472 research outputs found
A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration
[EN] Charcot-Marie-Tooth disease is a rare peripheral neuropathy for which there is no specific treatment. Some forms of Charcot-Marie-Tooth are due to mutations in the GDAP1 gene. A striking feature of mutations in GDAP1 is that they have a variable clinical manifestation, according to disease onset and progression, histology and mode of inheritance. Studies in cellular and animal models have revealed a role of GDAP1 in mitochondrial morphology and distribution, calcium homeostasis and oxidative stress. To get a better understanding of the disease mechanism we have generated models of over-expression and RNA interference of the Drosophila Gdapl gene. In order to get an overview about the changes that Gdapl mutations cause in our disease model, we have combined a comprehensive determination of the metabolic profile in the flies by nuclear magnetic resonance spectroscopy with gene expression analyses and biophysical tests. Our results revealed that both up- and down-regulation of Gdapl results in an early systemic inactivation of the insulin pathway before the onset of neuromuscular degeneration, followed by an accumulation of carbohydrates and an increase in the (3-oxidation of lipids. Our findings are in line with emerging reports of energy metabolism impairments linked to different types of neural pathologies caused by defective mitochondrial function, which is not surprising given the central role of mitochondria in the control of energy metabolism. The relationship of mitochondrial dynamics with metabolism during neurodegeneration opens new avenues to understand the cause of the disease, and for the discovery of new biomarkers and treatments.This work was supported by a project grant from the Association Francaise contre les Myopathies [AFM 18540 to M.I.G]; a collaborative grant from International Rare Diseases Research consortium (IRDiRC) and Institute de Salud Carlos III [IR11/TREAT-CMT to M.I.G. (partner 12) and F.V.P. (partner 8)]; funding from Institute de Salud Carlos III through Biomedical Network Research Center for Rare Diseases and the INGENIO 2010 program to F.V.P.; and a project grant from the Spanish Government (Secretaria de Estado de Investigacion, Desarollo e Innovacion, Ministerio de Economia y Competitividad) [SAF2014-53977-R to A.P.].Lopez Del Amo, V.; Palomino-SchÀtzlein, M.; Seco-Cervera, M.; Garcia-Gimenez, JL.; Pallardó-Calatayud, FV.; Pineda-Lucena, A.; Galindo-Orozco, MI. (2017). A Drosophila model of GDAP1 function reveals the involvement of insulin signalling in the mitochondria-dependent neuromuscular degeneration. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1863(3):801-809. https://doi.org/10.1016/j.bbadis.2017.01.003S8018091863
Cost-Utility Analysis of a Medication Review with Follow-Up Service for Older Adults with Polypharmacy in Community Pharmacies in Spain: The conSIGUE Program
Cost-Utility Analysis of a Medication Review with Follow-Up Service for Older Adults with Polypharmacy in Community Pharmacies in Spain: The conSIGUE Program
© 2015, Springer International Publishing Switzerland. Background: The concept of pharmaceutical care is operationalized through pharmaceutical professional services, which are patient-oriented to optimize their pharmacotherapy and to improve clinical outcomes. Objective: The objective of this study was to estimate the incremental cost-effectiveness ratio (ICER) of a medication review with follow-up (MRF) service for older adults with polypharmacy in Spanish community pharmacies against the alternative of having their medication dispensed normally. Methods: The study was designed as a cluster randomized controlled trial, and was carried out over a time horizon of 6 months. The target population was older adults with polypharmacy, defined as individuals taking five or more medicines per day. The study was conducted in 178 community pharmacies in Spain. Cost-utility analysis adopted a health service perspective. Costs were in euros at 2014 prices and the effectiveness of the intervention was estimated as quality-adjusted life-years (QALYs). In order to analyze the uncertainty of ICER results, we performed a non-parametric bootstrapping with 5000 replications. Results: A total of 1403 older adults, aged between 65 and 94 years, were enrolled in the study: 688 in the intervention group (IG) and 715 in the control group (CG). By the end of the follow-up, both groups had reduced the mean number of prescribed medications they took, although this reduction was greater in the IG (0.28 ± 1.25 drugs; p < 0.001) than in the CG (0.07 ± 0.95 drugs; p = 0.063). Older adults in the IG saw their quality of life improved by 0.0528 ± 0.20 (p < 0.001). In contrast, the CG experienced a slight reduction in their quality of life: 0.0022 ± 0.24 (p = 0.815). The mean total cost was âŹ977.57 ± 1455.88 for the IG and âŹ1173.44 ± 3671.65 for the CG. In order to estimate the ICER, we used the costs adjusted for baseline medications and QALYs adjusted for baseline utility score, resulting in a mean incremental total cost of ââŹ250.51 ± 148.61 (95 % CI â541.79 to 40.76) and a mean incremental QALY of 0.0156 ± 0.004 (95 % CI 0.008â0.023). Regarding the results from the cost-utility analysis, the MRF service emerged as the dominant strategy. Conclusion: The MRF service is an effective intervention for optimizing prescribed medication and improving quality of life in older adults with polypharmacy in community pharmacies. The results from the cost-utility analysis suggest that the MRF service is cost effective
