Efecto del chocolate con alto porcentaje de cacao sobre la salud en mujeres posmenopáusicas. Ensayo clínico aleatorizado

Tesis por compendio de publicaciones[ES] La ingesta de polifenoles ha demostrado ciertos beneficios para la salud. El objetivo de este estudio fue analizar el efecto de añadir 10 g diarios de chocolate comercial con alto porcentaje de cacao (99%) a la dieta habitual, durante 6 meses, sobre la presión arterial, la función vascular, el rendimiento cognitivo, la calidad de vida y la composición corporal en mujeres posmenopáusicas. Se trata de un ensayo clínico aleatorizado con dos grupos paralelos en el que se incluyeron 140 mujeres entre 50 y 64 años de edad en periodo posmenopáusico definido por amenorrea de al menos 12 meses consecutivos. La variable principal fue el cambio en la presión arterial. Las variables secundarias fueron los cambios en la función vascular, la composición corporal, el rendimiento cognitivo y la calidad de vida. El grupo de intervención recibió chocolate con una concentración del 99% de cacao y las instrucciones para tomar 10 g diarios de este producto añadidos a su alimentación habitual durante 6 meses. El aporte nutricional diario de esta cantidad de chocolate es de 59 kcal y 65,4 mg de polifenoles. El grupo control no recibió ninguna intervención. Todas las variables se midieron en la visita basal y a los 6 meses de esta. El periodo de estudio fue de junio de 2018 a agosto de 2019. Este ensayo fue aprobado por el Comité de Ética de la Investigación con Medicamentos (CEIm) del Área de Salud de Salamanca, España, en febrero de 2018, y se registró en clinicaltrials.gov perteneciente al US National Library of Medicine (número NCT03492983). Los análisis de la covarianza (ANCOVA) ajustados por los valores basales no mostraron diferencias significativas en la presión arterial sistólica (−1,45 mmHg; intervalo de confianza (IC) 95% −4,79 a 1,88; p = 0,391) o la VOP (0,18 m/s; IC 95% −0,14 a 0,50; p = 0,263) entre grupos. Se observó un descenso en la PP en el GI en comparación con el GC (−2,05 mmHg; IC 95% −4,08 a −0,02; p = 0,048). El resto de parámetros de estructura y función vascular, así como las demás variables medidas no mostraron cambios. El efecto principal de la intervención mostró una reducción favorable al GI respecto al GC en la masa grasa corporal (−0,63 kg [IC 95% −1,15 a −0,11], p = 0,019), (d de Cohen = −0,450) y en el porcentaje de grasa corporal (−0,79% [IC 95% −1,31 a −0,26], p = 0,004), (d de Cohen = −0,539). Se observó un descenso no significativo en el índice de masa corporal (−0,20 kg/m2 [IC 95% −0,44 a 0,03], p = 0,092), (d de Cohen = −0,345). El tiempo de ejecución del Trail Making Test B mostró un descenso de −12,08 s (IC 95% −23,99 a −0,18; p = 0,047) en el grupo de intervención en comparación con el grupo control, tras ajustar por la edad, el nivel de educación, el tiempo desde el inicio de la menopausia y el consumo energético diario (d de Cohen = −0,343). No se observaron cambios en la atención, la memoria verbal inmediata y demorada, la fluidez fonológica y categorial ni la memoria de trabajo. Los ANCOVA ajustados por los principales determinantes de la CdV considerados en este estudio no mostraron cambios en la puntuación global de la CdV evaluada con el EuroQoL-5D-3L. El grupo de intervención mostró un incremento de 6,0 puntos (intervalo de confianza (IC) 95% 0,4 a 11,7) en el EQ-VAS en comparación con el grupo control (p = 0,036). No se observaron cambios significativos entre grupos en la puntuación global de la CdV ni en las dimensiones o subdimensiones medidas con la escala Cervantes. En conclusión, el consumo de 10 g de chocolate rico en cacao parece que produce una discreta mejora en la salud cardiovascular, aunque tampoco provoca efectos adversos en los parámetros evaluados en mujeres posmenopáusicas a largo plazo. La adición diaria a la dieta habitual de 10 g de chocolate comercial rico en cacao en mujeres posmenopáusicas disminuye la masa grasa y el porcentaje de grasa corporal sin alterar el peso corporal. El consumo diario de 10 g de chocolate comercial rico en cacao añadido a la dieta habitual podría estar asociado a una leve mejora en el rendimiento cognitivo con respecto a la flexibilidad cognitiva y la velocidad de procesamiento en mujeres posmenopáusicas, sin producir cambios en las demás variables de rendimiento cognitivo evaluadas. El aporte adicional de 10 g de chocolate comercial rico en cacao en mujeres posmenopáusicas podría tener un ligero impacto en su percepción de su estado de salud, pero sin modificar la calidad de vida relacionada con la salud ni las dimensiones que la componen

Vascular and cognitive effects of cocoa-rich chocolate in postmenopausal women: a study protocol for a randomised clinical trial

Introduction The intake of polyphenols has certain health benefits. This study will aim to assess the effect of adding a daily amount of chocolate high in cocoa content and polyphenols to the normal diet on blood pressure, vascular function, cognitive performance, quality of life and body composition in postmenopausal women. Methods and analysis Here we plan a randomised clinical trial with two parallel groups involving a total of 140 women between 50 and 64 years in the postmenopausal period, defined by amenorrhoea of at least 12 consecutive months. The main variable will be the change in blood pressure. Secondary variables will be changes in vascular function, quality of life, cognitive performance and body composition. The intervention group will be given chocolate containing 99% cocoa, with instructions to add 10 g daily to their normal diet for 6 months. The daily nutritional contribution of this amount of chocolate is 59 kcal and 65.4 mg of polyphenols. There will be no intervention in the control group. All variables will be measured at the baseline visit and 3 and 6 months after randomisation, except cognitive performance and quality of life, which will only be assessed at baseline and at 6 months. Recruitment is scheduled to begin on 1 June 2018, and the study will continue until 31 May 2019. Ethics and dissemination This study was approved by the Clinical Research Ethics Committee of the Health Area of Salamanca, Spain (‘CREC of Health Area of Salamanca’), in February 2018. A SPIRIT checklist is available for this protocol. The clinical trial has been registered at ClinicalTrials. gov provided by the US National Library of Medicine, number NCT03492983. The results will be disseminated through open access peer-reviewed journals, conference presentations, broadcast media and a presentation to stakeholders.Gerencia Regional de Castilla y León (GRS 1583/B/1

TWIST1 Is Expressed in Colorectal Carcinomas and Predicts Patient Survival

TWIST1 is a transcription factor that belongs to the family of basic helix-loop-helix proteins involved in epithelial-to-mesenchymal transition and invasion processes. The TWIST1 protein possesses oncogenic, drug-resistant, angiogenic and invasive properties, and has been related with several human tumors and other pathologies. Colorectal cancer is one of the tumors in which TWIST1 is over-expressed, but its involvement in the clinical outcome of the disease is still unclear. We tested, by RT-PCR, the expression levels of TWIST1 in normal and tumor paired-sample tissues from a series of 151 colorectal cancer patients, in order to investigate its prognostic value as a tumor marker. TWIST1 expression was restricted to tumor tissues (86.1%) and correlated with lymph node metastasis (LNM). Adjusted analysis showed that the expression levels of TWIST1 correlated with overall survival (OS) and disease-free survival (DFS). Importantly, TWIST1 expression levels predicted OS specifically at stages I and II. Moreover, patients with stage II tumors and high TWIST1 levels showed even shorter survival than patients with stage III tumors. These results suggest that TWIST1 expression levels could be a tumor indicator in stage II patients and help select patients at greater risk of poor prognosis who might benefit from adjuvant chemotherapy

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Priming with a Recombinant Pantothenate Auxotroph of Mycobacterium bovis BCG and Boosting with MVA Elicits HIV-1 Gag Specific CD8+ T Cells

A safe and effective HIV vaccine is required to significantly reduce the number of people becoming infected with HIV each year. In this study wild type Mycobacterium bovis BCG Pasteur and an attenuated pantothenate auxotroph strain (BCGΔpanCD) that is safe in SCID mice, have been compared as vaccine vectors for HIV-1 subtype C Gag. Genetically stable vaccines BCG[pHS400] (BCG-Gag) and BCGΔpanCD[pHS400] (BCGpan-Gag) were generated using the Pasteur strain of BCG, and a panothenate auxotroph of Pasteur respectively. Stability was achieved by the use of a codon optimised gag gene and deletion of the hsp60-lysA promoter-gene cassette from the episomal vector pCB119. In this vector expression of gag is driven by the mtrA promoter and the Gag protein is fused to the Mycobacterium tuberculosis 19 kDa signal sequence. Both BCG-Gag and BCGpan-Gag primed the immune system of BALB/c mice for a boost with a recombinant modified vaccinia virus Ankara expressing Gag (MVA-Gag). After the boost high frequencies of predominantly Gag-specific CD8+ T cells were detected when BCGpan-Gag was the prime in contrast to induction of predominantly Gag-specific CD4+ T cells when priming with BCG-Gag. The differing Gag-specific T-cell phenotype elicited by the prime-boost regimens may be related to the reduced inflammation observed with the pantothenate auxotroph strain compared to the parent strain. These features make BCGpan-Gag a more desirable HIV vaccine candidate than BCG-Gag. Although no Gag-specific cells could be detected after vaccination of BALB/c mice with either recombinant BCG vaccine alone, BCGpan-Gag protected mice against a surrogate vaccinia virus challenge

WW Domains of the Yes-Kinase-Associated-Protein (YAP) Transcriptional Regulator Behave as Independent Units with Different Binding Preferences for PPxY Motif-Containing Ligands

YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor. YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases. We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling.This work was supported by the Spanish Ministry of Education and Science [grant BIO2009-13261-CO2], the Spanish Ministry of Economy and Competitivity [grant BIO2012-39922-CO2] including FEDER (European Funds for Regional Development) funds and the Governement of Andalusia [grant CVI-5915]. Marius Sudol was supported by PA Breast Cancer Coalition Grants (#60707 and #920093) plus the Geisinger Clinic

Neurodegeneration of the retina in mouse models of Alzheimer’s disease: what can we learn from the retina?

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease commonly found among elderly. In addition to cognitive and behavioral deficits, vision abnormalities are prevalent in AD patients. Recent studies investigating retinal changes in AD double-transgenic mice have shown altered processing of amyloid precursor protein and accumulation of β-amyloid peptides in neurons of retinal ganglion cell layer (RGCL) and inner nuclear layer (INL). Apoptotic cells were also detected in the RGCL. Thus, the pathophysiological changes of retinas in AD patients are possibly resembled by AD transgenic models. The retina is a simple model of the brain in the sense that some pathological changes and therapeutic strategies from the retina may be observed or applicable to the brain. Furthermore, it is also possible to advance our understanding of pathological mechanisms in other retinal degenerative diseases. Therefore, studying AD-related retinal degeneration is a promising way for the investigation on (1) AD pathologies and therapies that would eventually benefit the brain and (2) cellular mechanisms in other retinal degenerations such as glaucoma and age-related macular degeneration. This review will highlight the efforts on retinal degenerative research using AD transgenic mouse models

Synaptic processes and immune-related pathways implicated in Tourette syndrome

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS