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(1) Background: To assess the prevalence of mental disorders (depression and anxiety), psychological distress, and psychiatric medications consumption among persons suffering from COPD; to compare this prevalence with non-COPD controls and to identify which variables are associated with worse mental health. (2) Methods: This is an epidemiological case-control study. The data were obtained from the Spanish National Health Survey 2017. Subjects were classified as COPD if they reported suffering from COPD and the diagnosis of this condition had been confirmed by a physician. For each case, we selected a non-COPD control matched by sex, age, and province of residence. Conditional logistic regression was used for multivariable analysis. (3) Results: The prevalence of mental disorders (33.9% vs. 17.1%; p < 0.001), psychological distress (35.4% vs. 18.2%; p < 0.001), and psychiatric medications consumption (34.1% vs. 21.9%; p < 0.001) was higher among COPD cases compared with non-COPD controls. After controlling for possible confounding variables, such as comorbid conditions and lifestyles, using multivariable regression, the probability of reporting mental disorders (OR 1.41; 95% CI 1.10-1.82).), psychological distress (OR 1.48; 95% CI 1.12-1.91), and psychiatric medications consumption (OR 1.38 95% CI 1.11-1.71) remained associated with COPD. Among COPD cases, being a woman, poor self-perceived health, more use of health services, and active smoking increased the probability of suffering from mental disorders, psychological distress, and psychiatric medication use. Stroke and chronic pain were the comorbidities more strongly associated with these mental health variables. (4) Conclusions: COPD patients have worse mental health and higher psychological distress and consume more psychiatric medications than non-COPD matched controls. Variables associated with poorer mental health included being a woman, poor self-perceived health, use of health services, and active smoking.

Background: To assess gender differences in the prevalence of self-reported mental disorders, psychological distress and psychotropic drug consumption, and to identify sociodemographic and health-related variables associated with these conditions in the male and female population (aged ≥ 18 years)., Methods: A cross-sectional study was carried on 22,141 subjects aged 18 and over, using data from the Spanish National Health Interview Survey 2017., Results: We found an overall prevalence of mental disorders, psychological distress and psychotropic drug consumption of 13.8%, 18.3% and 13.9%, respectively. After multivariable adjustment, women showed significantly increased probabilities of 1.74-fold for mental disorders, 1.26-fold for psychological distress and 1.26-fold for psychotropic drug consumption compared to men. Variables such as gender, age, nationality, marital status, educational level, self-rated health, the presence of different chronic disorders, alcohol consumption and smoking habit were independently associated with mental disorders, psychological distress and psychotropic drug consumption. Several variables showed a differential effect on mental health status and psychotropic drug consumption according to gender., Conclusions: Women suffer from mental disorders, experience psychological distress and consume psychotropic drugs significantly more than men in Spain. Possible explanations for these results may be related to differences in emotional processing, willingness to report diseases and even intrinsic biological traits. Screening for mental health status and psychotropic drug consumption should be considered, particularly in Spanish women, younger adults and individuals who are not married, are obese, have poor self-rated health, suffer from chronic diseases or have a smoking habit., Competing Interests: The authors declare no conflicts of interest.

Background: The purpose of this study was to assess and compare the prevalence of self-reported mental disorders, psychological distress, and psychotropic drug consumption among people with diabetes mellitus (DM) and matched non-DM controls., Methods: A case-controlled study using data from the Spanish National Health Interview Survey was conducted in 2017. We identified 2116 DM adults (aged ≥35 years). Non-DM controls were matched 1:1 by age, sex, and province of residence., Results: Prevalence of mental disorders (25.0% vs. 19.2%; p < 0.001), psychological distress (29% vs. 19.5%; p < 0.001), and consumption of psychiatric medications (29.7% vs. 23.5%; p < 0.001) among DM cases were higher than those among matched non-DM controls. The DM patient variables associated with experiencing a mental disorder, psychological distress, and consumption of psychiatric medications were: being a woman, worse self-rated health, and a visit to a psychologist within the last year. Older age (≥80 years) was associated with a lower probability of reporting mental disorders and psychological distress among DM cases. Not practicing physical exercise was significantly associated with experiencing psychological distress., Conclusions: Adults with DM included in our investigation have a significantly higher prevalence of mental disorders, psychological distress, and consumption of psychiatric medications than non-DM controls. It is necessary to implement screening strategies and psychological interventions to improve the mental health of DM patients in Spain, focusing especially on women and those aged 35 to 59 years.

Objective: To prevent the deterioration of patients with fibromyalgia due to potentially avoidable harmful actions in clinical practice., Methods: A multidisciplinary panel of experts identified key areas, analysed the scientific evidence and formulated recommendations based on this evidence and qualitative techniques of «formal assessment» or «reasoned judgement»., Results: Thirty-nine recommendations were made on diagnosis, ineffective and unsafe treatments, patient education and practitioner training. This partII shows the 12 recommendations, referring to the latter two areas., Conclusions: Good knowledge of fibromyalgia on the part of patients improves their coping and acceptance of the disease and reduces the severity of some clinical manifestations. Healthcare professionals treating patients with fibromyalgia should be well trained in this disease to improve treatment outcomes and patient relationships., (Copyright © 2021 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objective: To prevent the impairment of fibromyalgia patients due to harmful actions in daily clinical practice that are potentially avoidable., Methods: A multidisciplinary team identified the main areas of interest and carried out an analysis of scientific evidence and established recommendations based on the evidence and "formal evaluation" or "reasoned judgment" qualitative analysis techniques., Results: A total of 39 recommendations address diagnosis, unsafe or ineffective treatment interventions and patient and healthcare workers' education. This part I shows the first 27 recommendations on the first 2 areas., Conclusions: Establishing a diagnosis improves the patient's coping with the disease and reduces healthcare costs. NSAIDs, strong opioids and benzodiazepines should be avoided due to side effects. There is no good evidence to justify the association of several drugs. There is also no good evidence to recommend any complementary medicine. Surgeries show a greater number of complications and a lower degree of patient satisfaction and therefore should be avoided if the surgical indication is not clearly established., (Copyright © 2021 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Stomach content analyses are a valuable tool in human forensic science to interpret perimortem events. While the identification of food components of plant and animal origin has traditionally been conducted by macro- and microscopical approaches in case of incomplete digestion, molecular methods provide the potential to increase sensitivity and taxonomic resolution. In particular, DNA metabarcoding (PCR-amplification and next generation sequencing of complex DNA mixtures) has seen a rapid growth in the field of wildlife ecology to assess species' diets from faecal and gastric samples. Despite clear advantages, molecular approaches have not yet been established in routine human forensics to investigate the last meal components of deceased persons. In this pilot study we applied for the first time a DNA metabarcoding approach to assess both plant and vertebrate components of 48 human stomach content samples taken during medicolegal autopsies. We obtained a final dataset with 34 vertebrate and 124 vegetal unique sequences, that were clustered to 9 and 33 operational taxonomic units (OTUs), respectively. Our results suggest that this approach can provide crucial information about circumstances preceding death, and open promising perspectives for biomedical dietary surveys based on digested food items found in the gastrointestinal tract.

Nicotine intake and cortical activity are closely related, as they can influence each other. Nicotine is implicated in the induction and modification of cortical plasticity and excitability, whereas a change on cortical plasticity and excitability can also lead to a modification of the smoking behaviour of an individual. The aim of this systematic review was, on the one hand, to evaluate the effects of nicotinergic modulation on cortical excitability and plasticity, and, on the other hand, to assess if modifying the brain's excitability and plasticity could influence one's smoking behaviour. Two systematic literature searches in the PubMed/MEDLINE and PsycINFO databases were conducted. Studies focusing either on the impact of nicotinergic modulation on cortical activity or the treatment effect of non-invasive brain stimulation techniques (NIBS) on smoking behaviour were included. A total of 22 studies for the first systematic search and 35 studies for the second one were included after full-text screening. Nicotine's effect on cortical activity appeared to depend on smoking status of the individual. While deprived smokers seem to generally profit from nicotine consumption in terms of cortical excitability and plasticity, the contrary was true for non-smokers. Regarding the questions of how changes in cortical excitability can influence smoking behaviour, a trend points towards NIBS being a potential intervention technique for smoking cessation.

One of the challenges in the emergency department (ED) is the early identification of patients with a higher risk of clinical deterioration. The objective is to evaluate the prognostic capacity of ΔLA (correlation between prehospital lactate (pLA) and hospital lactate (hLA)) with respect to in-hospital two day mortality. We conducted a pragmatic, multicentric, prospective and blinded-endpoint study in adults who consecutively attended and were transported in advanced life support with high priority from the scene to the ED. The corresponding area under the receiver operating characteristics curve (AUROC) was obtained for each of the outcomes. In total, 1341 cases met the inclusion criteria. The median age was 71 years (interquartile range: 54-83 years), with 38.9% (521 cases) females. The total 2 day mortality included 106 patients (7.9%). The prognostic precision for the 2 day mortality of pLA and hLA was good, with an AUROC of 0.800 (95% CI: 0.74-0.85; p < 0.001) and 0.819 (95% CI: 0.76-0.86; p < 0.001), respectively. Of all patients, 31.5% (422 cases) had an ΔLA with a decrease of <10%, of which a total of 66 patients (15.6%) died. A lactate clearance ≥ 10% is associated with a lower risk of death in the ED, and this value could potentially be used as a guide to determine if a severely injured patient is improving in response to the established treatment.

The objective of this study was to analyze and compare the usefulness of quick sequential organ failure assessment score (qSOFA) and sequential organ failure assessment (SOFA) scores for the detection of early (two-day) mortality in patients transported by emergency medical services (EMSs) to the emergency department (ED) (infectious and non-infectious). We performed a multicentric, prospective and blinded end-point study in adults transported with high priority by ambulance from the scene to the ED with the participation of five hospitals. For each score, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated. We included 870 patients in the final cohort. The median age was 70 years (IQR 54-81 years), and 338 (38.8%) of the participants were women. Two-day mortality was 8.3% (73 cases), and 20.9% of cases were of an infectious pathology. For two-day mortality, the qSOFA presented an AUC of 0.812 (95% CI: 0.75-0.87; p < 0.001) globally with a sensitivity of 84.9 (95% CI: 75.0-91.4) and a specificity of 69.4 (95% CI: 66.1-72.5), and a SOFA of 0.909 (95% CI: 0.86-0.95; p < 0.001) with sensitivity of 87.7 (95% CI: 78.2-93.4) and specificity of 80.7 (95% CI: 77.4-83.3). The qSOFA score can serve as a simple initial assessment to detect high-risk patients, and the SOFA score can be used as an advanced tool to confirm organ dysfunction.

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13-3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07-3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36-3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05-3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.

Background: The purpose of the study was to determine to what degree the health habits of university students influence their physiological response during a 10-min high-intensity exercise., Methods: We conducted a cross-sectional cohort study with 59 health science students, in which we analyzed their adherence to a Mediterranean and low-fat diet, as well as their activity levels. We correlated these factors with the physiological response (lactic acid and heart rate) and a series of anthropometric parameters in intense physical activity (cardiopulmonary resuscitation (CPR) for 10 min) in three scenarios: extreme cold, extreme heat and a control situation at room temperature., Results: The results of this study demonstrate that in university students, a greater adherence to the Mediterranean diet was associated with a better response to physical exercise, in this case, 10-min CPR, in hostile environments., Conclusions: Following healthy eating guidelines improves physical performance and delays the appearance of fatigue; both are important aspects for a better performance of CPR.

Background : In Spain, colorectal cancer screening using the fecal occult blood test, targeted towards the 50-69 age bracket, was implemented on different dates. We aim to assess the temporal trend of colorectal cancer (CRC) screening uptake according to the year of screening implementation in each region and to identify predictors for the uptake of CRC screening. Methods : A cross-sectional study with 12,657 participants from the Spanish National Health Surveys 2011 and 2017 was used. Uptake rates were analyzed according to the date that the screening program was implemented. Results : For regions with programs implemented before 2011, the uptake rate increased 3.34-fold from 2011 to 2017 (9.8% vs. 32.7%; p < 0.001). For regions that implemented screening within the 2011-2016 period, the uptake rose from 4.3% to 13.2% (3.07-fold; p < 0.001), and for regions that implemented screening after 2016, the uptake increased from 3.4% to 8.8% (2.59-fold; p < 0.001). For the entire Spanish population, the uptake increased 3.21-fold (6.8% vs. 21.8%; p < 0.001). Positive predictors for uptake were older age, Spanish nationality, middle-to-high educational level, suffering chronic diseases, non-smoking and living in regions where screening programs were implemented earlier. Conclusions : The different periods for the implementation of CRC screening as well as sociodemographic and health inequalities may have limited the improvement in the screening uptake from 2011 to 2017 in Spain.

