Desde la Genética Médica hacia la Medicina Genómica

En las dos primeras décadas del siglo 21 se ha producido una explosión del conocimiento y las tecnologías genéticas en el ámbito de la biomedicina. La consecuencia es un cambio radical de la comprensión de la enfermedad en cuanto a sus mecanismos moleculares y la aparición de nuevas estrategias para su tratamiento. Este impacto trasciende de los trastornos hereditarios clásicos, la mayoría de ellos individualmente raros, y afecta a toda la patología humana, incluidas las enfermedades con alta prevalencia en la población. Por ello, el conocimiento de los fundamentos de Genética ya no es una necesidad para una especialidad médica concreta, sino que es obligado para todas las profesiones sanitarias. En nuestro país existe una discordancia entre el excelente desarrollo tecnológico y científico en este campo y una traslación deficiente de sus avances a la práctica clínica. Es urgente poner los cimientos de la formación en Genética Médica para todos los profesionales de la salud. Sólo de esta manera será posible el desarrollo de la llamada Medicina Genómica en nuestro entorno, condición imprescindible para que sea una realidad el nuevo paradigma de la MedicinaPersonalizada o de Precisión.A high expanding of genetic knowledge and technologies was happened in the two first decades of 21stcentury. As a consequence, our understanding of the molecular mechanisms of the diseases has changed and we have now new strategies to its treatment. The impact goes beyond the classic hereditary disorders, most of them very rare, but it involves every human condition, even the most prevalent diseases of de population. For this reason, the domain of the basis of Genetics is not an exclusive need to a concrete medical specialty, but it is a requirement to all health professions. In our country there is an inconsistency between the excellent technological and scientific development on this field and a deficient translation of these advances to clinical practice. It is necessary to build the foundations of the training in Medical Genetics for all health care workers. Only this way the development of Genomic Medicinewill be possible on our setting, an essential condition for the new paradigm of Personalized or Precision Medicine become a reality

Characterizing affine C-semigroups

Let C subset of N-p be a finitely generated integer cone and S subset of C be an affine semigroup such that the real cones generated by C and by S are equal. The semigroup S is called C-semigroup if C \ S is a finite set. In this paper, we characterize the C-semigroups from their minimal generating sets, and we give an algorithm to check if S is a C-semigroup and to compute its set of gaps. We also study the embedding dimension of C-semigroups obtaining a lower bound for it, and introduce some families of C-semigroups whose embedding dimension reaches our bound. In the last section, we present a method to obtain a decomposition of a C-semigroup into irreducible C-semigroups.The authors thank the referees for their helpful observations. The authors were partially supported by Junta de Andalucia research group FQM-366. The first author was supported by the Programa Operativo de Empleo Juvenil 2014-2020, financed by the European Social Fund within the Youth Guarantee initiative. The second, third and fourth authors were partially supported by the project MTM2017-84890-P (MINECO/FEDER, UE), and the fourth author was partially supported by the project MTM2015-65764-C3-1-P (MINECO/FEDER, UE)

Estado y prospectiva de las posibilidades de mitigación de impacto del cambio climático en la región de la Costa Atlántica

Artículo (Maestría en Desarrollo Sostenible y Medio Ambiente). Universidad de Manizales. Facultad de Ciencias Contables, Económicas y Administrativas, 2013Maestría en Desarrollo Sostenible y Medio Ambiente, Facultad de Ciencias Contables, Económicas y Administrativas.La Universidad de Manizales, a través del Centro de Investigaciones en Medio Ambiente y Desarrollo Sostenible, –CIMAD-, y la Maestría en Desarrollo Sostenible y Medio Ambiente, elabora y ejecuta el proyecto de investigación “Estado y prospectiva de las posibilidades de adaptación y mitigación de impacto del cambio climático en diferentes regiones del país”. Este proyecto plantea, entre otros objetivos, conocer las condiciones mitigantes de los impactos del cambio que puedan estar presentes en las poblaciones vulnerables y su disposición a la prevención; así como, describir las acciones de mitigación del riesgo desarrolladas a nivel estatal y privado.En el presente artículo se dan a conocer las condiciones de mitigación en la Costa Atlántica Colombiana, y las acciones públicas y privadas que se están desarrollando para alcanzar este cometido; entendiéndose la mitigación como la intervención humana para reducir los impactos del clima sobre la población afectada por fenómenos climáticos, a través de estrategias de reducción de fuentes y emisiones de gases efecto invernadero(GEI), y la promoción de sumideros (conservación y restauración de bosques).Universidad de Manizales- Centro de Investigaciones en Medio Ambiente y Desarrollo Sostenible-CIMAD

