Ana Santurtún

Osterix and RUNX2 are Transcriptional Regulators of Sclerostin in Human Bone

Sclerostin, encoded by the SOST gene, works as an inhibitor of the Wnt pathway and therefore is an important regulator of bone homeostasis. Due to its potent action as an inhibitor of bone formation, blocking sclerostin activity is the purpose of recently developed anti-osteoporotic treatments. Two bone-specific transcription factors, RUNX2 and OSX, have been shown to interact and co-ordinately regulate the expression of bone-specific genes. Although it has been recently shown that sclerostin is targeted by OSX in mice, there is currently no information of whether this is also the case in human cells. We have identified SP-protein family and AML1 consensus binding sequences at the human SOST promoter and have shown that OSX, together with RUNX2, binds to a specific region close to the transcription start site. Furthermore, we show that OSX and RUNX2 activate SOST expression in a co-ordinated manner in vitro and that SOST expression levels show a significant positive correlation with OSX/RUNX2 expression levels in human bone. We also confirmed previous results showing an association of several SOST/RUNX2 polymorphisms with bone mineral density.

The Influence of Nitrogen Dioxide on Arrhythmias in Spain and Its Relationship with Atmospheric Circulation.

Epidemiological studies suggest that increased ambient NO2 concentrations are associated with cardiovascular disease. However, none of them have examined the association between ambient air pollution and cardiac arrhythmias in the general population in Spain. This paper assesses the short-term association between the aforementioned air pollutant and hospital admissions for arrhythmia in nine different regions of Spain during a 6-year period (2005–2010), and the possible season-specific effects of the compound on this pathology, by performing a time-series analysis based on Poisson regression models. The results show statistically significant positive relationship increases between arrhythmia admissions and increments in NO2 concentration during the whole year, most notably in wintertime. Moreover, while trying to establish a threshold for NO2 concentration above which the incidence of arrhythmia episodes increases significantly, this study reveals that hospital admissions increased linearly in response to an increase in as we move to higher NO2 concentration levels. Finally, an analysis of NO2 concentrations and their relationship with atmospheric circulation is performed, showing higher values of NO2 under anticyclonic conditions during winter that could be used for implementing pollution level alert protocols depending on forecast circulation patterns.

¿Afecta el medio a los suicidios que se cometen en España? Análisis descriptivo del patrón temporoespacial

INTRODUCTION Suicide is an important public health problem, it represents one of the major causes of unnatural death, and there are many factors that affect the risk of suicidal behaviour. The present study analyzes the temporal and spatial variations of mortality by suicide in Spain and its relationship with gross domestic product (GDP) per capita. MATERIAL AND METHODS A retrospective study was performed, in which deaths by suicide, sex and age group in 50 Spanish provinces between 2000 and 2012 were analyzed. The annual trend of suicide mortality was assessed using Kendalls tau-b correlation coefficient. Seasonality and monthly and weekly behaviour were evaluated by performing the ANOVA test and the Bonferroni adjustment. Finally, the relationship between GDP per capita and suicide was studied. RESULTS Between 2000 and 2012, 42,905adult people died by suicide in Spain. The annual average incidence rate was 95 suicides per million population. The regions located in the south and in the northwest of the country registered the highest per capita mortality rates. There is a decreasing trend in mortality by suicide over the period studied (CC=-.744; P=.0004) in adults over the age of 64, and a seasonal behaviour was identified with summer maximum and autumn minimum values (f=.504; P<.0001). The regions with the highest GDP per capita showed the lowest mortality by suicide (r=-.645; P<.0001) and the relationship is stronger among older age groups. CONCLUSIONS Mortality by suicide does not follow a homogenous geographical distribution in Spain. Mortality in men was higher than in women. Over the period of study, there has been a decrease in mortality by suicide in Spain in adults over the age of 64. The seasonal cycle of suicides and the inverse relationship with GDP per capita found in this study, provide information which may be used as a tool for developing prevention and intervention strategies.

Amyotrophic Lateral Sclerosis in Northern Spain 40 Years Later: What Has Changed?

Background: In the last years different studies have reported an increase of amyotrophic lateral sclerosis (ALS) incidence, highlighting the role of the environment in this disease. This prompted us to review ALS cases diagnosed at our hospital in the last decade and to compare them with a previous ALS series reported in our region 30 years ago. Methods: We reviewed those ALS cases diagnosed at our centre between 2004 and 2013. Subsequently, we compared them with the previous series regarding clinical and epidemiological features. Results: A total of 53 patients (30 males, 23 females) were included. The annual incidence was 1.7 cases per 100,000 inhabitants (2.2 and 1.2 per 100,000 in males and females, respectively), which was significantly higher than in the previous series (1 case per 100,000 inhabitants). Otherwise, the clinical and epidemiological features were similar in both series. The median age at symptom onset was 67 years, with a median diagnosis delay of 6 months. About two thirds of the patients presented with systemic ALS, whereas the remaining had a bulbar onset. Weakness, dysphagia, and dysarthria were the most common clinical symptoms at diagnosis. The median survival from symptom onset was 22 months. Conclusion: After 3 decades, the annual incidence of ALS has almost doubled in our region. We did not find significant differences regarding other clinical or epidemiological features.

The increasing importance of environmental conditions in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MNs). Although a small percentage of ALS has a familial origin, the vast majority of cases are sporadic in which genetic factors and environment interact with each other leading to disease onset in genetically predisposed individuals. In the current model of the disease, each individual has a determined genetic load, some degree of cell degeneration related to age and several risky environmental exposures. In this scenario, MN degeneration would occur when the sum of these factors reach a certain threshold. To date, an extensive list of environmental factors has been associated to ALS, including different categories, such as exposure to heavy metals and other toxicants, cyanotoxins or infectious agents. In addition, in recent years, lifestyle and other demographic parameters are gaining relevance in the genesis of the disease. Among them, physical activity, nutrition, body mass index, cardiovascular risk factors, autoimmune diseases and cancer are some of the conditions which have been related to the disease. In this review, we will discuss the potential mechanisms of environmental conditions in motor neuron degeneration. Understanding the role of each one of these factors as well as their interactions appears as a crucial step in order to develop new preventive, diagnostic and therapeutic approaches for ALS patients.

Population genetic data of 38 insertion-deletion markers in six populations of the northern fringe of the Iberian Peninsula

Insertion-deletions have been reported very useful markers for forensic purposes. To further deepen in this matter, 38 non-coding bi-allelic autosomal indels were analyzed in 575 individuals representing six populations from the northern fringe of the Iberian Peninsula. Autochthonous populations from the Basque Country, northern Navarre, the Pas Valley in Cantabria and Aragon were analyzed, together with non-autochthonous populations from the Basque Country and northern Navarre. At the intra-population level, all loci analyzed were in Hardy-Weinberg equilibrium except for marker rs33917182 in autochthonous Basques. Linkage disequilibrium (LD) test did not reveal statistically significant allelic association between the different loci pairs in all six populations. Forensic parameters proved to be highly informative in the six populations analyzed, even if a scenario with population substructure and local inbreeding was considered for match probability calculations, and the potential of this indels set to be used in combination with other genetic markers is remarkable. As for inter-population analyses, in general terms the six populations showed low but statistically significant genetic distances. However, though this indels set efficiently differentiate between main ancestries, it does not allow an accurate separation at a local level and, for the time being, their combination with other informative markers is needed to maximize the power to accurately differentiate populations with close genetic ancestry.

