Cardiovascular mortality and cardiovascular event rates in patients with inflammatory rheumatic diseases in the CARdiovascular in rheuMAtology (CARMA) prospective study-results at 5 years of follow-up.

OBJECTIVES: To determine cardiovascular (CV) mortality and incidence of the first CV event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) after 5 years of follow-up. METHODS: This is an analysis of the CARdiovascular in rheMAatology (CARMA) study after 5 years of follow-up. It includes patients with RA (n = 775), AS (n = 738) and PsA (n = 721), and individuals without CIRD (n = 677) attending outpatient rheumatology clinics from 67 public hospitals in Spain. Descriptive analyses were performed for the CV mortality at 5 years. The Systematic COronary Risk Evaluation (SCORE) function at 5 years was calculated to determine the expected risk of CV mortality. Poisson models were used to estimate the incidence rates of the first CVE. Hazard ratios of the risk factors involved in the development of the first CVE were evaluated using the Weibull proportional hazard model. RESULTS: Overall, 2382 subjects completed the follow-up visit at 5 years. Fifteen patients died due to CVE. CV deaths observed in the CIRD cohort were lower than that predicted by SCORE risk charts. The highest incidence rate of CVE [7.39 cases per 1000 person-years (95% CI 4.63, 11.18)] was found in PsA patients. However, after adjusting for age, sex and CV risk factors, AS was the inflammatory disease more commonly associated with CVE at 5 years [hazard ratio 4.60 (P =0.02)], compared with those without CIRD. CONCLUSIONS: Cardiovascular mortality in patients with CIRD at 5 years of follow-up is lower than estimated. Patients with AS have a higher risk of developing a first CVE after 5 years of follow-up.

Incidence of first cardiovascular event in Spanish patients with inflammatory rheumatic diseases: prospective data from the CARMA project.

OBJECTIVES: To determine the incidence and risk factors of first cardiovascular event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD). METHODS: Analysis of data after 2.5 years of follow-up from the prospective study CARMA project, that includes patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and matched individuals without CIRD from 67 hospitals in Spain. CVE cumulative incidence per 1000 patients was calculated after 2.5 years from the start of the project. Weibull proportional hazard model was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) of the risk factors. RESULTS: 2595 (89.1%) patients completed the 2.5 years of follow-up visit. Cumulative incidence of CVE in patients with CIRD was 15.30 cases per 1000 patients (95% CI: 12.93-17.67), being higher in the subgroup with AS; 22.03 (95% CI: 11.01-33.04). Patients with AS (HR: 4.11; 95% CI: 1.07-15.79), those with older age (HR: 1.09; 95% CI: 1.05-1.13), systolic hypertension (HR: 1.02; 95% CI: 1.00-1.04) and long duration of the disease (HR: 1.07; 95% CI: 1.03-1.12) were at higher risk of first CVE during the 2.5 years of follow-up. In contrast, female gender was a protective factor (HR: 0.43; 95% CI: 0.18-1.00). CONCLUSIONS: Among CIRD patients prospectively followed-up at rheumatology outpatient clinics, those with AS show higher risk of first CVE. Besides cardiovascular risk factors, such as hypertension, being a man and older as well as having a long disease duration increase the risk of CVE in patients with CIRD.

Emergencia de bienestar en enfermedades crónicas: una aproximación conceptual / Well-being in chronic diseases: A conceptual approach

