Association of the Gut Microbiota with the Host's Health through an Analysis of Biochemical Markers, Dietary Estimation, and Microbial Composition

This research was funded by Centro Tecnológico para el Desarrollo Industrial (CDTI) through the program Consorcio de Investigación Empresarial Nacional (Programa CIEN, BIOFOOD Project) and by CIBERobn (Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CB12/03/30002).This study aims to analyze the relationship between gut microbiota composition and health parameters through specific biochemical markers and food consumption patterns in the Spanish population. This research includes 60 Spanish adults aged 47.3 ± 11.2 years old. Biochemical and anthropometric measurements, and a self-referred dietary survey (food frequency questionnaire), were analyzed and compared with the participant's gut microbiota composition analyzed by 16s rDNA sequencing. Several bacterial strains differed significantly with the biochemical markers analyzed, suggesting an involvement in the participant's metabolic health. Lower levels of Lactobacillaceae and Oscillospiraceae and an increase in Pasteurellaceae, Phascolarctobacterium, and Haemophilus were observed in individuals with higher AST levels. Higher levels of the Christensenellaceae and a decrease in Peptococcaceae were associated with higher levels of HDL-c. High levels of Phascolarctobacterium and Peptococcus and low levels of Butyricicoccus were found in individuals with higher insulin levels. This study also identified associations between bacteria and specific food groups, such as an increase in lactic acid bacteria with the consumption of fermented dairy products or an increase in Verrucomicrobiaceae with the consumption of olive oil. In conclusion, this study reinforces the idea that specific food groups can favorably modulate gut microbiota composition and have an impact on host's health

Unexpected hypoxia-dependent erythropoietin secretion during experimental conditions not affecting tissue oxygen supply/demand ratio

Unexpected hypoxia-dependent erythropoietin secretion during experimental conditions not affecting tissue oxygen supply/demand ratio. Although a great deal of evidence supports the hypothesis that plasma erythropoietin (EPO) levels of mammals are related to the oxygen supply to the tissues relative to their oxygen needs, several observations millitate against its inherent simplicity. This study presents our results obtained from in vivo experiments that suggest that hypoxia-dependent EPO production can be altered by conditions which apparently do not modify the tissue oxygen supply/demand ratio. Hypoxia-dependent EPO production rate (EPO-PR), derived from plasma EPO titers and plasma EPO half-lives, were estimated in both transfused-polycythemic and normocy-themic mouse models subjected to different treatments. From calculations of the o2 carrying capacity of blood and body o2 consumption, it was assumed that the tissue supply/demand ratios were similar in both experimental and control mice of the same model at the time of induction of EPO production. The following observations were worth noting: (1) EPO-PRs in transfused polycythemic mice whose erythropoietic rates were stimulated by intermittent exposure to hypobaria (0·5 atm, 18 hr/day × 3 weeks), phenylhydrazine administration (40 mg/kg at weekly intervals × 3 weeks) or repeated rh-EPO injections (1500 U/kg 3 times a week × 3 weeks) before transfusion were more than five times higher than in comparabily polycythemic mice whose erythropoietic rates were not stimulated previously; and (2) EPO-PR in response to hypobaric hypoxia was 2·08 times normal in normocythemic mice with cyclophosphamide (100 mg/kg) induced depression of erythropoiesis, and 0·33 times normal in normocythemic mice with rh-EPO (400 U/kg × 2) induced enhancement of erythropoiesis. Although the results obtained in polycythemic mice are difficult to explain, those from normocythemic mice suggest the existence of a feedback mechanism between EPO-responsive cells and EPO-producing cells. Both demonstrate the existence of experimental conditions in which modulation of the hypoxia-dependent expression of the EPO gene appears to occur. This modulation would be dependent on factors other than oxygen

Casimir Effect, Achucarro-Ortiz Black Hole and the Cosmological Constant

We treat the two-dimensional Achucarro-Ortiz black hole (also known as (1+1) dilatonic black hole) as a Casimir-type system. The stress tensor of a massless scalar field satisfying Dirichlet boundary conditions on two one-dimensional "walls" ("Dirichlet walls") is explicitly calculated in three different vacua. Without employing known regularization techniques, the expression in each vacuum for the stress tensor is reached by using the Wald's axioms. Finally, within this asymptotically non-flat gravitational background, it is shown that the equilibrium of the configurations, obtained by setting Casimir force to zero, is controlled by the cosmological constant.Comment: 20 pages, LaTeX, minor corrections, comments and clarifications added, version to appear in Phys. Rev.

FACILITANDO EL ACCESO A LAS FUENTES DE INFORMACIÓN DE UN GRUPO DE MANTENIMIENTO DE SOFTWARE POR MEDIO DE UN MAPA DE CONOCIMIENTO

RESUMENEntre los problemas que enfrentan las organizaciones de desarrollo de software, y en particular los grupos encargados del mantenimiento de software, se encuentran la pérdida o desaprovechamiento del conocimiento que existe en las distintas fuentes disponibles dentro de estos grupos. Esto se produce debido a que con frecuencia esas fuentes son desconocidas o difíciles de localizar. Los Mapas de Conocimiento (MC) son una técnica que puede ser de utilidad para abordar este problema, dado que pueden ser usados para describir las fuentes de conocimiento disponibles, el conocimiento que puede ser obtenido de las mismas, y cómo éstas pueden ser localizadas. Un aspecto importante para la creación de un MC, es definir qué conocimiento y qué fuentes deberán ser tomadas en cuenta. Con este fin, la identificación del flujo del conocimiento dentro de una organización puede ayudar a identificar qué conocimiento es el requerido en las actividades que sus miembros deben llevar a cabo, así como las fuentes donde ese conocimiento puede ser obtenido, con el fin de centrar nuestro interés en aquellas que realmente puedan ser de ayuda para los usuarios del MC. En este trabajo describimos el proceso que se llevó a cabo para la creación de unMCen el ámbito del mantenimiento de software, por medio de una metodología para identificar flujos de conocimiento con base en técnicas de modelado de procesos. El objetivo es plantear nuestra experiencia en la realización de este esfuerzo, con la finalidad de que algunas de estas ideas puedan ayudar a otras organizaciones de desarrollo de software en trabajos similares. PALABRAS CLAVESMapa de conocimientoGestión de conocimientoIdentificación de flujos de conocimientoIngeniería de softwareMantenimiento de softwareMejoramiento de proceso software ABSTRACTSome of the problems in software development organizations, particularly in the groups in charge of software maintenance, are the scarce use of the knowledge that can be obtained from the sources available in the organization. This is because those sources are often unknown or difficult to locate. Knowledge maps can help to address this problem since these maps can be used to describe the knowledge sources available in the organization, the knowledge that can be obtained from them, and how or where those sources can be accessed. To create a knowledge map, an important factor is to define what knowledge and which sources should be considered. The identification of how knowledge flow through the organization can help to accomplish this, since it can help to identify the knowledge required by the members of the organization to carry on their activities, as well as the sources in which that knowledge can be obtained, in order to focus on those sources that may be really useful to the users of the knowledge map. This paper describes the process followed to create a knowledge map for a software maintenance group following a methodology to identify knowledge flows based on process modelling techniques. The main goal of this paper is to present our experience in the development of the map, expecting that some of these ideas could be useful to other software organizations that could engage similar works in the future. KEYWORDSKnowledge mapKnowledge managementKnowledge flows identificationSoftware engineeringSoftware maintenanceSoftware process improvement

Factors influencing participation in colorectal cancer screening programs in Spain

To analyze the sociodemographic and organizational factors influencing participation in population-based colorectal cancer screening programs (CRCSP) in Spain, a retrospective study was conducted in a cohort of people invited to participate in the first 3 screening rounds of 6 CRCSP from 2000 to 2012. Mixed logistic regression models were used to analyze the relationship between sociodemographic and organizational factors, such as the type of fecal occult blood test (FOBT) used and the FOBT delivery type. The analysis was performed separately in groups (Initial screening-first invitation, Subsequent invitation for previous never-responders, Subsequent invitation-regular, Subsequent invitation-irregular intervals). The results showed that, in the Initial screening-first invitation group, participation was higher in women than in men in all age groups (OR 1.05 in persons aged 50–59 years and OR 1.12 in those aged 60–69 years). Participation was also higher when no action was required to receive the FOBT kit, independently of the type of screening (Initial screening-first invitation [OR 2.24], Subsequent invitation for previous never-responders [OR 2.14], Subsequent invitation-regular [OR 2.03], Subsequent invitation-irregular intervals [OR 9.38]) and when quantitative rather than qualitative immunological FOBT (FIT) was offered (Initial screening-first invitation [OR 0.70], Subsequent invitation for previous never-responders [OR 0.12], Subsequent invitation-regular [OR 0.20]) or guaiac testing (Initial screening-first invitation [OR 0.81], Subsequent invitation for previous never-responders [OR 0.88], Subsequent invitation-regular [OR 0.73]). In conclusion, the results of this study show that screening participation could be enhanced by inclusion of the FOBT kit with the screening invitation and the use of the quantitative FIT.This Project was funded by the Fondo de Investigación Sanitario with cofunding from FEDER [PI12/00944

El papel de los estudios bioarqueológicos en las interpretaciones sobre las comunidades neolíticas del noreste peninsular

Resumen del trabajo presentado al VI Congreso del Neolítico en la Península Ibérica: "Los cambios económicos y sus implicaciones sociales durante el Neolítico de la Península Ibérica", celebrado en Granada del 22 al 26 de junio de 2016.-- et al.El marco del proyecto I+D: “Aproximación a las primeras comunidades neolíticas del NE peninsular a través de sus prácticas funerarias” (2011-2015), y su continuidad para los próximos cuatro años al haber sido renovado, tiene por objetivo conocer cada día más y mejor las comunidades de agricultores y pastores que entre finales del V e inicios del IV milenio cal BC ocuparon y enterraron a sus muertos en el noreste de la Península Ibérica. El contexto de estudio es excepcional, puesto que aquellas comunidades inhumaron sistemáticamente a sus congéneres en tumbas habitualmente individuales y ocasionalmente junto a otro individuo. En esta presentación no sólo queremos mostrar los nuevos análisis y metodologías que estamos aplicando al estudio de los restos humanos, sino también el modelo de trabajo que hemos seguido. A este respecto, tres aspectos son fundamentales: 1) las dataciones absolutas son el eje que vertebra los posteriores análisis; 2) la colaboración con los distintos investigadores/as y laboratorios debe ser estrecha (no es cuestión de solicitar los resultados de un análisis a un laboratorio sino trabajar con las personas que manipulan las muestras y conocen los pros y contras de cada una de las técnicas empleadas) y 3) los estudios y análisis a realizar confluyen para responder a las hipótesis planteadas. A este respecto, en el proyecto hemos tenido la fortuna de poder colaborar con numerosos investigadores/as cuya especialidad versa alrededor de los restos funerarios y que firman la presente comunicación: análisis isotópicos, Adn, tafonomía funeraria, estudios de stress muscular y análisis de morfología dental.Peer Reviewe

Differences in breast cancer-risk factors between screen-detected and non-screen-detected cases (MCC-Spain study)

Purpose: The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. Methods: We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase-control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. Results: TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10-0.89), as were intermediate (OR 0.18 IC 0.07-0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03-0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08-2.36; OR 1.48 IC 1.09-2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15-2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22-2.11) and HER2+ (OR 1.59 IC 1.03-2.45) tumors. Conclusion: Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories

Social mobility and healthy behaviours from a gender perspective in the Spanish multicase-control study (MCC-Spain)

There is evidence for the influence of socioeconomic status (SES) on healthy behaviours but the effect of social mobility (SM) is not yet well known. This study aims to analyse the influence of origin and destination SES (O-SES and D-SES) and SM on healthy behaviours and co-occurrence, from an integrated gender and age perspective. Data were obtained from the controls of MCC-Spain between 2008-2013 (3,606 participants). Healthy behaviours considered: healthy diet, moderate alcohol consumption, non-smoking and physical activity. SM was categorized as stable high, upward, stable medium, downward or stable low. Binary and multinomial logistic regression models were adjusted. Those aged <65, with a low O-SES, D-SES and stable low SM are less likely to have healthy behaviours in the case of both women (physically active: OR = 0.65 CI = 0.45-0.94, OR = 0.71 CI = 0.52-0.98, OR = 0.61 CI = 0.41-0.91) and men (non-smokers: OR = 0.44 CI = 0.26-0.76, OR = 0.54 CI = 0.35-0.83, OR = 0.41 CI 0.24-0.72; physically active: OR = 0.57 CI = 0.35-0.92, OR = 0.64 CI = 0.44-0.95, OR = 0.53 CI = 0.23-0.87). However, for those aged ≥65, this probability is higher in women with a low O-SES and D-SES (non-smoker: OR = 8.09 CI = 4.18-15.67, OR = 4.14 CI = 2.28-7.52; moderate alcohol consumption: OR = 3.00 CI = 1.45-6.24, OR = 2.83 CI = 1.49-5.37) and in men with a stable low SM (physically active: OR = 1.52 CI = 1.02-1.26). In the case of men, the same behaviour pattern is observed in those with a low O-SES as those with upward mobility, with a higher probability of co-occurring behaviours (three-to-four behaviours: OR = 2.00 CI = 1.22-3.29; OR = 3.13 CI = 1.31-7.48). The relationship of O-SES, D-SES and SM with healthy behaviours is complex and differs according to age and gender.This research was supported by the “Acción Transversal del Cancer”, approved by the Spanish Council of Ministers on 11th October 2007, by the Instituto de Salud Carlos III-FEDER [grant number:PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092], by the Fundación Marqués de Valdecilla [grant number: API 10/09], by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), by the Red Temática de Investigación del Cáncer (RTICC) del ISCIII [grant number: RD12/0036/0036], by the Junta de Castilla y León [grant number: LE22A10-2], by the Consejería de Salud of the Junta de Andalucía [grant number: PI-0571-2009, PI-0306-2011, salud201200057018tra], by the Conselleria de Sanitat of the Generalitat Valenciana [grant number: AP_061/10], by the Recercaixa [grant number: 2010ACUP00310], by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission [grant number: FOOD-CT-2006-036224-HIWATE], by the Spanish Association Against Cancer (AECC) Scientific Foundation [grant number: GCTRA18022MORE], by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) [grant number: 2014SGR647, 2014SGR850 and 2017SGR723], by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin

Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.This study was funded by the Spanish Group for Research on Sarcoma (GEIS) and partially by PharmaMar. The authors would like to thank the GEIS data center for data management. The authors also thank the donors and the Hospital Universitario Virgen del Rocío—Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT17/0015/0041) for part of the human specimens used in this study. David S. Moura is recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155)

Comprehensive description of clinical characteristics of a large systemic Lupus Erythematosus Cohort from the Spanish Rheumatology Society Lupus Registry (RELESSER) with emphasis on complete versus incomplete lupus differences

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement and pronounced racial and ethnic heterogeneity. The aims of the present work were (1) to describe the cumulative clinical characteristics of those patients included in the Spanish Rheumatology Society SLE Registry (RELESSER), focusing on the differences between patients who fulfilled the 1997 ACR-SLE criteria versus those with less than 4 criteria (hereafter designated as incomplete SLE (iSLE)) and (2) to compare SLE patient characteristics with those documented in other multicentric SLE registries. RELESSER is a multicenter hospital-based registry, with a collection of data from a large, representative sample of adult patients with SLE (1997 ACR criteria) seen at Spanish rheumatology departments. The registry includes demographic data, comprehensive descriptions of clinical manifestations, as well as information about disease activity and severity, cumulative damage, comorbidities, treatments and mortality, using variables with highly standardized definitions. A total of 4.024 SLE patients (91% with ≥4 ACR criteria) were included. Ninety percent were women with a mean age at diagnosis of 35.4 years and a median duration of disease of 11.0 years. As expected, most SLE manifestations were more frequent in SLE patients than in iSLE ones and every one of the ACR criteria was also associated with SLE condition; this was particularly true of malar rash, oral ulcers and renal disorder. The analysis-adjusted by gender, age at diagnosis, and disease duration-revealed that higher disease activity, damage and SLE severity index are associated with SLE [OR: 1.14; 95% CI: 1.08-1.20 (P < 0.001); 1.29; 95% CI: 1.15-1.44 (P < 0.001); and 2.10; 95% CI: 1.83-2.42 (P < 0.001), respectively]. These results support the hypothesis that iSLE behaves as a relative stable and mild disease. SLE patients from the RELESSER register do not appear to differ substantially from other Caucasian populations and although activity [median SELENA-SLEDA: 2 (IQ: 0-4)], damage [median SLICC/ACR/DI: 1 (IQ: 0-2)], and severity [median KATZ index: 2 (IQ: 1-3)] scores were low, 1 of every 4 deaths was due to SLE activity. RELESSER represents the largest European SLE registry established to date, providing comprehensive, reliable and updated information on SLE in the southern European population