Bone marrow/bone pre-metastatic niche for breast cancer cells colonization: The role of mesenchymal stromal cells.

Breast cancer is one of the most common oncological pathologies in women worldwide. While its early diagnosis has considerably improved, about 70 % of advanced patients develop bone metastases with a high mortality rate. Several authors demonstrated that primary breast cancer cells prepare their future metastatic niche -known as the pre-metastatic niche- to turn it into an "optimal soil" for colonization. The role of the different cellular components of the bone marrow/bone niche in bone metastasis has been well described. However, studying the changes that occur in this microenvironment before tumor cells arrival has become a novel research field. Therefore, the purpose of this review is to describe the current knowledge about the modulation of the normal bone marrow/bone niche by the primary breast tumor, in particular, highlighting the role of mesenchymal stem/stromal cells in transforming this soil into a pre-metastatic niche for breast cancer cells colonization.

Unnecessary overuse. Study of "inadvisable practices" for patients with atrial fibrillation. / Sobreutilización innecesaria. Estudio de los «no hacer¼ en pacientes con fibrilación auricular.

OBJECTIVE: To identify overuse (diagnostic, therapeutic and self-care practices that represent risks that outweigh the potential benefits) in patients with atrial fibrillation. METHOD: The study was based on qualitative research techniques. Using the "Metaplan" technique, we identified and ordered potentially inappropriate, ineffective and inefficient practices. By means of a consensus conference, we then established a number of "inadvisable practice" measures (relatively common practices that should be eliminated based on the scientific evidence or clinical experience). Professionals from the specialties of cardiology, haematology, neurology, internal medicine, family medicine and nursing participated in the consensus. RESULTS: We developed a catalogue of 19 "inadvisable practices" related to the diagnosis, treatment and care of anticoagulated patients that were inappropriate, had questionable effectiveness or were ineffective, as well as 13 beliefs or behaviours for anticoagulated patients that could result in injury or were useless or inefficient. CONCLUSION: The "inadvisable practices" approach helps identify practices that represent greater risks than benefits for patients. It seems appropriate to include algorithms in the clinical decision-making support systems that consider this information for the diagnosis, treatment and for home care. For this last case, recommendations have also been prepared that define specific contents for the healthcare education of these patients.

[Introduction of capillary glycosylated haemoglobin determination in a Primary Care Health Area: Multicentre study of the evolution of patients with type 2 diabetes mellitus]. / Implantación de la determinación de hemoglobina glucosilada capilar en un Área de Salud: estudio multicéntrico sobre evolución de pacientes con diabetes mellitus de tipo 2.

PURPOSE: The aim of this study was to evaluate the efficiency of a joint intervention that included educational components, self-assessment, and information to optimise diabetes control through the introduction of instant capillary glycosylated haemoglobin (HbA1c) determination in Primary Care. MATERIALS AND METHODS: A multicentre prospective descriptive study was carried out over 3years in 10Primary Care Centres of the Area VII Murcia East. At the end of the study there were 804 patients with type 2 diabetes (DM2). Patients were divided into 4 groups based on initial values of HbA1c, and if changes in their treatment were needed. HbA1c, body mass index, and blood pressure were monitored. A financial assessment was also performed on the impact of the implementation of a protocol to measure instant capillary RESULTS: A significant reduction was observed in HbA1c values. The initial HbA1c mean value was 7.4±1.4%, which decreased to a final value of 6.9±1.0% (P<.001). At the end of the study, 71.4% of patients included reached diabetic control objectives. In addition, the financial assessment demonstrated that the implementation of this diabetes control system led to a decrease of the 24.7% in spending on glucose strips after the first year of study in Area VII Murcia Health Service. CONCLUSIONS: The introduction of capillary HbA1c determination in Primary Care has demonstrated to improve diabetes control and the efficiency of the health personnel. Furthermore, a reduction in the health costs of patients with DM2 was also shown.

Ostreid herpesvirus in wild oysters from the Huelva coast (SW Spain).

This is the first report of ostreid herpesvirus 1 microvariant (OsHV-1 µVar) infecting natural oyster beds located in Huelva (SW Spain). The virus was detected in 3 oyster species present in the intertidal zone: Crassostrea gigas (Thunberg, 1793), C. angulata (Lamarck, 1819) and, for the first time, in Ostrea stentina Payraudeau, 1826. Oysters were identified by a specific polymerase chain reaction (PCR) and posterior restriction fragment length polymorphism (RFLP) analysis based on cytochrome oxidase I (COI) mitochondrial DNA. Results confirmed that C. angulata still remains the dominant oyster population in SW Spain despite the introduction of C. gigas for cultivation in the late 1970s, and its subsequent naturalization. C. angulata shows a higher haplotype diversity than C. gigas. OsHV-1 virus was detected by PCR with C2/C6 pair primers. Posterior RFLP analyses with the restriction enzyme MfeI were done in order to reveal the OsHV-1 µVar. Detections were confirmed by DNA sequencing, and infections were evidenced by in situ hybridization in C. gigas, C. angulata and O. stentina samples. The prevalence was similar among the 3 oyster species but varied between sampling locations, being higher in areas with greater harvesting activities. OsHV-1 µVar accounted for 93% of all OsHV-1 detected.

[Alagille's syndrome associated with proximal radio-ulnar synostosis: Clinical case and a literature review]. / Síndrome de Alagille asociado a sinostosis radiocubital proximal: caso clínico y revisión de la literatura.

Alagille's syndrome is an infrequent genetic condition with autosomal inheritance and variable expression. The complete form exhibits 5 clinical signs, chronic intrahepatic cholestasis, characteristic facies, cardiovascular anomalies, posterior embryotoxon, and vertebral defects. If only 3 or 4 of these are present the case is considered as an incomplete form. The association of Alagille's syndrome with radio-ulnar synostosis is extremely rare. There is only one case described in the indexed literature. A case is presented of Alagille's syndrome with bilateral proximal radioulnar synostosis. To the best of our knowledge this is the second reported case of this association.

[Osteosarcoma and ATR-16 syndrome: association or coincidence?]. / Osteosarcoma y síndrome ATR-16, ¿asociación o coincidencia?

ATR-16 syndrome is due to alterations on chromosome 16p13.3, and is usually accompanied by alpha-thalassemia, mild-moderate mental retardation, dysmorphic facial features, skeletal and genitourinary malformations. There are no references of the combination of ATR-16 syndrome and osteosarcoma in the literature. Osteosarcoma usually has a complex karyotype, characterized by a high degree of heterogeneity of chromosomal aberrations, among which is the involvement of chromosome 16. We report a case of a patient with ATR-16 syndrome diagnosed with femoral osteosarcoma.

Determining ACTB, ATP5B and RPL32 as optimal reference genes for quantitative RT-PCR studies of cryopreserved stallion semen.

Equine germplasm bank management involves not only the conservation and use of semen doses, in addition it can also be a resource to study stallion semen quality and after thawing semen properties for reproductive purposes. A possible criterion to measure quality may be based on differential gene expression of loci involved during spermatogenesis and sperm quality maturation. The rapid degradation of sperm after thawing affects the integrity and availability of RNA. In this study we have analyzed genes expressed in equine cryopreserved sperm, which provided an adequate amplification, specificity, and stability to be used as future reference genes in expression studies. Live spermatozoa were selected from cryopreserved semen straws derived from 20 stallions, through a discontinuous concentration gradient. RNA purification followed a combination of the organic and column extraction methods together with a deoxyribonuclease treatment. The selective amplification of nine candidate genes was undertaken using reverse transcription and real-time polymerase chain reaction (qPCR) carried out in a one-step mode (qRT-PCR). Specificities were tested by melting curves, agarose gel electrophoresis and sequencing. In addition, gene stabilities were also calculated. Results indicated that five out of the nine candidate genes amplified properly (ß-Actin, ATP synthase subunit beta, Protamine 1, L32 ribosomal protein and Ubiquitin B), of which ß-Actin and the L32 Ribosomal protein showed the highest stability thus being the most suitable to be considered as reference genes for equine cryopreserved sperm studies, followed by the ATP synthase subunit beta and Ubiquitin B.

[Prevention of medication errors in healthcare transition of patients treated with apomorphine]. / Intervenciones farmacéuticas relacionadas con la prevención de errores de medicación en la transición asistencial de pacientes tratados con apomorfina.

The transition of patients between different levels of care process is a particular risk in the production of medication errors. The aim of this paper is to analyze the role of the pharmacist in preventing errors transition care to ensure a safe and cross pharmacotherapy of patients.Transversal, observational and descriptive study in a University Hospital that has a pharmacy service that integrates specialized inpatient care and health centers. Transition of care a patient treated with Apormorfina was analyzed to determine the keypoints of action of the pharmacist. Demographics, disease and medication history, and care transition episodes were collected through the pharmacy program and electronics history.The pharmacist did tasks adapting, reconciliation, management and reporting of medication to the health care team to prevent medication errors in care transition of patients treated with drugs requiring special handling .In conclusion, this work represents perfectly the key role of the pharmacist as coordinator of safe and transverse pharmacotherapy of patients.

La transición de los pacientes entre los diferentes niveles asistencialesconstituye un proceso de especial riesgo en la producciónde errores de medicación. El objetivo de este trabajo esmostrar el papel del farmacéutico en la prevención errores paragarantizar una farmacoterapia segura y transversal de lospacientes.Estudio transversal, observacional y descriptivo en un ComplejoHospitalario Universitario que cuenta con un Servicio de Farmaciaque integra atención especializada a pacientes hospitalizadosy a residentes de centros sociosanitarios. Se analizó la transiciónasistencial de una paciente tratada con Apomorfina paradeterminar los puntos clave de actuación del farmacéutico. Serecogieron datos demográficos, patología e historia farmacoterapéutica,así como los episodios de transición asistencial, a travésdel programa de Farmacia y la historia electrónica.El farmacéutico realizó tareas de adecuación, conciliación, gestióne información de la medicación al equipo asistencial paraprevenir errores de medicación en la transición asistencial depacientes tratados con fármacos de especial manejo.En conclusión este trabajo representa los puntos críticos deintervención del farmacéutico como coordinador de la farmacoterapiasegura y transversal de los pacientes.

[Systematic assessment of the paediatrician's performance during simulated supraventricular tachycardia]. / Evaluación sistemática de la actuación de los pediatras ante un caso simulado de taquicardia supraventricular.

INTRODUCTION: The aims of this study are to: a) assess the quality in clinical management during a simulated scenario of acute supraventricular tachycardia (SVT) by means of a structured task-based checklist and to b) detect pitfalls and grey areas where reinforcement in training may be needed. MATERIAL AND METHODS: We systematically reviewed SVT simulated scenarios during simulation courses between June 2008 and April 2010. Three scenarios were programmed using SimBaby® simulation system, and included stable SVT (S-SVT), stable progressing to unstable SVT (SU-SVT) and unstable SVT (U-SVT). Scenarios were evaluated by means of an 18-task checklist based on ILCOR international recommendations. RESULTS: A total of 45 scenarios were assessed with the participation of 167 paediatricians, including 15 S-SVT, 25 SU-SVT and 5 U-SVT scenarios. Out of a total of 551 possible tasks, 328 (59.5%) were completed correctly. The mean percentage of correct tasks per scenario was 63.4 (16.7) for S-SVT, 47.8 (20.3) for SU-ST and 38.6 (31) for U-SVT (p=0.028). There were no significant differences between primary care paediatricians and hospital paediatricians. Most of the participants correctly identified non-sinus rhythm as SVT. However, important pitfalls were observed, including failure to identify haemodynamic instability in 20 out of 43 (48%) cases, an incorrect dose of adenosine in 18 out of 39 (48%), incorrect adenosine administration in 23 out of 39 (59%), and non-recognition of indication to emergent cardioversion in 15 out of 31 (48%). CONCLUSIONS: Paediatricians are able to diagnose SVT correctly, but need to improve their skills in treatment. Systematic analysis of clinical performance in a simulated scenario allows the identification of strengths, as well as weak points, where reinforcement is needed.

Incidence of complications and mortality in a type 2 diabetes patient cohort study followed up from diagnosis in a primary healthcare centre.

AIMS: To determine the microvascular and macrovascular complications and mortality incidence rates and to identify the related factors in patients recently diagnosed with type 2 diabetes between 1991 and 2000 and followed until 2006. METHODS: Retrospective longitudinal study in a primary healthcare center. Patients without any measure of glycaemia in the 3 years previous to diabetes diagnosis were excluded. Annual incidence rates for microvascular and macrovascular complications and mortality were estimated. Analysis of KaplanMeier survival curves and Cox proportional risk models by gender were done. RESULTS: Of 469 patients [mean age: 60.4 (SD 10.7) years, 53.9% women], 80 died principally of tumoral (38.7%) and cardiovascular (30%) causes. The mean follow-up period was 8.81 years. (SD 3.21). The complication rates per 1000 patients/year (95% CI) were: microvascular complications 29.11 (22.97-36.38), macrovascular complications 24.10 (19.05-30.08) and mortality 19.23 (15.25-23.93), all of those being significantly greater in males except for cerebrovascular disease. Complications and mortality were associated with age, HbA1c, HDL-cholesterol, blood pressure and smoking with a different significance for each gender. HbA1c was related to microvascular complications in both sexes and to macrovascular complications only in women. CONCLUSION: The annual rates for death and complications in a Mediterranean type 2 diabetic patient cohort followed from diagnosis were lower than those published in Anglo-Saxon countries. Males showed higher death and complication rates except in terms of cerebrovascular disease. Predictors of complication and death were different depending on gender. In terms of mortality, unlike in other studies, only one-third of the deaths were for cardiovascular causes.

[Advanced simulation for primary care paediatricians. Development of an itinerant program and opinions of participants]. / Simulación avanzada para pediatras de atención primaria. Desarrollo de un programa itinerante y opinión de los participantes.

INTRODUCTION AND OBJECTIVES: Advanced simulation (AS) is a teaching methodology that has shown to be useful for training health staff at hospital level; however, its application in primary care paediatrics is very limited. Our objective was the development of an AS project focused on the learning needs of the primary care paediatricians, as well as to know the participants' opinions as one of the elements to assess its appropriateness. MATERIAL AND METHODS: Phase 1: A multidisciplinary working group was organized and sponsored by the SEPEAP to design and put the course into practice. Phase 2: Itinerant courses were carried out in several cities in Spain. At the end of each course, a survey was carried out that was focused on motivation aspects, pertinence of contents and methodology. Each item was scored on a numerical scale from 0 (very bad) to 10 (very good). STUDY PERIOD: May 2008 to May 2009. RESULTS: After analysing the potential learning needs of target population, available time, teaching material available and methodology of simulation and debriefing, a course model was designed and the cases were programmed. Twelve courses were carried out in 12 cities. The total number of participants was 186; of them, 177 (95.2%) answered the survey. Mean+/-SD scores for main items were: organization (9.23+/-0.50), objectives related to prior expectation (9.29+/-0.43), usefulness of course program to work activity (9.42+/-0.43), cases that resemble reality (9.18+/-0.42) and good instructors-participants relationship (9.68+/-0.20). CONCLUSIONS: The AS course for primary care paediatrics, with the proposed format, is feasible and well adapted to the needs of the target population. Primary care paediatricians consider this type of teaching and learning activity as a useful tool for their continuing education and for improving their professional abilities.

Resveratrol promotes an inhibitory effect on the turbot scuticociliate parasite Philasterides dicentrarchi by mechanisms related to cellular detoxification.

The mechanisms involved in antiparasitic activity of the natural nonflavonoid polyphenol resveratrol (RESV) on the turbot (Psetta maxima) scuticoliate parasite Philasterides dicentarchi were investigated. At concentrations higher than 50microM, RESV caused significant inhibition of the in vitro growth of the ciliates, which was apparent on the third day of culture and, at the same concentration, RESV caused significant inhibition of O(2) consumption. RESV, at a concentration of 100microM, produced a significant increase in the production of intracellular reactive oxygen species (ROS), which were inhibited by the addition of 1mM of L (+) ascorbic acid. RESV (100microM) also caused significant inhibition of peroxidase, catalase and superoxide dismutase activities, but stimulated the activity of the redox regulating enzyme glutathione S-transferase. Confocal microscopy with the mitochondria-sensitive dye MitoTracker Orange CMTMRos revealed that RESV at concentrations higher than 50microM significantly increased the levels of fluorescence inside mitochondria and, at the same concentration, also caused an increase in the vacuolization of the trophozoites. The results obtained in the present study suggest that the inhibitory activity of RESV on the ciliate P. dicentrarchi is related to the induction of oxidative stress and to the inability of the parasite to eliminate ROS as a result of modified activity of antioxidant enzymes.

Resveratrol modulates innate and inflammatory responses in fish leucocytes.

Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene), a phytoalexin that is produced by some plants, among other effects has well-known antioxidant, anti-inflammatory and immunomodulatory activities in mammals. In the present study, the effects of RESV on several functions of turbot, Psetta maxima (L.), kidney leucocytes (KLs) related to the innate and inflammatory responses were investigated. RESV exerted a dose-dependent inhibitory effect on the migratory response and on the production of reactive oxygen species in KL, after stimulation of the respiratory burst activity with phorbol myristate acetate (PMA). RESV also significantly inhibited the generation of the pro-inflammatory mediator prostaglandin E(2) (PGE(2)) in the supernatant of KL cultures stimulated with acidic sulphated polysaccharides (ASPs) from the seaweed Ulva rigida. The effects of the polyphenol on enzymatic activity and on myeloperoxidase (MPO) gene expression in neutrophils were also tested. It was found that RESV strongly inhibited intracellular and extracellular MPO activity, behaving as a noncompetitive and reversible inhibitor, and also induced a decrease in MPO mRNA levels in turbot neutrophils. These findings indicate that RESV exerts important modulatory effects on inflammatory responses in fish, and considering the importance of innate immunity in these vertebrates and the similarities with mammals, it may be possible to use fish for analysis of the effects of different substances on inflammatory responses.

Antigenic and cross-protection studies on two turbot scuticociliate isolates.

The protection induced in turbot by inactivated vaccines containing either of two isolates (I(1) and C(1)) of the scuticociliate parasite Philasterides dicentrarchi, which causes important mortalities in turbot cultures, was evaluated in the present study. The results obtained after challenging the fish with the two isolates show that vaccination protected fish only against the homologous isolate, but did not confer cross-protection. The two isolates constitute two serotypes, as shown in the immobilization tests with mouse and turbot anti-I(1) and anti-C(1) antisera, in which only the homologous antisera immobilized the ciliates. ELISA assays, using total antigen free of proteases (TAWP), cytosolic antigens (CYA), ciliar antigens (CA) or membrane protein fraction (MPF), were also carried out. Differences in the levels of antibodies produced in mouse against the homologous and heterologous antigens were observed; these differences were significantly different when the antigen preparations used in the ELISA were TAWP, CYA or CA. Nevertheless, ELISA assays using turbot sera against TAWP did not show significant differences in the levels of antibodies against the homologous and heterologous antigens. Antigenic cross-reactivity was also detected in the Western blot assays, as well as significant differences in the patterns of antigenic recognition in the two isolates - in both reduced and non-reduced TAWP antigens, but which was noteworthy when mouse antisera were used. The results obtained in the present study demonstrate for the first time the existence of serotypes of the ciliate parasite of turbot Philasterides dicentrarchi that display clear antigenic differences, which must be taken into consideration in the future development of a vaccine against scuticociliatosis.