Evaluación ética de la memoria económica de los contratos de ensayos clínicos con medicamentos en España

Objetivos: Analizar el grado de homogeneidad de la memoria económica incluida en los contratos de centros sanitarios españoles participantes en ensayos clínicos (EC) con medicamentos para detectar puntos de potencial conflicto de interés en la investigación clínica. Material y métodos: Se ha analizado, mediante un autocuestionario, la memoria económica de 40 contratos, 31 correspondientes a centros sanitarios privados y públicos seleccionados al azar y 9 correspondientes a las comunidades autónomas con modelo de contrato único. Resultados: El equipo investigador, en el 97,5% de los casos (39 contratos), es el destinatario mayoritario de la remuneración económica por participar en un EC. El porcentaje aportado difiere según el centro, siendo mayor si es público (p=0,021) pero sin especificarse en el 50% de los contratos. En 38 de los 40 contratos analizados no se proporciona un listado de precios de las pruebas complementarias. En el 57,5%, (23 contratos), no se especifica si los gastos de los pacientes son abonados por el promotor. En el 77,5% (31 casos) no se especifica si los gastos derivados de reuniones relacionadas con el EC se incluyen en la memoria económica. Conclusiones: Existe una elevada heterogeneidad en el contenido de la memoria económica. La implantación de un modelo de memoria económica que incluyera una cantidad económica de remuneración fija por cada paciente reclutado por parte del promotor, para todos los centros participantes, podría disminuir las desigualdades entre centros, los conflictos de intereses, y además, incrementaría la trasparencia y la calidad de los EC.Abstract: Objectives: To analyze the homogeneity of the economic report of the contracts of Spanish medical centers participating in clinical trials with medicinal products for detecting points of potential conflict of interest in clinical research. Material and methods: We analyzed, through a selfautoquestionnaire, the budgetary information of the 40 contracts, 31 of them corresponding to public and private healthcare centers, randomly selected, and 9 corresponding to the Spanish regions who have only a model contract. Results: The investigator team is the recipient majority (97.5% of cases) the economic remuneration for participating in a clinical trial. The percentage differs according to the center considered, being greater in the public setting (p=0.021) but no specified in 50% of the contracts. In 38 of the 40 contracts analyzed a price list of tests is not provided. In 57.5% of the patients are paid by the promoter. In 17.5% failed to mention that the comparative drug to be supplied free of charge. And, 77.5% did not specify whether the costs of meetings relating to the clinical trial or not to include in the expenses of the promoter. Conclusions: There is a high heterogeneity in the content of the budgetary information. The implementation of a single contract model would reduce the inequalities between schools, conflict of interest and increase transparency and quality of the clinical trial

Identification of a Novel Modulator of Thyroid Hormone Receptor-Mediated Action

Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRa1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR a1 and to T3-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Significance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease

Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis

Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age-and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients

Genome-Wide Screening of Genes Whose Enhanced Expression Affects Glycogen Accumulation in Escherichia coli

Using a systematic and comprehensive gene expression library (the ASKA library), we have carried out a genome-wide screening of the genes whose increased plasmid-directed expression affected glycogen metabolism in Escherichia coli. Of the 4123 clones of the collection, 28 displayed a glycogen-excess phenotype, whereas 58 displayed a glycogen-deficient phenotype. The genes whose enhanced expression affected glycogen accumulation were classified into various functional categories including carbon sensing, transport and metabolism, general stress and stringent responses, factors determining intercellular communication, aggregative and social behaviour, nitrogen metabolism and energy status. Noteworthy, one-third of them were genes about which little or nothing is known. We propose an integrated metabolic model wherein E. coli glycogen metabolism is highly interconnected with a wide variety of cellular processes and is tightly adjusted to the nutritional and energetic status of the cell. Furthermore, we provide clues about possible biological roles of genes of still unknown functions

Mars Science Laboratory Observations of the 2018/Mars Year 34 Global Dust Storm

Mars Science Laboratory Curiosity rover observations of the 2018/Mars year 34 global/planet-encircling dust storm represent the first in situ measurements of a global dust storm with dedicated meteorological sensors since the Viking Landers. The Mars Science Laboratory team planned and executed a science campaign lasting approximately 100 Martian sols to study the storm involving an enhanced cadence of environmental monitoring using the rover's meteorological sensors, cameras, and spectrometers. Mast Camera 880-nanometer optical depth reached 8.5, and Rover Environmental Monitoring Station measurements indicated a 97 percent reduction in incident total ultraviolet solar radiation at the surface, 30 degrees Kelvin reduction in diurnal range of air temperature, and an increase in the semidiurnal pressure tide amplitude to 40 pascals. No active dust-lifting sites were detected within Gale Crater, and global and local atmospheric dynamics were drastically altered during the storm. This work presents an overview of the mission's storm observations and initial results

Mars Science Laboratory Observations of the 2018/Mars Year 34 Global Dust Storm

Mars Science Laboratory Curiosity rover observations of the 2018/Mars year 34 global/planetâ encircling dust storm represent the first in situ measurements of a global dust storm with dedicated meteorological sensors since the Viking Landers. The Mars Science Laboratory team planned and executed a science campaign lasting approximately 100 Martian sols to study the storm involving an enhanced cadence of environmental monitoring using the rover’s meteorological sensors, cameras, and spectrometers. Mast Camera 880â nm optical depth reached 8.5, and Rover Environmental Monitoring Station measurements indicated a 97% reduction in incident total ultraviolet solar radiation at the surface, 30K reduction in diurnal range of air temperature, and an increase in the semidiurnal pressure tide amplitude to 40 Pa. No active dustâ lifting sites were detected within Gale Crater, and global and local atmospheric dynamics were drastically altered during the storm. This work presents an overview of the mission’s storm observations and initial results.Plain Language SummaryThe 2018 Mars global dust storm was observed by six spacecraft in orbit and two rovers on the surface. This paper provides an overview and description of the Mars Science Laboratory Curiosity rover’s observations during the storm. For approximately 100 Martian days (sols), the rover conducted an enhanced cadence of environmental observations to study the storm. These are the first observations of a Martian global dust storm with meteorological sensors near the equator. Atmospheric opacity reached a peak of 8.5, attenuating ~97% of the total solar ultraviolet radiation at the surface. Most of the dust was sourced from outside Gale Crater, with no indications of dust lifting within the crater during the height of the storm. Meteorological conditions were substantially altered, with changes to the pressure, temperature, and humidity patterns. Dust devil activity ceased for several weeks due to the reduction in temperature contrast between the surface and atmosphere. There was no indication of unusual aeolian transport, suggesting Martian global dust storms are not a major cause of sand dune movement.Key PointsThe Curiosity rover conducted a dedicated science campaign to study the 2018 Mars global dust stormAtmospheric opacity reached a peak of 8.5, and horizontal visibility dropped to 2.7 kmMeteorological conditions in Gale Crater were substantially altered, with changes to the pressure, temperature, and humidity cyclesPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147828/1/grl58365_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147828/2/grl58365.pd

The Atmospheric Chemistry Suite (ACS) of Three Spectrometers for the ExoMars 2016 Trace Gas Orbiter

The Atmospheric Chemistry Suite (ACS) package is an element of the Russian contribution to the ESA-Roscosmos ExoMars 2016 Trace Gas Orbiter (TGO) mission. ACS consists of three separate infrared spectrometers, sharing common mechanical, electrical, and thermal interfaces. This ensemble of spectrometers has been designed and developed in response to the Trace Gas Orbiter mission objectives that specifically address the requirement of high sensitivity instruments to enable the unambiguous detection of trace gases of potential geophysical or biological interest. For this reason, ACS embarks a set of instruments achieving simultaneously very high accuracy (ppt level), very high resolving power (>10,000) and large spectral coverage (0.7 to 17 μm—the visible to thermal infrared range). The near-infrared (NIR) channel is a versatile spectrometer covering the 0.7–1.6 μm spectral range with a resolving power of ∼20,000. NIR employs the combination of an echelle grating with an AOTF (Acousto-Optical Tunable Filter) as diffraction order selector. This channel will be mainly operated in solar occultation and nadir, and can also perform limb observations. The scientific goals of NIR are the measurements of water vapor, aerosols, and dayside or night side airglows. The mid-infrared (MIR) channel is a cross-dispersion echelle instrument dedicated to solar occultation measurements in the 2.2–4.4 μm range. MIR achieves a resolving power of >50,000. It has been designed to accomplish the most sensitive measurements ever of the trace gases present in the Martian atmosphere. The thermal-infrared channel (TIRVIM) is a 2-inch double pendulum Fourier-transform spectrometer encompassing the spectral range of 1.7–17 μm with apodized resolution varying from 0.2 to 1.3 cm−1. TIRVIM is primarily dedicated to profiling temperature from the surface up to ∼60 km and to monitor aerosol abundance in nadir. TIRVIM also has a limb and solar occultation capability. The technical concept of the instrument, its accommodation on the spacecraft, the optical designs as well as some of the calibrations, and the expected performances for its three channels are described

The Present Habitability Potential of Gale Crater: What We Have Learned So Far From Mars Science Laboratory

The Mars Science Laboratory mission has comprehensively interrogated the surface environment of Mars as it explores Gale Crater. Both chemical and physical attributes of the present environment have been measured over the course of the mission, enabling us to compare the present state of the martian surface with the environmental requirements of prokaryotic microbes. While this approach does not exclude the possibility of martian life that may have evolved to adapt to the present conditions, it is advantageous in that it allows us to evaluate environmental requirements of known life and also provide insight into the likelihood of forward contamination by Earth organisms with the comparison of their environmental requirements with the measured attributes of the environment at Gale Crater. We have already modeled a paleoenvironment with high habitability potential (HP) based upon chemistry, mineralogy and other geological evidence such as sedimentary structures and larger scale geomorphology [1]. In this report, we turn our attention to the present HP of the Yellowknife Bay area, including the importance of the physical environmental metrics such as atmospheric pressure, air and ground temperature, ionizing radiation, wind speed and direction, slope, etc

Mars methane detection and variability at Gale crater

Reports of plumes or patches of methane in the martian atmosphere that vary over monthly time scales have defied explanation to date. From in situ measurements made over a 20-month period by the tunable laser spectrometer of the Sample Analysis at Mars instrument suite on Curiosity at Gale crater, we report detection of background levels of atmospheric methane of mean value 0.69 ± 0.25 parts per billion by volume (ppbv) at the 95% confidence interval (CI). This abundance is lower than model estimates of ultraviolet degradation of accreted interplanetary dust particles or carbonaceous chondrite material. Additionally, in four sequential measurements spanning a 60-sol period (where 1 sol is a martian day), we observed elevated levels of methane of 7.2 ± 2.1 ppbv (95% CI), implying that Mars is episodically producing methane from an additional unknown source

Mild Mitochondrial Uncoupling and Calorie Restriction Increase Fasting eNOS, Akt and Mitochondrial Biogenesis

Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis