Descriptive analysis of occupational accidents in Spain and their relationship with heatwaves.

OBJECTIVE: The purpose of this work is to carry out a descriptive analysis of occupational accidents and to evaluate the relationship between heatwaves and work accidents in Spain's three most populated provinces: Madrid, Barcelona and Valencia. METHODS: Daily data of work accidents (including for each case: gender, age, date, length of time in the position, type of work, place of accident and duration of medical leave) was collected. A heatwave was defined when daily mean temperatures above the threshold (95th percentile) of the climatological period (1990-2021) were recorded for at least three consecutive days. To estimate the association between daily workplace accidents and heatwave events, we applied a Generalized Additive Model combined with a Distributed Lag Non-linear Model with a quasi-Poisson distribution. RESULTS: The average annual accident rate was 33.2 work accidents/100,000 employees in Madrid, 35.8 work accidents/100,000 employees in Barcelona and 31.8 work accidents/100,000 employees in Valencia. The total accident rates followed a downward trend between 2005 and 2021. The difference in work accident rates between sex decreased over the studied period (p < 0.005). In the first month of work, the highest casualty rate occurs among construction workers in Madrid and Barcelona, and in primary sector workers in Valencia. Work accidents tend to increase during heatwaves. The highest risk was recorded when considering a cumulative lagged effect of 3 days in Madrid and Barcelona and 5 days in Valencia. CONCLUSIONS: Since work accidents increase during heatwaves, risk prevention services and public administrations must take special measures to prevent them.

Osteogenic capacity of mesenchymal stem cells from patients with osteoporotic hip fractures in vivo.

PURPOSE: Human mesenchymal stem cells (MSCs) have the ability to differentiate into bone-forming osteoblasts. The aim of this study was to elucidate if MSCs from patients with OP show a senescent phenotype and explore their bone-forming ability in vivo. MATERIALS AND METHODS: MSCs from patients with OP and controls with osteoarthritis (OA) were implanted into the subcutaneous tissue of immunodeficient mice for histological analysis and expression of human genes by RT-PCR. The expression of senescence-associated phenotype (SASP) genes, as well as p16, p21, and galactosidase, was studied in cultures of MSCs. RESULTS: In vivo bone formation was evaluated in 103 implants (47 OP, 56 OA). New bone was observed in 45% of the implants with OP cells and 46% of those with OA cells (p = 0.99). The expression of several bone-related genes (collagen, osteocalcin, alkaline phosphatase, sialoprotein) was also similar in both groups. There were no differences between groups in SASP gene expression, p16, and p21 expression, or in senescence-associated galactosidase activity. CONCLUSION: Senescence markers and the osteogenic capacity in vivo of MSCs from patients with OP are not inferior to that of cells from controls of similar age with OA. This supports the interest of future studies to evaluate the potential use of autologous MSCs from OP patients in bone regeneration procedures.

Exposure to particulate matter: Direct and indirect role in the COVID-19 pandemic.

Knowing the transmission factors and the natural environment that favor the spread of a viral infection is crucial to stop outbreaks and develop effective preventive strategies. This work aims to evaluate the role of Particulate Matter (PM) in the COVID-19 pandemic, focusing especially on that of PM as a vector for SARS-CoV-2. Exposure to PM has been related to new cases and to the clinical severity of people infected by SARS-CoV-2, which can be explained by the oxidative stress and the inflammatory response generated by these particles when entering the respiratory system, as well as by the role of PM in the expression of ACE-2 in respiratory cells in human hosts. In addition, different authors have detected SARS-CoV-2 RNA in PM sampled both in outdoor and indoor environments. The results of various studies lead to the hypothesis that the aerosols emitted by an infected person could be deposited in other suspended particles, sometimes of natural but especially of anthropogenic origin, that form the basal PM. However, the viability of the virus in PM has not yet been demonstrated. Should PM be confirmed as a vector of transmission, prevention strategies ought to be adapted, and PM sampling in outdoor environments could become an indicator of viral load in a specific area.

Epigenetic related changes on air quality.

The exposure to airborne particulate matter (PM) increases the risk of developing human diseases. Epigenetic mechanisms have been related to environmental exposures and human diseases. The present review is focused on current available studies, which show the relationship between epigenetic marks, exposure to air pollution and human's health. Air contaminants involved in epigenetic changes have been related to different specific mechanisms (DNA methylation, post-translational histone modifications and non-coding RNA transcripts), which are described in separate sections. Several studies describe how these epigenetic mechanisms are influenced by environmental factors including air pollution. This interaction between PM and epigenetic factors results in an altered profile of these marks, in both, globally and locus specific. Following this connection, specific epigenetic marks can be used as biomarkers, as well as, to find new therapeutic targets. For this purpose, some significant characteristics have been highlighted, such as, the spatiotemporal specificity of these marks, the relevance of the collected tissue and the specific changes stability. Air pollution has been related to a higher mortality rate due to non-accidental deaths. This exposure to particulate matter induces changes to the epigenome, which are increasing the susceptibility of human diseases. In conclusion, as several epigenetic change mechanisms remain unclear yet, further analyses derived from PM exposure must be performed to find new targets and disease biomarkers.