RESUMEN Se parte de una reflexión sobre el concepto de bienestar, asumido desde diferentes dominios del conocimiento para articularlo con su emergencia en enfermedades crónicas. Este artículo en principio, recoge perspectivas epistemológicas y disciplinares relacionadas con el bienestar y con diversas comprensiones sobre el proceso de salud-enfermedad, para avanzar luego en la articulación propuesta de comprender y aportar a la emergencia de bienestar en la relación de las personas en situación de enfermedad crónica, sus familias y profesionales del contexto de salud. La tarea consiste en desbordar predicciones y determinismos que definen la enfermedad y su intervención desde el modelo biomédico, y convocar interlocuciones de profesionales de diversos campos disciplinares con las personas en situación de enfermedad y sus familias, donde la experiencia de enfermedad y bienestar sea una emergencia que construyen conjuntamente y que les beneficia en un ejercicio colaborativo y de corresponsabilidad. Se espera aportar a la compresión y abordaje de situaciones de salud-enfermedad con los actores involucrados directamente en estos procesos; se busca igualmente contribuir a la generación de los marcos de políticas y a la sociedad en su relación con el sistema de salud, para cumplir con el propósito de construir bienestar para todos los seres humanos.(AU)

ABSTRACT The paper arises from a reflection about the concept of well-being from different knowledge domains in order to articulate its emergence in chronical diseases. In principle, this article gathers epistemologic and disciplinary perspectives in relation to well-being and comprehensions about the process of health-disease. In pursuance of advancing in the proposed articulation of understanding and contributing to the emergence of well-being in the relationship of people in chronic disease, their families and health professionals. The task consists in going beyond predictions and determinisms that define the disease and its intervention from the perspective of the biomedical model, and convening professional interlocutions from diverse disciplinary fields with people experiencing illness and their families; where the experience of disease and well-being are emergent of the joint construction between them, and benefits them in an exercise of collaboration and co-responsability. It is expected to enrich the comprehension and approach of health-disease situations with the actors directly involved in these processes; at the same time, it seeks to contribute in the generation of political frameworks and to society in its relation with the healthcare system, intending to fulfill the purpose of constructing welfare for all human beings.(AU)

[Well-being in chronic diseases: A conceptual approach]. / Emergencia de bienestar en enfermedades crónicas: una aproximación conceptual.

The paper arises from a reflection about the concept of well-being from different knowledge domains in order to articulate its emergence in chronical diseases. In principle, this article gathers epistemologic and disciplinary perspectives in relation to well-being and comprehensions about the process of health-disease. In pursuance of advancing in the proposed articulation of understanding and contributing to the emergence of well-being in the relationship of people in chronic disease, their families and health professionals. The task consists in going beyond predictions and determinisms that define the disease and its intervention from the perspective of the biomedical model, and convening professional interlocutions from diverse disciplinary fields with people experiencing illness and their families; where the experience of disease and well-being are emergent of the joint construction between them, and benefits them in an exercise of collaboration and co-responsability. It is expected to enrich the comprehension and approach of health-disease situations with the actors directly involved in these processes; at the same time, it seeks to contribute in the generation of political frameworks and to society in its relation with the healthcare system, intending to fulfill the purpose of constructing welfare for all human beings.

Se parte de una reflexión sobre el concepto de bienestar, asumido desde diferentes dominios del conocimiento para articularlo con su emergencia en enfermedades crónicas. Este artículo en principio, recoge perspectivas epistemológicas y disciplinares relacionadas con el bienestar y con diversas comprensiones sobre el proceso de salud-enfermedad, para avanzar luego en la articulación propuesta de comprender y aportar a la emergencia de bienestar en la relación de las personas en situación de enfermedad crónica, sus familias y profesionales del contexto de salud. La tarea consiste en desbordar predicciones y determinismos que definen la enfermedad y su intervención desde el modelo biomédico, y convocar interlocuciones de profesionales de diversos campos disciplinares con las personas en situación de enfermedad y sus familias, donde la experiencia de enfermedad y bienestar sea una emergencia que construyen conjuntamente y que les beneficia en un ejercicio colaborativo y de corresponsabilidad. Se espera aportar a la compresión y abordaje de situaciones de salud-enfermedad con los actores involucrados directamente en estos procesos; se busca igualmente contribuir a la generación de los marcos de políticas y a la sociedad en su relación con el sistema de salud, para cumplir con el propósito de construir bienestar para todos los seres humanos.