Background: To determine the relationship between physiological fatigue and the quality of cardiopulmonary resuscitation (CPR) in trained resuscitators in hostile thermal environments (extreme cold and heat) simulating the different conditions found in an out-of-hospital cardiorespiratory arrest., Methods: Prospective observational study involving 60 students of the health sciences with training in resuscitation, who simulated CPR on a mannequin for 10 min in different thermal environments: thermo-neutral environment (21 °C and 60% humidity), heat environment (41 °C and 98% humidity) and cold environment (-35 °C and 80% humidity). Physiological parameters (heart rate and lactic acid) and CPR quality were monitored., Results: We detected a significant increase in the number of compressions per minute in the "heat environment" group after three minutes and in the mean rate after one minute. We observed a negative correlation between the total number of compressions and mean rate with respect to mean depth. The fraction of compressions (proportion of time in which chest compressions are carried out) was significant over time and the mean rate was higher in the "heat environment". Physiological parameters revealed no differences in heart rate depending on the resuscitation scenario; however, there was a greater and faster increase in lactate in the "heat environment" (significant at minute 3). The total proportion of participants reaching metabolic fatigue was also higher in the "heat environment"., Conclusions: A warm climate modifies metabolic parameters, reducing the quality of the CPR maneuver.

Teaching and training cardiopulmonary resuscitation (CPR) through simulation is a priority in Health Sciences degrees. Although CPR is taught as a simulation, it can still be stressful for the trainees since it resembles a real-life circumstance. The aim of this study was to assess the physiological effects and anxiety levels of health sciences undergraduates when faced with CPR process in different temperatures (room temperature, extremely cold, or extremely warm). This was a descriptive cross-sectional before-after study conducted during the 2018/2019 academic year with 59 students registered in the Faculty of Health Sciences of the Castilla-La Mancha University (UCLM). State Trait Anxiety Inventory (STAI) questionnaires were distributed among the students before and after the CPR simulation. We found greater level of situational anxiety in undergraduates faced with extreme adverse temperature scenarios (extreme heat and cold), especially in conditions of extreme heat compared to controlled environment (at room temperature). We discovered differences regarding sex, in which men scored 6.4 ± 5.55 points (STAI after CPR score) and women scored 10.4 ± 7.89 points (STAI after CPR score). Furthermore, there was less lactate in blood, before and during the event in individuals with anxiety. In addition, beginning in Minute 7, we observed a remarkable decrease (but not significant) in the performance of rescuers with anxiety. Programs targeted at promoting coping mechanisms to reduce anxiety before a critical clinic situation should be implemented in academic training.

Background: Brain metastases challenge daily clinical practice, and the mechanisms by which cancer cells cross the blood-brain barrier remain largely undeciphered. Angiopoietin-like 4 (ANGPTL4) proteolytic fragments have controversial biological effects on endothelium permeability. Here, we studied the link between ANGPTL4 and the risk of brain metastasis in cancer patients., Materials and Methods: From June 2015 to June 2016, serum samples from 113 cancer patients were prospectively collected, and ANGPTL4 concentrations were assessed. Using a murine model of brain metastases, we investigated the roles of nANGPTL4 and cANGPTL4, the two cleaved fragments of ANGPTL4, in the occurrence of brain metastases., Results: An ANGPTL4 serum concentration over 0.1 ng/mL was associated with decreased overall-survival. Multivariate analyses found that only breast cancer brain metastases were significantly associated with elevated ANGPTL4 serum concentrations. 4T1 murine breast cancer cells were transfected with either nANGPTL4- or cANGPTL4 -encoding cDNAs. Compared to mice injected with wild-type 4T1 cells, mice injected with nANGPTL4 cells had shorter median survival ( p < 0.05), while mice injected with cANGPTL4 had longer survival ( p < 0.01). On tissue sections, compared to wild-type mice, mice injected with nANGPTL4 cells had significantly larger surface areas of lung metastases ( p < 0.01), and mice injected with cANGPTL4 had significantly larger surface areas of brain metastases ( p < 0.01)., Conclusions: In this study, we showed that a higher expression of Angiopoietin-like 4 Fibrinogen-Like Domain (cANGPTL4) was associated with an increased risk of brain metastases in women with breast cancer., Competing Interests: CONFLICTS OF INTEREST Authors have no conflicts of interest to delcare.

Syncope is defined as the nontraumatic, transient loss of awareness of rapid onset, short duration and with complete spontaneous recovery, and accounts for 1%-3% of all visits to the emergency department. The objective of this study was to evaluate the predictive capacity of the National Early Warning Score 2 (NEWS2) and prehospital lactate (pLA), individually and combined, at the prehospital level to detect patients with syncope at risk of early mortality (within 48 h) in the hospital environment. A prospective, multicenter cohort study without intervention was carried out on syncope patients aged over 18 who were given advanced life support and taken to the hospital. Our study included a total of 361 cases. Early mortality affected 21 patients (5.8%). The combined score formed by the NEWS2 and the pLA (NEWS2-L) obtained an AUC of 0.948 (95% CI: 0.88-1) and an odds ratio of 86.25 (95% CI: 11.36-645.57), which is significantly higher than that obtained by the NEWS2 or pLA in isolation ( p = 0.018). The NEWS2-L can help stratify the risk in patients with syncope treated in the prehospital setting, with only the standard measurement of physiological parameters and pLA., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Sponsor’s role: None.

Traumatic brain injuries are complex situations in which the emergency medical services must quickly determine the risk of deterioration using minimal diagnostic methods. The aim of this study is to analyze whether the use of early warning scores can help with decision-making in these dynamic situations by determining the patients who need the intensive care unit. A prospective, multicentric cohort study without intervention was carried out on traumatic brain injury patients aged over 18 given advanced life support and taken to the hospital. Our study included a total of 209 cases. The total number of intensive-care unit admissions was 50 cases (23.9%). Of the scores analyzed, the National Early Warning Score2 was the best result presented with an area under the curve of 0.888 (0.81-0.94; p < 0.001) and an odds ratio of 25.4 (95% confidence interval (CI):11.2-57.5). The use of early warning scores (and specifically National Early Warning Score2) can help the emergency medical services to differentiate traumatic brain injury patients with a high risk of deterioration. The emergency medical services should use the early warning scores routinely in all cases for the early detection of high-risk situations., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Sponsor’s role: none.