Temperature-related effects on respiratory medical prescriptions in Spain.

BACKGROUND: The increased risk of mortality during periods of high and low temperatures has been well established. However, most of the studies used daily counts of deaths or hospitalisations as health outcomes, although they are the ones at the top of the health impact pyramid reflecting only a limited proportion of patients with the most severe cases. OBJECTIVES: This study evaluates the relationship between short-term exposure to the daily mean temperature and medication prescribed for the respiratory system in five Spanish cities. METHODS: We fitted time series regression models to cause-specific medical prescriptions, including different respiratory subgroups and age groups. We included a distributed lag non-linear model with lags up to 14 days for daily mean temperature. City-specific associations were summarised as overall-cumulative exposure-response curves. RESULTS: We found a positive association between cause-specific medical prescriptions and daily mean temperature with a non-linear inverted J- or V-shaped relationship in most cities. Between 0.3% and 0.6% of all respiratory prescriptions were attributed to cold for Madrid, Zaragoza and Pamplona, while in cities with only cold effects the attributable fractions were estimated as 19.2% for Murcia and 13.5% for Santander. Heat effects in Madrid, Zaragoza and Pamplona showed higher fractions between 8.7% and 17.2%. The estimated costs are in general higher for heat effects, showing annual values ranging between €191,905 and €311,076 for heat per 100,000 persons. CONCLUSIONS: This study provides novel evidence of the effects of the thermal environment on the prescription of medication for respiratory disorders in Spain, showing that low and high temperatures lead to an increase in the number of such prescriptions. The consumption of medication can reflect exposure to the environment with a lesser degree of severity in terms of morbidity.

Air pollution and occupational accidents in the Community of Madrid, Spain.

Spain is the EU member country with the third highest total number of accidents in work and has the third highest incidence rate. We have performed a descriptive analysis of occupational accidents in the Community of Madrid (Spain) between 2005 and 2013 to study the impact of air quality on the prevalence of occupational accidents, clarifying how vulnerable to air pollution outdoor workers are. In order to evaluate the association between each air pollutant and work accidents, a quasi-Poisson generalized additive model was fitted. The accident rate followed a downward and statistically significant trend (p = 0.001). The year with the highest accident rate was 2006, with 4981 occupational accidents per 100,000. Occupational accidents follow a temporary pattern (there are differences in the number of accidents according to the month of the year and to the day of the week). Exposure to PM10 and NO2 increases the risk of having an accident at work, especially for outdoor workers. An increase of 10 µg/m3 in daily concentration resulted in increases in accidents for outdoor workers of 2.5% for PM10 and 6.4% for NO2.

The role of magnetic fields in neurodegenerative diseases.

The term neurodegenerative diseases include a long list of diseases affecting the nervous system that are characterized by the degeneration of different neurological structures. Among them, Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) are the most representative ones. The vast majority of cases are sporadic and results from the interaction of genes and environmental factors in genetically predisposed individuals. Among environmental conditions, electromagnetic field exposure has begun to be assessed as a potential risk factor for neurodegeneration. In this review, we discuss the existing literature regarding electromagnetic fields and neurodegenerative diseases. Epidemiological studies in AD, PD, and ALS have shown discordant results; thus, a clear correlation between electromagnetic exposure and neurodegeneration has not been demonstrated. In addition, we discuss the role of electromagnetic radiation as a potential non-invasive therapeutic strategy for some neurodegenerative diseases, particularly for PD and AD.

Nonpharmacological, nonsurgical treatments for freezing of gait in Parkinson's disease: A systematic review.

Freezing of gait is a disabling phenomenon that appears in a substantial number of Parkinson's disease (PD) patients as the disease evolves. It is considered to be one of the most relevant contributing factors to worsening of quality of life. Current pharmacological or surgical treatment options have limited efficacy. Thus, alternative nonpharmacological/nonsurgical approaches have emerged in recent years in an attempt to improve quality of life in PD. This systematic review summarizes studies of such therapies over the past 5 years. Thirty-five studies were evaluated by use of a qualitative evaluation, while the methodological quality was assessed using validated tools. According to our results, there appear to be two broad categories of nonpharmacological therapies: those that seek a long-lasting benefit and those that aim to achieve a transient effect to overcome the freezing of gait episode. Among the former, it is possible to differentiate between "passive" therapies, which include transcranial magnetic stimulation or transcranial direct current stimulation, and "active" therapies, which are based on different cognitive or physical training programs. Finally, "transient effect" therapies use different types of cues, such as visual, auditory, or proprioceptive stimuli, to attempt to shift the patient's habitual motor control to a goal-directed one. In conclusion, a broad spectrum of nonpharmacological/nonsurgical approaches for freezing of gait has emerged in recent years with promising results. © 2019 International Parkinson and Movement Disorder Society.

