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Introduction: Esophageal inflammatory diseases are frequent diagnoses in clinical practice and have diverse etiologies, the most common being those associated with the exposure to gastric content, drugs and allergens. In diseases, the immunological component is well identified in endoscopic biopsies, which mainly contain the epithelium and the lamina propria; however, deeper layers are less studied. Moreover, the esophageal capacity of sensing luminal compounds is poorly understood. Methods: In transmural sections from proximal, middle and distal esophagus obtained from deceased patients, we performed a phenotypic analysis of the main immune cell populations and acid-sensing receptors by immunohistochemistry and immunofluorescence methods. Results: A total of nine donors were studied (absence of pathology, optimal tissue preservation and orientation). We found the following: (1) the vascular papillae and the lamina propria are the most infiltrated layers by the lymphoid lineage (T and B lymphocytes), followed by the epithelium, while the smooth muscular layers are mainly populated by the myeloid lineage (macrophages and mast cells); (2) intraepithelial macrophages are consistently found along the esophagus; and (3) eosinophils are absent in all the esophageal layers. The acid-sensing receptors ASIC-1, ASIC-2 and δENAC are expressed in the esophageal epithelium and in the lamina propria, yet only ASIC-2 is expressed in the muscularis mucosae. Conclusions: The human esophagus contains a differential distribution of immune cells and acid-sensing receptors across its layers. This study extends the esophageal histological knowledge previously described and reinforces its role as a defensive and sensing organ.

Abstract Background Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a genetic rare disease characterized by recurrent, transient and unpredictable episodes of cold, non-pruriginous oedema without associated urticaria. The characteristics of the disease have a considerable impact on the quality of life of patients. The aim of this study was to increase understanding of the patient journey of HAE in Spain. Methods A multidisciplinary committee of 16 HAE experts (allergy, immunology, emergency department, hospital pharmacy and nursing) and 3 representatives of the Spanish Hereditary Angioedema Patient Association (AEDAF) who were patients or caregivers participated in the study. A review of the publications on HAE treatment was performed. Semi-structured interviews were performed to HAE experts, patients, or caregivers. Three meetings with the experts, patients and caregivers were held to share, discuss, and validate data obtained from literature and interviews and to build the model. Results Throughout the project, the patient journey has been drawn up, dividing it into the stages of pre-diagnosis, diagnosis and treatment/follow-up. Some areas for improvement have been identified. Firstly, there is a need to enhance awareness and training on HAE among healthcare professionals, with a particular emphasis on primary care and emergency department personnel. Secondly, efforts should be made to minimize patient referral times to allergy/immunology specialists, ensuring timely access to appropriate care. Thirdly, it is crucial to encourage the study of the relatives of diagnosed patients to early identify potential cases. Fourthly, equitable access to self-administered treatments should be ensured, facilitated by systems that enable medication delivery at home and proper education and training for patients. Equitable access to long-term prophylactic treatment should also be prioritized for all patients in need. To standardize HAE management, the development of consensus guidelines that reduce variability in clinical practice is essential. Lastly, promoting research studies to enhance knowledge of the disease and align its treatment with new developments in the healthcare field should be encouraged. Conclusions The knowledge of the patient journey in HAE allowed us to identify improvement areas with the final aim to optimize the disease management.

A 24/7 AI sound-based coughing monitoring system was applied in combination with oral fluids (OFs) and bioaerosol (AS)-based screening for respiratory pathogens in a conventional pig nursery. The objective was to assess the additional value of the AI to identify disease patterns in association with molecular diagnostics to gain information on the etiology of respiratory distress in a multimicrobially infected pig population. Respiratory distress was measured 24/7 by the AI and compared to human observations. Screening for swine influenza A virus (swIAV), porcine reproductive and respiratory disease virus (PRRSV), Mycoplasma (M.) hyopneumoniae, Actinobacillus (A.) pleuropneumoniae, and porcine circovirus 2 (PCV2) was conducted using qPCR. Except for M. hyopneumoniae, all of the investigated pathogens were detected within the study period. High swIAV-RNA loads in OFs and AS were significantly associated with a decrease in respiratory health, expressed by a respiratory health score calculated by the AI The odds of detecting PRRSV or A. pleuropneumoniae were significantly higher for OFs compared to AS. qPCR examinations of OFs revealed significantly lower Ct-values for swIAV and A. pleuropneumoniae compared to AS. In addition to acting as an early warning system, AI gained respiratory health data combined with laboratory diagnostics, can indicate the etiology of respiratory distress.

The International Consensus Classification of Myeloid Neoplasms and Acute Leukemias (ICC) and the 5th edition of the WHO classification (WHO 2022) have refined the diagnosis of myelodysplastic syndromes (MDS). Both classifications segregate MDS subtypes based on molecular or cytogenetic findings but rely on the subjective assessment of blast cell percentage and dysplasia in hematopoietic cell lineages. This study aimed to evaluate interobserver concordance among 13 cytomorphologists from eight hospitals in assessing blast percentages and dysplastic features in 44 MDS patients. The study found fair interobserver agreement for the PB blast percentage and moderate agreement for the BM blast percentage, with the best concordance in cases with 10% BM blasts. Monocyte count agreement was fair, and dysplasia assessment showed moderate concordance for megakaryocytic lineage but lower concordance for erythroid and granulocytic lineages. Overall, interobserver concordance for MDS subtypes was moderate across all classifications, with slightly better results for WHO 2022. These findings highlight the ongoing need for morphological evaluation in MDS diagnosis despite advances in genetic and molecular techniques. The study supports the blast percentage ranges established by the ICC but suggests refining BM blast cutoffs. Given the moderate interobserver concordance, a unified classification approach for MDS is recommended.

IntroductionIn primates, including humans, the centromedian/parafascicular (CM-Pf) complex is a key thalamic node of the basal ganglia system. Deep brain stimulation in CM-Pf has been applied for the treatment of motor disorders such as Parkinson’s disease or Tourette syndrome. Rodents have become widely used models for the study of the cellular and genetic mechanisms of these and other motor disorders. However, the equivalence between the primate CM-Pf and the nucleus regarded as analogous in rodents (Parafascicular, Pf) remains unclear.MethodsHere, we analyzed the neurochemical architecture and carried out a brain-wide mapping of the input–output motifs in the mouse Pf at micropopulation level using anterograde and retrograde labeling methods. Specifically, we mapped and quantified the sources of cortical and subcortical input to different Pf subregions, and mapped and compared the distribution and terminal structure of their axons.ResultsWe found that projections to Pf arise predominantly (>75%) from the cerebral cortex, with an unusually strong (>45%) Layer 5b component, which is, in part, contralateral. The intermediate layers of the superior colliculus are the main subcortical input source to Pf. On its output side, Pf neuron axons predominantly innervate the striatum. In a sparser fashion, they innervate other basal ganglia nuclei, including the subthalamic nucleus (STN), and the cerebral cortex. Differences are evident between the lateral and medial portions of Pf, both in chemoarchitecture and in connectivity. Lateral Pf axons innervate territories of the striatum, STN and cortex involved in the sensorimotor control of different parts of the contralateral hemibody. In contrast, the mediodorsal portion of Pf innervates oculomotor-limbic territories in the above three structures.DiscussionOur data thus indicate that the mouse Pf consists of several neurochemically and connectively distinct domains whose global organization bears a marked similarity to that described in the primate CM-Pf complex.

Abstract Background Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. Methods We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. Results IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. Conclusions These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.

Characterizing the connectomic and morphological diversity of thalamic neurons is key for better understanding how the thalamus relays sensory inputs to the cortex. The recent public release of complete single-neuron morphological reconstructions enables the analysis of previously inaccessible connectivity patterns from individual neurons. Here we focus on the Ventral Posteromedial (VPM) nucleus and characterize the full diversity of 257 VPM neurons, obtained by combining data from the MouseLight and Braintell projects. Neurons were clustered according to their most dominantly targeted cortical area and further subdivided by their jointly targeted areas. We obtained a 2D embedding of morphological diversity using the dissimilarity between all pairs of axonal trees. The curved shape of the embedding allowed us to characterize neurons by a 1-dimensional coordinate. The coordinate values were aligned both with the progression of soma position along the dorsal-ventral and lateral-medial axes and with that of axonal terminals along the posterior-anterior and medial-lateral axes, as well as with an increase in the number of branching points, distance from soma and branching width. Taken together, we have developed a novel workflow for linking three challenging aspects of connectomics, namely the topography, higher order connectivity patterns and morphological diversity, with VPM as a test-case. The workflow is linked to a unified access portal that contains the morphologies and integrated with 2D cortical flatmap and subcortical visualization tools. The workflow and resulting processed data have been made available in Python, and can thus be used for modeling and experimentally validating new hypotheses on thalamocortical connectivity.

The thalamus is a central link between cortical and subcortical brain motor systems. Axons from the deep nuclei of the cerebellum (DCN), or the output nuclei of the basal ganglia system (substantia nigra reticulata, SNr; and internal pallidum GPi/ENT) monosynaptically innervate the thalamus, prominently some nuclei of the ventral nuclear group. In turn, axons from these ventral nuclei innervate the motor and premotor areas of the cortex, where their input is critical for planning, execution and learning of rapid and precise movements. Mice have in recent years become a widely used model in motor system research. However, information on the distribution of cerebellar and basal ganglia inputs in the rodent thalamus remains poorly defined. Here, we mapped the distribution of inputs from DCN, SNr, and GPi/ENT to the ventral nuclei of the mouse thalamus. Immunolabeling for glutamatergic and GABAergic neurotransmission markers delineated two distinct main territories, characterized each by the presence of large vesicular glutamate transporter type 2 (vGLUT2) puncta or vesicular GABA transporter (vGAT) puncta. Anterograde labeling of axons from DCN revealed that they reach virtually all parts of the ventral nuclei, albeit its axonal varicosities (putative boutons) in the vGAT-rich sector are consistently smaller than those in the vGLUT2-rich sector. In contrast, the SNr axons innervate the whole vGAT-rich sector, but not the vGLUT2-rich sector. The GPi/ENT axons were found to innervate only a small zone of the vGAT-rich sector which is also targeted by the other two input systems. Because inputs fundamentally define thalamic cell functioning, we propose a new delineation of the mouse ventral motor nuclei that is consistent with the distribution of DCN, SNr and GPi/ENT inputs and resembles the general layout of the ventral motor nuclei in primates.

The non-destructive thermal characterization of building envelopes relies significantly on various factors such as climate conditions, monitoring devices used, indoor environment, and conditioning systems. In the case of both the temperature-based method (TBM) and heat flux meter (HFM) approaches, U-value is determined considering the ideal condition of steady state. However, it is challenging to accurately define the true thermal condition of buildings when monitoring is affected by inherent uncertainties of the chosen approach and inadequate instrumentation of building envelopes. This paper presents the outcomes of an experimental campaign, that aimed to evaluate the impact of incorrectly positioned exterior sensors, on the precision of U-value measurements. This study simultaneously employed the TBM and HFM approaches. To enhance the accuracy of the results, rigorous outlier detection and statistical analysis were employed on the data collected from three autonomous monitoring systems. The findings of this study revealed that the applied data analysis yielded more satisfactory results for the TBM approach compared to HFM. However, regardless of the approach used, the effectiveness of outlier detection relied heavily on the accuracy of the monitoring systems. When removing an individual outlier, the monitoring systems characterized with higher accuracies provided U-values that were closer to the theoretical values, than less accurate ones.

The research conducted under HABITA-RES explored the advisability of the integrative refurbishment of urban neighbourhoods on the outskirts of Madrid built between the end of the Civil War in 1939 and the enactment of the country’s first building code on the indoor environment in 1979. Characterised by highly inefficient buildings, many such neighbourhoods are listed as vulnerable urban areas. The study described hereunder analysed the feasibility of their conversion to energy self-sufficiency to improve residents’ environment, social circumstances and health. European directives and domestic legislation on energy production are introducing increasingly demanding requirements geared to achieving nearly zero energy buildings in 2020 and cities’ carbon neutrality by target year 2050. Possible approaches to achieve those ends were assessed under this study. The theoretical model used was validated with detailed information collected in situ on both social circumstances and energy efficiency. Designed to study improvement strategies for both individual and groups of buildings, the model prioritises passive improvements to lower demand. The findings will enable residents in such neighbourhoods to participate actively in improvement measures and access information on their costs and benefits.

Abstract Background Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax). Methods Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real‐life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020. Results Severe infections incidence was 23% during 17‐month median follow‐up; cumulative incidence was higher in the first 3–6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3–1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1–4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05–3.3). Infection‐related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed. Conclusion A high proportion of patients presented severe infections during follow‐up, with non‐negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered.

