Targeting macrophages with phosphatidylserine-rich liposomes as a potential antigen-specific immunotherapy for type 1 diabetes.

Type 1 diabetes (T1D) results from a breakdown in immunological tolerance, with pivotal involvement of antigen-presenting cells. In this context, antigen-specific immunotherapies have been developed to arrest autoimmunity, such as phosphatidylserine (PS)-liposomes. However, the role of certain antigen-presenting cells in immunotherapy, particularly human macrophages (Mφ) in T1D remains elusive. The aim of this study was to determine the role of Mφ in antigen-specific immune tolerance and T1D. To that end, we evaluated Mφ ability to capture apoptotic-body mimicking PS-liposomes in mice and conducted a phenotypic and functional characterisation of four human monocyte-derived Mφ (MoMφ) subpopulations (M0, M1, M2a and M2c) after PS-liposomes uptake. Our findings in mice identified Mφ as the most phagocytic cell subset in the spleen and liver. In humans, while phagocytosis rates were comparable between T1D and control individuals, PS-liposome capture dynamics differed among Mφ subtypes, favouring inflammatory (M1) and deactivated (M2c) Mφ. Notably, high nanoparticle concentrations did not affect macrophage viability. PS-liposome uptake by Mφ induced alterations in membrane molecule expression related to immunoregulation, reduced secretion of IL-6 and IL-12, and diminished autologous T-cell proliferation in the context of autoantigen stimulation. These results underscore the tolerogenic effects of PS-liposomes and emphasize their potential to target human Mφ, providing valuable insights into the mechanism of action of this preclinical immunotherapy.

Impact of the COVID-19 pandemic on demand for emergency department care for older patients: the EDEN-7 COVID cohort study. / Estudio EDEN-7: impacto de la pandemia COVID-19 sobre la demanda asistencial de personas mayores en los servicios de urgencias españoles.

OBJECTIVES: To analyze the impact of the COVID-19 pandemic on Spanish emergency department (ED) care for patients aged 65 years or older during the first wave vs. a pre-pandemic period. MATERIAL AND METHODS: Retrospective cross-sectional study of a COVID-19 portion of the EDEN project (Emergency Department and Elder Needs). The EDEN-COVID cohort included all patients aged 65 years or more who were treated in 52 EDs on 7 consecutive days early in the pandemic. We analyzed care variables, discharge diagnoses, use of diagnostic and therapeutic resources, use of observation units, need for hospitalization, rehospitalization, and mortality. These data were compared with data for an EDEN cohort in the same age group recruited during a similar period the year before the pandemic. RESULTS: The 52 participating hospital EDs attended 33 711 emergencies during the pandemic vs. 96 173 emergencies in the pre-COVID period, representing a 61.7% reduction during the pandemic. Patients aged 65 years or older accounted for 28.8% of the caseload during the COVID-19 period and 26.4% of the earlier cohort (P .001). The COVID-19 caseload included more men (51.0%). Comorbidity and polypharmacy were more prevalent in the pandemic cohort than in the earlier one (comorbidity, 92.6% vs. 91.6%; polypharmacy, 65.2% vs. 63.6%). More esturesources (analgesics, antibiotics, heparins, bronchodilators, and corticosteroids) were applied in the pandemic period, and common diagnoses were made less often. Observation wards were used more often (for 37.8% vs. 26.2% in the earlier period), and hospital admissions were more frequent (in 56.0% vs. 25.3% before the pandemic). Mortality was higher during the pandemic than in the earlier cohort either in ED (1.8% vs 0.5%) and during hospitalization (11.5 vs 2.9%). CONCLUSION: The proportion of patients aged 65 years or older decreased in the participating Spanish EDs. However, more resources were required and the pattern of diagnoses changed. Observation ward stays were longer, and admissions and mortality increased over the numbers seen in the reference period.

OBJETIVO: Analizar el impacto de la pandemia COVID-19 sobre la asistencia a las personas mayores ($ 65 años) en los servicios de urgencias hospitalarios (SUH) españoles durante la primera oleada pandémica, comparándola con un periodo previo. METODO: Estudio transversal retrospectivo de la cohorte EDEN-COVID (Emergency Department and Elder Needs during COVID), que incluyó a todos los pacientes $ 65 años atendidos en 52 SUH españoles durante 7 días consecutivos de un periodo pandémico. Se analizaron variables asistenciales, diagnósticos de alta, consumo de recursos diagnósticos y terapéuticos, utilización de las unidades de observación, necesidad de ingreso, rehospitalización y mortalidad. Estos datos se compararon con la cohorte EDEN (Emergency Department and Elder Needs), que reclutó a pacientes del mismogrupo de edad durante un periodo similar del año anterior. RESULTADOS: Durante el periodo COVID-19 se atendieron 33.711 episodios en los 52 SUH participantes, frente a 96.173 del periodo pre-COVID, lo que supone una disminución de la demanda de 61,7%. La proporción de asistencias a pacientes de 65 o más años fue de 28,8% en el periodo COVID-19 y 26,4% en el periodo previo (p 0,001). Durante el periodo COVID hubo mayor proporción de hombres (51,0% vs 44,9%), mayor comorbilidad (92,6% vs 91,6%) y polifarmacia (65,2% vs 63,6%), mayor uso de recursos, de analgésicos, antibióticos, heparinas, broncodilatadores y corticoides, menor proporción de los diagnósticos más habituales, mayor utilización de las unidades de observación (37,8% vs 26,2%) y un incremento de la proporción de ingresos (56,0% vs 25,3%), y de mortalidad en urgencias (1,8% vs 0,5%) y durante la hospitalización (11,5% vs 2,9%). CONCLUSIONES: La primera ola de la pandemia COVID-19 ha provocado una disminución global de las asistencias a personas mayores ($ 65 años) en los SUH españoles analizados, mayor consumo de recursos, un mapa diferente de procesos diagnósticos asistidos y un aumento proporcional de estancias en observación, de ingresos y de mortalidad, respecto al periodo de referencia.

A new platform for autoimmune diseases. Inducing tolerance with liposomes encapsulating autoantigens.

Autoimmune diseases (AIDs) are caused by the loss of self-tolerance and destruction of tissues by the host's immune system. Several antigen-specific immunotherapies, focused on arresting the autoimmune attack, have been tested in clinical trials with discouraging results. Therefore, there is a need for innovative strategies to restore self-tolerance safely and definitively in AIDs. We previously demonstrated the therapeutic efficacy of phosphatidylserine (PS)-liposomes encapsulating autoantigens in experimental type 1 diabetes and multiple sclerosis. Here, we show that PS-liposomes can be adapted to other autoimmune diseases by simply replacing the encapsulated autoantigen. After administration, they are distributed to target organs, captured by phagocytes and interact with several immune cells, thus exerting a tolerogenic and immunoregulatory effect. Specific PS-liposomes demonstrate great preventive and therapeutic efficacy in rheumatoid arthritis and myasthenia gravis. Thus, this work highlights the therapeutic potential of a platform for several autoimmunity settings, which is specific, safe, and with long-term effects.

Impact of Betamethasone Pretreatment on Engrafment of Cord Blood-Derived Hematopoietic Stem Cells.

Hematopoietic stem cell (HSC) transplantation is crucial to cure hematologic malignancies. Umbilical cord blood (UCB) is a source of stem cells, but 90% of UCB units are discarded due to low cellularity. Improving the engraftment capacities of CD34+ stem cells would allow the use of UCB that were so far rejected. Betamethasone induces long-term transcriptomic and epigenomic changes in immune cells through glucocorticoid receptor. We hypothesize that discarded UCB could be used owing to improvements induced by betamethasone. Isolated CD34+ HSC from UCB were exposed to the synthetic glucocorticoids betamethasone and fluticasone for 20 h, and cell phenotype was determined before transplantation. NSG mice were sub-lethally irradiated (1 Gy or 2 Gy) 6 h before intravenously transferring 2-5 × 105 CD34+ HSC. The peripheral blood engraftment levels and the leukocyte subsets were followed up for 20 weeks using flow cytometry. At end point, the engraftment and leukocyte subsets were determined in the spleen and bone marrow. We demonstrated that betamethasone has surprising effects in recovering immune system homeostasis. Betamethasone and fluticasone increase CXCR4 and decrease HLA class II and CD54 expression in CD34+ HSCs. Both glucocorticoids-exposed cells showed a similar engraftment in 2 Gy-irradiated NSG mice. Interestingly, betamethasone-exposed cells showed enhanced engraftment in 1 Gy-irradiated NSG mice, with a trend to increase regulatory T cell percentage when compared to control. Betamethasone induces alterations in CD34+ HSCs and improve the engraftment, leading to a faster immune system recovery, which will contribute to engrafted cells survival.

Predictors of revisits within 1 year by patients after acute COVID-19: the HUBCOVID365 cohort study. / Predictores de revisita en pacientes con infección aguda COVID-19 con seguimiento al año: estudio de cohorte HUBCOVID365.

OBJECTIVES: To analyze the frequencies of 3 types of hospital revisits by patients after treatment for COVID-19 in the emergency department. MATERIAL AND METHODS: Retrospective observational study of consecutive patients who came to the emergency department in March and April 2020 and were discharged alive with a diagnosis of COVID-19. Baseline and acute episode data were collected and the patients were followed for 1 year. We analyzed variables associated with revisits for any reason, revisits related to COVID-19, and early COVID-19-related revisits (within 30 days). RESULTS: A total of 1352 patients with a mean age of 62.1 years (52.9% male) were studied. A total of 553 revisits were made by 342 patients (25.3%) for any reason; 132 (9.8%) revisited in relation to COVID-19 at least once. Of those, 103 (7.6%) revisited within 30 days (early) and 29 (2.2%) came later. COVID-19-related revisits were associated with thrombotic events (odds ratio [OR], 7.58; 95% CI, 1.75-32.81) and pulmonary fibrosis (OR, 4.95; 95% CI, 1.27-19.24); early revisits were inversely associated with follow-up management by a contracted health care support service (OR, 0.18; 95% CI, 0.03-0.92). Hospital admission during the initial visit was significantly associated with fewer revisits for any reason or related to COVID-19 at any time. CONCLUSION: Fewer than half the total number of emergency department revisits after initial care for COVID-19 were related to the novel coronavirus infection. Revisits occurred more often in the first 30 days after discharge. Later COVID-19-related revisits were uncommon, but given the large number of patients with this infection, such visits can be expected.

OBJETIVO: Analizar diferentes categorías de revisita (RV) al año en pacientes con infección COVID-19 que consultan en un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional, retrospectivo, que incluyó pacientes consecutivos que consultaron al SUH en los meses de marzo y abril de 2020 con diagnóstico de COVID-19 y fueron dados de alta vivos del hospital. Se recogieron variables basales y del episodio agudo y se realizó un seguimiento al año. Se hicieron tres comparaciones identificando variables asociadas a la RV total, RV relacionada con COVID-19 (RCovid) y RCovid precoz (# 30 días). RESULTADOS: Se analizaron 1.352 pacientes con edad media de 62,1 años y 52,9% varones. En el seguimiento al año hubo 553 RV en 342 (25,3%) pacientes, 132 (9,8%) con al menos una RCovid, 103 (7,6%) precoz y 29 (2,2%) tardía. La RCovid se relacionó con la presencia de fenómenos trombóticos [OR 7,58 (IC 95%: 1,75-32,81)] y la fibrosis pulmonar [OR 4,95 (IC 95%: 1,27-19,24)]; y la RCovid precoz se relacionó inversamente con alta a dispositivo de soporte sanitario [OR 0,18 (IC 95%: 0,03-0,92)]. El ingreso hospitalario en el evento índice disminuyó la RV total y RCovid y las hospitalizaciones derivadas de esta RV de manera significativa a largo plazo. CONCLUSIONES: Menos de la mitad de la RV total tras una infección COVID-19 está relacionada con la infección, y es más frecuente en los primeros 30 días. La RCovid tardía no es frecuente, pero dado el elevado número de pacientes que han sido infectados por COVID-19 se debe tener en cuenta.

Predictores de revisita en pacientes con infección aguda COVID-19 con seguimiento al año: estudio de cohorte HUBCOVID365 / Predictors of revisits within 1 year by patients after acute COVID-19: the HUBCOVID365 cohort study

