414 research outputs found
The NMDA agonist D-cycloserine facilitates fear memory consolidation in humans
Animal research suggests that the consolidation of fear and
extinction memories depends on N-methyl D-aspartate (NMDA)-
type glutamate receptors. Using a fear conditioning and extinction
paradigm in healthy normal volunteers, we show that postlearning
administration of the NMDA partial agonist D-cycloserine (DCS)
facilitates fear memory consolidation, evidenced behaviorally by
enhanced skin conductance responses, relative to placebo, for
presentations of a conditioned stimulus (CS) at a memory test
performed 72 h later. DCS also enhanced CS-evoked neural
responses in a posterior hippocampus/collateral sulcus region and
in the medial prefrontal cortex at test. Our data suggest a role for
NMDA receptors in regulating fear memory consolidation in humans
Improving consistency in AHP decision-making processes
Decision making in engineering is becoming increasingly complex due to the large number
of alternatives and multiple conflicting goals. Powerful decision-support expert systems
powered by suitable software are increasingly necessary. In this paper, the multiple attribute
decision method known as analytical hierarchy process (AHP), which uses pairwise
comparisons with numerical judgments, is considered. Since judgments may lack a minimum
level of consistency, mechanisms to improve consistency are necessary. A method
to achieve consistency through optimisation is described in this paper. This method has
the major advantage of depending on just n decision variables – the number of compared
elements – and so is less computationally expensive than other optimisation methods, and
can be easily implemented in virtually any existing computer environment. The proposed
approach is exemplified by considering a simplified version of one of the most important
problems faced by water supply managers, namely, the minimisation of water loss. 2012 Elsevier Inc. All rights reserved.This work has been performed under the support of project IDAWAS, DPI2009-11591 of the Direccionn General de Investigacion del Ministerio de Educacion y Ciencia (Spain) and ACOMP/2011/188 of the Conselleria de Educacion de la Generalitat Valenciana. The first author was supported by Spanish project MTM2010-18539. The third author is also indebted to the Universitat Politecnica de Valencia for the sabbatical leave granted during the first semester of 2011. The use of English in this paper was revised by John Rawlins.Benítez López, J.; Delgado Galván, XV.; Izquierdo Sebastián, J.; Pérez García, R. (2012). Improving consistency in AHP decision-making processes. Applied Mathematics and Computation. 219(5):2432-2441. https://doi.org/10.1016/j.amc.2012.08.079S24322441219
Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology
To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS).Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula.More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels.Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.Copyright © 2022 Fernández-Velasco, Monreal, Kuhle, Meca-Lallana, Meca-Lallana, Izquierdo, Oreja-Guevara, Gascón-Giménez, Sainz de la Maza, Walo-Delgado, Lapuente-Suanzes, Maceski, Rodríguez-Martín, Roldán, Villarrubia, Saiz, Blanco, Diaz-Pérez, Valero-López, Diaz-Diaz, Aladro, Brieva, Íñiguez, González-Suárez, Rodríguez de Antonio, García-Domínguez, Sabin, Llufriu, Masjuan, Costa-Frossard and Villar
The insulin-like growth factor system is modulated by exercise in breast cancer survivors: a systematic review and meta-analysis
Abbreviations: CI, Confidence interval; ELISA, Enzyme-linked immunosorbent assay; IGF, Insulin-like growth factors;
IGFBP, Insulin-like growth factor binding protein; MD, Mean difference; PEDro, Physiotherapy evidence database;
RCT, Randomized controlled trials; SD, Standard deviation.Background: Insulin-like growth factors (IGF´s) play a crucial role in controlling cancer cell proliferation,
differentiation and apoptosis. Exercise has been postulated as an effective intervention in improving cancerrelated
outcomes and survival, although its effects on IGF´s are not well understood. This meta-analysis aimed
to determine the effects of exercise in modulating IGF´s system in breast cancer survivors.
Methods: Databases of PuMed, EMBASE, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials.
gov, SPORTDiscus, LILACS and Scopus were systematically searched up to November 2014. Effect estimates were
calculated through a random-effects model of meta-analysis according to the DerSimonian and Laird method.
Heterogeneity was evaluated with the I2 test. Risk of bias and methodological quality were evaluated using the
PEDro score.
Results: Five randomized controlled trials (n = 235) were included. Most women were post-menopausal. Highquality
and low risk of bias were found (mean PEDro score = 6.2 ± 1). Exercise resulted in significant improvements
on IGF-I, IGF-II, IGFBP-I, IGFBP-3, Insulin and Insulin resistance (P < 0.05). Non-significant differences were found for
Glucose. Aerobic exercise improved IGF-I, IGFBP-3 and Insulin. No evidence of publication bias was detected by
Egger´s test (p = 0.12).