We performed a pooled whole-genome sequencing on samples of the alpine plant Arabis alpina, harvested in ten populations along an elevation gradient in the French Alps. A large dataset of genetic variations was produced as single nucleotide polymorphisms (SNPs). A combined genome scan approach enabled detecting genomic regions associated with a synthetic environmental variable characterizing the climate at each sampling location. Positive loci detected by two methods were retained and belong to 19 regions in the Arabis alpina genome. The most significant region harbors an ortholog of the AtNAC062 gene, encoding a membrane-bound transcription factor described as linking the cold response and pathogen resistance that may confer protection to plants under extended snow coverage at high elevations. Other genes involved in the stress response or in flowering regulation were also detected. Altogether, our results indicated that Arabis alpina represent a suitable model for studying genomic adaptation in alpine perennial plants., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The ecological requirements of brown bears are poorly known in the Himalaya region, which complicates conservation efforts. We documented the diet of the Himalayan brown bear (Ursus arctos isabellinus) by combining classical scat analysis and a newly developed molecular genetic technique (the trnL approach), in Deosai National Park, Pakistan. Brown bears consumed over 50 plant species, invertebrates, ungulates, and several rodents. Eight plant families; Poaceae, Polygonaceae, Cyperaceae, Apiaceae, Asteraceae, Caryophyllaceae, Lamiaceae, and Rubiaceae were commonly eaten with graminoids comprising the bulk of the diet. Golden marmots comprised the major mammalian biomass in the park, and were also the main meat source for bears. Animal matter, making 36% of dietary content, contributed half of the digestible energy, due to its higher nutritious value. We did not find a significant temporal pattern in diet, perhaps because the availability of the major diet (graminoids) did not change over the foraging period. Male brown bears were more carnivorous than females, probably because of their larger size, which requires higher energy and also makes them more efficient in capturing marmots. Frequencies of three plant species were also significantly higher in male brown bears; Bistorta affinis, Carex diluta, and Carex sp. Diet of the brown bear differed significantly between the park and surrounding valleys. In valleys, diet consisted predominantly of graminoids and crops, whereas the park provided more nutritious and diverse foodThe estimated digestible energy available to brown bears in Deosai was the lowest documented among brown bear populations, due to the lack of fruits and a relatively lower meat content. The low nutritious diet and high cost of metabolism in a high-altitude environment, probably explains the very low reproductive potential of this population., Competing Interests: The authors have declared that no competing interests exist.

The 2016 WHO classification of tumours of the central nervous system represents the new paradigm among the specialists in the brain tumours and proposes a new approach combining histopathological and molecular features into diagnosis named 'integrated diagnosis'. The aim of this challenge is to overstep the interobserver variability of diagnosis based on previous classifications in order to ensure homogenous biological entities with a more accurate clinical significance. Over the last two decades, several molecular aberrations into gliomagenesis were highlighted and then confirmed as emerging biomarkers through prognostic stratification. In particular, IDH1/IDH2 genes mutations, 1p/19q codeletion and mutations in genes encoding histone H3 variants drastically changed the knowledge about diffuse gliomas inducing the WHO working group to consider the phenotype-genotype approach. In the present review, the historical development of the diagnosis of brain tumours from the 3D spatial configuration to the integration of multidisciplinary data up to recent molecular alterations is discussed. At the national level, the RENOCLIP network (supported by the National Cancer Institute) contributes to improve the standardization of histological diagnosis and the facilitation of access to molecular biology platforms for the detection of genetic aberrations necessary for integrated diagnosis. Importantly, the French POLA cohort allowed to test the clinical impact of the new criteria introduced by 2016 WHO classification of CNS tumours confirming the high accuracy in predicting clinical behaviour for diffuse gliomas., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Genetic bottlenecks resulting from human-induced population declines make alarming symbols for the irreversible loss of our natural legacy worldwide. The grey wolf ( Canis lupus ) is an iconic example of extreme declines driven by anthropogenic factors. Here, we assessed the genetic signatures of 150 years of wolf persecution throughout the Western Palaearctic by high-throughput mitochondrial DNA sequencing of historical specimens in an unprecedented spatio-temporal framework. Despite Late Pleistocene bottlenecks, we show that historical genetic variation had remained high throughout Europe until the last several hundred years. In Western Europe, where wolves nearly got fully exterminated, diversity dramatically collapsed at the turn of the twentieth century and recolonization from few homogeneous relict populations induced drastic shifts of genetic composition. By contrast, little genetic displacement and steady levels of diversity were maintained in Eastern European regions, where human persecution had lesser effects on wolf demography. By comparing prehistoric, historic and modern patterns of genetic diversity, our study hence traces the timeframe and the active human role in the decline of the grey wolf, an emblematic yet controversial animal which symbolizes the complex relationship between human societies and nature conservation., (© 2018 The Author(s).)

Background/aim: Genomic signatures are needed for the determination of prognosis in patients with early stage, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. EndoPredict test is a RNA-based multigene assay that assesses the risk of 10-year relapse in this context. Quality assessment is a mandatory requirement for a laboratory to address the analytical quality of these molecular analyses. The aim of the study was to demonstrate the robustness of this prognostic test, its usefulness for the patient's treatment strategy, at the national level., Materials and Methods: This study presents a pilot quality assessment (QA) of the EndoPredict test using composite design, including the follow-up of internal control values (qREF) of the 12 genes of the assay for 151 independent tests and one formalin-fixed paraffin embedded (FFPE) breast cancer sample. The evaluation of the test was performed by comparing the results of six independent medical laboratories., Results: All measures were highly reproducible and quantification of the qREF showed a standard deviation of less than 0.50 and a coefficient of variation always of <2%. All laboratories found concordant results for the breast cancer samples. The mean EndoPredict (EP) score for the breast cancer sample was 4.97±0.24. The mean of EPclin score was 3.07±0.05., Conclusion: This first French independent reported QA assessed the robustness and reproducibility of the EndoPredict test. Such a simple composite design could represent an adapted QA for an expensive diagnostic test., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

An intraductal carcinoma, 55 mm across, was diagnosed on a total mastectomy in a 45-year-old woman. The 2 micro-invasive areas found were too small for reliable immunostainings for estrogen, progesterone, and HER2 receptors. In the sentinel lymph-node, a subcapsular tumor embole of about 50 cancer cells was identified on the extemporaneous cryo-cut section, but not on further sections after paraffin-embedding of the sample. Considering this tumor metastatic potential, we decided to assess HER2 status on the metastatic embole using pathological and molecular micro-methods. We laser-microdissected the tumor cells, extracted their DNA, and performed droplet-digital-PCR (ddPCR) for HER2 gene copy number variation. The HER2/RNaseP allele ratio was 5.2 in the laser-microdissected tumor cells, similar to the 5.3 ratio in the HER2-overexpressing breast cancer cell line BT-474. We thus optimized the adjuvant treatment of our patient and she received a trastuzumab-based adjuvant chemotherapy., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing interests.

Cancer cells often express differentiation programs unrelated to their tissue of origin, although the contribution of these aberrant phenotypes to malignancy is poorly understood. An aggressive subgroup of medulloblastoma, a malignant pediatric brain tumor of the cerebellum, expresses a photoreceptor differentiation program normally expressed in the retina. We establish that two photoreceptor-specific transcription factors, NRL and CRX, are master regulators of this program and are required for tumor maintenance in this subgroup. Beyond photoreceptor lineage genes, we identify BCL-XL as a key transcriptional target of NRL and provide evidence substantiating anti-BCL therapy as a rational treatment opportunity for select MB patients. Our results highlight the utility of studying aberrant differentiation programs in cancer and their potential as selective therapeutic vulnerabilities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

OBJECTIVE The goal of this study was to provide insight into the influence of gliomas on gestational outcomes, the impact of pregnancy on gliomas, and the identification of patients at risk. METHODS In this multiinstitutional retrospective study, the authors identified 52 pregnancies in 50 women diagnosed with a glioma. RESULTS For gliomas known prior to pregnancy (n = 24), we found the following: 1) An increase in the quantified imaging growth rates occurred during pregnancy in 87% of cases. 2) Clinical deterioration occurred in 38% of cases, with seizures alone resolving after delivery in 57.2% of cases. 3) Oncological treatments were immediately performed after delivery in 25% of cases. For gliomas diagnosed during pregnancy (n = 28), we demonstrated the following: 1) The tumor was discovered during the second and third trimesters in 29% and 54% of cases, respectively, with seizures being the presenting symptom in 68% of cases. 2) The quantified imaging growth rates did not significantly decrease after delivery and before oncological treatment. 3) Clinical deterioration resolved after delivery in 21.4% of cases. 4) Oncological treatments were immediately performed after delivery in 70% of cases. Gliomas with a high grade of malignancy, negative immunoexpression of alpha-internexin, or positive immunoexpression for p53 were more likely to be associated with tumor progression during pregnancy. Deliveries were all uneventful (cesarean section in 54.5% of cases and vaginal delivery in 45.5%), and the infants were developmentally normal. CONCLUSIONS When a woman harboring a glioma envisions a pregnancy, or when a glioma is discovered in a pregnant patient, the authors suggest informing her and her partner that pregnancy may impact the evolution of the glioma clinically and radiologically. They strongly advise a multidisciplinary approach to management. ■ CLASSIFICATION OF EVIDENCE Type of question: association; study design: case series; evidence: Class IV.

Juvenile xanthogranuloma (JXG) is a rare disease that belongs to the non-Langerhans cell histiocytoses. It presents a wide clinical spectrum, usually occurs before 5 years of age, and is commonly confined to the skin; however, it can affect multiple sites, including the nervous system, and can lead to severe disorders. Although JXG is a benign disease that usually regresses spontaneously, several curative treatments have been proposed in cases of organ involvement. Treatment options include corticosteroids, chemotherapy, and radiotherapy; however, these can have severe, long-term adverse effects in children. The authors here describe the first case of spontaneous resolution of an intramedullary spinal cord lesion of JXG associated with cerebral and cutaneous lesions in a young boy with 9 years of follow-up. The initial neurological symptoms resolved without any surgical or medical treatment. This case shows that extracutaneous lesions of JXG, including those with intramedullary spinal cord involvement, can regress without curative treatment-like cutaneous lesions-although both multidisciplinary care and close follow-up should be implemented.

Purpose: Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases., Results: Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases., Materials and Methods: Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series., Conclusions: The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

Background: Information is lacking on the dermal penetration of topically applied formulations on in vitro skin models, under conditions where the stratum corneum (SC) is damaged. Therefore, we have developed a standardized in vitro barrier-disrupted skin model using tape stripping., Methods: Different tape stripping conditions were evaluated using histology, transepidermal water loss, infrared densitometry, and caffeine absorption., Results: The effects of tape stripping were comparable using pig and human skin. Optimized conditions were used to test the effect of SC damage and UV irradiation on the absorption of an UV filter combination present in a sunscreen. The bioavailability of the filters was extremely low regardless of the extent of skin damage, suggesting bioavailability would not be increased if the consumer applied the sunscreen to sun-damaged skin., Conclusion: This standardized in vitro methodology using pig or human skin for damaged skin will add valuable information for the safety assessment of topically applied products., (© 2017 S. Karger AG, Basel.)

Objective: Pilot project focusing on the implementation and evaluation of a health education (HE) program for inmates of the prison of Ocaña I (Spain). The objective was to analyze the intentions for change in health habits and perceptions, and to assess whether the HE-program had differential effects depending on whether the participants belonged to the PAIEM or not and their socio-demographic characteristics., Methodology: The participants were 65 men, who answered an ad hoc questionnaire at the end of each session. Data analysis applied was univariate and bivariate (one-way ANOVA, t-test for Equality of Means and Chi-Square test)., Results: The average rating of the sessions was 3.51 out of 4 (SD = 0.62). The percentage of positive answers about the intention to adopt healthy habits was higher among non-PAIEM subjects (84.8%) than among those who were part of this program (57.9%). All subjects having a couple indicated an intention to change negative habits, compared to 67.3% for those without a couple. The percentage of subjects who said that their perception on the issue had changed was highest among those without education (89.7%) than among those with education (61.5%)., Conclusions: The evaluation of implanted HE-program implemented in the Ocaña I prison was very positive, there are differences between subjects belonging to the PAIEM and those who do not.

Objective: To establish the profile of elderly patients, and to assess current preventive actions in hospitals, geriatric residences, and different health-care centres in Spain., Design: Cross-sectional descriptive study, based on a questionnaire to be answered by doctors who treat the elderly population in Spain (2013)., Setting: Health-care centres from different regions of Spain., Participants: A total of 420 practitioners from hospitals, residences and other community centres, with data from 840 geriatric clinics., Main Measurements: Main outcome variables are: dependence, reason for assistance, comorbidity, professional consultation, and life style recommendations. Association factor, type of institution where patients have been attended. Analysis of prevalence and association using Chi-squared test., Outcomes: Two-thirds (66.7%) of the study population were shown to be dependent, with a higher percentage among women than men: 68.9% vs. 62.4% (P=.055). It was also found that among the population aged 85 or more, 88.6% of the women and 85.2% of the men suffered comorbidity. In spite of these results, only 6.6% of the patients suffering comorbidity received additional advice concerning healthy-lifestyle. A large majority (79.6%) of the patients treated in hospitals received advice concerning healthy lifestyle, while 59.62% of those treated in nursing homes received it (P<.001)., Conclusions: It was observed that there is a lack of preventive action related to health promotion among the elderly, with differences between hospitals and geriatric residences. This suggests that it is time to put forward new specialised programs addressed to health professionals, in order to reinforce health promotion attitudes and preventive interventions in gerontology clinical practice., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

The aim of this study was to better define the clinical and biopathological features of patients with desmoplastic/nodular medulloblastoma (DNMB) and to further characterize this subgroup. 17 children aged < 5 years, with initial DNMB treated according to the HIT-SKK protocol, were evaluated. A retrospective central radiological review, a pathological and immunohistochemical study, and array-CGH and sequencing of germline SUFU and PTCH1 genes were performed. 15 histologically reviewed cases were confirmed as DNMB including three cases of medulloblastoma with extensive nodularity. Median age at diagnosis was 26 months. Radiology showed five cases with a vermis location and one with T2 hyperintensity. All cases showed a SHH immunoprofile. A 9q deletion was found in 6 cases, a MYCN-MYCL amplification in 1 case, and a SUFU germline mutation in 1 case (/9). The presence of SUFU and PTCH1 germline mutations agreed with previous reports. At 3 years, progression-free survival and overallsurvival rates were 72 ± 15% and 85 ± 10%, respectively. The rate of recurrence was relatively high (4 patients). This may have been because chemotherapy was delayed in two cases. Age > 3 years, and residual tumor may also have been an explanation for recurrence.

The "niche variation hypothesis" (NVH) predicts that populations with wider niches should display higher among-individual variability. This prediction originally stated at the intra-specific level may be extended to the inter-specific level: individuals of generalist species may differ to a greater extent than individuals of a specialist species. We tested the NVH at intra- and inter-specific levels based on a large diet database of three large herbivore feces collected in the field and analyzed using DNA metabarcoding. The three herbivores (roe deer Capreolus capreolus, chamois Rupicapra rupicapra and mouflon Ovis musimon) are highly contrasted in terms of sociality (solitary to highly gregarious) and diet. The NVH at the intraspecific level was tested by relating, for the same population, diet breadth and inter-individual variation across the four seasons. Compared to null models, our data supported the NVH both at the intra- and inter-specific levels. Inter-individual variation of the diet of solitary species was not larger than in social species, although social individuals feed together and could therefore have more similar diets. Hence, the NVH better explained diet breadth than other factors such as sociality. The expansion of the population niche of the three species was driven by resource availability, and achieved by an increase in inter-individual variation, and the level of inter-individual variability was larger in the generalist species (mouflon) than in the specialist one (roe deer). This mechanism at the base of the NVH appears at play at different levels of biological organization, from populations to communities.

Background: Social inequality in health is an increasing phenomenon in the world. The aim was to compare in 2002 and 2012, the magnitude of inequalities in leisure-time physical inactivity by educational level in Spain, but also the trends in health perception, in physically inactive people., Methods: A cross-sectional study from the National Health Survey in Spain in 2002 (n=21,650) and 2012 (n=21,007). The population aged from 25 to 64 years. At the first stage, physical inactivity in leisure-time was the dependent variable, and educational level was the independent variable. At the second stage, self-perception of health in last 12 months was the dependent variable. Logistic regression was adjusted using other variables: age, marital status, employment status and social class of the head of the family., Results: Prevalence of leisure time physical inactivity was in 2012, up to 53.9% (men) and 67.5% (women), in the group aged between 25-44 with primary education. It declined in all age and sex groups in 2012, compared to 2002 (down to 18.7 percentage points). More than three times inactive women in between those who have primary or less education: OR 3.27 (2.35-4.55) in 2012. Bad health perceived in women with less educational level comparing with those with higher education. It also has declined over time: OR 1.45 in 2002 to OR 1.91, in 2012 (45-64 aged group)., Conclusions: Although the prevalence of physical inactivity has decreased, inequalities in such behavior have increased in 2012 respect 2002.

Objective: The DEPDC5 (DEP domain-containing protein 5) gene, encoding a repressor of the mTORC1 signaling pathway, has recently emerged as a major gene mutated in familial focal epilepsies. We aimed to further extend the role of DEPDC5 to focal cortical dysplasias (FCDs)., Methods: Seven patients from 4 families with DEPDC5 mutations and focal epilepsy associated with FCD were recruited and investigated at the clinical, neuroimaging, and histopathological levels. The DEPDC5 gene was sequenced from genomic blood and brain DNA., Results: All patients had drug-resistant focal epilepsy, 5 of them underwent surgery, and 1 had a brain biopsy. Electroclinical phenotypes were compatible with FCD II, although magnetic resonance imaging (MRI) was typical in only 4 cases. Histopathology confirmed FCD IIa in 2 patients (including 1 MRI-negative case) and showed FCD I in 2 other patients, and remained inconclusive in the last 2 patients. Three patients were seizure-free postsurgically, and 1 had a worthwhile improvement. Sequencing of blood DNA revealed truncating DEPDC5 mutations in all 4 families; 1 mutation was found to be mosaic in an asymptomatic father. A brain somatic DEPDC5 mutation was identified in 1 patient in addition to the germline mutation., Interpretation: Germline, germline mosaic, and brain somatic DEPDC5 mutations may cause epilepsy associated with FCD, reinforcing the link between mTORC1 pathway and FCDs. Similarly to other mTORopathies, a "2-hit" mutational model could be responsible for cortical lesions. Our study also indicates that epilepsy surgery is a valuable alternative in the treatment of drug-resistant DEPDC5-positive focal epilepsies, even if the MRI is unremarkable., (© 2015 American Neurological Association.)

Objective: To compare the magnitude of inequalities in the frequency of physical inactivity in Spain in 1987 and 2007, and assess whether the magnitude of inequality varies depending on the wealth of the area of residence., Design: Descriptive cross-sectional study, national scope., Participants: Data from the National Health Survey, 1987 and 2007, adult population between 25-64 years: 30,000 individuals (1987) and 29,478 (2006/7)., Main Measurements: Main outcomes variable, leisure-time physical inactivity; exposure factor, educational level. An analysis was made of the prevalence and association using odds ratio (OR). Adjustment for socioeconomic variables: age, marital status, employment status, social class of head of household, and household income., Results: Physical inactivity prevalence decreased in the two decades. There were more than three times more inactive males among those with primary education or less, compared to those with university studies. The magnitude of inequalities has increased in time: in a 45-64 years old man with primary school education: OR 2.43 (1.91-3.09) in 1987, to OR 2.77 (2.17-3.54) in 2007, adjusted for all socioeconomic variables., Conclusions: The prevalence of physical inactivity decreased between 1987 and 2007, and the largest decreases were in individuals with university studies. The gap in the differences in prevalence and OR of leisure-time physical inactivity has increased over time. It's necessary to contribute, with health education strategies and equity promotion are needed to help reduce the inequalities in risk behaviors., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)

