Interdisciplinary Integrated Tools to Problem Solving 2.0

Everyone understands the events they witness or read about according to their mental models, and that is one of the main reasons there are a lot of disagreements at workplaces and between friends and families. Considering this situation, plus the difficulty that most people face when trying to conceptualize problems, I suggest a course that includes series methodologies, working synergistically to deal with this problem that goes from understanding the differences between people to test multiple hypotheses and planning the solution implementation. Since 2014, I have been teaching with some colleagues this tool in the format of a short course that articulates systems thinking, mapping studies, information quality, and competing hypotheses. This course has been presented often not only in Argentina and also in Peru with great success. Considering the pandemic situation, since 2020, it has been taught virtually. The latest modification to the original structure of the course was the incorporation of the Gantt chart to design the implementation of the solution found. This paper will present our course and the logic behind it, its outcomes, and how it evolved with the different iterations

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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

The impact of past introductions on an iconic and economically important species, the red deer of Scotland

The red deer (Cervus elaphus) is an iconic species in Scotland and, due to its value as a game species, an important element of the Scottish rural economy. The native status of this species is sometimes questioned because of many recorded introductions of nonnative deer in the past that were an attempt to improve trophy size. In this study, we assessed the impact of past introductions on the genetic makeup of Scottish red deer by genotyping at 15 microsatellite loci a large number of samples (n = 1152), including mainland and island Scottish red deer and individuals from several putative external source populations used in introductions to improve trophy size. Population structure and introgression assessment analyses revealed that the impact of introductions was weak in Highland red deer populations but more prominent on the islands, especially on those where current red deer populations are mostly or entirely derived from introductions (Harris & Lewis, Arran, and Rum). Frequent imports of Central-Eastern European red deer into English deer parks were reflected in the higher genetic introgression values found in some of the individuals collected in parks

Analyse de l’angle naso-labial

We analyzed the nasolabial angle and different factors that influence it in patients of 9.0 ± 1.4 years of age. An average value of 115.30 ± 10.8 was obtained. The inclination and the position of the upper incisive and the ANB angle constituted the osseous and dental factors with greatest repercussion on the nasolabial angle. Sex and age did not condition significant differences. The labial incompetence determined a more acute angle.Nous avons analysé l’angle naso-labial et les différents facteurs qui l’influencent, chez des patients de 9 ans ± 1,4. Nous avons obtenu une valeur moyenne de 115,30 ± 10,8. L’inclinaison et la position de l’incisive supérieure et l’angle ANB constituent les facteurs osseux et dentaires qui ont la plus grande répercussion sur l’angle naso-labial. Le sexe et l’âge n’ont pas eu d’influences statistiquement significatives sur les résultats. L’incompétence labiale s’est avérée être la cause d’un angle plus aigu

Intrapericardial delivery of apa-microcapsules as promising stem cell therapy carriers in an experimental acute myocardial infarction model

The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-L-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area. We aimed to evaluate IP therapy using a saline vehicle as a control (CON), a dose of 30 × 106 CDCs (CDCs) or APA microcapsules containing 30 × 106 CDCs (APA-CDCs) at 72 h in a porcine AMI model. Magnetic resonance imaging (MRI) was used to determine the left ventricular ejection fraction (LVEF), infarct size (IS), and indexed end diastolic and systolic volumes (EDVi; ESVi) pre-and 10 weeks post-injection. Programmed electrical stimulation (PES) was performed to test arrhythmia inducibility before euthanasia. Histopathological analysis was carried out afterwards. The IP infusion was successful in all animals. At 10 weeks, MRI revealed significantly higher LVEF in the APA-CDC group compared with CON. No significant differences were observed among groups in IS, EDVi, ESVi, PES and histopathological analyses. In conclusion, the IP injection of CDCs (microencapsulated or not) was feasible and safe 72 h post-AMI in the porcine model. Moreover, CDCs APA encapsulation could have a beneficial effect on cardiac function, reflected by a higher LVEF at 10 weeks. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

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

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

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