El confort térmico y la calidad del aire en los centros docentes son dos parámetros que deben ser estudiados en profundidad. Tienen consecuencias en la salud de las personas cuyo cuerpo está en desarrollo y en los resultados de aprendizaje que se obtienen en los espacios educativos. En este trabajo se toman datos de concentración de CO2 y temperatura en un total de ocho aulas que pertenecen a tres centros docentes públicos durante un año con el objetivo de analizar la situación, determinar las causas que influyen en los aspectos mencionados y ofrecer medidas para corregir las desviaciones registradas y mejorar la calidad del ambiente interior en las aulas. Los datos obtenidos muestran que durante un tercio del tiempo lectivo las concentraciones de CO2 superan los valores límite establecidos y que durante más de dos tercios del tiempo lectivo los valores de temperatura se encuentran fuera de la zona de confort.

BackgroundRadiation-induced late effects are a common cause of morbidity among cancer survivors. The biomarker with the best evidence as a predictive test of late reactions is the radiation-induced lymphocyte apoptosis (RILA) assay. We aimed to investigate the molecular basis underlying the distinctive RILA levels by using gene expression analysis in patients with and without late effects and in whom we had also first identified differences in RILA levels.Patients and MethodsPeripheral blood mononuclear cells of 10 patients with late severe skin complications and 10 patients without symptoms, selected from those receiving radiotherapy from 1993 to 2007, were mock-irradiated or irradiated with 8 Gy. The 48-h response was analyzed in parallel by RILA assay and gene expression profiling with Affymetrix microarrays. Irradiated and non-irradiated gene expression profiles were compared between both groups. Gene set enrichment analysis was performed to identify differentially expressed biological processes.ResultsAlthough differentially expressed mRNAs did not reach a significant adjusted p-value between patients suffering and not suffering clinical toxicity, the enriched pathways indicated significant differences between the two groups, either in irradiated or non-irradiated cells. In basal conditions, the main differentially expressed pathways between the toxicity and non-toxicity groups were the transport of small molecules, interferon signaling, and transcription. After 8 Gy, the differences lay in pathways highly related to cell senescence like cell cycle/NF-κB, G-protein-coupled receptors, and interferon signaling.ConclusionPatients at risk of developing late toxicity have a distinctive pathway signature driven by deregulation of immune and cell cycle pathways related to senescence, which in turn may underlie their low RILA phenotype.

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder linked to intestinal barrier dysfunction and life stress. We have previously reported that female sex per se determines an increased susceptibility to intestinal barrier dysfunction after cold pain stress (CPS). We aimed to identify sex-related molecular differences in response to CPS in healthy subjects to understand the origin of sex bias predominance in IBS. In 13 healthy males and 21 females, two consecutive jejunal biopsies were obtained using Watson’s capsule, at baseline, and ninety minutes after CPS. Total mucosal RNA and protein were isolated from jejunal biopsies. Expression of genes related to epithelial barrier (CLDN1, CLDN2, OCLN, ZO-1, and ZO-3), mast cell (MC) activation (TPSAB1, SERPINA1), and the glucocorticoid receptor (NR3C1) were analyzed using RT-qPCR. NR3C1, ZO-1 and OCLN protein expression were evaluated through immunohistochemistry and western blot, and mucosal inflammation through MC, lymphocyte, and eosinophil numbering. Autonomic, hormonal, and psychological responses to CPS were monitored. We found an increase in jejunal MCs, a reduced CLDN1 and OCLN expression, and an increased CLDN2 and SERPINA1 expression 90 min after CPS. We also found a significant decrease in ZO-1, OCLN, and NR3C1 gene expression, and a decrease in OCLN protein expression only in females, when compared to males. CPS induced a significant increase in blood pressure, plasma cortisol and ACTH, and subjective stress perception in all participants. Specific and independent sex-related molecular responses in epithelial barrier regulation are unraveled by acute stress in the jejunum of healthy subjects and may partially explain female predominance in IBS.

There is converging and increasing evidence, but also uncertainty, for the role of abnormal intestinal epithelial barrier function in the origin and development of a growing number of human gastrointestinal and extraintestinal inflammatory disorders, and their related complaints. Despite a vast literature addressing factors and mechanisms underlying changes in intestinal permeability in humans, and its connection to the appearance and severity of clinical symptoms, the ultimate link remains to be established in many cases. Accordingly, there are no directives or clinical guidelines related to the therapeutic management of intestinal permeability disorders that allow health professionals involved in the management of these patients to carry out a consensus treatment based on clinical evidence. Instead, there are multiple pseudoscientific approaches and commercial propaganda scattered on the internet that confuse those affected and health professionals and that often lack scientific rigor. Therefore, in this review we aim to shed light on the different therapeutic options, which include, among others, dietary management, nutraceuticals and medical devices, microbiota and drugs, and epigenetic and exosomes-manipulation, through an objective evaluation of the scientific publications in this field. Advances in the knowledge and management of intestinal permeability will sure enable better options of dealing with this group of common disorders to enhance quality of life of those affected.

Unaddressed occupational stress and trauma contribute to elevated rates of mental illness and suicide in policing, and to violent and aggressive behavior that disproportionately impacts communities of color. Emerging evidence suggests mindfulness training with police may reduce stress and aggression and improve mental health, but there is limited evidence for changes in biological outcomes or the lasting benefits of mindfulness training. We conducted a randomized controlled trial (RCT) of 114 police officers from three Midwestern U.S. law enforcement agencies. We assessed stress-related physical and mental health symptoms, blood-based inflammatory markers, and hair and salivary cortisol. Participants were then randomized to an 8-week mindfulness intervention or waitlist control (WLC), and the same assessments were repeated post-intervention and at 3-month follow-up. Relative to waitlist control, the mindfulness group had greater improvements in psychological distress, mental health symptoms, and sleep quality post-training, gains that were maintained at 3-month follow-up. Intervention participants also had a significantly lower cortisol awakening response (CAR) at 3-month follow-up relative to waitlist control. Contrary to hypotheses, there were no intervention effects on hair cortisol, diurnal cortisol slope, or inflammatory markers. In summary, an 8-week mindfulness intervention for police officers led to self-reported improvements in distress, mental health, and sleep, and a lower CAR. These benefits persisted (or emerged) at 3-month follow-up, suggesting that this training may buffer against the long-term consequences of chronic stress. Future research should assess the persistence of these benefits over a longer period while expanding the scope of outcomes to consider the broader community of mindfulness training for police.Clinical Trial Registration: ClinicalTrials.gov#NCT03488875.

The research focuses on the interoperability of Building Information Modeling (BIM) and Building Performance Simulation (BPS) using Revit2015 software. for BIM and Design Builder software for BPS Information and data exchange between BIM and BPS is explored. The reasons and criteria for the use of each methodology according to the selected project is addressed, explaining the benefits of using each tool. The analysis is presented for a case study of an existing building in Madrid Resumen La investigación se centra en la interoperabilidad de Building Information Modeling (BIM) y Building Performance Simulation (BPS) usando como software para cada caso Revit2015 para BIM y DesignBuilder para BPS. Se analiza el intercambio de datos entre BIM y BPS. Además se exponen las razones y criterios para la utilización de esta metodología según el proyecto seleccionado, y las prestaciones se tiene con la utilización de cada herramienta. El análisis se presenta a través de caso de estudio con una edificación existente de Madrid.

The optical response of opaque materials in an urban envelope plays an important role in a city’s energy exchange with the environment as it defines the absorption of radiation and emission of heat. In the present work, the most common surfaces of the finishing materials of pavement and walls in the city of Madrid (Spain) were identified, and their reflectance was measured in situ to determine their solar absorptance and color coordinates. Most of the selected pavement showed a relatively high solar absorptance in the range of 0.87 to 0.60, while in vertical surfaces, the range was 0.85 to 0.29. The variations of the color coordinates obtained for pavement were 27.1, 11.4, and 6.7 for ΔL*, Δa*, and Δb*, respectively. Significantly higher values were obtained in the case of vertical surfaces (47.5, 20.5, and 23.6, respectively). The results were included into a database intended to be the seed for a catalogue of the experimental thermo-optical properties of opaque envelope materials in Madrid. The catalogue will be useful for the analysis of the stimuli generated by the urban environment for citizens and for achieving more reliable results from energy simulation tools in the search for strategies to improve urban comfort and sustainability.

Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.

According to current guidelines, in chronic lymphocytic leukemia (CLL), only the TP53 molecular status must be evaluated prior to every treatment’s initiation. However, additional heterogeneous genetic events are known to confer a proliferative advantage to the tumor clone and are associated with progression and treatment failure in CLL patients. Here, we describe the implementation of a comprehensive targeted sequencing solution that is suitable for routine clinical practice and allows for the detection of the most common somatic single-nucleotide and copy number variants in genes relevant to CLL. We demonstrate that this cost-effective strategy achieves variant detection with high accuracy, specificity, and sensitivity. Furthermore, we identify somatic variants and copy number variations in genes with prognostic and/or predictive value, according to the most recent literature, and the tool provides evidence about subclonal events. This next-generation sequencing (NGS) capture-based target assay is an improvement on current approaches in defining molecular prognostic and/or predictive variables in CLL patients.

Resumen: La esofagitis eosinofílica es una enfermedad emergente, crónica, mediada por el sistema inmune y caracterizada por síntomas de disfunción esofágica e inflamación con infiltración eosinofílica aislada en el esófago. Es más frecuente en varones y en sujetos atópicos y los síntomas varían con la edad: en niños pequeños se manifiesta con vómitos, dolor abdominal y problemas con la alimentación y en niños mayores y adolescentes con disfagia e impactación alimentaria. El diagnóstico se basa en la presencia de síntomas e inflamación esofágica con ≥ 15 eosinófilos/campo de gran aumento, tras descartar otras causas de eosinofilia esofágica. Sin tratamiento, la enfermedad suele persistir y puede evolucionar a formas fibroestenóticas más frecuentes en el adulto. Las opciones terapéuticas incluyen inhibidores de la bomba de protones, dieta de eliminación empírica y corticoides deglutidos. Tras el tratamiento de inducción es aconsejable la terapia de mantenimiento. La dieta es el único tratamiento que se dirige a la causa de la enfermedad, al identificar los alimentos desencadenantes. La respuesta a los tratamientos requiere la evaluación histológica, por la escasa concordancia entre los síntomas y la inflamación esofágica.El manejo práctico de la esofagitis eosinofílica presenta desafíos debido, entre otras causas, a la falta de disponibilidad actual de fármacos específicos y a su abordaje con tratamientos dietéticos, en ocasiones, complejos. El presente documento, elaborado por el Grupo de Trabajo de Trastornos Gastrointestinales Eosinofílicos de la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátricas, tiene como objetivo facilitar el abordaje diagnóstico y terapéutico de la esofagitis eosinofílica pediátrica, con base en las recientes guías de consenso basadas en la evidencia. Abstract: Eosinophilic oesophagitis is an emerging and chronic disorder mediated by the immune system, and is characterised by symptoms of oesophageal dysfunction and inflammation with isolated eosinophil infiltration in the oesophagus. It is more common in males and in atopic subjects, and the symptoms vary with age. In younger children, there is vomiting, abdominal pain and dietary problems, with dysphagia and food impaction in older children and adolescents. The diagnosis is based on the presence of symptoms and oesophageal inflammation with ≥ 15 eosinophils / high power field, and after ruling out other causes of oesophageal eosinophilia. Without treatment, the disease usually persists and can progress to fibrostenotic forms more common in adults. The treatment options included proton pump inhibitors, empirical elimination diets, and swallowed topical corticosteroids. Maintenance therapy is advisable after the induction treatment. Diet is the only treatment that is directed at the cause of the disease, on identifying the triggering food or foods. The response to the treatments requires a histological assessment due to the poor agreement between the symptoms and the oesophageal inflammation.The practical management of Eosinophilic oesophagitis presents with challenges, due to, among other causes, the current lack of availability of specific drugs, and to its approach with, occasionally complex, diet treatments. The present document, prepared by the Working Group on Eosinophilic Gastrointestinal Disorders of the Spanish Society of Paediatric Gastroenterology, Hepatology and Nutrition, has as its objective to help in the diagnostic and therapeutic approach to paediatric eosinophilic oesophagitis, based on the recent evidence-based consensus guidelines.

Eosinophilic oesophagitis is an emerging and chronic disorder mediated by the immune system, and is characterised by symptoms of oesophageal dysfunction and inflammation with isolated eosinophil infiltration in the oesophagus. It is more common in males and in atopic subjects, and the symptoms vary with age. In younger children, there is vomiting, abdominal pain and dietary problems, with dysphagia and food impaction in older children and adolescents. The diagnosis is based on the presence of symptoms and oesophageal inflammation with ≥15 eosinophils/high power field, and after ruling out other causes of oesophageal eosinophilia. Without treatment, the disease usually persists and can progress to fibrostenotic forms more common in adults. The treatment options included proton pump inhibitors, empirical elimination diets, and swallowed topical corticosteroids. Maintenance therapy is advisable after the induction treatment. Diet is the only treatment that is directed at the cause of the disease, on identifying the triggering food or foods. The response to the treatments requires a histological assessment due to the poor agreement between the symptoms and the oesophageal inflammation.The practical management of Eosinophilic oesophagitis presents with challenges, due to, among other causes, the current lack of availability of specific drugs, and its approach with, occasionally complex, diet treatments. The present document, prepared by the Working Group on Eosinophilic Gastrointestinal Disorders of the Spanish Society of Paediatric Gastroenterology, Hepatology and Nutrition, has as its objective to help in the diagnostic and therapeutic approach to paediatric eosinophilic oesophagitis, based on the recent evidence-based consensus guidelines. Resumen: La esofagitis eosinofílica es una enfermedad emergente, crónica, mediada por el sistema inmune y caracterizada por síntomas de disfunción esofágica e inflamación con infiltración eosinofílica aislada en el esófago. Es más frecuente en varones y en sujetos atópicos y los síntomas varían con la edad: en niños pequeños se manifiesta con vómitos, dolor abdominal y problemas con la alimentación y en niños mayores y adolescentes con disfagia e impactación alimentaria. El diagnóstico se basa en la presencia de síntomas e inflamación esofágica con ≥ 15 eosinófilos/campo de gran aumento, tras descartar otras causas de eosinofilia esofágica. Sin tratamiento, la enfermedad suele persistir y puede evolucionar a formas fibroestenóticas más frecuentes en el adulto. Las opciones terapéuticas incluyen inhibidores de la bomba de protones, dieta de eliminación empírica y corticoides deglutidos. Tras el tratamiento de inducción es aconsejable la terapia de mantenimiento. La dieta es el único tratamiento que se dirige a la causa de la enfermedad, al identificar los alimentos desencadenantes. La respuesta a los tratamientos requiere la evaluación histológica, por la escasa concordancia entre los síntomas y la inflamación esofágica.El manejo práctico de la esofagitis eosinofílica presenta desafíos debido, entre otras causas, a la falta de disponibilidad actual de fármacos específicos y a su abordaje con tratamientos dietéticos, en ocasiones, complejos. El presente documento, elaborado por el Grupo de Trabajo de Trastornos Gastrointestinales Eosinofílicos de la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátricas, tiene como objetivo facilitar el abordaje diagnóstico y terapéutico de la esofagitis eosinofílica pediátrica, con base en las recientes guías de consenso basadas en la evidencia.

Fundamento: La asignatura Atención Integral a la Población, se imparte durante el quinto año de la carrera de Estomatología. Objetivo: Exponer los criterios de los estudiantes, egresados y profesores respecto al proceso docente educativo de la asignatura Atención Integral a la Población. Métodos: Se realizó una investigación educacional observacional-descriptiva transversal en la Facultad de Estomatología de la Universidad de Ciencias Médicas de Camagüey, desarrollada desde septiembre 2015 a octubre 2017. El universo estuvo constituido por 63 estudiantes del quinto año, 90 egresados del curso 2015-2016 y 14 profesores. Fueron utilizados métodos de investigación educacional cualitativos. Resultados: Los estudiantes, en la totalidad, percibieron que la asignatura influye en su formación como futuro profesional de la Estomatología, refirieron sentirse desorientados en cuestiones referidas a la distribución de contenidos, mientras que los profesores reconocieron la necesidad de determinar los temas, objetivos, sistema de conocimientos y habilidades para lograr una uniformidad en el trabajo sistemático y la evaluación frecuente en las diferentes sedes universitarias, los estudiantes carecen de una guía para realizar el estudio independiente; con vistas al examen final de la asignatura y estatal que contenga un plan de temas organizados y reúna los conocimientos esenciales a estudiar. Conclusiones: El diagnóstico develó que los estudiantes, egresados y profesores coincidieron en la necesidad de la consolidación de conocimientos, adquisición de habilidades y la interdisciplinariedad, así como la orientación del estudio independiente para el examen final de la asignatura y estatal.

The scope of this work lies in analyzing the bundle of rights, prerogatives, duties and responsibilities that at present are part of the legal status of the local elected members, by previously determining the special configuration of their legal frame and then successively analyzing the exhausting content of this status in the State basic legislation and its possible interpretation by the Supreme and Constitutional courts case law, the specialities resulted from the Basque autonomous legislation and finally the important role that Local organic rules may have in that task.

Se presentan los resultados de la excavación arqueológica de dos asentamientos al aire libre fechados entre mediados del IV y III milenio cal BC, prácticamente los únicos testimonios publicados de este tipo de poblamiento en la margen derecha del río Ebro en La Rioja. Ambos presentan características comunes en su tamaño, organización y criterios de emplazamiento, propios de las sociedades segmentarias constructoras de grandes megalitos. Poseen elementos de cultura material de transición del Neolítico Final-Calcolítico y Calcolítico-Bronce Antiguo, respectivamente, contextualizados por dataciones 14C. A pesar de ello, sus perfiles arqueológicos tienen diferencias en la concepción y las actividades que en cada uno se desarrollaron, dentro de las dinámicas que se suponen para los “campos de hoyos”. El déficit de intervenciones en poblados sincrónicos frente a sepulcros megalíticos y contextos habitacionales en cavidad, hace necesario diversificar la información para obtener perfiles más ajustados de estas comunidades. ___ We present the results of the archaeological excavation in two open-air settlements dated between the middle of the IV and III millennium cal BC, practically only published testimonies in the right margin of the Ebro River (La Rioja, Spain). Both show common characteristics in their size (2-2.5 ha), organization and location criteria in an intermediate fluvial terrace, characteristics of segmental societies that built megaliths; also because the low number of archaeological materials that suggest a temporary and recurrent occupation. The settlement of Igay (Varea-Logroño, Spain) is chronologically located in the Late Neolithic (4750 ± 30 BP, 3637-3382 cal BC 2σ); the structural record is formed by 15 pits (storage pits, furnace, post hole and other indeterminate pits). Geometrical and retouching flat cover coexist as elements of lithic industry transition to the Chalcolithic, which could be placed ca. 3500 cal BC. Pottery are related to the Cameros megalithic stations, 20 km away and with evident contextual and chronological relation. The settlement is explained by the temporary exploitation of the resources in Ebro River fertile plain, with agricultural and hunting activities evidenced by hand querns and lithic arrowheads, respectively. Los Cascajos (Grañón, Spain) site is an open-air Chalcolithic settlement with an appreciable organization in disposition of the 32 negative structures documented. Approximately, 47% are combustion structures; the rest are interpreted as pits storage, post holes, indeterminate pits and a possible hut. Two almost continuous ditches delimit the nuclear area, inscribed on a small hill. In the archaeological site there are elements of transition to the Early Bronze Age, especially in the pottery repertoire. The lithic industry technique is laminar and with foliaceous; the absence of sickle and hand querns elements is striking, but in the settlement metal processing is present. The site is located chronologically at advanced Chalcolithic, dating 4097 ± 36 BP (2866-2498 cal BC 2σ); it anticipates the features of regional Early Bronze Age (ca. 2400 cal BC) without an abrupt rupture. The deficit of interventions in synchronic settlements in front of megalith tombs and cavity contexts requires diversifying the information at a regional scale to obtain more adjusted profiles of these communities.

Desde la Edad Moderna y hasta mediados del siglo XX, en España y otros países de Europa se practicó un ritual funerario a medio camino entre lo religioso y lo pagano cuyo recuerdo en la Península Ibérica aún se rastrea en la tradición oral entre las personas de mayor edad. En el ritual se utilizaba recipientes con sal que se colocaban encima del difunto durante el velatorio o las exequias. Las cerámicas procedentes del osario de la iglesia de Quintanalara (Burgos) –su origen, dispersión y su concepción como elementos cotidianos vs funerarios- sirve de estudio de caso para profundizar en este ritual funerario tan escasamente conocido y estudiado como geográficamente extendido, acotarlo desde el punto de vista cronológico y espacial, e investigar su origen y significado.

Background: The aim of the present study is to describe the occurrence of Blastocystis sp. detection among asymptomatic subjects and patients with irritable bowel syndrome in order to evaluate the potential association between irritable bowel syndrome and the parasitic infection. Methods: Cross-sectional study where adult patients with irritable bowel syndrome diagnosed according to Rome IV criteria were included. A control group was formed by asymptomatic subjects older than 18 years. Exclusion criteria were: immunosuppressive condition or having received any drug with demonstrated activity against Blastocystis sp. within the last 6 months before study inclusion. Epidemiological and clinical information was collected from all included participants. Two stool samples were obtained from all participants: one sample for microscopic examination and one sample for Blastocystis sp. PCR detection. Blastocystis sp. infection was defined by the positivity of any of the diagnostic techniques. Results: Seventy-two participants were included (36 asymptomatic subjects and 36 patients with irritable bowel syndrome). Thirty-five (48.6%) were men, and median age of participants was 34 (IQR 29–49) years. The overall rate of Blastocystis sp. carriage was 27.8% (20/72). The prevalence assessed through microscopic examination was 22.2% (16/72), while the prevalence measured by PCR was 15.3% (11/72). When comparing the presence of Blastocystis sp. between asymptomatic subjects and IBS patients, we did not find any statistically significant difference (36.1% vs. 19.4% respectively, p = 0.114). Conclusions: regarding the occurrence of Blastocystis sp., no differences were found between asymptomatic participants and patients with irritable bowel disease irrespective of the diagnostic technique performed.

Introducción: Empezar de nuevo se repite a lo largo de la vida profesional de muchos individuos, siendo una vivencia diferente para cada persona. Es habitual detectar carencias en la capacitación y dificultades en la integración de las personas noveles a los nuevos equipos, por ello, a lo largo de estos años en la Organización Sanitaria Integrada Eskerraldea Enkarterri Cruces, se han buscado diferentes herramientas que puedan ayudar a los profesionales en la adquisición de competencias y en la transición para integrarse a los equipos de trabajo. Objetivo: Favorecer la integración de las personas a través de un programa de información-formación. Material y Método: Estudio descriptivo observacional transversal; Población: profesionales de nueva incorporación; Criterios de inclusión: contratación prevista superior a un mes; Variables: entrevista, formación, evaluación. Recogida de datos: Excel, análisis mediante tablas dinámicas. Inicio estudio: mayo 2014, continúa en la actualidad. Resultados: Contamos con 12 formaciones de acogida integral, 3 más inicio en mayo 2018. A 31 diciembre 2017 han sido matriculadas en formación 598 personas, 393 enfermeras, 191 auxiliares de Enfermería y 14 técnicos de laboratorio. Evaluación cuantitativa 2014-2016: superior a 7 (escala 1-10), destacando el contenido y la utilidad. Valoración cualitativa, lo más positivo trato, preocupación tutores, contenido y comodidad de hacerlo online. Aspectos a mejorar: contradicciones entre apuntes y test evaluación, incluir temas específicos, formación presencial y videos. Valoración del proceso global: destaca la satisfacción en general, recepción por la supervisora, contenido del curso y seguimiento (escala 1-6). Supervisoras se muestran satisfechas con el valor aportado por la acogida y la formación. Discusión Esta propuesta favorece la adquisición de competencias para profesionales noveles, teniendo un impacto inmediato en el cuidado del paciente, y contribuyendo a una mejor adaptación al puesto de trabajo. Conclusiones e implicaciones para la práctica:Seguiremos avanzando en la acogida al personal novel con formación que le facilite la adquisición de competencias específicas al área de incorporación. Tenemos que mejorar el procedimiento y la evaluación en todas las formaciones, que nos permita mejorar las necesidades de los profesionales.

Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways.

The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra- and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism.

Las manifestaciones funerarias documentadas en El Hundido pertenecientes al Neolítico Final y Calcolítico aportan interesantes novedades al conocimiento de los rituales funerarios del inicio de la Edad de los Metales en la Península Ibérica y de las conexiones culturales entre la Meseta y la cuenca alta y media del Valle del Ebro. La tumba colectiva, que acogió a casi un centenar de individuos, es un excepcional ejemplo de monumento funerario tanto por su estructura como por el complejo ritual en ella practicado, que culminó con su destrucción premeditada mediante cremación.

La excavación arqueológica realizada en el yacimiento de El Prado ha permitido documentar un asentamiento al aire libre del Neolítico antiguo a partir del registro de casi una treintena de estructuras negativas que formaron parte de un poblado en los inicios del v milenio cal bc. Su situación geográfica en un fondo de valle, junto al desfiladero de Pancorbo, corredor natural aprovechado desde la Prehistoria para conectar el valle del Ebro y la Meseta, explica en parte la elección del asentamiento. Entre las estructuras documentadas destacan varios silos acondicionados con gruesos manteados de barro, un pozo/abrevadero y dos fosas funerarias. Estas últimas suponen, tanto por sus características estructurales como por el ritual, una importante aportación al conocimiento de las prácticas funerarias durante el Neolítico antiguo y vienen a completar el exiguo mapa y la desigual distribución de hallazgos documentados a nivel peninsular hasta finales del v milenio cal bc. El estudio palinológico proporciona interesantes datos sobre las características bioclimáticas y la antropización del medio; y el material arqueológico recuperado pone de manifiesto una clara conexión con los contextos del valle del Ebro, aunque sin ser ajeno a las peculiaridades culturales de la cuenca del Duero.

Alzheimer’s disease (AD) is a chronically progressive neurodegenerative disease highly correlated to aging. Whether AD originates by targeting a localized brain area and propagates to the rest of the brain across disease-severity progression is a question with an unknown answer. Here, we aim to provide an answer to this question at the group-level by looking at differences in diffusion-tensor brain networks. In particular, making use of data from Alzheimer’s Disease Neuroimaging Initiative (ADNI), four different groups were defined (all of them matched by age, sex and education level): G1 (N1 = 36, healthy control subjects, Control), G2 (N2 = 36, early mild cognitive impairment, EMCI), G3 (N3 = 36, late mild cognitive impairment, LMCI) and G4 (N4 = 36, AD). Diffusion-tensor brain networks were compared across three disease stages: stage I (Control vs. EMCI), stage II (Control vs. LMCI) and stage III (Control vs. AD). The group comparison was performed using the multivariate distance matrix regression analysis, a technique that was born in genomics and was recently proposed to handle brain functional networks, but here applied to diffusion-tensor data. The results were threefold: First, no significant differences were found in stage I. Second, significant differences were found in stage II in the connectivity pattern of a subnetwork strongly associated to memory function (including part of the hippocampus, amygdala, entorhinal cortex, fusiform gyrus, inferior and middle temporal gyrus, parahippocampal gyrus and temporal pole). Third, a widespread disconnection across the entire AD brain was found in stage III, affecting more strongly the same memory subnetwork appearing in stage II, plus the other new subnetworks, including the default mode network, medial visual network, frontoparietal regions and striatum. Our results are consistent with a scenario where progressive alterations of connectivity arise as the disease severity increases and provide the brain areas possibly involved in such a degenerative process. Further studies applying the same strategy to longitudinal data are needed to fully confirm this scenario.

Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis.

Los resultados obtenidos en la excavación arqueológica realizada en la antigua ermita de la Vera Cruz de Frandovínez (Burgos), en concreto los relacionados con un taller de fundición de campanas del siglo XVIII, constituyen un importante avance en el conocimiento de este tipo de elementos del patrimonio histórico industrial, ya que de manera excepcional han sido documentadas la totalidad de las estructuras integrantes del taller. Por otro lado, la documentación existente de 1788, ha permitido indagar en aspectos relacionados con la contratación de la obra, el montante económico y los diferentes oficios que participaron en la empresa.

In human and veterinary medicine, there have been multiple reports of pathogens being airborne under experimental and field conditions, highlighting the importance of this transmission route. These studies shed light on different aspects related to airborne transmission such as the capability of pathogens becoming airborne, the ability of pathogens to remain infectious while airborne, the role played by environmental conditions in pathogen dissemination, and pathogen strain as an interfering factor in airborne transmission. Data showing that airborne pathogens originating from an infectious individual or population can infect susceptible hosts are scarce, especially under field conditions. Furthermore, even though disease outbreak investigations have generated important information identifying potential ports of entry of pathogens into populations, these investigations do not necessarily yield clear answers on mechanisms by which pathogens have been introduced into populations. In swine, the aerosol transmission route gained popularity during the late 1990’s as suspicions of airborne transmission of porcine reproductive and respiratory syndrome virus (PRRSV) were growing. Several studies were conducted within the last 15 years contributing to the understanding of this transmission route; however, questions still remain. This paper reviews the current knowledge and identifies knowledge gaps related to PRRSV airborne transmission.

The gastrointestinal tract harbours the largest population of mast cells in the body; this highly specialised leukocyte cell type is able to adapt its phenotype and function to the microenvironment in which it resides. Mast cells react to external and internal stimuli thanks to the variety of receptors they express, and carry out effector and regulatory tasks by means of the mediators of different natures they produce. Mast cells are fundamental elements of the intestinal barrier as they regulate epithelial function and integrity, modulate both innate and adaptive mucosal immunity, and maintain neuro-immune interactions, which are key to functioning of the gut. Disruption of the intestinal barrier is associated with increased passage of luminal antigens into the mucosa, which further facilitates mucosal mast cell activation, inflammatory responses, and altered mast cell⁻enteric nerve interaction. Despite intensive research showing gut dysfunction to be associated with increased intestinal permeability and mucosal mast cell activation, the specific mechanisms linking mast cell activity with altered intestinal barrier in human disease remain unclear. This review describes the role played by mast cells in control of the intestinal mucosal barrier and their contribution to digestive diseases.

We provide the first annotated checklist of ophiuroids from the continental shelf of the State of Paraíba, northeastern Brazil. Identification keys and taxonomic diagnoses for 23 species, belonging to 14 genera and 8 families, are provided. The material is deposited in the Invertebrate Collection Paulo Young, at the Federal University of Paraíba. Ophiopsila hartmeyeri represents the first record for the northeastern region of Brazil, while Ophiolepis impressa, O. paucispina, Amphiura stimpsoni, Amphiodia riisei, Ophiactis quinqueradia, Ophiocoma wendtii and Ophionereis olivaceae are new records for the State of Paraíba. The number of species known for the state was increased from 16 to 23, representing approximately 17% of the species known for Brazil and 54% of the species known for northeastern Brazil. The recorded fauna has a large geographical and bathymetrical distribution.

We report the case of a 50-year-old woman with a history of diabetes mellitus who underwent left breast lumpectomy and ipsilateral lymphadenectomy in 1994 because of an infiltrating ductal carcinoma. Chemotherapy followed by radiotherapy to the breast and nodal areas were performed. In 2010, in a routine screening for diabetic retinopathy, two choroidal elevated masses above and below the optic nerve associated to serous retinal detachment of her right eye were noted. The patient was asymptomatic. Carcinoma was positive for hormone receptor. Hormone treatment with letrozole was established. Complete regression of the choroidal metastasis was observed 3 months later. Ophthalmologic screening in asymptomatic patients with breast cancer has the advantage of being a noninvasive procedure and enables an early treatment in isolated cases. However, some studies are an argument against the usefulness of eye screening due to the low incidence of asymptomatic choroidal metastasis and the cost that involves performing it routinely in a large number of patients. Aromatase inhibitors are well-tolerated drugs that may be a powerful tool in the management of metastatic breast cancer that express hormone receptors.

Objetivo: Evaluar la efectividad de un programa multicomponente aplicado en atención primaria por enfermeras. Método: Estudio no experimental pre-post. Se incluyeron 145 fumadores pertenecientes al Área V de Asturias. La intervención consistió en un tratamiento multicomponente grupal, de 7 semanas de duración, aplicado por enfermeras de atención primaria. Resultados: La media de edad fue de 52 años. Los varones representaban el 39,73% de la población estudiada. La tasa de abstinencia en el postratamiento fue del 51,1% (intervalo de confianza del 95%: 42,4-59,6). A los 12 meses, la tasa de abstinencia era del 41,1% (intervalo de confianza del 95%: 32,6-49,6). El cambio observado entre el final de la intervención y el control a los 6 y 12 meses fue en ambos casos estadísticamente significativo (p = 0,035 y p = 0,013, respectivamente). Entre los que no habían dejado de fumar se observó un descenso del consumo de cigarrillos al día estadísticamente significativo. El mayor consumo previo, una mayor puntuación en el test de Fagerström y un número menor de sesiones recibidas se relacionaron de manera estadísticamente significativa con la persistencia del hábito tabáquico a los 12 meses. Conclusiones: El tratamiento multicomponente aplicado fue altamente efectivo. Se sugiere la conveniencia de realizar un entrenamiento específico a los profesionales de la salud de cara a implantar este tipo de intervenciones en el ámbito de la atención primaria, como alternativa al consejo médico para aquellos fumadores que lo precisen.

El hasta ahora inédito depósito de armas de «Los Cascajos» es excepcional dentro de su contexto geográfico, ya que es el único recuperado en la provincia de La Rioja, pero también a nivel peninsular por las piezas que lo integran: por su número, tipología, origen y conservación. Se trata de un conjunto de metales del tránsito del BFI al BFII (1200-1000 a.C.), algunos de ellos inéditos en la Península, ya que no son de factura local, sino importados de otros territorios del Bronce Atlántico. Las características formales de algunas piezas señalan el Valle del Támesis como lugar de procedencia, aunque sin descartar el origen galo de otras.

When pathogens become airborne, they travel associated with particles of different size and composition. Particle size determines the distance across which pathogens can be transported, as well as the site of deposition and the survivability of the pathogen. Despite the importance of this information, the size distribution of particles bearing viruses emitted by infectious animals remains unknown. In this study we characterized the concentration and size distribution of inhalable particles that transport influenza A virus (IAV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine epidemic diarrhea virus (PEDV) generated by acutely infected pigs and assessed virus viability for each particle size range. Aerosols from experimentally infected pigs were sampled for 24 days using an Andersen cascade impactor able to separate particles by size (ranging from 0.4 to 10 micrometer (μm) in diameter). Air samples collected for the first 9, 20 and the last 3 days of the study were analyzed for IAV, PRRSV and PEDV, respectively, using quantitative reverse transcription polymerase chain reaction (RT-PCR) and quantified as geometric mean copies/m(3) within each size range. IAV was detected in all particle size ranges in quantities ranging from 5.5x10(2) (in particles ranging from 1.1 to 2.1 μm) to 4.3x10(5) RNA copies/m(3) in the largest particles (9.0-10.0 μm). PRRSV was detected in all size ranges except particles between 0.7 and 2.1 μm in quantities ranging from 6x10(2) (0.4-0.7 μm) to 5.1x10(4) RNA copies/m(3) (9.0-10.0 μm). PEDV, an enteric virus, was detected in all particle sizes and in higher quantities than IAV and PRRSV (p < 0.0001) ranging from 1.3x10(6) (0.4-0.7 μm) to 3.5x10(8) RNA copies/m(3) (9.0-10.0 μm). Infectious status was demonstrated for the 3 viruses, and in the case of IAV and PRRSV, viruses were isolated from particles larger than 2.1 μm. In summary, our results indicated that airborne PEDV, IAV and PRRSV can be found in a wide range of particle sizes. However, virus viability is particle size dependent.

Cation-exchange resins are used in the management of hyperkalemia, particularly in patients with end-stage renal disease. These resins were associated with gastrointestinal tract lesions, especially sodium polystyrene sulfonate (Kayexalate) mixed with sorbitol. We present a case of colonic necrosis after the administration of calcium polystyrene sulfonate (Kalimate) not suspended in sorbitol.

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), but additional chromosomal abnormalities (ACA) and other rearrangements can contribute in the development of the whole leukemic phenotype. We hypothesized that some ACA not detected by conventional techniques may be informative of the onset of APL. We performed the high-resolution SNP array (SNP-A) 6.0 (Affymetrix) in 48 patients diagnosed with APL on matched diagnosis and remission sample. Forty-six abnormalities were found as an acquired event in 23 patients (48%): 22 duplications, 23 deletions and 1 Copy-Neutral Loss of Heterozygocity (CN-LOH), being a duplication of 8(q24) (23%) and a deletion of 7(q33-qter) (6%) the most frequent copy-number abnormalities (CNA). Four patients (8%) showed CNAs adjacent to the breakpoints of the translocation. We compared our results with other APL series and found that, except for dup(8q24) and del(7q33-qter), ACA were infrequent (≤3%) but most of them recurrent (70%). Interestingly, having CNA or FLT3 mutation were mutually exclusive events. Neither the number of CNA, nor any specific CNA was associated significantly with prognosis. This study has delineated recurrent abnormalities in addition to t(15;17) that may act as secondary events and could explain leukemogenesis in up to 40% of APL cases with no ACA by conventional cytogenetics.

Recientes trabajos arqueológicos en la Sierra de San Blas, en Ágreda (Soria), han permitido identificar un sistema inédito de tres atalayas o torres-vigíafechadas en el siglo X, concebido para la defensa del núcleo emiral de Ágreda y de esta región de frontera de la Marca Media Hispánica. Este complejo es el contrapunto al vacío de estaciones afines que se viene postulando para el oriente soriano frente a la densa red defensiva del occidente, al tiempo que permite introducir nuevas acotaciones histórico-arqueológicas sobre la desaparición del núcleo califal de Ágreda en un momento avanzado del siglo X. A pesar de la simpleza de las estructuras que se han conservado hasta nuestros días, todas siguen un modelo constructivo similar al de otras estaciones afines de sierras próximas, como las de la Sierra del Madero, con las que mantendrían relación funcional. Este sincronismo vendríaavalado por la homogeneidad de los materiales arqueológicos recuperados en San Blas, los cuales vienen a enriquecer el registro conocido hasta el momento en Soria.

Circulating tumor cells (CTCs) are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR) using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20) performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.