A time series analysis of the relationship between apparent temperature, air pollutants and ischemic stroke in Madrid, Spain.

The understanding of the role of environment on the pathogenesis of stroke is gaining importance in the context of climate change. This study analyzes the temporal pattern of ischemic stroke (IS) in Madrid, Spain, during a 13-year period (2001-2013), and the relationship between ischemic stroke (admissions and deaths) incidence and environmental factors on a daily scale by using a quasi-Poisson regression model. To assess potential delayed and non-linear effects of air pollutants and Apparent Temperature (AT), a biometeorological index which represents human thermal comfort on IS, a lag non-linear model was fitted in a generalized additive model. The mortality rate followed a downward trend over the studied period, however admission rates progressively increased. Our results show that both increases and decreases in AT had a marked relationship with IS deaths, while hospital admissions were only associated with low AT. When analyzing the cumulative effects (for lag 0-14 days), with an AT of 1.7 °C (percentile 5%) a RR of 1.20 (95% CI, 1.05-1.37) for IS mortality and a RR of 1.09 (95% CI, 0.91-1.29) for morbidity is estimated. Concerning gender differences, men show higher risks of mortality in low temperatures and women in high temperatures. No significant relationship was found between air pollutant concentrations and IS morbi-mortality, but this result must be interpreted with caution, since there are strong spatial fluctuations of the former between nearby geographical areas that make it difficult to perform correlation analyses.

The genetic profile of bone marrow transplant patients in different samples of forensic interest.

Humans constantly lose epithelial cells, and these biological traces are frequently studied in the context of criminal investigations. The objective of this work was to examine the genetic profile in samples of forensic interest (nail and skin epithelial cells) of bone marrow transplant patients and discuss its forensic and clinical implications. The genetic profile of nail, epidermal cells and blood samples of patients receiving HSCT was analyzed by the amplification and sequencing of 38 insertion/deletion polymorphisms and 15 short tandem repeat polymorphisms. In this analysis, the age of patients and donors, the time elapsed from the transplant, the type of conditioning prior to the transplant and whether the patient suffered graft-versus-host disease were considered. Donor chimerism can be detected in the DNA extracted from nail and skin epithelial cells of transplant patients. No statistically significant correlation was found between the type of conditioning and the percentage of donor DNA in nail (p > 0.05). A positive correlation, without statistical significance, was encountered when we analyzed the relationship between the time elapsed from the transplant with the percent donor chimerism found in epithelial cells of the epidermis and in nails. We conclude that within a judicial context (e.g. when testifying as an expert witness) it is necessary to consider whether we are facing a possible transplant patient or a person who has been a bone marrow donor.

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.

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.

Integrating and analyzing medical and environmental data using ETL and Business Intelligence tools.

Processing data that originates from different sources (such as environmental and medical data) can prove to be a difficult task, due to the heterogeneity of variables, storage systems, and file formats that can be used. Moreover, once the amount of data reaches a certain threshold, conventional mining methods (based on spreadsheets or statistical software) become cumbersome or even impossible to apply. Data Extract, Transform, and Load (ETL) solutions provide a framework to normalize and integrate heterogeneous data into a local data store. Additionally, the application of Online Analytical Processing (OLAP), a set of Business Intelligence (BI) methodologies and practices for multidimensional data analysis, can be an invaluable tool for its examination and mining. In this article, we describe a solution based on an ETL + OLAP tandem used for the on-the-fly analysis of tens of millions of individual medical, meteorological, and air quality observations from 16 provinces in Spain provided by 20 different national and regional entities in a diverse array for file types and formats, with the intention of evaluating the effect of several environmental variables on human health in future studies. Our work shows how a sizable amount of data, spread across a wide range of file formats and structures, and originating from a number of different sources belonging to various business domains, can be integrated in a single system that researchers can use for global data analysis and mining.

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.

Association Between Suicide and Environmental Variables in the North of Spain: A 14-Year Analysis.

Suicide is a serious public health problem around the world. Since the nineteenth century, the impact of socio-environmental factors on suicide has attracted much public attention, especially in the context of global climate change. We have performed a retrospective correlation study that analyzes the demographic pattern of suicide in Cantabria, a northern coastland region of Spain. Moreover, we have created a multivariable binomial regression model to study the relationship between suicide and environmental factors (atmospheric pollutants and meteorological variables) among January 1, 2000, and December 31, 2013 in the province. During the 14-year study period, there was a suicide annual incidence of 4.9 cases per 100,000 population in Cantabria. The incidence was highest in adults aged 70-74 years old (11.8 per 100,000 population). The most common method group of suicide was hanging, strangulation and suffocation, accounting for 49.3% of all suicide deaths. When correlating suicide and meteorological variables, a statistically significant association was found with the level of cloudiness (p = 0.007). According to our results, an increase of one eighth of sky cloud-cover correlated to a 7% increase in total deaths by suicide and the association was especially strong during spring.

Indel analysis by droplet digital PCR: a sensitive method for DNA mixture detection and chimerism analysis.

Several methods have been developed to determinate genetic profiles from a mixed samples and chimerism analysis in transplanted patients. The aim of this study was to explore the effectiveness of using the droplet digital PCR (ddPCR) for mixed chimerism detection (a mixture of genetic profiles resulting after allogeneic hematopoietic stem cell transplantation (HSCT)). We analyzed 25 DNA samples from patients who had undergone HSCT and compared the performance of ddPCR and two established methods for chimerism detection, based upon the Indel and STRs analysis, respectively. Additionally, eight artificial mixture DNA samples were created to evaluate the sensibility of ddPCR. Our results show that the chimerism percentages estimated by the analysis of a single Indel using ddPCR were very similar to those calculated by the amplification of 15 STRs (r 2 = 0.970) and with the results obtained by the amplification of 38 Indels (r 2 = 0.975). Moreover, the amplification of a single Indel by ddPCR was sensitive enough to detect a minor DNA contributor comprising down to 0.5 % of the sample. We conclude that ddPCR can be a powerful tool for the determination of a genetic profile of forensic mixtures and clinical chimerism analysis when traditional techniques are not sensitive enough.

Pulmonary Langerhans cell histiocytosis "de novo" after lung transplantation.

A pulmonary Langerhans cell histiocytosis is presented in a 40 year-old woman two years after bilateral lung transplantation for emphysema without any signs of Langerhans cells proliferation in the explanted lungs. A microsatellite molecular analysis showed the proliferating cells were generated in a recipient cellular clone. The patient did not quit smoking after transplantation. No signs of disease were detected in the implanted lungs before surgery. Strict control of immunosupressive drug levels stabilized the disease. A "de novo" monoclonal origin of stem cells, probably from the bone marrow is suggested. The reason she did not develop disease in the native lungs is unknown, although we suggest an interaction between tobacco or some other antigens and local cellular receptors.

Genetic DNA profile in urine and hair follicles from patients who have undergone allogeneic hematopoietic stem cell transplantation.

Biological samples from patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) constitute a challenge for individual identification. In this study we analyzed the genetic profiles (by the amplification of 15 autosomic STRs) of HSCT patients found in different types of samples (blood, hair and urine) that may be the source of DNA in civil or criminal forensic cases. Our results show that while in hair follicles the donor component was not detected in any patient, thus being a reliable source of biological material for forensic identification, mixed chimerism was detected in urine samples from all patient, and no correlation was found between the time elapsed from the transplant and the percentage of chimerism. These results certainly have practical implications if the urine is being considered as a source of DNA for identification purposes in HSTC patients. Moreover, taking into consideration that chimerism was found not only in patients with leukocyturia (given the hematopoietic origin of leukocytes, this was expected), but also in those without observable leukocytes in the sediment, we conclude that an alternative source or sources of donor DNA must be implicated.

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.

Trends in motor neuron disease: association with latitude and air lead levels in Spain.

Motor neuron diseases (MND) are a group of disorders characterized by motor neuron degeneration. Among them, amyotrophic lateral sclerosis (ALS) is by far the most common in adulthood. This paper assesses the trend and geographical pattern in MND incidence in Spain and the possible air lead levels effect on this pathology. To confirm this concept, we performed a retrospective analysis of the deaths due to MND in Spain during 2000 and 2013, determined the geographical differences, and explored the relationship between MND and the air levels of lead. Overall, between 2000 and 2013, 11,355 people died in Spain because of MND. Disease mortality significantly increased in recent years (2007-2013) when compared with the first time of the period. Spearman's rank correlation coefficient also showed a statistically significant positive trend (CC = 0.824, p = 0.0002). Among people over 65 years, mortality rates were higher in Northern provinces. Moreover, we found a significant association of MND mortality with higher air lead levels (CC = 0.457, p = 0.01). Our study confirms that MND mortality is increasing in Spain, with a significant latitude gradient, which suggests an important role of environmental exposures. This ecological study suggests that air lead levels may be implicated in ALS pathogenesis.