Exposure to residential traffic and trajectories of unhealthy ageing: results from a nationally-representative cohort of older adults.

BACKGROUND: Traffic exposure has been associated with biomarkers of increased biological ageing, age-related chronic morbidities, and increased respiratory, cardiovascular, and all-cause mortality. Whether it is associated with functional impairments and unhealthy ageing trajectories is unknown. METHODS: Nationally representative population-based cohort with 3,126 community-dwelling individuals aged ≥60 years who contributed 8,291 biannual visits over a 10 year period. Unhealthy ageing was estimated with a deficit accumulation index (DAI) based on the number and severity of 52 health deficits, including 22 objectively-measured impairments in physical and cognitive functioning. Differences in DAI at each follow-up across quintiles of residential traffic density (RTD) at 50 and 100 meters, and closest distance to a petrol station, were estimated using flexible marginal structural models with inverse probability of censoring weights. Models were adjusted for sociodemographic and time-varying lifestyle factors, social deprivation index at the census tract and residential exposure to natural spaces. RESULTS: At baseline, the mean (SD) age and DAI score of the participants were 69.0 (6.6) years and 17.02 (11.0) %, and 54.0% were women. The median (IQR) RTD at 50 and 100 meters were 77 (31-467) and 509 (182-1802) vehicles/day, and the mean (SD) distance to the nearest petrol station of 962 (1317) meters. The average increase in DAI (95%CI) for participants in quintiles Q2-Q5 (vs Q1) of RTD at 50 meters was of 1.51 (0.50, 2.53), 0.98 (-0.05, 2.01), 2.20 (1.18, 3.21) and 1.98 (0.90, 3.05), respectively. Consistent findings were observed at 100 meters. By domains, most of the deficits accumulated with increased RTD were of a functional nature, although RTD at 50 meters was also associated with worse self-reported health, increased vitality problems and higher incidence of chronic morbidities. Living closer to a petrol station was associated with a higher incidence of functional impairments and chronic morbidities. CONCLUSIONS: Exposure to nearby residential traffic is associated with accelerated trajectories of unhealthy ageing. Diminishing traffic pollution should become a priority intervention for adding healthy years to life in the old age.

SOCS3 deregulation contributes to aberrant activation of the JAK/STAT pathway in precursor T-cell neoplasms.

Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBL.

SARS-CoV-2 Infection During the First and Second Pandemic Waves in Spain: the ENE-COVID Study.

Objectives. To describe participant characteristics associated with severe acute respiratory syndrome coronavirus 2 infection in Spain's first 2 COVID-19 waves per the Spanish National Seroepidemiological Survey of SARS-CoV-2 Infection (ENE-COVID). Methods. A representative cohort of the noninstitutionalized Spanish population, selected through stratified 2-stage sampling, answered a questionnaire and received point-of-care testing April to June 2020 (first wave: n = 68 287); previously seronegative participants repeated the questionnaire and test November 2020 (second wave: n = 44 451). We estimated seropositivity by wave and participant characteristics, accounting for sampling weights, nonresponse, and design effects. Results. We found that 6.0% (95% confidence interval [CI] = 5.7%, 6.4%) of Spain's population was infected by June and 3.8% (95% CI = 3.5%, 4.1%) more by November 2020. Both genders were equally affected. Seroprevalence decreased with age in adults 20 years and older in the second wave; socioeconomic differences increased. Health care workers were affected at 11.1% (95% CI = 9.0%, 13.6%) and 6.1% (95% CI = 4.4%, 8.5%) in the first and second waves, respectively. Living with an infected person increased infection risk to 22.1% (95% CI = 18.9%, 25.6%) in the first and 35.0% (95% CI = 30.8%, 39.4%) in the second wave. Conclusions. ENE-COVID characterized the first 2 pandemic waves, when information from surveillance systems was incomplete. (Am J Public Health. 2023;113(5):533-544. https://doi.org/10.2105/AJPH.2023.307233).

Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data.

When responding to infectious disease outbreaks, rapid and accurate estimation of the epidemic trajectory is critical. However, two common data collection problems affect the reliability of the epidemiological data in real time: missing information on the time of first symptoms, and retrospective revision of historical information, including right censoring. Here, we propose an approach to construct epidemic curves in near real time that addresses these two challenges by 1) imputation of dates of symptom onset for reported cases using a dynamically-estimated "backward" reporting delay conditional distribution, and 2) adjustment for right censoring using the NobBS software package to nowcast cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020. We evaluate how these real-time estimates compare with more complete epidemiological data that became available later. We explore the impact of the different assumptions on the estimates, and compare our estimates with those obtained from commonly used surveillance approaches. Our framework can help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health systems in other locations.

Socio-economic inequalities in lung cancer mortality in Spain: a nation-wide study using area-based deprivation.

BACKGROUND: Lung cancer is the main cause of cancer mortality worldwide and in Spain. Several previous studies have documented socio-economic inequalities in lung cancer mortality but these have focused on specific provinces or cities. The goal of this study was to describe lung cancer mortality in Spain by sex as a function of socio-economic deprivation. METHODS: We analysed all registered deaths from lung cancer during the period 2011-2017 in Spain. Mortality data was obtained from the National Institute of Statistics, and socio-economic level was measured with the small-area deprivation index developed by the Spanish Society of Epidemiology, with the census tract of residence at the time of death as the unit of analysis. We computed crude and age-standardized rates per 100,000 inhabitants by sex, deprivation quintile, and type of municipality (rural, semi-rural, urban) considering the 2013 European standard population (ASR-E). We further calculated ASR-E ratios between the most deprived (Q5) and the least deprived (Q1) areas and mapped census tract smoothed standardized lung cancer mortality ratios by sex. RESULTS: We observed 148,425 lung cancer deaths (80.7% in men), with 73.5 deaths per 100,000 men and 17.1 deaths per 100,000 women. Deaths from lung cancer in men were five times more frequent than in women (ASR-E ratio = 5.3). Women residing in the least deprived areas had higher mortality from lung cancer (ASR-E = 22.2), compared to women residing in the most deprived areas (ASR-E = 13.2), with a clear gradient among the quintiles of deprivation. For men, this pattern was reversed, with the highest mortality occurring in areas of lower socio-economic level (ASR-E = 99.0 in Q5 vs. ASR-E = 86.6 in Q1). These socio-economic inequalities remained fairly stable over time and across urban and rural areas. CONCLUSIONS: Socio-economic status is strongly related to lung cancer mortality, showing opposite patterns in men and women, such that mortality is highest in women residing in the least deprived areas and men residing in the most deprived areas. Systematic surveillance of lung cancer mortality by socio-economic status may facilitate the assessment of public health interventions aimed at mitigating cancer inequalities in Spain.

Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia.

The standard-of-care treatment of T-cell acute lymphoblastic leukaemia (T-ALL) with chemotherapy usually achieves reasonable rates of initial complete response. However, patients who relapse or do not respond to conventional therapy show dismal outcomes, with cure rates below 10% and limited therapeutic options. To ameliorate the clinical management of these patients, it is urgent to identify biomarkers able to predict their outcomes. In this work, we investigate whether NRF2 activation constitutes a biomarker with prognostic value in T-ALL. Using transcriptomic, genomic, and clinical data, we found that T-ALL patients with high NFE2L2 levels had shorter overall survival. Our results demonstrate that the PI3K-AKT-mTOR pathway is involved in the oncogenic signalling induced by NRF2 in T-ALL. Furthermore, T-ALL patients with high NFE2L2 levels displayed genetic programs of drug resistance that may be provided by NRF2-induced biosynthesis of glutathione. Altogether, our results indicate that high levels of NFE2L2 may be a predictive biomarker of poor treatment response in T-ALL patients, which would explain the poor prognosis associated with these patients. This enhanced understanding of NRF2 biology in T-ALL may allow a more refined stratification of patients and the proposal of targeted therapies, with the ultimate goal of improving the outcome of relapsed/refractory T-ALL patients.

Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci.

BACKGROUND: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. METHODS: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. RESULTS: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes. CONCLUSIONS: Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.

Metal and metalloid levels in topsoil and municipal cardiovascular mortality in Spain.

The role of metals and metalloids beyond arsenic, copper, lead and cadmium in cardiovascular disease is not entirely clear. The aim of this study was to assess the association between 18 metal or metalloid levels in topsoil (upper soil horizon) with all-cause and specific cardiovascular mortality endpoints in Spain. We designed an ecological spatial study, to assess cardiovascular mortality in 7941 Spanish mainland towns from 2010 to 2014. The estimation of metals and metalloids concentration in topsoil came from the Geochemical Atlas of Spain from 13,317 soil samples. We also summarized the joint variability of the metals using principal components analysis (PCA). These components (PCs) were included in a Besag, York, and Mollié model to assess their association with cardiovascular mortality from all causes, coronary heart disease, cerebrovascular, hypertension, and conduction disorders. Our results showed, both in men and women, that at the lowest component scores range, PC2 (mainly reflecting Al, Be, Tl and U) was positively associated with coronary heart disease and cerebrovascular mortality. At medium/highest scores range, PC4 (mainly reflecting Hg) was positively associated with cerebrovascular mortality. For PC3 (reflecting Se), the association with coronary heart disease mortality was positive only in men at the highest PC scores range. For PC1 (partly reflecting metals such as Pb, As, Cu or Cd), we observed a strongly suggestive positive association with all-cause cardiovascular diseases mortality. Our ecological results are consistent with the available evidence supporting a cardiovascular role of excessive exposure to Se, Hg, Pb, As, Cu and Cd, but also identify Al, Be, Tl and U as potentially novel cardiovascular factors. Additional research is needed to confirm the biological relevance of our findings.

Innovative moments in recovered cases treated with the unified protocol for transdiagnostic treatment of emotional disorders.

OBJECTIVE: Innovative moments (IMs) are moments in which the previous problematic pattern of meaning is challenged. Studies have shown that IMs are associated with good psychotherapy outcomes. A three-level hierarchy of IMs was observed in recent studies, with level 1 IMs being more elementary and levels 2 and 3 being more complex and associated with treatment success. However, studies with manualized protocol treatments are thus far lacking. This study analyzed the longitudinal progression of IMs in the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) and explored its associations with changes in psychological distress. METHODS: Data were collected from a Portuguese university-based outpatient clinic and included 18 cases with positive outcomes. Nine sessions of each case were coded with the IM coding system (N=162). RESULTS: Multilevel analyses showed a significant increase in all IM levels across treatments. The decrease in psychological distress predicted an increase in level 2 IMs in the same session. CONCLUSION: The evolution of IMs is similar to what was found previously in other studies. Contrary to what was found in previous studies, IMs did not predict outcomes in the following session, whereas the reduction in psychological distress predicted the emergence of level 2 IMs.

Cancer incidence estimation from mortality data: a validation study within a population-based cancer registry.

BACKGROUND: Population-based cancer registries are required to calculate cancer incidence in a geographical area, and several methods have been developed to obtain estimations of cancer incidence in areas not covered by a cancer registry. However, an extended analysis of those methods in order to confirm their validity is still needed. METHODS: We assessed the validity of one of the most frequently used methods to estimate cancer incidence, on the basis of cancer mortality data and the incidence-to-mortality ratio (IMR), the IMR method. Using the previous 15-year cancer mortality time series, we derived the expected yearly number of cancer cases in the period 2004-2013 for six cancer sites for each sex. Generalized linear mixed models, including a polynomial function for the year of death and smoothing splines for age, were adjusted. Models were fitted under a Bayesian framework based on Markov chain Monte Carlo methods. The IMR method was applied to five scenarios reflecting different assumptions regarding the behavior of the IMR. We compared incident cases estimated with the IMR method to observed cases diagnosed in 2004-2013 in Granada. A goodness-of-fit (GOF) indicator was formulated to determine the best estimation scenario. RESULTS: A total of 39,848 cancer incidence cases and 43,884 deaths due to cancer were included. The relative differences between the observed and predicted numbers of cancer cases were less than 10% for most cancer sites. The constant assumption for the IMR trend provided the best GOF for colon, rectal, lung, bladder, and stomach cancers in men and colon, rectum, breast, and corpus uteri in women. The linear assumption was better for lung and ovarian cancers in women and prostate cancer in men. In the best scenario, the mean absolute percentage error was 6% in men and 4% in women for overall cancer. Female breast cancer and prostate cancer obtained the worst GOF results in all scenarios. CONCLUSION: A comparison with a historical time series of real data in a population-based cancer registry indicated that the IMR method is a valid tool for the estimation of cancer incidence. The goodness-of-fit indicator proposed can help select the best assumption for the IMR based on a statistical argument.

Approximate Bayesian inference for multivariate point pattern analysis in disease mapping.

We present a novel approach for analysing multivariate case-control georeferenced data in a Bayesian disease mapping context using stochastic partial differential equations (SPDEs) and the integrated nested Laplace approximation (INLA) for model fitting. In particular, we propose smooth terms based on SPDE models to estimate the underlying spatial variation as well as risk associated to pollution sources. Log-Gaussian Cox processes are used to estimate the intensity of the cases and controls, to account for risk factors and include a term to measure spatial residual variation. Each intensity is modelled on a baseline spatial effect (estimated from both controls and cases), a disease-specific spatial term and the effects of some covariates. By fitting these models, the residual spatial terms can be easily compared to detect high-risk areas not explained by the covariates. Three different types of effects to model exposure to pollution sources are considered on the distance to the source: a fixed effect, a smooth term to model non-linear effects by means of a discrete random walk of order one and a Gaussian process in one dimension with a Matérn covariance function. Spatial terms are modelled using a Gaussian process in two dimensions with a Matérn covariance function and are approximated using an approach based on solving an SPDE through INLA. Finally, this new framework is applied to a dataset of three different types of cancer and a set of controls from Alcalá de Henares (Madrid, Spain). Covariates available include the distance to several polluting industries and socioeconomic indicators. Our findings point to a possible risk increase due to the proximity to some of these industries.

The use of PanDrugs to prioritize anticancer drug treatments in a case of T-ALL based on individual genomic data.

BACKGROUND: Acute T-cell lymphoblastic leukaemia (T-ALL) is an aggressive disorder derived from immature thymocytes. The variability observed in clinical responses on this type of tumours to treatments, the high toxicity of current protocols and the poor prognosis of patients with relapse or refractory make it urgent to find less toxic and more effective therapies in the context of a personalized medicine of precision. METHODS: Whole exome sequencing and RNAseq were performed on DNA and RNA respectively, extracted of a bone marrow sample from a patient diagnosed with tumour primary T-ALL and double negative thymocytes from thymus control samples. We used PanDrugs, a computational resource to propose pharmacological therapies based on our experimental results, including lists of variants and genes. We extend the possible therapeutic options for the patient by taking into account multiple genomic events potentially sensitive to a treatment, the context of the pathway and the pharmacological evidence already known by large-scale experiments. RESULTS: As a proof-of-principle we used next-generation-sequencing technologies (Whole Exome Sequencing and RNA-Sequencing) in a case of diagnosed Pro-T acute lymphoblastic leukaemia. We identified 689 disease-causing mutations involving 308 genes, as well as multiple fusion transcript variants, alternative splicing, and 6652 genes with at least one principal isoform significantly deregulated. Only 12 genes, with 27 pathogenic gene variants, were among the most frequently mutated ones in this type of lymphoproliferative disorder. Among them, 5 variants detected in CTCF, FBXW7, JAK1, NOTCH1 and WT1 genes have not yet been reported in T-ALL pathogenesis. CONCLUSIONS: Personalized genomic medicine is a therapeutic approach involving the use of an individual's information data to tailor drug therapy. Implementing bioinformatics platform PanDrugs enables us to propose a prioritized list of anticancer drugs as the best theoretical therapeutic candidates to treat this patient has been the goal of this article. Of note, most of the proposed drugs are not being yet considered in the clinical practice of this type of cancer opening up the approach of new treatment possibilities.

Relational schemas as mediators of innovative moments in symptom improvement in major depression.

OBJECTIVES: Innovative moments (IMs) are exceptions to the maladaptive framework of meaning that typically motivates clients to seek psychotherapy, and previous studies have shown that IMs are associated with psychotherapy outcomes. While IMs are exceptions that occur at the level of the therapeutic conversation, relational schemas are more stable patterns, and their increased flexibility may facilitate change during psychotherapy. With this in mind, we tested the hypothesis that IMs contribute to outcomes by improving the flexibility of relational schemas. METHOD: The Core Conflictual Relationship Theme (CCRT) was used to assess relational schemas. IMs were evaluated using the Innovative Moments Coding System. The sample included 22 clients diagnosed with major depressive disorder. The flexibility of the three components of the CCRT (Wishes, responses of the self (RS), and responses of others (RO)) were tested as mediators between IMs and outcomes. RESULTS: The flexibility of the RS was a mediator between IMs and outcomes, but Wishes and RO were not. CONCLUSION: These findings align with previous research showing that RS is the component most open to change, whereas the other components seem less sensitive to change during brief therapy. Clinical or methodological significance of this article: This study shows the mediation role of relational schemas in the association between in-session events (innovative moments (IMs)) and the symptoms improvement. It contributes to the literature that emphasizes the importance of relational schemas in psychotherapy by using a mediation model, which has rarely been tested.

RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas.

