagation campaigns are presented. The experiments are carried out in Ottawa, Canada (satellite Anik F2); Aveiro, Portugal; Madrid, Spain; and Toulouse, France (satellite HotBird 6 in the last three cases) and have been running since 2004 in Aveiro, 2006 in Ottawa and Madrid, and 2008 in Toulouse. After a brief introduction of the experiments, rain rate and excess attenuation results are discussed, first for a common two-year measurement period and later for the whole database available. Seasonal attenuation statistics for Madrid, Ottawa and Aveiro are compared. Finally, fade duration and fade slope statistics derived at three locations are presented and discussed

Transfer of MicroRNAs by Embryonic Stem Cell Microvesicles

Microvesicles are plasma membrane-derived vesicles released into the extracellular environment by a variety of cell types. Originally characterized from platelets, microvesicles are a normal constituent of human plasma, where they play an important role in maintaining hematostasis. Microvesicles have been shown to transfer proteins and RNA from cell to cell and they are also believed to play a role in intercellular communication. We characterized the RNA and protein content of embryonic stem cell microvesicles and show that they can be engineered to carry exogenously expressed mRNA and protein such as green fluorescent protein (GFP). We demonstrate that these engineered microvesicles dock and fuse with other embryonic stem cells, transferring their GFP. Additionally, we show that embryonic stem cells microvesicles contain abundant microRNA and that they can transfer a subset of microRNAs to mouse embryonic fibroblasts in vitro. Since microRNAs are short (21–24 nt), naturally occurring RNAs that regulate protein translation, our findings open up the intriguing possibility that stem cells can alter the expression of genes in neighboring cells by transferring microRNAs contained in microvesicles. Embryonic stem cell microvesicles may be useful therapeutic tools for transferring mRNA, microRNAs, protein, and siRNA to cells and may be important mediators of signaling within stem cell niches

A Ligand Peptide Motif Selected from a Cancer Patient Is a Receptor-Interacting Site within Human Interleukin-11

Interleukin-11 (IL-11) is a pleiotropic cytokine approved by the FDA against chemotherapy-induced thrombocytopenia. From a combinatorial selection in a cancer patient, we isolated an IL-11-like peptide mapping to domain I of the IL-11 (sequence CGRRAGGSC). Although this motif has ligand attributes, it is not within the previously characterized interacting sites. Here we design and validate in-tandem binding assays, site-directed mutagenesis and NMR spectroscopy to show (i) the peptide mimics a receptor-binding site within IL-11, (ii) the binding of CGRRAGGSC to the IL-11Rα is functionally relevant, (iii) Arg4 and Ser8 are the key residues mediating the interaction, and (iv) the IL-11-like motif induces cell proliferation through STAT3 activation. These structural and functional results uncover an as yet unrecognized receptor-binding site in human IL-11. Given that IL-11Rα has been proposed as a target in human cancer, our results provide clues for the rational design of targeted drugs

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy : international individual patient data pooled analysis

Altres ajuts: JF reports grants from Instituto de Salud Carlos III, grants from Fundació Marató TV3, grants from NIH, grants from Departament de Salut de la Generalitat de Catalunya.To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions. The online version contains supplementary material available at 10.1007/s00415-021-10706-3

Exploring Cosmic Origins with CORE: Cosmological Parameters

We forecast the main cosmological parameter constraints achievable with theCORE space mission which is dedicated to mapping the polarisation of the CosmicMicrowave Background (CMB). CORE was recently submitted in response to ESA'sfifth call for medium-sized mission proposals (M5). Here we report the resultsfrom our pre-submission study of the impact of various instrumental options, inparticular the telescope size and sensitivity level, and review the great,transformative potential of the mission as proposed. Specifically, we assessthe impact on a broad range of fundamental parameters of our Universe as afunction of the expected CMB characteristics, with other papers in the seriesfocusing on controlling astrophysical and instrumental residual systematics. Inthis paper, we assume that only a few central CORE frequency channels areusable for our purpose, all others being devoted to the cleaning ofastrophysical contaminants. On the theoretical side, we assume LCDM as ourgeneral framework and quantify the improvement provided by CORE over thecurrent constraints from the Planck 2015 release. We also study the jointsensitivity of CORE and of future Baryon Acoustic Oscillation and Large ScaleStructure experiments like DESI and Euclid. Specific constraints on the physicsof inflation are presented in another paper of the series. In addition to thesix parameters of the base LCDM, which describe the matter content of aspatially flat universe with adiabatic and scalar primordial fluctuations frominflation, we derive the precision achievable on parameters like thosedescribing curvature, neutrino physics, extra light relics, primordial heliumabundance, dark matter annihilation, recombination physics, variation offundamental constants, dark energy, modified gravity, reionization and cosmicbirefringence. (ABRIDGED

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Leveraging Natural History Data in One- and Two-Arm Hierarchical Bayesian Studies of Rare Disease Progression

peer reviewedThe small sample sizes inherent in rare and pediatric disease settings offer significant challenges for clinical trial design. In such settings, Bayesian adaptive trial methods can often pay dividends, allowing the sensible incorporation of auxiliary data and other relevant information to bolster that collected by the trial itself. Previous work has also included the use of one-arm trials augmented by the participants’ own natural history data, from which the future course of the disease in the absence of intervention can be predicted. Patient response can then be defined by the degree to which post-intervention observations are inconsistent with the predicted “natural” trajectory. While such trials offer obvious advantages in efficiency and ethical hazard (since they expose no new patients to a placebo, anathema to patients or their parents and caregivers), they can offer no protection against bias arising from the presence of any “placebo effect,” the tendency of patients to improve merely by being in the trial. In this paper, we investigate the impact of both static and transient placebo effects on one-arm responder studies of this type, as well as two-arm versions that incorporate a small concurrent placebo group but still borrow strength from the natural history data. We also propose more traditional Bayesian changepoint models that specify a parametric functional form for the patient’s post-intervention trajectory, which in turn allow quantification of the treatment benefit in terms of the model parameters, rather than semi-parametrically in terms of a response relative to some “null” model. We compare the operating characteristics of our designs in the context of an ongoing investigation of centronuclear myopathies (CNMs), a group of congenital neuromuscular diseases whose most common and severe form is X-linked, affecting approximately 1 in 50,000 newborn boys. Our results indicate our two-arm responder and changepoint methods can offer protection against placebo effects, improving power while protecting the trial’s Type I error rate. However, further research into innovative trial designs as well as ongoing dialog with regulatory authorities remain critically important in rare disease research