Herramienta SIG para estimar la distancia de visibilidad disponible en carreteras. Análisis de la influencia de la separación de los puntos de cálculo

Se ha desarrollado una herramienta basada en ArcGIS e implementada en .NET para el cálculo, análisis y documentación de la Distancia de Visibilidad Disponible (DVD) en carretera a partir de la trayectoria del vehículo y un Modelo Digital del Terreno (MDT). Esta herramienta se integra en ArcGIS Desktop como una add-in, pudiendo añadirse a cualquier barra de herramientas como un botón. La herramienta propuesta permite determinar si los distintos puntos situados sobre la trayectoria que tiene que recorrer un vehículo son vistos desde la localización en la que se encuentra el vehículo. Para ello, se utiliza la función “GetLineOfSight” de la extensión “3D Analyst” de ArcMap. La herramienta desarrollada se ha utilizado para evaluar la influencia de la equidistancia entre los puntos de cálculo. Se ha determinado la DVD en una carretera de 14,5 km de longitud calculando para diferentes equidistancias (1, 2, 5, 10 y 20 m) y utilizando un MDT de 1 m de resolución.Al Ministerio de Economía y Competitividad por su financiación en el proyecto de investigación TRA2011-25479 (Convocatoria de 2011 de Proyectos de Investigación Fundamental no Orientada del Plan Nacional de I+D+i 2008-2011)

Tunable injectable alginate-based hydrogel for cell therapy in Type 1 Diabetes Mellitus

Islet transplantation has the potential of reestablishing naturally-regulated insulin production in Type 1 diabetic patients. Nevertheless, this procedure is limited due to the low islet survival after transplantation and the lifelong immunosuppression to avoid rejection. Islet embedding within a biocompatible matrix provides mechanical protection and a physical barrier against the immune system thus, increasing islet survival. Alginate is the preferred biomaterial used for embedding insulin-producing cells because of its biocompatibility, low toxicity and ease of gelation. However, alginate gelation is poorly controlled, affecting its physicochemical properties as an injectable biomaterial. Including different concentrations of the phosphate salt Na2HPO4 in alginate hydrogels, we can modulate their gelation time, tuning their physicochemical properties like stiffness and porosity while maintaining an appropriate injectability. Moreover, these hydrogels showed good biocompatibility when embedding a rat insulinoma cell line, especially at low Na2HPO4 concentrations, indicating that these hydrogels have potential as injectable biomaterials for Type 1 Diabetes Mellitus treatment

Force Spectroscopy Imaging and Constriction Assays Reveal the Effects of Graphene Oxide on the Mechanical Properties of Alginate Microcapsules

Microencapsulation of cells in hydrogel-based porous matrices is an approach that has demonstrated great success in regenerative cell therapy. These microcapsules work by concealing the exogenous cells and materials in a robust biomaterial that prevents their recognition by the immune system. A vast number of formulations and additives are continuously being tested to optimize cell viability and mechanical properties of the hydrogel. Determining the effects of new microcapsule additives is a lengthy process that usually requires extensive in vitro and in vivo testing. In this paper, we developed a workflow using nanoindentation (i.e., indentation with a nanoprobe in an atomic force microscope) and a custom-built microfluidic constriction device to characterize the effect of graphene oxide (GO) on three microcapsule formulations. With our workflow, we determined that GO modifies the microcapsule stiffness and surface properties in a formulation-dependent manner. Our results also suggest, for the first time, that GO alters the conformation of the microcapsule hydrogel and its interaction with subsequent coatings. Overall, our workflow can infer the effects of new additives on microcapsule surfaces. Thus, our workflow can contribute to diminishing the time required for the validation of new microcapsule formulations and accelerate their clinical translation

Prescripción de antibióticos en la infección del tracto urinario: adecuación a criterios de calidad en atención primaria

