Maintenance of immune tolerance by Foxp3+ regulatory T cells requires CD69 expression

Although FoxP3+ regulatory T cells are key players in the maintenance of immune tolerance and autoimmunity, the lack of specific markers constitute an obstacle to their use for immunotherapy protocols. In this study, we have investigated the role of the C-type lectin receptor CD69 in the suppressor function of Tregs and maintenance of immune tolerance towards harmless inhaled antigens. We identified a novel FoxP3+CD69+ Treg subset capable to maintain immune tolerance and protect to developing inflammation. Although CD69+ and CD69−FoxP3+ Tregs exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4, ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of TGFβ and have potent suppressor activity. This activity is regulated by STAT5 and ERK signaling pathways and is impaired by antibody-mediated down-regulation of CD69 expression. Moreover, immunotherapy with FoxP3+CD69+ Tregs restores the homeostasis in Cd69−/− mice, that fail to induce tolerance, and is also highly proficient in the prevention of inflammation. The identification of the FoxP3+CD69+ Treg subset paves the way toward the development of new therapeutic strategies to control immune homeostasis and autoimmunityThis work was supported by funding from the Spanish Ministry of Economy and Competitiveness: SAF2011-27330 to P.M., SAF2010-15106 to M.L.T and SAF2011-25834 to F.S-M.; grant INDISNET (S2010/BMD-2332) from Comunidad de Madrid and RETICS Enfermedades Cardiovasculares (RD12/0042/0056) from Instituto de Salud Carlos III to P.M and F. S-M; and ERC-2011-AdG294340-GENTRIS to F.S-M. J.R.C. was supported by a CNIC post-doctoral fellowship, R. S-D is funded with a pre-doctoral fellowship from Comunidad de Madrid and E.R.B. and A.M-M. were supported by a FPI pre-doctoral fellowship from the Spanish Ministry of Economy and Competitiveness. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and the Pro CNIC Foundatio

Implantación y evaluación de un sistema de calidad de los cuidados de atención especializada en en el área de salud de Plasencia

Uno de los pilares estratégicos del mantenimiento del estado de bienestar y, por consiguiente, instrumento para la mejora de la calidad de vida de los ciudadanos y también de la justicia social, han sido los cuidados de enfermería. La enfermería moderna tiene la obligación de mantener los cuidados basados en la calidad con el fin de lograr el compromiso de todos los integrantes de la organización y obtener un producto o servicio que sea lo mejor posible, empleando para ello los mejores componentes, la mejor gestión y los mejores procesos posibles.One of the strategic pillars to keep the welfare state improving the citizen’s quality and social justice are nursing cares. The modern nursing have to keep quality to bring off the engagement of all the parts. The objective is a good service with the best people, the best management and the best possible processe

Actividad de albendazol y los aceites esenciales de menta (Mentha piperita) y manzanilla (Matricaria chamomilla) frente Anisakis tipo I

Objetivos: Estudiar la posible actividad sinérgica de los aceites esenciales de Mentha piperita y Matricaria chamomilla frente Anisakis tipo I. Material y métodos: Se ensayó tanto in vitro como in vivo, la actividad larvicida de la mezcla de los aceites esenciales utilizando albendazol como fármaco de referencia y midiéndo su eficacia mediante un modelo estadístico. Resultados: En los ensayos in vitro, a las concentraciones de 250 y 187.5 μg/ml, la mortalidad de las larvas fue del 100% mientras que albendazol no mostró eficacia. In vivo, la mezcla de aceites esenciales fue más eficaz, reduciendo las lesiones en ratas en comparación con las tratadas con albendazol y control. Albendazol no redujo de forma significativa el porcentaje de lesiones producidas por las larvas frente al control. Conclusión: La mezcla de aceite esencial de menta y manzanilla podría ser candidata para su uso en el tratamiento/profilaxis de la anisakiasis humana.Aim: We have studied the possible synergistic activity of the essential oils of Mentha piperita and Matricaria chamomile against Anisakis type I. Materials and methods: the larvicidal activity of the mixture of essential oils was tested in vitro and in vivo, using as a reference the drug Albendazole and effectiveness measured through a statistical model. Results: The in vitro and in vivo experiments both evidenced that the larvicidal activity of essential oils, was higher than the Albendazole activity. In the in vitro assay, at concentrations of 250 and 187.5 μg/ml, the mortality was 100% with the mixture of essential oils while albendazole was ineffective at the concentrations studied. In the in vivo assay, the mixture of essential oils, was significantly more effective in the reduction of numbers of lesions with rats in comparison to albendazole treatments and control. Albendazole did not significantly reduce the percentage of lesions caused by larvae vs. control. Conclusion: Considering the results, we have come to the conclusion that the mixture of peppermint essential oils and chamomile could be used in the treatment/prophylaxis of human Anisakis.Trabajo financiado por el proyecto: P07-CVI-03249

In vivo larvicidal activity of menthol against Anisakis type I

Se ha estudiado la actividad larvicida in vivo de mentol, principal componente del aceite esencial de Mentha pipperita, frente a larvas de Anisakis tipo I aisladas del hospedador Micromesistius poutassou (bacaladilla), adquiridas en diversas pescaderías de la ciudad de Granada. Los resultados obtenidos en el ensayo muestran que en el grupo tratado con mentol no se apreciaron lesiones en el aparato digestivo, mientras que en el grupo control estas lesiones fueron observadas en el 93’3% de los animales de experimentación. En este mismo grupo se encontraron larvas que habían perforado la pared gástrica, localizándose libres en la cavidad corporal.We have studied the in vivo larvicidal activity of menthol, the main component of the essential oil of Mentha pipperita, against Anisakis type I larvae isolated from the host Micromesistius poutassou (blue whiting), acquired in several fishmongers in the city of Granada. The in vivo test results showed no gastric wall lesions in the group treated with menthol, while in the control group, 93.3% of infected rats showed those lesions. In the same control group were found larvae that had drilled the gastric wall, located free in the abdominal cavity.Trabajo financiado por el proyecto: P07-CVI-03249

Implantación y evaluación de un sistema de calidad de los cuidados de atención especializada en en el área de salud de Plasencia

Uno de los pilares estratégicos del mantenimiento del estado de bienestar y, por consiguiente, instrumento para la mejora de la calidad de vida de los ciudadanos y también de la justicia social, han sido los cuidados de enfermería. La enfermería moderna tiene la obligación de mantener los cuidados basados en la calidad con el fin de lograr el compromiso de todos los integrantes de la organización y obtener un producto o servicio que sea lo mejor posible, empleando para ello los mejores componentes, la mejor gestión y los mejores procesos posibles.One of the strategic pillars to keep the welfare state improving the citizen’s quality and social justice are nursing cares. The modern nursing have to keep quality to bring off the engagement of all the parts. The objective is a good service with the best people, the best management and the best possible processe

Evidence on port-locking with heparin versus saline in patients with cancer not receiving chemotherapy: A randomized clinical trial

Objective: To assess the safety and efficacy of port-locking with heparin every 2 months vs. every 4 months and vs. saline solution every 2 months in patients with cancer not receiving active chemotherapy. The hypothesis stated that locking with heparin at four-month intervals and saline at two-month intervals would not increment > 10% of port obstructions. Methods: Multicentre, phase IV parallel, post-test control group study took place at the two chemotherapy units of oncology hospitals. Included patients with cancer with ports that completed the chemotherapy treatment but still having port maintenance care or blood samples taken up to four months. A sample of 126 patients with cancer in three arms was needed to detect a maximum difference of 10% for bioequivalence on the locking methods. Consecutive cases non-probabilistic sampling and randomized to one of the three groups; group A: received heparin 60 IU/mL every two months (control) vs. group B heparin every four months and vs. saline every two months in group C. Primary variables were the type of locking regimen, port obstruction, and absence of blood return, port-related infection, or venous thrombosis during the study period. Clinical and sociodemographic variables were also collected. Results: A total of 143 patients were randomly assigned; group A, 47 patients with heparin every 2 months, group B, 51 patients with heparin 4 months, and group C, 45 patients with saline every 2 months. All participants presented an adequate blood return and no obstructions, until the month of the 10th, when one participant in the group A receiving was withdrawn due to an absence of blood flow ( P 1/4 0.587). Conclusions: Port locks with heparin every 4 months or saline every 2 months did not show differences in safety maintenance, infection, or thrombosis compared to heparin every 2 months

IN VIVO activity of essential oil Origanum elongatum against larva L3 of Anisakis pegreffii

En este trabajo se aborda la posible actividad larvicida in vivo del aceite esencial de Origanum elongatum, recolectado en Marruecos, frente a las larvas L3 de Anisakis pegreffii, que parasitan distintas especies marinas. Los resultados obtenidos son demostrativos del interés potencial de este aceite esencial como preventivo de la infección por Anisakis, tras ingestión del pescado parasitado.Anisakiasis is an emerging zoonotic disease caused by species of the genus Anisakis. In humans, this parasite is manifested by digestive symptoms. In the virtual absence of effective treatments against this infection, our working group has initiated a series of investigations aimed at finding natural products such as essential oils and their major components, which might be of interest in the treatment of the infectious form of these zoonoses. OBJECTIVE: Establishment of the possible in vivo activity of essential oil of O. elongatum, against L3 larva of Anisakis pegreffii. METHODOLOGY: For the study in vivo, parasites were isolated from the host Scomber japonicus (mackerel) and Trachurus trachurus (horse mackerel). The experimental animals (female Wistar rats) were infected with 6 Anisakis larva by gastric catheter, this technique was used also for the administration of O. elongatum (46.9 mg / 0.5 ml of olive oil), according to the following guidelines: infection and joint treatment and sacrifice at 4 hours. Parallel to this, a control test was performed, administering 0.5 ml olive oil together with six larvae of the parasite to a group of animals. The identification of the larvae was carried out using molecular techniques (PCR-RFLP). The identification of the main components of essential oil was performed by GC-MS.Trabajo financiado por el proyecto: P07-CVI-0324

Long-term follow-up of certolizumab pegol in uveitis due to immune-mediated inflammatory diseases: multicentre study of 80 patients

Objectives: To evaluate effectiveness and safety of certolizumab pegol (CZP) in uveitis due to immune-mediated inflammatory diseases (IMID). Methods: Multicentre study of CZP-treated patients with IMID uveitis refractory to conventional immunosuppressant. Effectiveness was assessed through the following ocular parameters: best-corrected visual acuity, anterior chamber cells, vitritis, macular thickness and retinal vasculitis. These variables were compared between the baseline, and first week, first, third, sixth months, first and second year. Results: We studied 80 (33 men/47 women) patients (111 affected eyes) with a mean age of 41.6±11.7 years. The IMID included were: spondyloarthritis (n=43), Behçet's disease (n=10), psoriatic arthritis (n=8), Crohn's disease (n=4), sarcoidosis (n=2), juvenile idiopathic arthritis (n=1), reactive arthritis (n=1), rheumatoid arthritis (n=1), relapsing polychondritis (n=1), CONCLUSIONS: CZP seems to be effective and safe in uveitis related to different IMID, even in patients refractory to previous biological drugs.Funding: This work was also partially supported by RETICS Programmes, RD08/0075 (RIER) and RD12/0009/0013 from 'Instituto de Salud Carlos III' (ISCIII) (Spain)

Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization

Simple Summary Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancer (RCC), with no data on its prevalence worldwide. No genotype-phenotype associations have been described. The aim of our study was to describe the genotypic and phenotypic features of the largest series of patients with HLRCC from Spain reported to date. Of 27 FH germline pathogenic variants, 12 were not previously reported in databases. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants. The frequency of RCCs (10.9%) was lower than those reported in the previously published series. Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys

Effect of mistimed eating patterns on breast and prostate cancer risk (MCC-Spain Study)

Modern life involves mistimed sleeping and eating patterns that in experimental studies are associated with adverse health effects. We assessed whether timing of meals is associated with breast and prostate cancer risk taking into account lifestyle and chronotype, a characteristic correlating with preference for morning or evening activity. We conducted a population-based case-control study in Spain, 2008-2013. In this analysis we included 621 cases of prostate and 1,205 of breast cancer and 872 male and 1,321 female population controls who had never worked night shift. Subjects were interviewed on timing of meals, sleep and chronotype and completed a Food Frequency Questionaire. Adherence to the World Cancer Research Fund/American Institute of Cancer Research recommendations for cancer prevention was examined. Compared with subjects sleeping immediately after supper, those sleeping two or more hours after supper had a 20% reduction in cancer risk for breast and prostate cancer combined (adjusted Odds Ratio [OR] = 0.80, 95%CI 0.67-0.96) and in each cancer individually (prostate cancer OR = 0.74, 0.55-0.99; breast cancer OR = 0.84, 0.67-1.06). A similar protection was observed in subjects having supper before 9 pm compared with supper after 10 pm. The effect of longer supper-sleep interval was more pronounced among subjects adhering to cancer prevention recommendations (OR both cancers= 0.65, 0.44-0.97) and in morning types (OR both cancers = 0.66, 0.49-0.90). Adherence to diurnal eating patterns and specifically a long interval between last meal and sleep are associated with a lower cancer risk, stressing the importance of evaluating timing in studies on diet and cancer