Objetivo. Analizar diferentes categorías de revisita (RV) al año en pacientes con infección COVID-19 que consultan en un servicio de urgencias hospitalario (SUH). Método. Estudio observacional, retrospectivo, que incluyó pacientes consecutivos que consultaron al SUH en los meses de marzo y abril de 2020 con diagnóstico de COVID-19 y fueron dados de alta vivos del hospital. Se recogieron variables basales y del episodio agudo y se realizó un seguimiento al año. Se hicieron tres comparaciones identifican- do variables asociadas a la RV total, RV relacionada con COVID-19 (RCovid) y RCovid precoz (# 30 días). Resultados. Se analizaron 1.352 pacientes con edad media de 62,1 años y 52,9% varones. En el seguimiento al año hubo 553 RV en 342 (25,3%) pacientes, 132 (9,8%) con al menos una RCovid, 103 (7,6%) precoz y 29 (2,2%) tardía. La RCovid se relacionó con la presencia de fenómenos trombóticos [OR 7,58 (IC 95%: 1,75-32,81)] y la fibrosis pulmonar [OR 4,95 (IC 95%: 1,27-19,24)]; y la RCovid precoz se relacionó inversamente con alta a dispositivo de so- porte sanitario [OR 0,18 (IC 95%: 0,03-0,92)]. El ingreso hospitalario en el evento índice disminuyó la RV total y RCovid y las hospitalizaciones derivadas de esta RV de manera significativa a largo plazo. Conclusión. Menos de la mitad de la RV total tras una infección COVID-19 está relacionada con la infección, y es más frecuente en los primeros 30 días. La RCovid tardía no es frecuente, pero dado el elevado número de pacientes que han sido infectados por COVID-19 se debe tener en cuenta.

Objective. To analyze the frequencies of 3 types of hospital revisits by patients after treatment for COVID-19 in the emergency department. Methods. Retrospective observational study of consecutive patients who came to the emergency department in March and April 2020 and were discharged alive with a diagnosis of COVID-19. Baseline and acute episode data were collected and the patients were followed for 1 year. We analyzed variables associated with revisits for any reason, revisits related to COVID-19, and early COVID-19–related revisits (within 30 days). Results. A total of 1352 patients with a mean age of 62.1 years (52.9% male) were studied. A total of 553 revisits were made by 342 patients (25.3%) for any reason; 132 (9.8%) revisited in relation to COVID-19 at least once. Of those, 103 (7.6%) revisited within 30 days (early) and 29 (2.2%) came later. COVID-19–related revisits were associated with thrombotic events (odds ratio [OR], 7.58; 95% CI, 1.75–32.81) and pulmonary fibrosis (OR, 4.95; 95% CI, 1.27–19.24); early revisits were inversely associated with follow-up management by a contracted health care support service (OR, 0.18; 95% CI, 0.03–0.92). Hospital admission during the initial visit was significantly associated with fewer revisits for any reason or related to COVID-19 at any time. Conclusions. Fewer than half the total number of emergency department revisits after initial care for COVID-19 were related to the novel coronavirus infection. Revisits occurred more often in the first 30 days after discharge. Later COVID-19–related revisits were uncommon, but given the large number of patients with this infection, such visits can be expected.

Propiedades Psicométricas de la Escala de Medida de la Identidad Docente / Psychometric Properties of the Teacher Identity Measurement Scale (TIMS)

RESUMEN: La identidad docente desempeña un papel fundamental en el ejercicio de la profesión. El objetivo de este estudio es mostrar las propiedades psicométricas de la Escala de Medida de la Identidad Docente para ser empleada en investigaciones en el contexto chileno y aportar lineamientos para la utilización de este instrumento en el contexto hispanoparlante. Participaron 242 estudiantes de la carrera de Pedagogía en Educación Especial de 10 universidades chilenas. Se empleó el procedimiento de traducción y retrotraducción, obteniendo evidencia de validez de contenido mediante el juicio de expertos y el índice de concordancia V de Aiken. A través de un análisis factorial confirmatorio, se comprueba un buen nivel de ajuste del instrumento, mientras que la consistencia interna es verificada mediante el Coeficiente de Omega (ω), evidenciando buenos índices de confiabilidad. Los hallazgos muestran que la versión traducida y adaptada de la escala es válida y fiable para ser empleada en estudiantes universitarios de Pedagogía en Chile, pudiendo contribuir a la comprensión del desarrollo de la identidad docente en futuros profesores

ABSTRACT: Teacher identity plays a fundamental role in the exercise of the profession. Te aim of this study is to show the psychometric properties of the Teacher Identity Measurement Scale for use in research in the Chilean context and to provide guidelines for the use of this instrument in the Spanish-speaking context. A sample of 242 Special Education Preservice Teachers from ten Chilean universities participated in the study. Te translation and back-translation procedure was used, obtaining evidence of content validity through expert judgment and Aiken's V concordance index. Trough a confirmatory factor analysis, a good level of adjustment of the instrument was verified, while the internal consistency was verified through the McDonald's Omega Coefficient (ω), evidencing good reliability indexes. Te findings show that the translated and adapted version of the scale is valid and reliable to be used in university student teachers in Chile, and can contribute to the understanding of the development of the teachers identity during initial teachers training.

Antibody Protection against Long-Term Memory Loss Induced by Monomeric C-Reactive Protein in a Mouse Model of Dementia.

Monomeric C-reactive protein (mCRP), the activated isoform of CRP, induces tissue damage in a range of inflammatory pathologies. Its detection in infarcted human brain tissue and its experimentally proven ability to promote dementia with Alzheimer's disease (AD) traits at 4 weeks after intrahippocampal injection in mice have suggested that it may contribute to the development of AD after cerebrovascular injury. Here, we showed that a single hippocampal administration of mCRP in mice induced memory loss, lasting at least 6 months, along with neurodegenerative changes detected by increased levels of hyperphosphorylated tau protein and a decrease of the neuroplasticity marker Egr1. Furthermore, co-treatment with the monoclonal antibody 8C10 specific for mCRP showed that long-term memory loss and tau pathology were entirely avoided by early blockade of mCRP. Notably, 8C10 mitigated Egr1 decrease in the mouse hippocampus. 8C10 also protected against mCRP-induced inflammatory pathways in a microglial cell line, as shown by the prevention of increased generation of nitric oxide. Additional in vivo and in vitro neuroprotective testing with the anti-inflammatory agent TPPU, an inhibitor of the soluble epoxide hydrolase enzyme, confirmed the predominant involvement of neuroinflammatory processes in the dementia induced by mCRP. Therefore, locally deposited mCRP in the infarcted brain may be a novel biomarker for AD prognosis, and its antibody blockade opens up therapeutic opportunities for reducing post-stroke AD risk.

A century later, still fighting back: antigen-specific immunotherapies for type 1 diabetes.

Type 1 diabetes (T1D) is a chronic metabolic disease caused by the autoimmune destruction of insulin-producing ß-cells. Ever since the 1920s, the fate of patients suffering from T1D was dramatically improved owing to the isolation and production of insulin, and the scientific field has largely progressed as a result of the evidence gathered about its underpinnings and mechanisms. The last years have seen this knowledge transformed into actual antigen-specific immunotherapies with potential to restore selectively the breach of tolerance to ß-cell autoantigens and halt the autoimmune aggression. However, so far, the results of both prevention and reversion trials in T1D have been rather discouraging, so there is still an urgent need to optimize those immunotherapies and their associated factors, for example, posology and administration patterns, route and timing. In this review, we look back on what has been achieved in the last century and identify the main autoantigens driving the autoimmune attack in T1D. Then, we take a deep dive into the numerous antigen-specific immunotherapies trialed and the ones still at a preclinical phase, ranging from peptides, proteins and agent combinations to gene transfer, nanoparticles, cell-based strategies and novel approaches exploiting naturally occurring tolerogenic processes. Finally, we provide insight into the several features to be considered in a T1D clinical trial, the ideal time point for intervention and the biomarkers needed for monitoring the successful regulatory effect of the antigen-specific immunotherapy. Although further research and optimization remain imperative, the development of a therapeutic armamentarium against T1D autoimmunity is certainly advancing with a confident step.

Evidencia de sobrediagnóstico en el TDAH en base a evaluación neuropsicológica: un estudio en escolares chilenos / Evidence of overdiagnosis in Attention Deficit Hyperactivity Disorder (ADHD) based on neuropsychological evaluation: a study in Chilean students