Little is known about the genomic basis of primary central nervous system lymphoma (PCNSL) tumorigenesis. To investigate the mutational profile of PCNSL, we analyzed nine paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Eight genes of interest have been further investigated by focused resequencing in 28 additional PCNSL tumors to better estimate their incidence. Our study identified recurrent somatic mutations in 37 genes, some involved in key signaling pathways such as NFKB, B cell differentiation and cell cycle control. Focused resequencing in the larger cohort revealed high mutation rates for genes already described as mutated in PCNSL such as MYD88 (38%), CD79B (30%), PIM1 (22%) and TBL1XR1 (19%) and for genes not previously reported to be involved in PCNSL tumorigenesis such as ETV6 (16%), IRF4 (14%), IRF2BP2 (11%) and EBF1 (11%). Of note, only 3 somatically acquired SNVs were annotated in the COSMIC database. Our results demonstrate a high genetic heterogeneity of PCNSL and mutational pattern similarities with extracerebral diffuse large B cell lymphomas, particularly of the activated B-cell (ABC) subtype, suggesting shared underlying biological mechanisms. The present study provides new insights into the mutational profile of PCNSL and potential targets for therapeutic strategies.

Atypical teratoid/rhabdoid tumour is a rare and highly malignant tumour of the posterior fossae nervous system that occurs in children especially in the first few years of life. Cutaneous location is not previously reported. A newborn boy was referred for both aqueductal stenosis detected antenatally and skin tags mimicking hamartoma. The cerebral tumour increased in size during a few months leading to both skin and cerebral biopsies. Integrase Interactor-1 (INI-1) immunostaining and tumoural and leukocytes INI-1 gene sequencing confirmed the atypical teratoid/rhabdoid tumour nature of the cerebral tumour. INI-1 immunostaining in skin biopsy confirmed the dermal location of rhabdoid tumour. Thus, unusual cutaneous lesions may be part of atypical teratoid/rhabdoid tumour. The loss of Integrase INI-1 on immunohistochemical staining is characteristic.

Small ArfGAP1 (stromal membrane-associated protein 1, SMAP1), a GTPase-activating protein specific for ADP-ribosylation factor 6 (Arf6), which is a small GTPase acting on membrane trafficking and actin remodeling, is frequently mutated in various tumors displaying microsatellite instability (MSI), notably in MSI colorectal cancers (CRC). Genotyping of 93 MSI CRCs (40 stage II, 32 stage III and 21 stage IV) allowed us to underscore that SMAP1 mutation frequency was inversely correlated with disease stage (P=0.01). Analysis of 46 cancer cell lines showed that SMAP1 mutations occurred only in MSI tumors, and consisted exclusively in short insertion or deletion in the coding 10-adenine repeat, generating a premature termination codon located downstream the ArfGAP domain. SMAP1 transcript levels were significant decreased (P=0.006), and truncated SMAP1 protein could not be detected in cells displaying biallelic SMAP1 mutations, owing to its sensitivity to proteasome degradation. To investigate the role of SMAP1 mutations, we used the SMAP1-null HCT116 cell line and we established three isogenic SMAP1-complemented clones. Cell proliferation was first assessed in vivo using subcutaneous xenografts into immunodeficient mice. Tumors developed in all animals regardless of the cell line injected, but tumor volumes were significantly smaller for both SMAP1-complemented clones compared with HCT116 (P<0.0001, at the time of killing). In vitro, SMAP1 mutations also increased cell clonogenicity (P=0.02-0.04), cell proliferation (P=0.008) by shortening the G2/M phase and decreased cell invasiveness (P=0.03-0.003). In keeping, SMAP1-complemented HCT116 gained several mesenchymal markers (Snail, Slug and vimentin) considered as a hallmark of epithelial-to-mesenchymal transition. These observations are reminiscent of some clinical characteristics of MSI CRCs, notably their larger size and lower rate of metastasis. Our observations suggest that SMAP1 loss-of-function mutations in MSI CRC may contribute to the emerging oncogenic pathway involving abnormal Arf6 regulation.

Ecological understanding of the role of consumer-resource interactions in natural food webs is limited by the difficulty of accurately and efficiently determining the complex variety of food types animals have eaten in the field. We developed a method based on DNA metabarcoding multiplexing and next-generation sequencing to uncover different taxonomic groups of organisms from complex diet samples. We validated this approach on 91 faeces of a large omnivorous mammal, the brown bear, using DNA metabarcoding markers targeting the plant, vertebrate and invertebrate components of the diet. We included internal controls in the experiments and performed PCR replication for accuracy validation in postsequencing data analysis. Using our multiplexing strategy, we significantly simplified the experimental procedure and accurately and concurrently identified different prey DNA corresponding to the targeted taxonomic groups, with ≥ 60% of taxa of all diet components identified to genus/species level. The systematic application of internal controls and replication was a useful and simple way to evaluate the performance of our experimental procedure, standardize the selection of sequence filtering parameters for each marker data and validate the accuracy of the results. Our general approach can be adapted to the analysis of dietary samples of various predator species in different ecosystems, for a number of conservation and ecological applications entailing large-scale population level diet assessment through cost-effective screening of multiple DNA metabarcodes, and the detection of fine dietary variation among samples or individuals and of rare food items., (© 2013 John Wiley & Sons Ltd.)

Diagnosis of paediatric tumours of the central nervous system is often difficult because WHO classification criteria are mainly defined for adults tumours and do not always apply to their paediatric counterparts. These tumours are rare (400 cases/year among more than 50 pathological subtypes per year in France). Pathological diagnosis may be a challenge for a general pathologist with a too low number of paediatric cases in his recruitment. Hence, a reference group of paediatric neuropathologists was formed (GENOP) on the behalf of the comité "Tumeurs Cérébrales" de la Société Française de lutte contre les Cancers de l'Enfant. This network is supported by the Institut National du Cancer (INCa). GENOP aim is to structure a centralised review of paediatric central nervous system tumours in order to harmonise neuropathological diagnosis at the national level and enhance patients care. Cases assessed during the last 3 years led GENOP to better identify tumours subtypes for which there is a diagnostic challenge. A set of immunohistochemical or molecular specialised techniques was developed, leading to an increased diagnostic accuracy. It allowed a better distinction between diffuse and circumscribed glioma, a better recognition of glioneuronal differentiation and a better subtyping of embryonal tumours such as medulloblastomas. Inter-observer agreement varied according to the tumour subtypes., (Copyright © 2014. Published by Elsevier Masson SAS.)