ObjetivoDeterminar la prevalencia de insuficiencia renal crónica (IRC) sin tratamiento sustitutivo (TSR), describir el tipo de enfermedades renales primarias y los factores de riesgo asociados que pueden favorecer su evolución hacia la insuficiencia renal terminal.DiseñoEstudio descriptivo, transversal.EmplazamientoPoblación atendida por un centro de atención primaria.ParticipantesMayores de 14 años con historia clínica abierta en el CAP Bon Pastor.ResultadosDurante el período 1-I-1997 hasta 1-XII-1997 se revisaron 12.241 historias clínicas. Se identificaron 64 pacientes que cumplían criterios de IRC sin TSR; prevalencia, 5.228 pacientes por millón de habitantes (pmp) (IC del 95%, 3.950–6.510 pmp). Un 71,9% era varón, la edad media era de 72 años (DE, 13,5). La media de la última creatinina plasmática fue de 2 mg/dl (DE, 0,66). La frecuencia según tipo de nefropatía fue: glomerular, 3 (4,7%); diabética, 5 (7,8%); intersticial, 3 (4,7%); vascular (HTA), 41 (64,1%); indeterminada, 2 (3,1%), e inclasificable, 10 (15,6%). Los factores de riesgo asociados en estos pacientes fueron: hipertensos, 47 (73,4%); diabéticos, 16 (25%); hipercolesterémicos, 26 (40,6%); consumidores crónicos de analgésicos, 20 (31,3%), y 10 (15,6%), fumadores. Un 51,6% de los pacientes presentaba otras enfermedades cardiovasculares.ConclusionesLa prevalencia estimada de IRC sin TRS en la población es de 5.228 pmp, y la hipertensión es el factor de riesgo más frecuente asociado a esta patología.ObjectiveTo determine the prevalence of chronic renal failure (CRF) without replacement treatment (RT), and to describe the primary renal diseases and associated risk factors that might favour its evolution to terminal renal failure.DesignCross-sectional, descriptive study.SettingPopulation attended at a primary care centre (PCC).ParticipantsOver-14s with a clinical history opened at the Bon Pastor PCC.ResultsBetween the 1st of January 1997 and the 1st of December 1997, 12241 clinical histories were reviewed. 64 patients were identified who satisfied criteria of CRF without RT, a prevalence of 5228 patients per million inhabitants (95% CI, 3,950–6,510). 71.9% were men, and mean age was 72 (SD, 13.5). The most recent plasma creatinine averaged 2 mg/dl (SD, 0.66). Frequency according to kind of nephropathy was: 3 (4.7%) glomerular, 5 (7.8%) diabetic, 3 (4.7%) interstitial, 41 (64.1%) vascular (hypertension), 2 (3.1%) indeterminate and 10 (15.6%) unclassifiable. Associated risk factors in these patients were: 47 (73.4%) with hypertension, 16 (25%) diabetic, 26 (40.6%) with hypercholesterolaemia, 20 (31.3%) chronic consumers of analgesics, and 10 (15.6%) smokers. 51.6% of the patients suffered other cardiovascular illnesses.ConclusionsThe estimated prevalence in the population of CRF without RT is 5,228 per million inhabitants. Hypertension is the risk factor most closely associated with this pathology

Development, characterization and sterilisation of Nanocellulose-alginate-(hyaluronic acid)- bioinks and 3D bioprinted scaffolds for tissue engineering

3D-bioprinting is an emerging technology of high potential in tissue engineering (TE), since it shows effective control over scaffold fabrication and cell distribution. Biopolymers such as alginate (Alg), nanofibrillated cellulose (NC) and hyaluronic acid (HA) offer excellent characteristics for use as bioinks due to their excellent biocompatibility and rheological properties. Cell incorporation into the bioink requires sterilisation assurance, and autoclave, β-radiation and γ-radiation are widely used sterilisation techniques in biomedicine; however, their use in 3D-bioprinting for bioinks sterilisation is still in their early stages. In this study, different sterilisation procedures were applied on NC-Alg and NC-Alg-HA bioinks and their effect on several parameters was evaluated. Results demonstrated that NC-Alg and NC-Alg-HA bioinks suffered relevant rheological and physicochemical modifications after sterilisation; yet, it can be concluded that the short cycle autoclave is the best option to sterilise both NC-Alg based cell-free bioinks, and that the incorporation of HA to the NC-Alg bioink improves its characteristics. Additionally, 3D scaffolds were bioprinted and specifically characterized as well as the D1 mesenchymal stromal cells (D1-MSCs) embedded for cell viability analysis. Notably, the addition of HA demonstrates better scaffold properties, together with higher biocompatibility and cell viability in comparison with the NC-Alg scaffolds. Thus, the use of MSCs containing NC-Alg based scaffolds may become a feasible tissue engineering approach for regenerative medicine.Author thanks the Basque Government for granted fellowship to S. Ruiz-Alonso (PRE_2020_2_0143). This study was financially supported by the Basque Country Government (IT907-16), the Ministerio de Economía, Industria y Competitividad (FEDER funds, project RTC-2016- 5451-1), Fundación Mutua Madrileña (project FMM-AP17196-2019), the Instituto de Salud Carlos III, ERDF funds (DTS19/00145) and by the Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (project no. PY18-2470 and SOMM17/6109/UGR, FEDER Funds). Authors also wish to thank the intellectual and technical assistance from the ICTS “NANBIOSIS”, more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of Basque Country (UPV/ EHU

Type 1 Diabetes Mellitus reversal via implantation of magnetically purified microencapsulated pseudoislets

