Search

Despite remarkable advances in tumor treatment, many patients still die from common tumors (breast, prostate, lung, CNS, colon, and pancreas), and thus, new approaches are needed. Many of these tumors synthesize bombesin (Bn)-related peptides and over-express their receptors (BnRs), hence functioning as autocrine-growth-factors. Recent studies support the conclusion that Bn-peptides/BnRs are well-positioned for numerous novel antitumor treatments, including interrupting autocrine-growth and the use of over-expressed receptors for imaging and targeting cytotoxic-compounds, either by direct-coupling or combined with nanoparticle-technology.The unique ability of common neoplasms to synthesize, secrete, and show a growth/proliferative/differentiating response due to BnR over-expression, is reviewed, both in general and with regard to the most frequently investigated neoplasms (breast, prostate, lung, and CNS). Particular attention is paid to advances in the recent years. Also considered are the possible therapeutic approaches to the growth/differentiation effect of Bn-peptides, as well as the therapeutic implication of the frequent BnR over-expression for tumor-imaging and/or targeted-delivery.Given that Bn-related-peptides/BnRs are so frequently ectopically-expressed by common tumors, which are often malignant and become refractory to conventional treatments, therapeutic interventions using novel approaches to Bn-peptides and receptors are being explored. Of particular interest is the potential of reproducing with BnRs in common tumors the recent success of utilizing overexpression of somatostatin-receptors by neuroendocrine-tumors to provide the most sensitive imaging methods and targeted delivery of cytotoxic-compounds.

Resumen: Introducción: La actividad de guardia es un componente fundamental de la práctica médica y representa elevada carga asistencial y de tiempo laboral. Existen pocos estudios publicados que las analicen. Pacientes y métodos: Realizamos un estudio observacional, prospectivo, en el Hospital Virgen de la Salud de Toledo, hospital de tercer nivel. El objetivo principal fue describir la actividad asistencial de las guardias de medicina interna a partir de los motivos de consulta y llamadas al médico de guardia. Resultados: La media de pacientes ingresados en el hospital fue de 532, de los cuales 156 (29,4%) pacientes estaban ingresados en los servicios del equipo de guardia de medicina interna (medicina interna, oncología, neumología, endocrinología y reumatología son atendidos de guardia por medicina interna).Hubo una media de 30 consultas de enfermería y de especialista médico por guardia, una cada 18 minutos. Junto con los ingresos valorados en la guardia, suponen 43 actos asistenciales por guardia, uno cada 12 minutos.De las consultas realizadas por enfermería, aquellas por motivo burocrático representaron el 44% y por motivo clínico el 55%. Conclusión: Nuestro estudio refleja la importante actividad asistencial llevada a cabo durante las guardias de medicina interna.Un gran porcentaje de las consultas fueron de carácter burocrático, debiéndose implementar medidas que disminuyan las mismas.Un gran porcentaje fueron llamadas de carácter clínico en las que enfermería valoró presencialmente al paciente y precisó ayuda telefónica del médico.La facilidad de acceso y de comunicación médico-enfermería es imprescindible para asegurar una atención de calidad. Abstract: Introduction: On-call activity is a fundamental component of medical practice and represents a high burden of care and working time. There are few published studies that analyse these issues. Patients and methods: We conducted an observational, prospective study at the Virgen de la Salud Hospital in Toledo, a tertiary level hospital. The main objective was to describe the healthcare activity of internal medicine shifts based on the reasons for consultation and calls to the duty doctor. Results: The mean number of patients admitted to the hospital was 532, of which 156 (29.4%) were admitted to the departments of the duty internal medicine team (internal medicine, oncology, pneumology, endocrinology and rheumatology are attended by the duty internal medicine team).There was an average of 30 nursing and medical specialist consultations per shift, one every 18 minutes. Together with the admissions assessed during the shift, this represents 43 acts of care per shift, one every 12 minutes.Of the nurse consultations, 44% were for bureaucratic reasons and 55% for clinical reasons. Conclusion: Our study reflects the important healthcare activity carried out during internal medicine shifts.A large percentage of the consultations were bureaucratic in nature, and measures should be implemented to reduce them.A large percentage were clinical calls in which the nurse assessed the patient in person and required telephone help from the doctor.Ease of access and doctor-nurse communication is essential to ensure quality care.

Carcinosarcoma of the pancreas is a rare entity with short case series reported in the literature. Diagnosis is established by immunohistochemical examination including both carcinomatous and sarcomatous components. Prognosis is usually limited to 6-9 months life expectancy. Standard chemotherapy regimen is not well defined. We present a case of pancreatic carcinosarcoma with long-time progression-free-survival under first line chemotherapy treatment with gemcitabine-nabpaclitaxel combination. Tumor histopathological and clinical characteristics are reviewed.