Experiencia de hipertensión arterial en la relación paciente, familia y contexto de ayuda / Experience of arterial hypertension in the patient-family relationship in a care context

Objetivo Comprender la forma como se configura narrativa y conversacionalmente la experiencia de hipertensión arterial en la relación que establecen paciente, familia, médicos, e investigadores interventores y su reconfiguración en contextos de ayuda que faciliten la emergencia de relatos generadores de bienestar. Metodología Investigación cualitativa, con diseño narrativo-conversacional, reflexivo y contextual. Participaron un paciente con diagnóstico de hipertensión arterial, su familia, una psicóloga y dos médicos. Los métodos de construcción de la información fueron: encuentros conversacionales dialógicos y revisión de literatura. Para la interpretación de los resultados se utilizaron los análisis narrativo y conversacional. Resultados En la construcción de la experiencia de hipertensión arterial no se tienen en cuenta aspectos importantes como: la solicitud de escucha, la demanda de vinculación afectiva, la vivencia de enfermedad y en este caso la vejez, en relación con la vida cotidiana. En este contexto, se configuran formas de relación que facilitan que los acontecimientos asociados a la enfermedad sean vividos desde el malestar o sufrimiento. La conversación generativa con todos los actores, posibilita la construcción de espacios dialógicos-reflexivos que brindan la oportunidad de reconfigurar las relaciones y la experiencia. Conclusiones La construcción de contextos de ayuda en los que es posible hablar y escuchar acerca de los aspectos que evitan las familias y que no escuchan los médicos, facilita la reconfiguración de la experiencia de enfermedad.(AU)

Objective To understand how the narrative and conversational experience of arterial hypertension is configured in the relationships established among patients, family members, physicians and researchers-auditors, placing the illness in a care context to facilitate the dissemination of wellbeing narratives. Method Qualitative research with reflective and contextual conversational-narrative design, which involveda patient diagnosed with hypertension, his family and two doctors. The methods of constructing information was semi structured interviews, reflective observation and literature review. The systematization of information was carried out using frameworks designed for that purpose. For the interpretation of results, narrative and conversational analyses were used. Results In the process of constructing the experience of hypertension by family members or the physician, important aspects are not taken into account such as: the listening request, a demand for bonding, the experience of illness and in this case, the daily experience of old age. In this context, these kinds of relationships can lead to discomfort and suffering in the patient's experience of the illness. The conversation generated by all stakeholders enables the construction of dialogic-reflexive spaces that provide an opportunity to reshape relationships and experience of illness Conclusions The construction of contexts of care where one can talk and hear about issues without families and doctors facilitates the reconfiguration of the experience of illness, allowing for the inclusion of family and physicians in the generation of conversational-narrative positions. This implies personal and collective agency in order to mobilize and organize the resources they have, consistent with the patient's age and diagnosis.(AU)

[Experience of arterial hypertension in the patient-family relationship in a care context]. / Experiencia de hipertensión arterial en la relación paciente, familia y contexto de ayuda.

Objective To understand how the narrative and conversational experience of arterial hypertension is configured in the relationships established among patients, family members, physicians and researchers-auditors, placing the illness in a care context to facilitate the dissemination of wellbeing narratives. Method Qualitative research with reflective and contextual conversational-narrative design, which involveda patient diagnosed with hypertension, his family and two doctors. The methods of constructing information was semi structured interviews, reflective observation and literature review. The systematization of information was carried out using frameworks designed for that purpose. For the interpretation of results, narrative and conversational analyses were used. Results In the process of constructing the experience of hypertension by family members or the physician, important aspects are not taken into account such as: the listening request, a demand for bonding, the experience of illness and in this case, the daily experience of old age. In this context, these kinds of relationships can lead to discomfort and suffering in the patient's experience of the illness. The conversation generated by all stakeholders enables the construction of dialogic-reflexive spaces that provide an opportunity to reshape relationships and experience of illness Conclusions The construction of contexts of care where one can talk and hear about issues without families and doctors facilitates the reconfiguration of the experience of illness, allowing for the inclusion of family and physicians in the generation of conversational-narrative positions. This implies personal and collective agency in order to mobilize and organize the resources they have, consistent with the patient's age and diagnosis.