Understanding the ecosystem of patients with lysosomal storage diseases in Spain: a qualitative research with patients and health care professionals

Background Lysosomal Storage Diseases (LSDs) are a group of Rare Diseases (RDs) caused by lysosomal enzyme deficiencies. Patients with LSDs suffer from a wide range of symptoms with a strong impact in their daily routines. In this study we aimed to explore the impact of the disease on the lives of patients with four LSDs, as well as how they experience Patient Journey from diagnosis to follow up. Unmet Needs (UNs) perceived by patients and clinicians were assessed to have a better understanding of which initiatives could improve LSDs management and especially those that could result in an improvement of patients' quality of life. Methods Qualitative research was the research methodology selected for the study. It provides plentiful and holistic insights into people's views and actions. The study was conducted through in-depth face-to-face semi-structured interviews. Results In total, 20 patients and 25 Health Care Professionals (HCPs) from different Spanish regions were interviewed. Patients perceived that the highest impact of the LSDs was on their daily routines, specifically on their emotional side, their work/school environment, their family and their social life. Regarding the Patient Journey experience, the worst perceived stage was the pre-diagnosis, where patients only reported negative perceptions, being the delay in diagnosis and misdiagnosis the most commented issues. On the contrary, the follow-up stage was the one with less negative perceptions. Overall, patients and HCPs agreed on the priority UNs, such as accelerating diagnosis, reducing bureaucracy for the treatment access and a more coordinated attention for the patients, not only among different physicians but also with other professionals such as genetic counselors or social workers. Conclusions Our data shows that there are still UNs to be addressed from the perspective of patients and HCPs. The main UN is accelerating diagnosis, which could be achieved by medical awareness and education, according to clinicians. A more comprehensive disease management was another main point to be worked on to improve LSD-patient experience and quality of life

Circadian rhythms regulate the environmental responses of net CO2 exchange in bean and cotton canopies

Studies on the dependence of the rates of ecosystem gas exchange on environmental parameters often rely on the up-scaling of leaf-level response curves ('bottom-up' approach), and/or the down-scaling of ecosystem fluxes ('top-down' approach), where one takes advantage of the natural diurnal covariation between the parameter of interest and photosynthesis rates. Partly independent from environmental variation, molecular circadian clocks drive ∼24 h oscillations in leaf-level photosynthesis, stomatal conductance and other physiological processes in plants under controlled laboratory conditions. If present and of sufficient magnitude at ecosystem scales, circadian regulation could lead to different results when using the bottom-up approach (where circadian regulation exerts a negligible influence over fluxes because the environment is modified rapidly) relative to the top-down approach (where circadian regulation could affect fluxes as it requires the passage of a few hours). Here we dissected the drivers of diurnal net CO2 exchange in canopies of an annual herb (bean) and of a perennial shrub (cotton) through a set of experimental manipulations to test for the importance of circadian regulation of net canopy CO2 exchange, relative to that of temperature and vapor pressure deficit, and to understand whether circadian regulation could affect the derivation of environmental flux dependencies. Contrary to conventional wisdom, we observed how circadian regulation exerted controls over net CO2 exchange that were of similar magnitude to the controls exerted by direct physiological responses to temperature and vapor pressure deficit. Diurnal patterns of net CO2 exchange could only be explained by considering effects of environmental responses combined with circadian effects. Consequently, we observed significantly different results when inferring the dependence of photosynthesis over temperature and vapor pressure deficit when using the top-down and the bottom up approaches.We remain indebted to E. Gerardeau, D. Dessauw, J. Jean, P. Prudent (Aïda CIRAD), J.-J. Drevon, C. Pernot (Eco&Sol INRA), B. Buatois, A. Rocheteau (CEFE CNRS), A. Pra, A. Mokhtar and the full Ecotron team, in particular C. Escape, for outstanding technical assistance during experiment set-up, plant cultivation and measurements. Earlier versions of the manuscript benefitted from comments by M. Dietze, B. Medlyn, R. Duursma and Y.-S. Lin. This study benefited from the CNRS human and technical resources allocated to the ECOTRONS Research Infrastructures as well as from the state allocation ‘Investissement d'Avenir’ ANR-11-INBS-0001, ExpeER Transnational Access program, Ramón y Cajal fellowships (RYC-2012-10970 to VRD and RYC-2008-02050 to JPF), the Erasmus Mundus Master Course Mediterranean Forestry and Natural Resources Management (MEDfOR) and internal grants from UWS-HIE to VRD and ZALF to AG. We thank the Associate Editor T. Vesala and two anonymous reviewers for their help to improve this manuscript