Humans can vary considerably in their healthy immune phenotypes and in their immune responses to various stimuli. We have developed an interactive web-based tool, ImmuneRegulation, to enable discovery of human regulatory elements that drive some of the phenotypic differences observed in gene expression profiles. ImmuneRegulation currently provides the largest centrally integrated resource available in the literature on transcriptome regulation in whole blood and blood cell types, including genotype data from 23,040 individuals, with associated gene expression data from 30,562 experiments, that provide genetic variant-gene expression associations on ∼200 million eQTLs. In addition, it includes 14 million transcription factor (TF) binding region hits extracted from 1945 TF ChIP-seq peaks and the latest GWAS catalog of 67,230 published SNP-trait associations. Users can interactively explore ImmuneRegulation to visualize and discover associations between their gene(s) of interest and their regulators (genetic variants or transcription factors) across multiple cohorts and studies. These regulators can explain cohort or cell type dependent gene expression variations and may be critical in selecting the ideal cohorts or cell types for follow-up studies. Overall, ImmuneRegulation aims to contribute to our understanding of the effects of eQTLs and TFs on heterogeneous transcriptional responses reported in studies on the blood; in the development of molecular signatures of immune response; and facilitate their future application in patient management. ImmuneRegulation is freely available at http://icahn.mssm.edu/immuneregulation.

Neurotensin is a 13 amino acid peptide which is present in many lung cancer cell lines. Neurotensin binds with high affinity to the neurotensin receptor 1, and functions as an autocrine growth factor in lung cancer cells. Neurotensin increases tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) and the neurotensin receptor 1 antagonist SR48692 blocks the transactivation of the EGFR. Here the effects of reactive oxygen species on the transactivation of the EGFR and HER2 were investigated. Using non-small cell lung cancer (NSCLC) cell lines, neurotensin receptor 1 mRNA and protein were present. Using NCI–H838 cells, neurotensin or neurotensin8−13 but not neurotensin1−8 increased EGFR, ERK and HER2 tyrosine phosphorylation which was blocked by SR48692. Neurotensin addition to NCI–H838 cells increased significantly reactive oxygen species which was inhibited by SR48692, Tiron (superoxide scavenger) and diphenylene iodonium (DPI inhibits the ability of NADPH oxidase and dual oxidase enzymes to produce reactive oxygen species). Tiron or DPI impaired the ability of neurotensin to increase EGFR, ERK and HER2 tyrosine phosphorylation. Neurotensin stimulated NSCLC cellular proliferation whereas the growth was inhibited by SR48692, DPI or lapatinib (lapatinib is tyrosine kinase inhibitor of the EGFR and HER2). Lapatinib inhibited the ability of the neurotensin receptor 1 to transactivate the EGFR and HER2. The results indicate that neurotensin receptor 1 regulates the transactivation of the EGFR and HER2 in a reactive oxygen species-dependent manner.

Neuropeptide G protein-coupled receptors (GPCRs) are overexpressed on numerous cancer cells. In a number of tumors, such as small cell lung cancer (SCLC), bombesin (BB) like peptides and neurotensin (NTS) function as autocrine growth factors whereby they are secreted from tumor cells, bind to cell surface receptors and stimulate growth. BB-drug conjugates and BB receptor antagonists inhibit the growth of a number of cancers. Vasoactive intestinal peptide (VIP) increases the secretion rate of BB-like peptide and NTS from SCLC leading to increased proliferation. In contrast, somatostatin (SST) inhibits the secretion of autocrine growth factors from neuroendocrine tumors (NETs) and decreases proliferation. SST analogs such as radiolabeled octreotide can be used to localize tumors, is therapeutic for certain cancer patients and has been approved for four different indications in the diagnosis/treatment of NETs. The review will focus on how BB, NTS, VIP, and SST receptors can facilitate the early detection and treatment of cancer.

Una parte importante de las investigaciones actuales sobre riesgos online están encaminadas a analizar las ciberagresiones, su frecuencia y forma. En cambio, hay menos acumulación de conocimiento científico centrado en la percepción de riesgo, el análisis de sus componentes y la medición e impacto sobre la actuación de los menores en la red. Por ello, el objetivo principal del estudio es establecer una clasificación de menores a partir de su percepción de riesgo, hábitos de consumo digital, factores de protección familiares y/o educativos y flujos de comunicación. Se ha aplicado un cuestionario estructurado a una muestra de 865 menores, de 10 a 17 años de la Comunidad de Madrid. Los datos se han procesado con SPSS 15.0 y SPAD 5.0. Tras un análisis factorial y de clasificación se han obtenido siete grupos diferenciados. El perfil predominante, en un 42% de los casos, es el de «prudentes», caracterizado por tener una alta percepción de riesgo, no pasar excesivo tiempo en la red, evitar comportamientos no seguros, conversar con los padres sobre las dificultades online, recibir consejos y tener normas claras sobre el uso de Internet. La percepción de riesgo se muestra como un constructo relevante en relación a otros indicadores como la intervención educativa de los padres, el tiempo que se pasa en Internet, la dependencia del dispositivo y el tipo de comportamiento digital. An important part of current research regarding online risks is aimed at analysing cyber aggression according to its frequency and type. By contrast, there is less scientific knowledge available on risk perception, the analysis of its components, and the measurement and impact on the behaviour of minors on the Internet. Therefore, the main objective of this study is to establish a classification of minors based on their perception of risk, digital consumption habits, family and/or educational protection factors, and the flow of communication. A structured questionnaire was used from a sample of 865 minors aged 10 to 17 from the Autonomous Region of Madrid. Data were processed using SPSS 15.0 and SPAD 5.0. After a factor and classification analysis was conducted, seven different groups were obtained. The predominant profile, in 42% of the cases, is that of a ‘prudent person’, characterized by a high perception of risk, not spending an excessive amount of time on the Internet, avoiding unsafe behaviour, talking with parents about online difficulties, receiving advice, and having clear rules on Internet use. The perception of risk is shown as a relevant construct in relation to other indicators such as child-rearing techniques used by parents, the time children spend on Internet, dependency on the device, and the type of digital behavior involved. Este manuscrito difunde resultados del proyecto de investigación «Auctoritas doméstica, capacitación digital y comunidad de aprendizaje en familias con menores escolarizados», financiado por el Plan Nacional (CSO2013-42166-R) en el marco del Programa de Actividades sobre Vulnerabilidad Digital, PROVULDIG (S2015/HUM-3434), cofinanciado por la Comunidad de Madrid y el Fondo Social Europeo.