Neural nitric oxide synthase participates in pemphigus vulgaris acantholysis through upregulation of Rous sarcoma, mammalian target of rapamycin and focal adhesion kinase.

Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis produced as a consequence of desmoglein (Dsg) and non-Dsg autoantibodies binding to several targeting molecules localized on the membrane of keratinocytes. Nitric oxide (NO) may exert a pathogenic function in several immunological processes. We have previously demonstrated that neural nitric oxide synthase (nNOS) plays part in PV acantholysis. Also, our group has described a relevant role for HER [human epidermal growth factor receptor (EGFR) related] isoforms and several kinases such as Src (Rous sarcoma), mammalian target of rapamycin (mTOR) and focal adhesion kinase (FAK), as well as caspases in PV development. Using a passive transfer mouse model of PV, we aimed to investigate the relationship between the increase in nNOS and EGFR, Src, mTOR and FAK kinase upregulation observed in PV lesions. Our results revealed a new function for nNOS, which contributes to EGFR-mediated PV acantholysis through the upregulation of Src, mTOR and FAK. In addition, we found that nNOS participates actively in PV at least in part by increasing caspase-9 and caspase-3 activities. These findings underline the important issue that in PV acantholysis, caspase activation is a nNOS-linked process downstream of Src, mTOR and FAK kinase upregulation.

Inhibition of FAK prevents blister formation in the neonatal mouse model of pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis and by autoantibodies against desmoglein 3 localized on desmosomes. In addition, caspases also seem to participate in this blistering disease. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in cytoskeleton remodelling and formation and disassembly of cell adhesion structures. We have previously demonstrated that HER (human epidermal growth factor receptor related) isoforms, Src (Rous sarcoma) and mammalian target of rapamycin (mTOR), three molecules implicated in signalling processes, take part in suprabasal acantholysis and apoptosis induced by PV-IgG in a mouse model. Our aim was to investigate whether upregulation of FAK is implicated in the development of PV lesions. Herein, using a mouse model, PV-IgG administration showed an increased level of FAK phosphorylated on 397 and 925 tyrosine residues in the basal layer of epidermis. When mice were pretreated with a FAK inhibitor (FI), the acantholysis of the basal layer of epidermis was absent. More interestingly, we observed that phosphorylated FAK (Y397/925) decreased when HER isoforms, Src, mTOR and pan-caspases inhibitors were employed before PV-IgG administration. In addition, pretreatment with the FI before PV-IgG injection prevented the changes in both Bax and Bcl-2 expression and caspase-9 and caspase-3 activities induced by PV-IgG. Finally, FI reduced the expression of phosphorylated Src and mTOR in the basal cells of epidermis. In conclusion, our data reveal a novel role of phosphorylated FAK (Y397/925) in PV development involving HER isoforms, Src and mTOR kinases.

Templated synthesis, characterization, and sensing application of macroscopic platinum nanowire network electrodes.

Novel platinum nanowire network electrodes have been fabricated through electrodeposition using mesoporous silica thin films as templates. These electrodes were characterized by X-ray diffraction, transmission electron microscope, and scanning electron microscope. The electrochemical properties of the electrodes, such as electrochemical active area and methanol oxidation, have also been studied. Compared with conventional polycrystalline Pt electrodes, these novel nanowire network electrodes possess high electrochemical active areas and demonstrate higher current densities and a lower onset potential for methanol electro-oxidation. Enzymatic Pt nanowire-network-based sensors show higher sensitivity for glucose detection than that using conventional polycrystalline Pt electrode. Such macroscopic nanowire network electrodes provide ideal platforms for sensing and other device applications.