Fabry Nephropathy: An Evidence-Based Narrative Review.

Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. A correct diagnosis of FD, although challenging, has considerable implications regarding treatment, management, and counseling. The diagnosis may be confirmed by demonstrating the enzyme deficiency in males and by identifying the specific GLA gene mutation in male and female patients. Treatment with enzyme replacement therapy, as part of the therapeutic strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline, particularly in the early stages of the disease. Emergent treatments for FD include the recently approved chaperone molecule migalastat for patients with amenable mutations. The objective of this report is to provide an updated overview on Fabry nephropathy, with a focus on the most relevant aspects of its epidemiology, diagnosis, pathophysiology, and treatment options.S

Primary constitutional MLH1 epimutations: a focal epigenetic event

BACKGROUND: Constitutional MLH1 epimutations are characterised by monoallelic methylation of the MLH1 promoter throughout normal tissues, accompanied by allele-specific silencing. The mechanism underlying primary MLH1 epimutations is currently unknown. The aim of this study was to perform an in-depth characterisation of constitutional MLH1 epimutations targeting the aberrantly methylated region around MLH1 and other genomic loci. METHODS: Twelve MLH1 epimutation carriers, 61 Lynch syndrome patients, and 41 healthy controls, were analysed by Infinium 450 K array. Targeted molecular techniques were used to characterise the MLH1 epimutation carriers and their inheritance pattern. RESULTS: No nucleotide or structural variants were identified in-cis on the epimutated allele in 10 carriers, in which inter- generational methylation erasure was demonstrated in two, suggesting primary type of epimutation. CNVs outside the MLH1 locus were found in two cases. EPM2AIP1-MLH1 CpG island was identified as the sole differentially methylated region in MLH1 epimutation carriers compared to controls. CONCLUSION: Primary constitutional MLH1 epimutations arise as a focal epigenetic event at the EPM2AIP1-MLH1 CpG island in the absence of cis-acting genetic variants. Further molecular characterisation is needed to elucidate the mechanistic basis of MLH1 epimutations and their heritability/reversibility

Programa SALUD 5-10: Programa para el tratamiento del sobrepeso y la obesidad en niños de 5 a 10 años: Antecedentes, Diseño y Metodología