Resumen Objetivo: El Trastorno por Déficit de Atención con Hiperactividad/impulsividad (TDAH) es una de las dificultades de aprendizaje más comunes en las escuelas chilenas. Se caracteriza por un patrón de funcionamiento atípico en atención e inhibición, con fuerte compromiso de otras funciones ejecutivas. Uno de los desafíos que plantea este trastorno está referido al proceso de diagnosis, el cual no suele ser suficientemente preciso. Se pretende explorar las diferencias en la distribución de dos muestras de estudiantes con y sin TDAH diagnosticadas con una escala de observación conductual a través de la evaluación de las funciones ejecutivas de atención, inhibición y flexibilidad cognitiva. Método: En este estudio se evaluó a 132 escolares, 66 con TDAH y 66 sin TDAH, en las variables de atención, inhibición y flexibilidad cognitiva de un colegio de la ciudad de Concepción en Chile. Se contrastó el rendimiento cognitivo con los diagnósticos y se reagrupó a los estudiantes en los subtipos conocidos del trastorno. Resultados: La evaluación neuropsicológica mostró que en el grupo con TDAH había alumnos que no cumplían los criterios diagnósticos para estar incluidos en él. En el grupo sin TDAH se observó un fenómeno semejante. En ambos grupos la evaluación neuropsicológica de la atención y la inhibición resultaron útiles para diagnosticar con mayor certeza y para determinar el subtipo al que pertenecía cada estudiante con TDAH detectado. La flexibilidad cognitiva solo permitió diferenciar a los sujetos con y sin TDAH. Conclusiones: En ambos grupos estudiados fue posible encontrar sujetos mal diagnosticados; el sobrediagnóstico fue de 43,93 % en el grupo con TDAH, mientras que el infradiagnóstico fue de 42,42 % en el grupo sin TDAH.

Abstract Objective: Attention Deficit Hyperactivity/Impulsivity Disorder (ADHD) is one of the most common learning difficulties in Chilean schools. It is characterized by an atypical functioning pattern in attention and inhibition, strongly compromising other executive functions. One of the challenges posed by this disorder is the diagnosis process, which is often not sufficiently accurate. The intention is to study the distribution of two students samples, with and without ADHD, diagnosed by a behavioral observation scale through the evaluation of attention, inhibition, and cognitive flexibility executive functions. Method: This study evaluated 132 students, 66 with ADHD and 66 without ADHD, considering the attention, inhibition, and cognitive flexibility variables of a school in the city of Concepción in Chile. Cognitive performance was contrasted with the diagnoses, and students were regrouped in the disorder known subtypes. Results: The neuropsychological evaluation showed that in the ADHD group, there were students who did not meet the diagnostic criteria to be included in the group. A similar phenomenon was observed in the group without ADHD. In both the groups, the neuropsychological evaluation of attention and inhibition was useful in providing a more certain dignosis and in determining the subtype to which each student detected with ADHD belonged. Cognitive flexibility was only useful in differentiating betwen the subjects with and without ADHD. Conclusions: In both the groups studied, it was possible to find misdiagnosed subjects; the overdiagnosis was 43,93 % in the ADHD group, while the under-diagnosis was 42,42 % in the group without ADHD.

Evolving dynamic self-adaptation policies of mHealth systems for long-term monitoring.

Tele-rehabilitation can complement traditional rehabilitation therapies by providing valuable information that can help in the evaluation, monitoring, and treatment of patients. Many patient tele-monitoring systems that integrate wearable technology are emerging as an effective tool for the long-term surveillance of rehabilitation progression, enabling continuous sampling of patient real-time movement in a non-invasive way, without affecting the normal daily activity of the outpatient, who, therefore, will not need to make frequent clinic visits. One of the main challenges of tele-rehabilitation systems is to pay special attention to the diversity of dysfunctions in patients by offering devices with customized behaviours adaptable to the physical conditions of each patient at the different stages of the rehabilitation therapy. Long-term monitoring systems need an adaptation policy to autonomously reconfigure their behaviour according to vital signs read during the physical activity of the patient, the remaining battery level, or the required accuracy of collected data. However, it would alsobe desirable to adjust such adaptation policies over time, according to the patient's evolution. This work presents a wearable patient-monitoring system for tele-rehabilitation that is able to dynamically self-configure its internal behaviour to the current context of the outpatient according to a set of adaptation policies that optimize battery consumption, taking into account other QoS parameters at the same time. Our system is also able to self-adapt its internal adaptation policies as a patient's condition improves, while maintaining the system's efficiency. We illustrate our proposal with a real mHealth case study. The results of the experiments show that the system updates the adaptation policies, taking into account specific indicators of the disease. The validation results show that the evolution of the self-adaptation policies correlates with the progression of different patients.

Exploring DNA binding ability of two novel α-N-heterocyclic thiosemicarbazone palladium(II) complexes.

One mononuclear and another dinuclear Pd(II) complexes bearing a α-N-heterocyclic thiosemicarbazone ligand have been synthesized, fully characterized and studied as biological agents. In both complexes, the palladium center is coordinated to 3,5-diacetyl-1,2,4-triazol bis(N4,N4-dimethylthiosemicarbazone) via three sites (N, N and S). Their binding ability to DNA has been evaluated using spectroscopic and biophysical techniques. Molecular docking and molecular dynamics calculations supports the existence of a minor groove binding mode between the studied compounds and DNA.

A Software Product Line Process to Develop Agents for the IoT.

One of the most important challenges of this decade is the Internet of Things (IoT), which aims to enable things to be connected anytime, anyplace, with anything and anyone, ideally using any path/network and any service. IoT systems are usually composed of heterogeneous and interconnected lightweight devices that support applications that are subject to change in their external environment and in the functioning of these devices. The management of the variability of these changes, autonomously, is a challenge in the development of these systems. Agents are a good option for developing self-managed IoT systems due to their distributed nature, context-awareness and self-adaptation. Our goal is to enhance the development of IoT applications using agents and software product lines (SPL). Specifically, we propose to use Self-StarMASMAS, multi-agent system) agents and to define an SPL process using the Common Variability Language. In this contribution, we propose an SPL process for Self-StarMAS, paying particular attention to agents embedded in sensor motes.

Dynamic reconfiguration of security policies in wireless sensor networks.

Providing security and privacy to wireless sensor nodes (WSNs) is very challenging, due to the heterogeneity of sensor nodes and their limited capabilities in terms of energy, processing power and memory. The applications for these systems run in a myriad of sensors with different low-level programming abstractions, limited capabilities and different routing protocols. This means that applications for WSNs need mechanisms for self-adaptation and for self-protection based on the dynamic adaptation of the algorithms used to provide security. Dynamic software product lines (DSPLs) allow managing both variability and dynamic software adaptation, so they can be considered a key technology in successfully developing self-protected WSN applications. In this paper, we propose a self-protection solution for WSNs based on the combination of the INTER-TRUST security framework (a solution for the dynamic negotiation and deployment of security policies) and the FamiWare middleware (a DSPL approach to automatically configure and reconfigure instances of a middleware for WSNs).We evaluate our approach using a case study from the intelligent transportation system domain.

iMuseumA: an agent-based context-aware intelligent museum system.

Currently, museums provide their visitors with interactive tour guide applications that can be installed in mobile devices and provide timely tailor-made multimedia information about exhibits on display. In this paper, we argue that mobile devices not only could provide help to visitors, but also to museum staff. Our goal is to integrate, within the same system, multimedia tour guides with the management facilities required by museums. In this paper, we present iMuseumA (intelligent museum with agents), a mobile-based solution to customize visits and perform context-aware management tasks. iMuseumA follows an agent-based approach, which makes it possible to interact easily with the museum environment and make decisions based on its current status. This system is currently deployed in the Museum of Informatics at the Informatics School of the University of Málaga, and its main contributions are: (i) a mobile application that provides management facilities to museum staff by means of sensing and processing environmental data; (ii) providing an integrated solution for visitors, tour guides and museum staff that allows coordination and communication enrichment among different groups of users; (iii) using and benefiting from group communication for heterogeneous groups of users that can be created on demand.

Configuring a context-aware middleware for Wireless Sensor Networks.

In the Future Internet, applications based on Wireless Sensor Networks will have to support reconfiguration with minimum human intervention, depending on dynamic context changes in their environment. These situations create a need for building these applications as adaptive software and including techniques that allow the context acquisition and decisions about adaptation. However, contexts use to be made up of complex information acquired from heterogeneous devices and user characteristics, making them difficult to manage. So, instead of building context-aware applications from scratch, we propose to use FamiWare, a family of middleware for Ambient Intelligence specifically designed to be aware of contexts in sensor and smartphone devices. It provides both, several monitoring services to acquire contexts from devices and users, and a context-awareness service to analyze and detect context changes. However, the current version of FamiWare does not allow the automatic incorporation related to the management of new contexts into the FamiWare family. To overcome this shortcoming, in this work, we first present how to model the context using a metamodel to define the contexts that must to be taken into account in an instantiation of FamiWare for a certain Ambient Intelligence system. Then, to configure a new context-aware version of FamiWare and to generate code ready-to-install within heterogeneous devices, we define a mapping that automatically transforms metamodel elements defining contexts into elements of the FamiWare family, and we also use the FamiWare configuration process to customize the new context-aware variant. Finally, we evaluate the benefits of our process, and we analyze both that the new version of the middleware works as expected and that it manages the contexts in an efficient way.