Conclusions: Exercise improved IGF´s in breast cancer survivors. These findings provide novel insight regarding the
molecular effects of exercise on tumoral microenvironment, apoptosis and survival in breast cancer survivors
Exercise and postprandial lipemia: effects on vascular health in inactive adults
Background: There is evidence to suggest that postprandial lipemia are is linked to the impairment of endothelial
function, which is characterized by an imbalance between the actions of vasodilators and vasoconstrictors. The aim
of this study was to determine the effects of a 12-week high-intensity training (HIT) and moderate continuous
training (MCT) protocol on postprandial lipemia, vascular function and arterial stiffness in inactive adults after
high-fat meal (HFM) ingestion.
Methods: A randomized clinical trial was conducted in 20 healthy, inactive adults (31.6 ± 7.1 years). Participants followed
the two exercise protocols for 12 weeks. To induce a state of postprandial lipemia (PPL), all subjects received a HFM.
Endothelial function was measured using flow-mediated vasodilation (FMD), normalized brachial artery FMD (nFMD),
aortic pulse wave velocity (PWV) and augmentation index (AIx). Plasma total cholesterol, high-density lipoprotein
cholesterol (HDL-c), triglycerides and glucose were also measured.
Results: The effects of a HFM were evaluated in a fasted state and 60, 120, 180, and 240 min postprandially. A significant
decrease in serum glucose between 0 min (fasted state) and 120 min postprandially was found in the HIT group (P= 0.
035). Likewise, FMD (%) was significantly different between the fasted state and 60 min after a HFM in the HIT group
(P = 0.042). The total cholesterol response expressed as area under curve (AUC)(0–240) was lower following HIT than
following MCT, but no significant differences were observed (8%, P > 0.05). Similarly, triglycerides AUC(0–240) was also
lower after HIT compared with MCT, which trended towards significance (24%, P= 0.076). The AUC(0–240) for the glucose
response was significantly lower following HIT than MCT (10%, P = 0.008). FMD and nFMD AUC(0–240) were significantly
higher following HIT than following MCT (46.9%, P = 0.021 and 67.3%, P = 0.009, respectively). PWV AUC(0–240) did not
differ following between the two exercise groups (2.3%, P > 0.05).
Conclusions: Supervised exercise training mitigates endothelial dysfunction and glucose response induced by PPL.
Exercise intensity plays an important role in these protective effects, and medium-term HIT may be more effective than
MCT in reducing postprandial glucose levels and attenuating vascular impairment.This study as funded in part by the Center for Studies on Measurement of
Physical Activity, School of Medicine and Health Sciences, Universidad del
Rosario (Code N° FIUR DN-BG001). We declare that the results of the study
are presented clearly, honestly, and without fabrication, falsification, or appropriate
data manipulatio
Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation
The ubiquitously expressed RNA-binding protein HuR increases the stability and translation of mRNAs encoding growth regulatory proteins that promote proliferation in a variety of cell types. However, the three neuron-specific ELAV/Hu proteins, HuB, HuC and HuD, while binding to the same types of mRNAs, are required instead for neuronal differentiation, and it becomes difficult to reconcile these contrary functions when all four Hu proteins are expressed in the same neuron. HuR mRNA exists as three alternatively polyadenylated variants, a 1.5-kb testes-specific mRNA isoform, a ubiquitous 2.4-kb isoform and a 6.0-kb isoform that we now show is induced during neuronal differentiation and appears to be neuron-specific. This 6.0-kb neuron-specific mRNA isoform is inherently less stable and produces less HuR protein than the ubiquitous 2.4-kb mRNA. Furthermore, we show that neuronal HuB, HuC and HuD, as well as HuR itself, can bind at the 2.4-kb mRNA polyadenylation site, and when overexpressed can affect alternative polyadenylation to generate an extended HuR 3′-UTR that is translationally suppressed. We propose that the regulation of HuR protein expression by alternative polyadenylation allows neurons to post-transcriptionally regulate mRNAs-encoding factors required for proliferation versus differentiation to facilitate neuronal differentiation
The Continuous Sample of Working Lives: improving its representativeness
This paper studies the representativeness of the Continuous Sample of Working Lives (CSWL), a set of anonymized microdata containing information on individuals from Spanish Social Security records. We examine several CSWL waves (2005-2013) and show that it is not representative for the population with a pension income. We then develop a methodology to draw a large dataset from the CSWL that is much more representative of the retired population in terms of pension type, gender and age. This procedure also makes it possible for users to choose between goodness of fit and subsample size. In order to illustrate the practical significance of our methodology, the paper also contains an application in which we generate a large subsample distribution from the 2010 CSWL. The results are striking: with a very small reduction in the size of the original CSWL, we significantly reduce errors in estimating pension expenditure for 2010, with a p value greater or equal to 0.999
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