BACKGROUND: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene may induce a differentiation block at the DN3 to DN4 transition, and that the loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas. RESULTS: In this manuscript, we demonstrated that the simultaneous deregulation of CDKN1C, E2F1, and TP53 genes by epigenetic mechanisms and/or the deregulation of specific microRNAs, together with additional impairing of TP53 function by the expression of dominant-negative isoforms are common features in primary human T-LBLs. CONCLUSIONS: Previous experimental work in mice revealed that T-cell specific deletion of Cdkn1c accelerates lymphomagenesis in the absence of Tp53. If, as expected, the consequences of the deregulation of the CDKN1C-E2F1-TP53 axis were the same as those experimentally demonstrated in mouse models, the disruption of this axis might be useful to predict tumor aggressiveness, and to provide the basis towards the development of potential therapeutic strategiesin human T-LBL.

Reconceptualization innovative moments as a predictor of symptomatology improvement in treatment for depression.

OBJECTIVES: In previous studies, reconceptualization innovative moments were associated with successful psychotherapy. Reconceptualization has two components-(a) a positive temporal contrast between the past self and the present self (contrasting self [CS]) and (b) a description of how and/or why this change has occurred (change process [CP])-from the perspective of the client. The aim of this study is to analyse if CS and CP have the same association with outcomes as reconceptualization. METHOD: Sixteen cases of clients with major depression (305 sessions) were analysed. Longitudinal regression models were used to explore if proportions of CS, CP, and reconceptualization predicted outcome measures and if outcome measures predicted CS, CP, and reconceptualization. RESULTS: Reconceptualization is less frequent than CS and CP taken separately, but reconceptualization was a better predictor of treatment outcomes than were its separate components. Moreover, symptom improvement did not predict reconceptualization. CONCLUSION: The construction of new meanings is important in improving depressive symptomatology. Psychotherapists can elicit these new meanings in their regular practice by posing questions that may help clients to conceptualize what is changing in themselves (CS) and questions of how this change is occurring (CP). The construction of an integrative account of these new meanings is associated with psychotherapeutic gains, and thus, reconceptualizing change could improve symptoms of depression.

Compositional analysis of topsoil metals and its associations with cancer mortality using spatial misaligned data.

The presence of toxic metals in soil per se, and in soil impacted by mining, industry, agriculture and urbanisation in particular, is a major concern for both human health and ecotoxicology. The dual aim of this study was: to ascertain whether topsoil composition could influence the spatial distribution of mortality due to different types of cancer and to identify possible errors committed by epidemiological studies which analyse soil composition data as a closed number system. We conducted an ecological cancer mortality study, covering 861,440 cancer deaths (27 cancer sites) in 7917 Spanish mainland towns, from 1999 to 2008. Topsoil levels of Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were determined by ICP-MS at 13,317 sampling points. We transformed the topsoil data in two ways, i.e. log transformation and centred logratio transformation. Principal factor analysis was performed to obtain independent latent factors for the transformed variables. To estimate the effect on mortality of topsoil factor loadings, we fitted Besag, York and Mollié models embedded in geostatistical-spatial models. This model included soil sample locations and town centroids (non-aligned data), fitted using the integrated nested Laplace approximation (INLA) as a tool for Bayesian inference and stochastic partial differential equations (SPDE). All results were adjusted for socio-demographic variables. The results indicated that soil composition could have an influence on the spatial distribution and mortality patterns of cancer. The analysis adjusted for socio-demographic variables showed excess male mortality due to digestive system tumours in areas with soils containing higher Cd, Pb, Zn, Mn and Cu concentrations, bladder cancer in areas with soils containing higher Cd concentrations, and brain cancer in areas with soils containing As. In both sexes, cancer of oesophagus was associated with soils containing a higher lead content, while lung cancer was associated with soils containing a higher copper content. Stress should be laid on the importance of taking into account the compositional nature of the data in this type of analysis.

Industrial pollution and cancer in Spain: An important public health issue.