[Abstract] Microencapsulation of pancreatic islets for the treatment of Type I Diabetes Mellitus (T1DM) generates a high quantity of empty microcapsules, resulting in high therapeutic graft volumes that can enhance the host’s immune response. We report a 3D printed microfluidic magnetic sorting device for microcapsules purification with the objective to reduce the number of empty microcapsules prior transplantation. In this study, INS1E pseudoislets were microencapsulated within alginate (A) and alginate-poly-L-lysine-alginate (APA) microcapsules and purified through the microfluidic device. APA microcapsules demonstrated higher mechanical integrity and stability than A microcapsules, showing better pseudoislets viability and biological function. Importantly, we obtained a reduction of the graft volume of 77.5% for A microcapsules and 78.6% for APA microcapsules. After subcutaneous implantation of induced diabetic Wistar rats with magnetically purified APA microencapsulated pseudoislets, blood glucose levels were restored into normoglycemia (<200 mg/dL) for almost 17 weeks. In conclusion, our described microfluidic magnetic sorting device represents a great alternative approach for the graft volume reduction of microencapsulated pseudoislets and its application in T1DM disease.Universidad del País Vasco; ESPPOC 16/65Universidad del País vasco; EHUa16/06Gobierno Vasco; IT907-16Gobierno Vasco; KK-2017/0000088Gobierno Vasco; 307616FKA4Ministerio de Economía y Competitividad; RYC-2012-1079

Phosphoprotein Phosphatase 1 isoforms alpha and gamma respond differently to prodigiosin treatment and present alternative kinase targets in melanoma cells

Reversible protein phosphorylation is a central regulatory mechanism of cell function. Deregulation of the balanced actions of protein kinases and phosphatases has been frequently associated with several pathological conditions, including cancer. Many studies have already addressed the role of protein kinases misregulation in cancer. However, much less is known about protein phosphatases influence. Phosphoprotein Phosphatase 1 (PPP1) is one of the major serine/threonine protein phosphatases who has three catalytic isoforms: PPP1CA, PPP1CB, and PPP1CC. Its function is achieved by binding to regulatory subunits, known as PPP1-interacting proteins (PIPs), which may prefer a catalytic isoform. Also, some inhibitors/enhancers may exhibit isoform specificity. Here we show that, prodigiosin (PG), a molecule with anticancer properties, promotes the formation of PPP1CA-AKT complex and not of PPP1CC-MAPK complex. Both, AKT and MAPK, are wellknown PIPs from two pathways that crosstalk and regulate melanoma cells survival. In addition, the analysis performed using surface plasmon resonance (SPR) technology indicates that PPP1 interacts with obatoclax (OBX), a drug that belongs to the same family of PG. Overall, these results suggest that PG might, at least in part, act through PPP1C/PIPs. Also, this study is pioneer in demonstrating PPP1 isoform-specific modulation by small molecules.publishe

A survey of the hybridisation status of Cervus deer species on the island of Ireland

Red deer (Cervus elaphus) did not recolonise Ireland after the last glaciation, but the population in Co. Kerry is descended from an ancient (c. 5000 BP) introduction and merits conservation. During the mid-19th century exotic species including North American wapiti (C. canadensis) and Japanese sika deer (C. nippon nippon) were introduced to Ireland, mainly via Powerscourt Park, Co. Wicklow. While wapiti failed to establish, sika thrived, dispersed within Co. Wicklow and were translocated to other sites throughout Ireland. Red deer and sika are known to have hybridised in Ireland, particularly in Co. Wicklow, but an extensive survey with a large, highly diagnostic marker panel is required to assess the threat hybridisation potentially poses to the Co. Kerry red deer population. Here, 374 individuals were genotyped at a panel of 22 microsatellites and at a single mtDNA marker that are highly diagnostic for red deer and Japanese sika. The microsatellites are also moderately diagnostic for red deer and wapiti. Wapiti introgression was very low [trace evidence in 2 (0.53 %) individuals]. Despite long-standing sympatry of red deer and sika in the area, no red deer-sika hybrids were detected in Co. Kerry suggesting strong assortative mating by both species in this area. However, 80/197 (41 %) of deer sampled in Co. Wicklow and 7/15 (47 %) of deer sampled in Co. Cork were red-sika hybrids. Given their proximity and that hybrids are less likely to mate assortatively than pure individuals, the Co. Cork hybrids pose a threat to the Co. Kerry red deer.UK Natural Environment Research Council PhD studentshi

Molecular Interactions of Prodiginines with the BH3 Domain of Anti-Apoptotic Bcl-2 Family Members

Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that are currently under preclinical and clinical trials. The molecular target(s) of these agents, however, is an open question. Combining experimental and computational techniques we find that prodigiosin binds to the BH3 domain in some BCL-2 protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicate a large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstrate that prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulations with the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecular interactions. These results provide new data to understand the mechanism of action of these molecules, and assist in the development of more specific inhibitors of anti-apoptotic BCL-2 proteins.Spanish government and the European Union (FIS-PI10/00338) and from the ERC-2009-Adg 25027-PELE European project