Medulloblastomas (MB) are classified in four subgroups: the well defined WNT and Sonic Hedgehog (SHH) subgroups, and the less defined groups 3 and 4. They occasionally occur in the context of a cancer predisposition syndrome. While germline APC mutations predispose to WNT MB, germline mutations in SUFU, PTCH1, and TP53 predispose to SHH tumors. We report on a child with a Rubinstein-Taybi syndrome (RTS) due to a germline deletion in CREBBP, who developed a MB. Biological profilings demonstrate that this tumor belongs to the group 3. RTS may therefore be the first predisposition syndrome identified for non-WNT/non-SHH MB., (© 2013 Wiley Periodicals, Inc.)

Food preferences and food availability are two major determinants of the diet of generalist herbivores and of their spatial distribution. How do these factors interact and eventually lead to diet differentiation in co-occurring herbivores? We quantified the diet of four grasshopper species co-occurring in subalpine grasslands using DNA barcoding of the plants contained in the faeces of individuals sampled in the field. The food preferences of each grasshopper species were assessed by a choice (cafeteria) experiment from among 24 plant species common in five grassland plots, in which the four grasshoppers were collected, while the habitat was described by the relative abundance of plant species in the grassland plots. Plant species were characterised by their leaf economics spectrum (LES), quantifying their nutrient vs. structural tissue content. The grasshoppers' diet, described by the mean LES of the plants eaten, could be explained by their plant preferences but not by the available plants in their habitat. The diet differed significantly across four grasshopper species pairs out of six, which validates food preferences assessed in standardised conditions as indicators for diet partitioning in nature. In contrast, variation of the functional diversity (FD) for LES in the diet was mostly correlated to the FD of the available plants in the habitat, suggesting that diet mixing depends on the environment and is not an intrinsic property of the grasshopper species. This study sheds light on the mechanisms determining the feeding niche of herbivores, showing that food preferences influence niche position whereas habitat diversity affects niche breadth.

Background: Solitary fibrous tumors (SFTs) are rare spindle-cell tumors. Their cell-of-origin and molecular basis are poorly known. They raise several clinical problems. Differential diagnosis may be difficult, prognosis is poorly apprehended by histoclinical features, and no effective therapy exists for advanced stages., Methods: We profiled 16 SFT samples using whole-genome DNA microarrays and analyzed their expression profiles with publicly available profiles of 36 additional SFTs and 212 soft tissue sarcomas (STSs). Immunohistochemistry was applied to validate the expression of some discriminating genes., Results: SFTs displayed whole-genome expression profiles more homogeneous and different from STSs, but closer to genetically-simple than genetically-complex STSs. The SFTs/STSs comparison identified a high percentage (∼30%) of genes as differentially expressed, most of them without any DNA copy number alteration. One of the genes most overexpressed in SFTs encoded the ALDH1 stem cell marker. Several upregulated genes and associated ontologies were also related to progenitor/stem cells. SFTs also overexpressed genes encoding therapeutic targets such as kinases (EGFR, ERBB2, FGFR1, JAK2), histone deacetylases, or retinoic acid receptors. Their overexpression was found in all SFTs, regardless the anatomical location. Finally, we identified a 31-gene signature associated with the mitotic count, containing many genes related to cell cycle/mitosis, including AURKA., Conclusion: We established a robust repertoire of genes differentially expressed in SFTs. Certain overexpressed genes could provide new diagnostic (ALDH1A1), prognostic (AURKA) and/or therapeutic targets.

Background: Solitary Fibrous Tumours (SFT) and haemangiopericytomas (HPC) are rare meningeal tumours that have to be distinguished from meningiomas and more rarely from synovial sarcomas. We recently found that ALDH1A1 was overexpressed in SFT and HPC as compared to soft tissue sarcomas. Using whole-genome DNA microarrays, we defined the gene expression profiles of 16 SFT/HPC (9 HPC and 7 SFT). Expression profiles were compared to publicly available expression profiles of additional SFT or HPC, meningiomas and synovial sarcomas. We also performed an immunohistochemical (IHC) study with anti-ALDH1 and anti-CD34 antibodies on Tissue Micro-Arrays including 38 SFT (25 meningeal and 13 extrameningeal), 55 meningeal haemangiopericytomas (24 grade II, 31 grade III), 163 meningiomas (86 grade I, 62 grade II, 15 grade III) and 98 genetically confirmed synovial sarcomas., Results: ALDH1A1 gene was overexpressed in SFT/HPC, as compared to meningiomas and synovial sarcomas. These findings were confirmed at the protein level. 84% of the SFT and 85.4% of the HPC were positive with anti-ALDH1 antibody, while only 7.1% of synovial sarcomas and 1.2% of meningiomas showed consistent expression. Positivity was usually more diffuse in SFT/HPC compared to other tumours with more than 50% of tumour cells immunostained in 32% of SFT and 50.8% of HPC. ALDH1 was a sensitive and specific marker for the diagnosis of SFT (SE = 84%, SP = 98.8%) and HPC (SE = 84.5%, SP = 98.7%) of the meninges. In association with CD34, ALDH1 expression had a specificity and positive predictive value of 100%., Conclusion: We show that ALDH1, a stem cell marker, is an accurate diagnostic marker for SFT and HPC, which improves the diagnostic value of CD34. ALDH1 could also be a new therapeutic target for these tumours which are not sensitive to conventional chemotherapy.

As prognostic factors, MYC and MYCN amplifications are routinely assessed in medulloblastomas. Fluorescence in situ hybridization (FISH) is currently considered as the technique of reference. Recently, array comparative genomic hybridization (aCGH) has been developed as an alternative technique to evaluate genomic abnormalities in other tumor types; however, this technique has not been widely adopted as a replacement for FISH in medulloblastoma. In this study, 34 tumors were screened by both FISH and aCGH. In all cases showing amplification by FISH, aCGH also unambiguously revealed the abnormality. The aCGH technique was also performed on tumors showing no amplification by FISH, and the absence of amplification was confirmed in all cases. Interestingly, one tumor showed a subclonal MYC amplification by FISH. This subclonal amplification was observed in approximately 20% of tumor cells and was clearly evident on aCGH. In conclusion, our analysis confirms that aCGH is as safe as FISH for the detection of MYC/MYCN gene amplification. Given its cost efficiency in comparison to two FISH tests and the global genomic information additionally provided by an aCGH experiment, this reproducible technique can be safely retained as an alternative to FISH for routine investigation of medulloblastoma., (Copyright © 2013 Elsevier Inc. All rights reserved.)