Cancer can be caused by exposure to air pollution released by industrial facilities. The European Pollutant Release and Transfer Register (E-PRTR) has made it possible to study exposure to industrial pollution. This study seeks to describe the industrial emissions in the vicinity of Spanish towns and their temporal changes, and review our experience studying industrial pollution and cancer. Data on industrial pollutant sources (2007-2010) were obtained from the E-PRTR registries. Population exposure was estimated by the distance from towns to industrial facilities. We calculated the amount of carcinogens emitted into the air in the proximity (<5km) of towns and show them in municipal maps. We summarized the most relevant results and conclusions reported by ecological E-PRTR-based on studies of cancer mortality and industrial pollution in Spain and the limitations and result interpretations of these types of studies. There are high amounts of carcinogen emissions in the proximity of towns in the southwest, east and north of the country and the total amount of emitted carcinogens is considerable (e.g. 20Mt of arsenic, 63Mt of chromium and 9Mt of cadmium). Although the emissions of some carcinogens in the proximity of certain towns were reduced during the study period, emissions of benzene, dioxins+furans and polychlorinated biphenyls rose. Moreover, the average population of towns lying within a 5km radius from emission sources of carcinogens included in the International Agency for Research on Cancer list of carcinogens was 9 million persons. On the other hand, the results of the reviewed studies suggest that those Spanish regions exposed to the pollution released by certain types of industrial facilities have around 17% cancer excess mortality when compared with those unexposed. Moreover, excess mortality is focused on digestive and respiratory tract cancers, leukemias, prostate, breast and ovarian cancers. Despite their limitations, ecological studies are a useful tool in environmental epidemiology, not only for proposing etiological hypotheses about the risk of living close to industrial pollutant sources, but also for providing data to account for situations of higher mortality in specific areas. Nevertheless, the reduction of emissions should be a goal, with special relevance given to establishing limits for known carcinogens and other toxic substances in the environs of population centers, as well as industry-specific emission limits.

Three narrative-based coding systems: Innovative moments, ambivalence and ambivalence resolution.

Narrative and dialogical perspectives suggest that personal meaning systems' flexibility is an important resource for change in psychotherapy. Drawn from these theoretical backgrounds, a research program focused on the identification of Innovative Moments (IMs)-exceptions to the inflexible meaning systems present in psychopathological suffering-has been carried out. For this purpose, three process-oriented coding systems were developed: The IMs Coding System, the Ambivalence Coding System, and the Ambivalence Resolution Coding System. They allow, respectively, for the study of change, ambivalence, and ambivalence resolution in therapy. This paper presents these coding systems, the main findings that resulted from their application to different samples and therapeutic models, the main current and future lines of research, as well as the clinical applications of this research program.

Transcriptomic analysis reveals sex-specific differences in the expression of Dcl1 and Fis1 genes in the radio-adaptive response of thymocytes to TRP53-mediated apoptosis.

BACKGROUND: Radio-Adaptive Response (RAR) is a biological defense mechanism whereby exposure to low dose ionizing radiation (IR) mitigates the detrimental effects of high dose irradiation. RAR has been widely observed in vivo using as endpoint less induction of apoptosis. However, sex differences associated with RAR and variations between males and females on global gene expression influenced by RAR have not been still investigated. In addition, the response to radiation-induced apoptosis is associated with phosphorylation of TRP53 at both the serine 15 (ser-18 in the mouse) and serine 392 (ser-389 in mice) residues, but the role of these two phosphorylated forms in male and female RAR remains to be elucidated. RESULTS: We analyzed the effect of administering priming low dose radiation (0.075 Gy of X-rays) prior to high dose radiation (1.75 Gy of γ-rays) on the level of caspase-3-mediated apoptosis and on global transcriptional expression in thymocytes of male and female mice. Here, we provide the first evidence of a differential sex effect of RAR on the reduction of thymocyte apoptosis with males showing lesser levels of caspase-3-mediated apoptosis than females. Analysis of transcriptomic profiles of 1944 genes involved in apoptosis signaling in radio-adapted thymocytes identified 17 transcripts exhibiting differential expression between both sexes. Among them, Dlc1 and Fis1 are closely related to the apoptosis mediated by the TRP53 protein. Our data demonstrate that overexpression of Dlc1 and Fis1 occur concomitantly with a highest accumulation of phosphoserine-18-TRP53 and caspase-3 in radio-adapted thymocytes of female mice. In an opposite way, both down-modulation of Fis1 and phosphoserine-389-TRP53 accumulation appear to be associated with protection from thymocyte apoptosis mediated by caspase-3 in males. CONCLUSIONS: Transcriptomic analysis performed in this work reveals for the first time sex-specific differences in gene expression influenced by RAR. Our results also suggest a sex-dependent dual role for phosphoserine-18-TRP53 and phosphoserine-389-TRP53 in the regulation of the radio-adaptive response in mouse thymocytes.