Male condom use, multiple sexual partners and HIV: a prospective case-control study in Kinshasa (DRC)
Light hadron, Charmonium(-like) and Bottomonium(-like) states
Hadron physics represents the study of strongly interacting matter in all its
manifestations and the understanding of its properties and interactions. The
interest on this field has been revitalized by the discovery of new light
hadrons, charmonium- and bottomonium-like states. I review the most recent
experimental results from different experiments.Comment: Presented at Lepton-Photon 2011, Mumbai, India; 21 pages, 18 figures;
add more references; some correctio
Study of DJ meson decays to D+Ïâ, D0Ï+ and Dâ+Ïâ final states in pp collisions
A study of D+Ïâ, D0Ï+ and Dâ+Ïâ final states is performed using pp collision data, corresponding to an integrated luminosity of 1.0 fbâ1, collected at a centre-of-mass energy of 7 TeV with the LHCb detector. The D1(2420)0 resonance is observed in the Dâ+Ïâ final state and the Dâ2(2460) resonance is observed in the D+Ïâ, D0Ï+ and Dâ+Ïâ final states. For both resonances, their properties and spin-parity assignments are obtained. In addition, two natural parity and two unnatural parity resonances are observed in the mass region between 2500 and 2800 MeV. Further structures in the region around 3000 MeV are observed in all the Dâ+Ïâ, D+Ïâ and D0Ï+ final states
Study of B0(s)âK0Sh+hâČâ decays with first observation of B0sâK0SK±Ïâ and B0sâK0SÏ+Ïâ
A search for charmless three-body decays of B 0 and B0s mesons with a K0S meson in the final state is performed using the pp collision data, corresponding to an integrated luminosity of 1.0 fbâ1, collected at a centre-of-mass energy of 7 TeV recorded by the LHCb experiment. Branching fractions of the B0(s)âK0Sh+hâČâ decay modes (h (âČ) = Ï, K), relative to the well measured B0âK0SÏ+Ïâ decay, are obtained. First observation of the decay modes B0sâK0SK±Ïâ and B0sâK0SÏ+Ïâ and confirmation of the decay B0âK0SK±Ïâ are reported. The following relative branching fraction measurements or limits are obtained B(B0âK0SK±Ïâ)B(B0âK0SÏ+Ïâ)=0.128±0.017(stat.)±0.009(syst.), B(B0âK0SK+Kâ)B(B0âK0SÏ+Ïâ)=0.385±0.031(stat.)±0.023(syst.), B(B0sâK0SÏ+Ïâ)B(B0âK0SÏ+Ïâ)=0.29±0.06(stat.)±0.03(syst.)±0.02(fs/fd), B(B0sâK0SK±Ïâ)B(B0âK0SÏ+Ïâ)=1.48±0.12(stat.)±0.08(syst.)±0.12(fs/fd)B(B0sâK0SK+Kâ)B(B0âK0SÏ+Ïâ)â[0.004;0.068]at90%CL
Evidence for the η_b(1S) Meson in Radiative ΄(2S) Decay
We have performed a search for the η_b(1S) meson in the radiative decay of the ΄(2S) resonance using a sample of 91.6 Ă 10^6 ΄(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at E_Îł = 609.3^(+4.6)_(-4.5)(stat)±1.9(syst) MeV, corresponding to an η_b(1S) mass of 9394.2^(+4.8)_(-4.9)(stat) ± 2.0(syst) MeV/c^2. The branching fraction for the decay ΄(2S) â γη_b(1S) is determined to be [3.9 ± 1.1(stat)^(+1.1)_(-0.9)(syst)] Ă 10^(-4). We find the ratio of branching fractions B[΄(2S) â γη_b(1S)]/B[΄(3S) â γη_b(1S)]= 0.82 ± 0.24(stat)^(+0.20)_(-0.19)(syst)
First observation of the decay and a measurement of the ratio of branching fractions
The first observation of the decay using
data collected by the LHCb detector at a centre-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 36 pb, is reported. A
signal of events is obtained and the absence of signal is
rejected with a statistical significance of more than nine standard deviations.
The branching fraction is measured relative to
that of : , where the first uncertainty is statistical, the second systematic and
the third is due to the uncertainty on the ratio of the and
hadronisation fractions.Comment: 10 pages, 3 figures, submitted to Phys. Lett. B; ISSN 0370-269
Genome-Wide Transcriptome Analyses of Silicon Metabolism in Phaeodactylum tricornutum Reveal the Multilevel Regulation of Silicic Acid Transporters
BACKGROUND:Diatoms are largely responsible for production of biogenic silica in the global ocean. However, in surface seawater, Si(OH)(4) can be a major limiting factor for diatom productivity. Analyzing at the global scale the genes networks involved in Si transport and metabolism is critical in order to elucidate Si biomineralization, and to understand diatoms contribution to biogeochemical cycles. METHODOLOGY/PRINCIPAL FINDINGS:Using whole genome expression analyses we evaluated the transcriptional response to Si availability for the model species Phaeodactylum tricornutum. Among the differentially regulated genes we found genes involved in glutamine-nitrogen pathways, encoding putative extracellular matrix components, or involved in iron regulation. Some of these compounds may be good candidates for intracellular intermediates involved in silicic acid storage and/or intracellular transport, which are very important processes that remain mysterious in diatoms. Expression analyses and localization studies gave the first picture of the spatial distribution of a silicic acid transporter in a diatom model species, and support the existence of transcriptional and post-transcriptional regulations. CONCLUSIONS/SIGNIFICANCE:Our global analyses revealed that about one fourth of the differentially expressed genes are organized in clusters, underlying a possible evolution of P. tricornutum genome, and perhaps other pennate diatoms, toward a better optimization of its response to variable environmental stimuli. High fitness and adaptation of diatoms to various Si levels in marine environments might arise in part by global regulations from gene (expression level) to genomic (organization in clusters, dosage compensation by gene duplication), and by post-transcriptional regulation and spatial distribution of SIT proteins
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