Obesity is a particularly expensive and costly in economic and social terms disease for both people who suffer as public health institutions. Therefore, in recent decades, various international and national organizations have shown great concern for its implications, going to be treated as a real social problem. According to the World Health Organization, Spain is one of the EU countries with the highest prevalence of overweight children as recorded by 33% in the population between 5 and 17 years, whereas in Europe one in four children has overweight or obese. Furthermore, Spain is one of the countries where this disease has grown (in the eighties the prevalence was 15%). Several systematic reviews assessing the effectiveness of intervention programs based on increasing physical activity and dietary control of overweight and / or obesity in children and adolescents highlight the need to design specific programs for schoolchildren, and to assess objectively the effectiveness of such long-term programs in children and adolescents are overweight or obese. The aim of this paper is to describe the design and methodology used in 5-10 Health Program, a program that has been designed with the objective of addressing overweight and obesity in schoolchildren in the age group between 5-10 years.La obesidad es una enfermedad especialmente cara y costosa en términos económicos y sociales tanto para las personas que la padecen como para las instituciones públicas sanitarias. Por ello, en las últimas décadas distintas organizaciones internacionales y nacionales han mostrado una enorme preocupación por sus implicaciones, pasando a ser tratado como un verdadero problema social. Según la Organización Mundial de la Salud, España es uno de los países de la Unión Europea con mayor prevalencia de sobrepeso infantil, ya que registra un 33% en la población entre 5 y 17 años, mientras que en Europa uno de cada cuatro niños tiene sobrepeso o es obeso. Además, España es uno de los países donde más ha crecido esta enfermedad (en la década de los ochenta la prevalencia era de un 15%). Diversas revisiones sistemáticas que evalúan la efectividad de los programas de intervención basados en el aumento de la actividad física y el control dietético sobre el sobrepeso y/u obesidad en población infantil y adolescente resaltan la necesidad de diseñar programas específicos para los escolares, así como valorar objetivamente la eficacia de dichos programas a largo plazo en niños y adolescentes con sobrepeso u obesidad. El objetivo del presente trabajo es describir el diseño y metodología utilizada en el Programa SALUD 5-10, un programa que ha sido diseñado con el objetivo de abordar el sobrepeso y la obesidad en escolares de una franja de edad entre 5 a 10 años

Psychosocial and sociodemographic predictors of attrition in a longitudinal study of major depression in primary care: the predictD-Spain study

Few data exist on the psychosocial factors associated with attrition in longitudinal surveys. This study was undertaken to determine psychosocial and sociodemographic predictors of attrition from a longitudinal study of the onset and persistence of episodes of major depression in primary care

Night and day - Circadian regulation of night-time dark respiration and light-enhanced dark respiration in plant leaves and canopies

The potential of the vegetation to sequester C is determined by the balance between assimilation and respiration. Respiration is under environmental and substrate-driven control, but the circadian clock might also contribute. To assess circadian control on night-time dark respiration (RD) and on light enhanced dark respiration (LEDR) - the latter providing information on the metabolic reorganization in the leaf during light-dark transitions - we performed experiments in macrocosms hosting canopies of bean and cotton. Under constant darkness (plus constant air temperature and air humidity), we tested whether circadian regulation of RD scaled from leaf to canopy respiration. Under constant light (plus constant air temperature and air humidity), we assessed the potential for leaf-level circadian regulation of LEDR. There was a clear circadian oscillation of leaf-level RD in both species and circadian patterns scaled to the canopy. LEDR was under circadian control in cotton, but not in bean indicating species-specific controls. The circadian rhythm of LEDR in cotton might indicate variable suppression of the normal cyclic function of the tricarboxylic-acid-cycle in the light. Since circadian regulation is assumed to act as an adaptive memory to adjust plant metabolism based on environmental conditions from previous days, circadian control of RD may help to explain temporal variability of ecosystem respiration.This study benefited from the CNRS human and technical resources allocated to the ECOTRONS Research Infrastructures as well as from the state allocation ‘Investissement d'Avenir’ AnaEE-France ANR-11-INBS-0001, ExpeER Transnational Access program, Ramón y Cajal fellowships (RYC-2012-10970 to VRD and RYC-2008-02050 to JPF), the Erasmus Mundus Master Course MEDfOR, internal grants from UWS-HIE to VRD and ZALF to AG and Juan de la Cierva-fellowships (IJCI-2014-21393 to JGA). We remain indebted to E. Gerardeau, D. Dessauw, J. Jean, P. Prudent (Aïda CIRAD), J.-J. Drevon, C. Pernot (Eco&Sol INRA), B. Buatois, A. Rocheteau (CEFE CNRS), A. Pra, A. Mokhtar and the full Ecotron team, in particular C. Escape, for outstanding technical assistance