Kawasaki disease in Spanish paediatric population and synoptic weather types: an observational study

Kawasaki disease (KD) is a vasculitis of unelucidated pathogenesis that usually occurs in paediatric patients. In this study we analyse the temporal pattern and geographical distribution of the disease in Spain, and its relationship with atmospheric circulation patterns. We performed a retrospective study in which we collected all hospital admissions due to KD in the country between 2005 and 2015 and explored their relationship with demographic and geographical characteristics. Moreover, we calculated daily surface atmospheric patterns over Spain to study the relationship between weather types (WT) and KD Admissions. The average admission rate for KD in the paediatric population was 3.90 per 100,000, with a male to female ratio of 1.56:1. The highest rate of admissions was found in the 0–4-year-old group, with an incidence of 11.7 cases per 100,000. Admissions followed an annual cyclic pattern with a peak of incidence in January (p = 0.022) and a nadir in September. There was an upwards trend in the number of KD admissions in male sex during the study period (p = 0.004). However, there were marked geographical differences in the incidence rate. Finally, the analysis of the relationship between the WT and the number of admissions by KD revealed no statistically significant association. KD admissions follow a peculiar seasonal and spatial distribution, that suggest the involvement of environmental factors in the disease; however, the absence of an association with WT should be interpreted with caution and regional studies should be done to explore this relationship.

Role of Apparent Temperature and Air Pollutants in Hospital Admissions for Acute Myocardial Infarction in the North of Spain

INTRODUCTION AND OBJECTIVES The role of the environment on cardiovascular health is becoming more prominent in the context of global change. The aim of this study was to analyze the relationship between apparent temperature (AT) and air pollutants and acute myocardial infarction (AMI) and to study the temporal pattern of this disease and its associated mortality. METHODS We performed a time-series study of admissions for AMI in Cantabria between 2001 and 2015. The association between environmental variables (including a biometeorological index, AT) and AMI was analyzed using a quasi-Poisson regression model. To assess potential delayed and non-linear effects of these variables on AMI, a lag non-linear model was fitted in a generalized additive model. RESULTS The incidence rate and the mortality followed a downward trend during the study period (CC=-0.714; P=.0002). An annual pattern was found in hospital admissions (P=.005), with the highest values being registered in winter; a weekly trend was also identified, reaching a minimum during the weekends (P=.000005). There was an inverse association between AT and the number of hospital admissions due to AMI and a direct association with particulate matter with a diameter smaller than 10 μm. CONCLUSIONS Hospital admissions for AMI followed a downward trend between 2007 and 2015. Mortality associated with admissions due to this diagnosis has decreased. Predictive factors for this disease were AT and particulate matter with a diameter smaller than 10 μm.

Who is legally responsible for deaths caused by air pollution

A person’s death is deemed unnatural when it is the result of an external force. This definition, however, does not apply when the cause of death is a respiratory or cardiovascular process triggered by a high concentration of an air pollutant, even if other deaths from toxicological causes (poisonings, overdoses, etc.) are. The distinction between natural and unnatural cause of death, although not internationally standardized, is critical in determining wrongfulness and liability, which in turn can have financial and/or legal repercussions. Even though the World Health Organization and other medical and scientific organizations have shown that air pollution contributes to several million deaths every year, there are currently no practical means to determine whether a person was subjected to high concentrations of atmospheric pollution before their death; indeed, the ability to find evidence of this type of exposition could prove very interesting from a forensic standpoint.

A GHEP-ISFG collaborative study on the genetic variation of 38 autosomal indels for human identification in different continental populations

A collaborative effort was carried out by the Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) to promote knowledge exchange between associate laboratories interested in the implementation of indel-based methodologies and build allele frequency databases of 38 indels for forensic applications. These databases include populations from different countries that are relevant for identification and kinship investigations undertaken by the participating laboratories. Before compiling population data, participants were asked to type the 38 indels in blind samples from annual GHEP-ISFG proficiency tests, using an amplification protocol previously described. Only laboratories that reported correct results contributed with population data to this study. A total of 5839 samples were genotyped from 45 different populations from Africa, America, East Asia, Europe and Middle East. Population differentiation analysis showed significant differences between most populations studied from Africa and America, as well as between two Asian populations from China and East Timor. Low FST values were detected among most European populations. Overall diversities and parameters of forensic efficiency were high in populations from all continents.