The incoming influenza A virus (IAV) genome must pass through two distinct barriers in order to establish infection in the cell: the plasma membrane and the nuclear membrane. A precise understanding of the challenges imposed by the nuclear barrier remains outstanding. Passage across is mediated by host karyopherins (KPNAs), which bind to the viral nucleoprotein (NP) via its N-terminal nuclear localization sequence (NLS). The binding affinity between the two molecules is low, but NP is present in a high copy number, which suggests that binding avidity plays a compensatory role during import. Using nanobody-based technology, we demonstrate that a high binding avidity is required for infection, though the absolute value differs between cell types and correlates with their relative susceptibility to infection. In addition, we demonstrate that increasing the affinity level caused a decrease in avidity requirements for some cell types but blocked infection in others. Finally, we show that genomes that become frustrated by low avidity and remain cytoplasmic trigger the type I interferon response. Based on these results, we conclude that IAV balances affinity and avidity considerations in order to overcome the nuclear barrier across a broad range of cell types. Furthermore, these results provide evidence to support the long-standing hypothesis that IAV’s strategy of import and replication in the nucleus facilitates immune evasion. IMPORTANCE We used intracellular nanobodies to block influenza virus infection at the step prior to nuclear import of its ribonucleoproteins. By doing so, we were able to answer an important but outstanding question that could not be addressed with conventional tools: how many of the ∼500 available NLS motifs are needed to establish infection? Furthermore, by controlling the subcellular localization of the incoming viral ribonucleoproteins and measuring the cell’s antiviral response, we were able to provide direct evidence for the long-standing hypothesis that influenza virus exploits nuclear localization to delay activation of the innate immune response.

Desde que ocurre la desaparición de los cuarenta y tres estudiantes de la escuela normal rural de Ayotzinapa este acontecimiento ha sido difundido gracias a la voluntad de sus compañeros y familiares de hacer visibles y públicas las circunstancias de esta desaparición, así como el proceso que ha seguido la investigación judicial. Sin embargo, prevalece una tensión entre lo visible y lo invisible en la manera como ha sido investigada, publicitada y consignada la trayectoria de los estudiantes desaparecidos y sus cuerpos. Con base en una sucinta restitución de los hechos, este ensayo busca interrogarse sobre la manera en que las acciones de diferentes actores como: estudiantes, familiares de los desaparecidos, autoridades nacionales y expertos internacionales contribuyen a dar visibilidad (o invisibilidad) a la desaparición forzada. Since the disappearance of forty-three students of the Ayotzinapa rural teacher training school, awareness of this event has spread thanks to the willingness of colleagues and relatives to make visible and public the circumstances of this disappearance, as well as the judicial investigation process that followed. However, a tension between the visible and the invisible prevails regarding how the missing students and their bodies have been investigated, publicized and recorded. Based on a succinct restitution of facts, this essay questions how the actions of different actors such as students, relatives of the disappeared, national authorities and international experts contribute to the visibility (or invisibility) of enforced disappearance. Depuis la disparition de quarante-trois étudiants de l’École normale rurale d’Ayotzinapa, cet événement a été rendu public et médiatisé grâce à la volonté des compagnons et des parents des disparus qui ont donné de la visibilité aux circonstances de cette disparition ainsi qu’à l’ultérieure évolution de l’enquête judiciaire. Pourtant, une tension prévaut entre le visible et l’invisible dans la manière dans laquelle l’enquête sur les étudiants disparus et leurs corps a été menée, médiatisée et consignée. À partir d’une rapide restitution des faits, cet article cherche à comprendre comment les agissements de différents acteurs : étudiants, parents des disparus, autorités nationales et experts internationaux contribuent à donner de la visibilité (ou de l’invisibilité) à la disparition forcée.

Die Studie untersucht die Auswirkungen der Finanzmarktkrise auf die Arbeitsbeziehungen des offentlichen Sektors in vier Landern. Es zeigen sich deutliche Unterschiede: Der offentliche Sektor in Gro ...

[EN]: The impact of the 2008 financial crisis led to the imposition of severe ‘crisis measures’ focused on alleviating budget deficits at all levels of Spanish government. In this context, the central government sought to restrict regional and local government spending. One of the key mechanisms at the Spanish government’s disposal was restricting public sector employment. This paper examines the responses to these centrally imposed measures in two local municipal governments, Bilbao (Basque Country) and Parla (Madrid) between 2010 and 2015. The paper applies a ‘varieties of capitalism’ conceptual approach to investigate what it refers to as subnational institutional systems and suggests that processes of economic and social adjustment in Spain are also influenced by distinctive regional and local political economic arrangements. Key factors contributing to the different industrial relations outcomes observed in the two case study locations are described and discussed. The results show that different types and degrees of coordination can co-exist within a decentralised national political economy., [DE]: Die Finanzkrise zog seit 2008 schwerwiegende „Krisenmaßnahmen“ nach sich, die auf allen Verwaltungsebenen Spaniens darauf konzentriert waren, das Haushaltsdefizit zu verringern. In diesem Kontext versuchte die Zentralregierung die Ausgaben regionaler und lokaler Verwaltungen zu beschränken. Eines der zentralen Instrumente über welche die spanische Regierung verfügte, war die Reduktion der öffentlichen Beschäftigung. Der Beitrag untersucht, wie die zwei Lokalverwaltungen von Bilbao (Baskenland) und Parla (Madrid) 2010 bis 2015 auf die zentral auferlegten Maßnahmen reagierten, indem ein Varieties of Capitalism-Konzept zur Untersuchung sub-nationaler Institutionen angewandt wird. Es wird der Schluss gezogen, dass Prozesse wirtschaftlicher und sozialer Anpassung in Spanien auch durch verschiedene regionale und lokale politische und wirtschaftliche Arrangements beeinflusst werden. Es werden Schlüsselfaktoren der unterschiedlichen Folgen für die industriellen Beziehungen beschrieben und diskutiert. Die Befunde zeigen, dass verschiedene Typen und Grade der Koordination innerhalb einer dezentralisierten Ökonomie existieren können.

There is an increasing social expectation regarding the joint realisation of scientific and societal impact from publicly funded research. Achieving this goal involves facing important challenges, which affect individual researchers, research performing organisations, and the science governance system as a whole. This special section includes conceptual, methodological, and empirical papers that aim to contribute to the building of an improved appreciation of the factors and dynamics shaping the intertwined quest for scientific quality and societal impact., This research was supported by the Spanish Ministry of Ministry of Economy, Industry and Competitiveness through the State Plan of Scientific and Technical Research and Innovation (EXTRA project, grant CSO2013-48053-R) and by the Oslo Institute for Research on the Impact of Science (OSIRIS, grant 256240) funded by the Research Council of Norway.

A preliminary version of the manuscript was presented at the EU-SPRI 2014 Manchester Conference, University of Manchester (June, 2014)., The behavior of academic researchers who engage in cooperation with industrial partners has already been the subject of considerable research. A lack of understanding exists regarding the motivations of scientific research groups to engage in cooperation with other types of external non-academic organizations and the perceived barriers that may inhibit this activity. In this paper we analyse the motivations and perceptions of risks that shape scientific research groups’ cooperation with industry and government partners. We find that motivations to cooperate are partly dependent on the type of partner organization involved, with advancing research goals mainly acting as an inducement to cooperate with government agencies, while searching for opportunities to apply knowledge motivates partnerships with firms. We also find that the majority of research groups cooperate with both firms and government, with their major motivation being to apply their knowledge. Among research groups that only cooperate with firms, interaction effects between motivations influence the likelihood of cooperation. Research groups do not consider risk to scientific autonomy a barrier to cooperating with firms, while risk to scientific credibility inhibits cooperation independently of the type of external partner. However, being motivated to advance research can reduce the effect of perceived barriers, independent of the type of partner organisation., Funding for this project (Ref. CSO2009-07805) was provided by the Spanish National Programme of Scientific Research, Development and Innovation.

Three cases of influenza A(H10N8) virus infection in humans have been reported; 2 of these infected persons died. Characterization of the receptor binding pattern of H10 hemagglutinin from avian and human isolates showed that both interact weakly with human-like receptors and maintain strong affinity for avian-like receptors.

Introduction The aim of this study was twofold: First, to assess the personality profile of treatment-seeking adult outpatients with pathological gambling compared to a matched control group under the Alternative Five Factor Model perspective, and second, to determine which personality variables would predict treatment outcome. Methods The final total sample consisted of 44 consecutive treatment-seeking pathological gamblers (PGs) and 88 controls paired by age and sex who completed the Zuckerman–Kuhlman Personality Questionnaire (ZKPQ). Twelve months after starting an open program of individual cognitive-behavioral therapy, PGs were categorized as abstinent or treatment failure. Results PGs scored significantly higher on Neuroticism–Anxiety. Those who had relapsed or dropped out showed higher Impulsivity and Sensation Seeking scores. Impulsivity emerged as a significant predictor of treatment failure. Treatment-seeking PGs scored higher on Neuroticism–Anxiety and Impulsivity appeared as a risk factor of relapsing or dropping out. Conclusions Our findings support the importance of individual differences in personality on therapy outcomes. The ZKPQ may constitute a useful tool to identify these individual differences that might be considered when making personalized treatment decisions to improve the effectiveness and quality of treatment interventions.

Dengue virus (DENV) is the most prevalent mosquito-borne virus causing human disease. Of the 4 DENV serotypes, epidemiological data suggest that DENV-2 secondary infections are associated with more severe disease than DENV-4 infections. Mass cytometry by time-of-flight (CyTOF) was used to dissect immune changes induced by DENV-2 and DENV-4 in human DCs, the initial targets of primary infections that likely affect infection outcomes. Strikingly, DENV-4 replication peaked earlier and promoted stronger innate immune responses, with increased expression of DC activation and migration markers and increased cytokine production, compared with DENV-2. In addition, infected DCs produced higher levels of inflammatory cytokines compared with bystander DCs, which mainly produced IFN-induced cytokines. These high-dimensional analyses during DENV-2 and DENV-4 infections revealed distinct viral signatures marked by different replication strategies and antiviral innate immune induction in DCs, which may result in different viral fitness, transmission, and pathogenesis.

Mycobacterium bovis Bacille Calmette-Guerin (BCG) is listed as an intralesional therapeutic option for inoperable stage III in-transit melanoma in the National Comprehensive Cancer Network Guidelines. Although the mechanism is unknown, others have reported up to 50% regression of injected lesions and 17% regression of uninjected lesions in immunocompetent patients have been reported after direct injection of BCG into metastatic melanoma lesions in the skin. BCG and other mycobacteria express ligands capable of stimulating the g9d2 T cells. Therefore, we hypothesized that g9d2 T cells play a role in promoting BCG-mediated antitumor immunity in patients treated with intralesional BCG for in-transit cutaneous melanoma metastases. Indeed, we found g9d2 T cell infiltration in melanoma skin lesions during the course of ILBCG treatment. Gene expression analysis revealed that BCG injection elicits the expression of a vast array of chemokines in tumor lesions, including strong expression of CXCL9, 10, and 11, a set of chemokines that attract T cells expressing the CXCR3 chemokine receptor. In corroboration with our hypothesis, approximately 85% of gd T cells express high levels of CXCR3 on their surface. Importantly, the injected tumor lesions also express genes whose protein products are the antigenic ligands for gd T cells (BTN3A1 and MICB), and the cytokines that are the typical products of activated gd T cells. Interestingly, we also found that gd T cells infiltrate the regressed lesions which did not receive BCG injections. Our study suggests that g9d2 T cells may contribute to melanoma regression induced by ILBCG treatment.

The 2016 series of the RIO Country Report analyses and assesses the development and performance of the national research and innovation system of the EU-28 Member States and related policies. It aims at monitoring and evaluating the EU policy implementation as well as facilitating policy learning in the Member States., JRC.B.7-Knowledge for Finance, Innovation and Growth

Aunque no se trata de un fenómeno reciente, la Nomofobia (No Mobile Phone Phobia) entendida como una adicción comportamental que implica un alto temor a quedarse sin teléfono móvil, está siendo objeto de investigación desde diferentes disciplinas dada las importantes consecuencias que se están observando entre la población más joven. Sin embargo, son pocos los instrumentos capaces de medir esta adicción no reconocida como tal por el DSM-V. En el presente trabajo se ha llevado a cabo el proceso de adaptación y validación de la escala de medición de la Nomofobia de Yildirim y Correia. Para ello se procedió a una adaptación lingüística y cultural de la misma, seguida de una revisión por parte de expertos en la materia. La decisión del grupo de expertos supuso una modificación de la redacción y la inclusión de un nuevo ítem. La escala resultante se aplicó a una muestra de 372 estudiantes de Educación Secundaria Obligatoria, en institutos públicos de la provincia de Alicante. Los resultados permitieron la validación de la escala objeto de este estudio. Although is not a recent phenomenon, Nomophobia (No Mobile Phone Phobia), understood as a behavioral addiction that implies a high fear of being left without a mobile phone, is being researched from different disciplines given the important consequences that are being observed between the younger population. However, there are few instruments to measure this addiction not recognized by the DSM-V. In the present work the process of adaptation and validation of the measurement scale of the Nomophobia of Yildirim and Correia has been carried out. A linguistic and cultural adaptation of the scale was carried out, followed by a review by the experts in the field. The group of experts proposed a modification of the wording and the inclusion of a new item. The final scale was applied to a sample of 372 students of Compulsory Secondary Education, in public institutes of the Province of Alicante. The results allowed the validation of the Yildirim and Correia scale.

"Este artículo trata sobre la alianza matrimonial en el pueblo de Yalálag, en la Sierra Norte de Oaxaca. Por una parte, se observan las transfor- maciones de las normas y prácticas matrimoniales a lo largo del siglo xx. Por otro lado, se examinan las categorías locales gozona y fandango , empleadas para describir cómo se establece la alianza y que designan las fuentes de legitimidad del matrimonio. Si bien los criterios de legitimidad de la alianza no son inteligibles sino a través de un conoci- miento preciso de los sistemas normativos locales, también pueden ser analizados a partir de una perspectiva antropológica más general, como hecho social total , a través de categorías analíticas como don , prestación matrimonial y dote ."

"Distintos recuerdos acerca de una serie de asesinatos ocurridos en 1945 en un pueblo de la Sierra Norte de Oaxaca constituyen el objeto de este artículo. A través de las experiencias y narraciones de tres abuelas indígenas de esta región, se analiza la manera como se expresan respecto a la violencia política al momento de evocar la historia de su pueblo. Aunque sus memorias se presentan de una forma fragmentada, un análisis detallado permite observar que sus relatos, según el contexto de enunciación, ponen de manifiesto un aspecto particular de la violencia política que estremece a su pueblo."

El envase ha sido considerado un comunicador silencioso. Para los juguetes sin inversión publicitaria en otros medios, el envase representa un elemento clave en la comunicación con el consumidor. Tras una revisión de la literatura se identifican tres dimensiones básicas de estudio -forma, función y comunicación- configuradas por 24 variables. Las preguntas de investigación formuladas son: ¿Qué aspectos formales caracterizan los envases de juguetes? ¿Qué utilidades presentan? ¿Existe un tratamiento diferenciado del envase en las distintas categorías de juguetes? ¿Se identifican diferencias entre los envases según el origen del fabricante? Se investiga el contenido de 301 envases de juguetes de 82 fabricantes (70% internacionales) y se realizan dos análisis: descriptivo y caracterizante. Se concluye que formalmente son bastante convencionales y, sin embargo, contienen conceptos novedosos de producto, resultando paradójico. Funcionalmente, cubren satisfactoriamente las necesidades de contención, protección, transporte y almacenamiento aunque se desaprovecha como elemento comunicativo creador de experiencias emocionales. La gestión estratégica del envase en el sector de juguetes es potencialmente mejorable. Packaging has been considered by Marketing experts as a silent sales agent. Specially, for those toys without advertising support, packaging represents the key element to communicate with the end consumer. After revising all published articles about this matter, we found three dimensions to be considered: formal, functional, and communicational, all them aggregating a number of 24 different considerations. The questions we have formulated are as follows: Which are the formal aspects we can consistently find in the Toy industry packaging? Which are the utilities found in those Toy packaging? Is there a particular treatment of packaging depending on the Toy category? Can we find packaging peculiarities considering the origin of the manufacturer? We have investigated 301 different packaging coming from 82 different manufacturers (70% of those manufacturers were not spanish manufacturers) and we have made a deep analysis considering both, structure and characteristics. We conclude that formally, packaging is quite similar and conventional but they have some very special products inside and this is not what this should be. Under the point of view of functionality, packaging are good enough to cover, protect, transport and warehouse the products, but they do not take advantage of the potential communication and emotional influence on the end consumer. We conclude that the strategic treatment of packaging inside Toy industry is something that could be improved. Esta investigación ha sido financiada por el proyecto “Análisis estructural comparado del proceso comunicativo sobre características de los juguetes de las Empresas Valencianas vs. Empresas Internacionales –LUDICOM- (IMDEEA/2011/15) en la convocatoria pública competitiva del programa de desarrollo estratégico del Instituto de la Mediana y Pequeña Industria Valenciana (IMPIVA) dependiente de la Consellería de Economía, Industria y Comercio de la Generalitat Valenciana.

The incidence of infections related to cardiac devices (such as permanent pacemakers) has been increasing out of proportion to implantation rates. As management of device infections typically requires explantation of the device, optimal prophylactic strategies are needed. Cefazolin and vancomycin are widely used as single agents for surgical prophylaxis against cardiac device-related infections. However, combination antibiotic prophylaxis may further reduce infectious complications. To model a localized subcutaneous implant-related infection, a bioluminescent strain of Staphylococcus epidermidis was inoculated onto a medical-procedure-grade titanium disc, which was placed into a subcutaneous pocket in the backs of mice. In vivo bioluminescence imaging, quantification of ex vivo CFU from the capsules and implants, variable-pressure scanning electron microscopy (VP-SEM), and neutrophil enhanced green fluorescent protein (EGFP) fluorescence in LysEGFP mice were employed to monitor the infection. This model was used to evaluate the efficacies of low- and high-dose cefazolin (50 and 200 mg/kg of body weight) and vancomycin (10 and 110 mg/kg) intravenous prophylaxis with or without rifampin (25 mg/kg). High-dose cefazolin and high-dose vancomycin treatment resulted in almost complete bacterial clearance, whereas both low-dose cefazolin and low-dose vancomycin reduced the in vivo and ex vivo bacterial burden only moderately. The addition of rifampin to low-dose cefazolin and vancomycin was highly effective in further reducing the CFU harvested from the implants. However, vancomycin-rifampin was more effective than cefazolin-rifampin in further reducing the CFU harvested from the surrounding tissue capsules. Future studies in humans will be required to determine whether the addition of rifampin has improved efficacy in preventing device-related infections in clinical practice.

Herpes simplex virus 2 (HSV-2) may cause frequent recurrences, highlighting its ability to evade host defense. This study tested the hypothesis that HSV-2 interferes with dendritic cell (DC) function as an escape mechanism, which may contribute to enhanced HIV replication in coinfected populations. Immature monocyte-derived human DCs were exposed to live or UV-inactivated HSV-2 or lipopolysaccharide. Little or no increase in the maturation marker CD83 was observed in response to HSV-2 and HSV-2 exposed DCs were impaired in their ability to present antigen (influenza) to T cells. Exposure to UV-inactivated virus stimulated a modest, but significant increase in CD83, suggesting that viral gene expression contributes to the block in DC maturation. The functional impairment of HSV-2-exposed DCs could be partially attributed to the induction of apoptosis. Live and inactivated HSV-2 triggered an increase in the number of early and late apoptotic cells in both the infected and bystander cell populations; apoptosis was associated with a decrease in cellular FLICE-inhibitory protein (c-FLIP). Paradoxically, HSV-2 induced Akt phosphorylation, which typically promotes DC maturation and survival. Despite these aberrant responses, live and inactivated HSV-2 induced the release of cytokines into culture supernatants, which were sufficient to activate HIV-1 replication in latently infected U1 cells. Together, these findings suggest that in the presence of overt or subclinical HSV-2, the function of mucosal DCs would be impaired. These responses may allow HSV to escape immune surveillance but may also promote HIV infection and contribute to the epidemiological link between HIV and HSV.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents.

Cet article se propose d’analyser la manière dont la disparition de quarante-trois étudiants de l’École Normale rurale d’Ayotzinapa est devenue une affaire. Autrement dit, il s’agit de s’interroger sur la manière dont des revendications locales ont pu émerger et monter en généralité pour accéder à la sphère publique, comme celles des mobilisations collectives au Mexique et ailleurs. Nous essayerons de répondre en observant l’événement durant les jours qui ont suivi cette disparition. Deux sources principales sont consultées : les comptes rendus judicaires et les récits des victimes. L’analyse des descriptions et catégorisations élaborées par les personnes et institutions concernées s’avère donc nécessaire pour avoir accès aux différentes compréhensions internes à cette affaire., The analysis proposed in this article aims at showing how it happened that the disappearance of forty-three students of École Normale rurale d’Ayotzinapa became « une affaire ». We examine how local claims could thus emerge on a larger scale and become publicly known issues, linked to social mobilization in Mexico and elsewhere. The two main sources used in order to gain an understanding of this event are police or court records and testimonies from the victims, as reported by the media in the days following the disappearance.

Bombesin-receptor-subtype-3 (BB3 receptor) is a G-protein-coupled-orphan-receptor classified in the mammalian Bombesin-family because of high homology to gastrin-releasing peptide (BB2 receptor)/neuromedin-B receptors (BB1 receptor). There is increased interest in BB3 receptor because studies primarily from knockout-mice suggest it plays roles in energy/glucose metabolism, insulin-secretion, as well as motility and tumor-growth. Investigations into its roles in physiological/pathophysiological processes are limited because of lack of selective ligands. Recently, a selective, peptide-antagonist, Bantag-1, was described. However, because BB3 receptor has low-affinity for all natural, Bn-related peptides, little is known of the molecular basis of its high-affinity/selectivity. This was systematically investigated in this study for Bantag-1 using a chimeric-approach making both Bantag-1 loss-/gain-of-affinity-chimeras, by exchanging extracellular (EC) domains of BB3/BB2 receptor, and using site-directed-mutagenesis. Receptors were transiently expressed and affinities determined by binding studies. Bantag-1 had >5000-fold selectivity for BB3 receptor over BB2/BB1 receptors and substitution of the first EC-domain (EC1) in loss-/gain-of affinity-chimeras greatly affected affinity. Mutagenesis of each amino acid difference in EC1 between BB3 receptor/BB2 receptor showed replacement of His(107) in BB3 receptor by Lys(107) (H107K-BB3 receptor-mutant) from BB2 receptor, decreased affinity 60-fold, and three replacements [H107K, E11D, G112R] decreased affinity 500-fold. Mutagenesis in EC1's surrounding transmembrane-regions (TMs) demonstrated TM2 differences were not important, but R127Q in TM3 alone decreased affinity 400-fold. Additional mutants in EC1/TM3 explored the molecular basis for these changes demonstrated in EC1, particularly important is the presence of aromatic-interactions by His(107), rather than hydrogen-bonding or charge-charge interactions, for determining Bantag-1 high affinity/selectivity. In regard to Arg(127) in TM3, both hydrogen-bonding and charge-charge interactions contribute to the high-affinity/selectivity for Bantag-1.

In pancreatic acinar cells, the Src family of kinases (SFK) is involved in the activation of several signaling cascades that are implicated in mediating cellular processes (growth, cytoskeletal changes, apoptosis). However, the role of SFKs in various physiological responses such as enzyme secretion or in pathophysiological processes such as acute pancreatitis is either controversial, unknown, or incompletely understood. To address this, in this study, we investigated the role/mechanisms of SFKs in acute pancreatitis and enzyme release. Enzyme secretion was studied in rat dispersed pancreatic acini, in vitro acute-pancreatitis-like changes induced by supramaximal COOH-terminal octapeptide of cholecystokinin (CCK). SFK involvement assessed using the chemical SFK inhibitor (PP2) with its inactive control, 4-amino-7-phenylpyrazol[3,4-d]pyrimidine (PP3), under experimental conditions, markedly inhibiting SFK activation. In CCK-stimulated pancreatic acinar cells, activation occurred of trypsinogen, various MAP kinases (p42/44, JNK), transcription factors (signal transducer and activator of transcription-3, nuclear factor-κB, activator protein-1), caspases (3, 8, and 9) inducing apoptosis, LDH release reflective of necrosis, and various chemokines secreted (monocyte chemotactic protein-1, macrophage inflammatory protein-1α, regulated on activation, normal T cell expressed and secreted). All were inhibited by PP2, not by PP3, except caspase activation leading to apoptosis, which was increased, and trypsin activation, which was unaffected, as was CCK-induced amylase release. These results demonstrate SFK activation is playing a dual role in acute pancreatitis, inhibiting apoptosis and promoting necrosis as well as chemokine/cytokine release inducing inflammation, leading to more severe disease, as well as not affecting secretion. Thus, our studies indicate that SFK is a key mediator of inflammation and pancreatic acinar cell death in acute pancreatitis, suggesting it could be a potential therapeutic target in acute pancreatitis.

"n este artículo se describen las formas de dominación y ejercicio efectivo de la autoridad en las haciendas de Ocosingo, Chia - pas. Se analizan narraciones, descripciones y percepciones de peones, caporales y patrones, con el fin de comprender las normas que pre - valecían y sus reflexiones acerca de la jerarquía social. Se presentan interpretaciones y críticas que la población indígena formula acerca de su propia experiencia respecto de la dominación, la autoridad y el poder, así como las razones que condujeron a los peones a abandonar la hacienda y fundar, posteriormente, una nueva comunidad."

Avian influenza virus infections in the human population are rare due to their inefficient direct human-to-human transmission. However, when humans are infected, a strong inflammatory response is usually induced, characterized by elevated levels of cytokines and chemokines in serum, believed to be important in the severe pathogenesis that develops in a high proportion of these patients. Extensive research has been performed to understand the molecular viral mechanisms involved in the H5N1 pathogenesis in humans, providing interesting insights about the virus-host interaction and the regulation of the innate immune response by these highly pathogenic viruses. In this review we summarize and discuss the most important findings in this field, focusing mainly on H5N1 virulence factors and their impact on the modulation of the innate immunity in humans.

Objective Systemic lupus erythematosus (SLE) patients exhibit T cell dysfunction, which can be regulated through mitochondrial transmembrane potential (Δψm) and mammalian target of rapamycin (mTOR) by glutathione (GSH). This randomized, double-blind, placebo-controlled study was undertaken to examine the safety, tolerance, and efficacy of the GSH precursor N-acetylcysteine (NAC). Methods A total of 36 SLE patients received either daily placebo or 1.2 gm, 2.4 gm, or 4.8 gm of NAC. Disease activity was evaluated monthly by the British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index (SLEDAI), and the Fatigue Assessment Scale (FAS) before, during, and after a 3-month treatment period. Mitochondrial transmembrane potential and mTOR were assessed by flow cytometry. Forty-two healthy subjects matched to patients for age, sex, and ethnicity were studied as controls. Results NAC up to 2.4 gm/day was tolerated by all patients, while 33% of those receiving 4.8 gm/day had reversible nausea. Placebo or NAC 1.2 gm/day did not influence disease activity. Considered together, 2.4 gm and 4.8 gm NAC reduced the SLEDAI score after 1 month (P = 0.0007), 2 months (P = 0.0009), 3 months (P = 0.0030), and 4 months (P = 0.0046); the BILAG score after 1 month (P = 0.029) and 3 months (P = 0.009); and the FAS score after 2 months (P = 0.0006) and 3 months (P = 0.005). NAC increased Δψm (P = 0.0001) in all T cells, profoundly reduced mTOR activity (P = 0.0009), enhanced apoptosis (P = 0.0004), reversed expansion of CD4−CD8− T cells (mean ± SEM 1.35 ± 0.12-fold change; P = 0.008), stimulated FoxP3 expression in CD4+CD25+ T cells (P = 0.045), and reduced anti-DNA production (P = 0.049). Conclusion This pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes.