37 research outputs found
Evaluation of the Predictive Ability, Environmental Regulation and Pharmacogenetics Utility of a BMI-Predisposing Genetic Risk Score during Childhood and Puberty
The authors would like to thank the Spanish children and parents who participated in
the study.Polygenetic risk scores (pGRSs) consisting of adult body mass index (BMI) genetic
variants have been widely associated with obesity in children populations. The implication of
such obesity pGRSs in the development of cardio-metabolic alterations during childhood as well
as their utility for the clinical prediction of pubertal obesity outcomes has been barely investigated
otherwise. In the present study, we evaluated the utility of an adult BMI predisposing pGRS for the
prediction and pharmacological management of obesity in Spanish children, further investigating
its implication in the appearance of cardio-metabolic alterations. For that purpose, we counted
on genetics data from three well-characterized children populations (composed of 574, 96 and 124
individuals), following both cross-sectional and longitudinal designs, expanding childhood and
puberty. As a result, we demonstrated that the pGRS is strongly associated with childhood BMI
Z-Score (B = 1.56, SE = 0.27 and p-value = 1.90 Ă 10â8
), and that could be used as a good predictor of
obesity longitudinal trajectories during puberty. On the other hand, we showed that the pGRS is not
associated with cardio-metabolic comorbidities in children and that certain environmental factors
interact with the genetic predisposition to the disease. Finally, according to the results derived from a
weight-reduction metformin intervention in children with obesity, we discarded the utility of the
pGRS as a pharmacogenetics marker of metformin response.Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER)
PI1102042
PI1102059
PI1601301
PI1600871Spanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health Products
EC10-243
EC10-056
EC10-281
EC10-227Regional Government of Andalusia ("Plan Andaluz de investigacion, desarrollo e innovacion (2018)")
P18-RT-2248Mapfre Foundation ("Research grants by Ignacio H. de Larramendi 2017")Instituto de Salud Carlos III
IFI17/0004
Systemic Toll-Like Receptor Stimulation Suppresses Experimental Allergic Asthma and Autoimmune Diabetes in NOD Mice
BackgroundInfections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR) stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. Methods and Findings Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA)-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD) that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-ÎČ and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. Conclusions/Significance These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses. They provide a plausible explanation for the hygiene hypothesis. They also open new therapeutic perspectives for the prevention of these pathologies
Lawson criterion for ignition exceeded in an inertial fusion experiment
For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37Â MJ of fusion for 1.92Â MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
Meeting abstrac
Comparison of Classical Models for Evaluating the Heat Requirements of Olive (Olea europeae L.) in Portugal
The Modified Rockwell Test: A New Probe for Mechanical Properties of Metals
In the present work a novel methodology is proposed, based on the combination of the Rockwell and the Vickers tests, to provide estimates of the mechanical properties of metal substrates. The analysis is based on some novel invariants obtained from the finite element solution of the Vickers indentation (the imprint diagonal relates to the maximum indentation depth and the residual indentation depth with the average pressure and the elastic modulus). Several other useful results are discussed and experiments are performed with a modified Rockwell apparatus on steel and aluminium alloys. The results are important for the interpretation of micro indentation tests. Inverting the indentation data, reasonably accurate results can be obtained for strain hardening properties for "power law" behaviour, whereas more complex strain hardening would require further investigation