9,584 research outputs found
Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging
An inverse correlation between thyroid hormone levels and longevity has been reported in several species and reduced thyroid hormone levels have been proposed as a biomarker for healthy aging and metabolic fitness. However, hypothyroidism is a medical condition associated with compromised health and reduced life expectancy. Herein, we show, using wild-type and the Pax8 ablated model of hypothyroidism in mice, that hyperthyroidism and severe hypothyroidism are associated with an overall unhealthy status and shorter lifespan. Mild hypothyroid Pax8 +/- mice were heavier and displayed insulin resistance, hepatic steatosis and increased prevalence of liver cancer yet had normal lifespan. These pathophysiological conditions were precipitated by hepatic mitochondrial dysfunction and oxidative damage accumulation. These findings indicate that individuals carrying mutations on PAX8 may be susceptible to develop liver cancer and/or diabetes and raise concerns regarding the development of interventions aiming to modulate thyroid hormones to promote healthy aging or lifespan in mammals
HLA association with the susceptibility to anti-synthetase syndrome
Objective: To investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD). Methods: We conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing. Results: A statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56Eâ09, odds ratioâOR [95% confidence intervalâCI] = 2.54 [1.84â3.50] and 21.4% versus 5.5%, P = 18.95Eâ18, OR [95% CI] = 4.73 [3.18â7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31â0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39â4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed. Conclusions: Our results support the association of the HLA complex with the susceptibility to ASSD
Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)
Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear.
Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese.
Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire.
Results: The mHealth intervention produced a greater loss of body weight (â1.97 kg, 95% CI â2.39 to â1.54) relative to standard counselling at 3 months (â1.13 kg, 95% CI â1.56 to â0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; â1.84 kg, 95% CI â2.48 to â1.20), percentage of body fat (PBF; â1.22%, 95% CI â1.82% to 0.62%), and BMI (â0.77 kg/m2, 95% CI â0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of â1.18 kg (95% CI â2.30 to â0.06) and BMI of â0.47 kg/m2 (95% CI â0.80 to â0.13), whereas the obese group only experienced a change in BMI of â0.53 kg/m2 (95% CI â0.86 to â0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of â1.03 kg (95% CI â1.74 to â0.33), PBF of â0.76% (95% CI â1.32% to â0.20%), and BMI of â0.5 kg/m2 (95% CI â0.83 to â0.19).
Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect
Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications
Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Råbago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Råbago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions
Gene Therapy Corrects Mitochondrial Dysfunction in Hematopoietic Progenitor Cells and Fibroblasts from Coq9R239X Mice
This study has been submitted to the patent's offices at the "University of Granada" and "FundaciĂłn Progreso y Salud". Please note that the results of this manuscript have been submitted to patent protection (application number P201630630; title: âUses of Coenzyme Q biosynthetic proteinsâ; date:05/16/2016).Recent clinical trials have shown that in vivo and ex vivo gene therapy strategies can be an option for the treatment of several neurological disorders. Both strategies require efficient and safe vectors to 1) deliver the therapeutic gene directly into the CNS or 2) to genetically modify stem cells that will be used as Trojan horses for the systemic delivery of the therapeutic protein. A group of target diseases for these therapeutic strategies are mitochondrial encephalopathies due to mutations in nuclear DNA genes. In this study, we have developed a lentiviral vector (CCoq9WP) able to overexpress Coq9 mRNA and COQ9 protein in mouse embryonic fibroblasts (MEFs) and hematopoietic progenitor cells (HPCs) from Coq9R239X mice, an animal model of mitochondrial encephalopathy due to primary Coenzyme Q (CoQ) deficiency. Ectopic over-expression of Coq9 in both cell types restored the CoQ biosynthetic pathway and mitochondrial function, improving the fitness of the transduced cells. These results show the potential of the CCoq9WP lentiviral vector as a tool for gene therapy to treat mitochondrial encephalopathies.This work was supported by grants from Ministerio de EconomĂa y Competitividad (Spain) and the European Regional Development Fund (ERDF) from the European Union, to LCL through the research grants SAF2013-47761-R and SAF2015-65786-R; by Fondo de Investigaciones Sanitarias ISCIII (Spain) and the European Regional Development Fund (ERDF) from the European Union through the research grants PI12/01097 and ISCIII Red de Terapia Celular TerCel RD12/0019/0006 to FM; by the ConsejerĂa de EconomĂa, InnovaciĂłn, Ciencia y Empleo, Junta de AndalucĂa-FEDER/Fondo de Cohesion Europeo (FSE) de AndalucĂa through the research grants P10-CTS-6133 to LCL; P09-CTS-04532, PI-57069, PI-0001/2009 and PAIDI-Bio-326 to F.M.; PI-0160/2012 to KB and PI-0407/2012 to MC; by the NIH through the research P01HD080642 to LCL and by the foundation âtodos somos raros, todos somos Ășnicosâ to LCL. LCL is supported by the âRamĂłn y Cajalâ National Programme, Ministerio de EconomĂa y Competitividad, Spain (RYC-2011-07643)
Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at âs=7 TeV
Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected
by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the
form of an enhancement of pairs of like-sign charged pions with small four-momentum
difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source
is investigated, determining both the correlation radius and the chaoticity parameter. The
measured correlation radius is found to increase as a function of increasing charged-particle
multiplicity, while the chaoticity parameter is seen to decreas
First observation of Bs -> D_{s2}^{*+} X mu nu decays
Using data collected with the LHCb detector in proton-proton collisions at a
centre-of-mass energy of 7 TeV, the semileptonic decays Bs -> Ds+ X mu nu and
Bs -> D0 K+ X mu nu are detected. Two structures are observed in the D0 K+ mass
spectrum at masses consistent with the known D^+_{s1}(2536) and
$D^{*+}_{s2}(2573) mesons. The measured branching fractions relative to the
total Bs semileptonic rate are B(Bs -> D_{s2}^{*+} X mu nu)/B(Bs -> X mu nu)=
(3.3\pm 1.0\pm 0.4)%, and B(Bs -> D_{s1}^+ X munu)/B(Bs -> X mu nu)= (5.4\pm
1.2\pm 0.5)%, where the first uncertainty is statistical and the second is
systematic. This is the first observation of the D_{s2}^{*+} state in Bs
decays; we also measure its mass and width.Comment: 8 pages 2 figures. Published in Physics Letters
Study of charmonium production in b -hadron decays and first evidence for the decay Bs0
Using decays to Ï-meson pairs, the inclusive production of charmonium states in b-hadron decays is studied with pp collision data corresponding to an integrated luminosity of 3.0 fbâ1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. Denoting byBC ⥠B(b â C X) Ă B(C â ÏÏ) the inclusive branching fraction of a b hadron to a charmonium state C that decays into a pair of Ï mesons, ratios RC1C2 ⥠BC1 /BC2 are determined as RÏc0ηc(1S) = 0.147 ± 0.023 ± 0.011, RÏc1ηc(1S) =0.073 ± 0.016 ± 0.006, RÏc2ηc(1S) = 0.081 ± 0.013 ± 0.005,RÏc1 Ïc0 = 0.50 ± 0.11 ± 0.01, RÏc2 Ïc0 = 0.56 ± 0.10 ± 0.01and Rηc(2S)ηc(1S) = 0.040 ± 0.011 ± 0.004. Here and below the first uncertainties are statistical and the second systematic.Upper limits at 90% confidence level for the inclusive production of X(3872), X(3915) and Ïc2(2P) states are obtained as RX(3872)Ïc1 < 0.34, RX(3915)Ïc0 < 0.12 andRÏc2(2P)Ïc2 < 0.16. Differential cross-sections as a function of transverse momentum are measured for the ηc(1S) andÏc states. The branching fraction of the decay B0s â ÏÏÏ is measured for the first time, B(B0s â ÏÏÏ) = (2.15±0.54±0.28±0.21B)Ă10â6. Here the third uncertainty is due to the branching fraction of the decay B0s â ÏÏ, which is used for normalization. No evidence for intermediate resonances is seen. A preferentially transverse Ï polarization is observed.The measurements allow the determination of the ratio of the branching fractions for the ηc(1S) decays to ÏÏ and p p asB(ηc(1S)â ÏÏ)/B(ηc(1S)â p p) = 1.79 ± 0.14 ± 0.32
Study of J /Ï production in Jets
The production of J/Ï mesons in jets is studied in the forward region of proton-proton collisions using data collected with the LHCb detector at a center-of-mass energy of 13 TeV. The fraction of the jet transverse momentum carried by the J/Ï meson, z(J/Ï)âĄpT(J/Ï)/pT(jet), is measured using jets with pT(jet)>20 GeV in the pseudorapidity range 2.5<η(jet)<4.0. The observed z(J/Ï)distribution for J/Ï mesons produced in b-hadron decays is consistent with expectations. However, the results for prompt J/Ï production do not agree with predictions based on fixed-order nonrelativistic QCD. This is the first measurement of the pT fraction carried by prompt J/Ï mesons in jets at any experiment
Measurement of the lifetime
Using a data set corresponding to an integrated luminosity of ,
collected by the LHCb experiment in collisions at centre-of-mass energies
of 7 and 8 TeV, the effective lifetime in the
decay mode, , is measured to be ps. Assuming
conservation, corresponds to the lifetime of the light
mass eigenstate. This is the first measurement of the effective
lifetime in this decay mode.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-017.htm
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