Histological Assessment of Rat Retinas with Ischemia-Reperfusion Injury.

INTRODUCTION: Retinal ischemia-reperfusion (IR) injury occurs in pathological situations that interrupt the blood flow to the retina, such as is the case during central retinal artery occlusion (CRAO). The animal models described in the literature are based on the pressure produced by the weight of a given quantity of saline elevated to a certain height; however, to establish these parameters it is necessary to perform mathematical calculations that cannot be easily redone in the case of punctual variations of intraocular pressure (IOP). The aim of this study was to present a new system that allows us to reproduce the conditions of retinal IR and thereby properly assess the level of injury in retinal histological samples. METHODS: We developed a retinal IR model in WAG/RijHsd rats based on CRAO through increasing IOP. To develop this model, we produced ischemia for 1 h using a hydrostatic pressure system that maintained a constant high IOP and then allowed reperfusion for 1 h. The injury attributable to IR was assessed by histological examination of retinal samples, determining whether there was histological damage and/or dendritic swelling and counting the outer nuclear layer cells showing cytoplasmic swelling. RESULTS: The increase in IOP to 150 mm Hg produced CRAO, in turn causing observable histological damage and dendritic swelling in all retinas subjected to IR. Counting the number of cells showing cytoplasmic swelling yielded a mean of 102.5 ± 35 cells/field. The contralateral retinas were healthy, showing no significant changes. CONCLUSION: The retinal IR model proposed is simple, reproducible, and allows variable durations of ischemia and reperfusion, and most importantly, it allows easy correction by adjusting the pressure of the sphygmomanometer, of any change in IOP to keep the ischemia stable, without having to recalculate the elevation height of the ischemia induction system. Moreover, the damage caused by IR can be effectively assessed by the type of histopathological assessment performed. For these reasons, it can be considered a reliable method for studying drugs that may prevent retinal IR injury.

Impact of the Combined Use of Magnetite Nanoparticles and Cellulose Nanocrystals on the Shape-Memory Behavior of Hybrid Polyurethane Bionanocomposites.

Hybrid bionanocomposites with shape-memory behavior are reported. The materials were accessed by combining a polyurethane matrix with a highly renewable carbon content, cellulose nanocrystals (CNCs), and magnetite nanoparticles (MNPs). The integration of the two nanoparticle types resulted in tough materials that display a higher stiffness and storage modulus in the glassy and rubbery state, thus contributing to the structural reinforcement, as well as magnetic properties, reflecting a synergistic effect of this combination. A quantitative characterization of the thermoactivated shape-memory effect made evident that the addition of CNCs increases the shape fixity, due to the higher glass transition temperature (Tg) and the higher stiffness below Tg than the neat PU, while the addition of MNPs made it possible to activate the shape recovery by applying an alternating magnetic field. Moreover, the new hybrid bionanocomposites showed good bio- and hemocompatibility.

Hydrogen Peroxide-Preconditioned Human Adipose-Derived Stem Cells Enhance the Recovery of Oligodendrocyte-Like Cells after Oxidative Stress-Induced Damage.

Oxidative stress associated with neuroinflammation is a key process involved in the pathophysiology of neurodegenerative diseases, and therefore, has been proposed as a crucial target for new therapies. Recently, the therapeutic potential of human adipose-derived stem cells (hASCs) has been investigated as a novel strategy for neuroprotection. These cells can be preconditioned by exposing them to mild stress in order to improve their response to oxidative stress. In this study, we evaluate the therapeutic potential of hASCs preconditioned with low doses of H2O2 (called HC016 cells) to overcome the deleterious effect of oxidative stress in an in vitro model of oligodendrocyte-like cells (HOGd), through two strategies: i, the culture of oxidized HOGd with HC016 cell-conditioned medium (CM), and ii, the indirect co-culture of oxidized HOGd with HC016 cells, which had or had not been exposed to oxidative stress. The results demonstrated that both strategies had reparative effects, oxidized HC016 cell co-culture being the one associated with the greatest recovery of the damaged HOGd, increasing their viability, reducing their intracellular reactive oxygen species levels and promoting their antioxidant capacity. Taken together, these findings support the view that HC016 cells, given their reparative capacity, might be considered an important breakthrough in cell-based therapies.

Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering.

Articular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristics of the cartilaginous matrix, as well as the avascular nature of cartilage and its cells' peculiar arrangement in isogenic groups. Keeping these factors in mind, we have designed a 3D porous scaffold based on genipin-crosslinked chitosan/chitin nanocrystals for spheroid chondral differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) induced in hypoxic conditions. First, we demonstrated that, under low oxygen conditions, the chondrospheroids obtained express cartilage-specific markers including collagen type II (COL2A1) and aggrecan, lacking expression of osteogenic differentiation marker collagen type I (COL1A2). These results were associated with an increased expression of hypoxia-inducible factor 1α, which positively directs COL2A1 and aggrecan expression. Finally, we determined the most suitable chondrogenic differentiation pattern when hASC spheroids were seeded in the 3D porous scaffold under hypoxia and obtained a chondral extracellular matrix with a high sulphated glycosaminoglycan content, which is characteristic of articular cartilage. These findings highlight the potential use of such templates in cartilage tissue engineering.

Chitin Nanoforms Provide Mechanical and Topological Cues to Support Growth of Human Adipose Stem Cells in Chitosan Matrices.

The precise role and value of incorporating nanoforms in biologically active matrices for medical applications is not known. In our current work, we incorporate two chitin nanoforms (i.e., nanocrystals or nanofibers) into Genipin-chitosan crosslinked matrices. These materials were studied as 2D films and 3D porous scaffolds to assess their potential as primary support and guidance for stem cells in tissue engineering and regenerative medicine applications. The incorporation of either nanoforms in these 2D and 3D materials reveals significantly better swelling properties and robust mechanical performance in contrast to nanoform-free chitosan matrices. Furthermore, our data shows that these materials, in particular, incorporation of low concentration chitin nanoforms provide specific topological cues to guide the survival, adhesion, and proliferation of human adipose-derived stem cells. These findings demonstrate the potential of Genipin-chitosan crosslinked matrices impregnated with chitin nanoforms as value added materials for stem cell-based biomedical applications.

Biocompatible hydrogel nanocomposite with covalently embedded silver nanoparticles.

Bionanocomposite materials, combining the properties of biopolymers and nanostructured materials, are attracting interest of the wider scientific community due to their potential application in design of implants, drug delivery systems, and tissue design platforms. Herein, we report on the use of maleimide-coated silver nanoparticles (Ag NPs) as cocross-linkers for the preparation of a bionanocomposite gelatin based hydrogel. Diels-Alder cycloaddition of benzotriazole maleimide (BTM) functionalized Ag NPs and furan containing gelatin in combination with additional amide coupling resulted in stable and biocompatible hybrid nanocomposite. The storage moduli values for the hydrogel are nearly three times higher than that of control hydrogel without NPs indicating a stabilizing role of the covalently bound NPs. Finally, the swelling and drug release properties of the materials as well as the biocompatibility and toxicity tests indicate the biomedical potential of this type of material.

All-trans-retinoic acid counteract the tumor-stimulating effect of hepatectomy and increases survival of rats bearing liver metastases.

BACKGROUND: We previously demonstrated a stimulating effect of hepatectomy on residual tumor cells after resection of liver metastases. The aim of this study was to analyze the effect of all-trans-retinoic acid (ATRA) on the protumor effect of hepatectomy and survival of hepatectomized rats bearing liver metastases. We also explored whether ATRA interfered with the tumor promoting effect of hepatotropic growth factors (GFs). METHODS: The in vitro effect of ATRA on proliferation of S4MH rhabdomyosarcoma tumor cells was assessed when cultured with laparotomized or hepatectomized rat serum (HRS), or in the presence of GFs (hepatocyte growth factor, insulin growth factor 2, Platelet Derived Growth Factor (PDGF)-BB, and vascular endothelial growth factor). For the in vivo studies, rats were partially hepatectomized on day 10 after metastasis induction, one group being treated with ATRA from day 7 to 14, and a second receiving cyclophosphamide (CY; on days 10 and 14) alone or with ATRA. We determined the size and number of liver and lung metastases. Finally, we analyzed the effect of treatments on rat survival. RESULTS: Hepatotropic GFs increased cell proliferation in a similar manner to HRS. In vitro, ATRA blocked the protumor effect of both HRS and GFs. In vivo, ATRA reduced the size and number of liver and lung metastases, and significantly increased rat survival. Furthermore, adding ATRA to CY significantly increased survival compared with CY alone. CONCLUSIONS: In our model, ATRA minimizes the tumor-stimulating effect of hepatectomy, reducing the number and size of liver metastases and improving survival. The results suggest that the ATRA may be useful for blocking the growth-promoting effect of hepatotropic GFs released after liver metastasis resection.

Shape-memory bionanocomposites based on chitin nanocrystals and thermoplastic polyurethane with a highly crystalline soft segment.

Shape-memory bionanocomposites based on a naturally sourced segmented thermoplastic polyurethane and chitin nanocrystals were synthesized, and their mechanical properties and thermally activated shape-memory behavior were studied. The chitin nanocrystals were incorporated during the synthesis of the prepolymer made from a castor oil-based difunctional polyol and hexamethylene diisocyanate. The polymerization was completed by addition of propanediol, as a corn-sugar based chain extender, bringing the weight content of components from renewable resources to >60%. Thermal analysis of the bionanocomposites revealed a phase-separated morphology, which is composed of soft and hard domains, which bestow the material with two melting transitions at 60 and 125 °C, that are exploitable for a shape memory effect. The soft segment is responsible for temporary shape fixing, while the hard segment crystallites are responsible for the permanent shape. The introduction of small amounts (0.25-2 wt %) of chitin nanocrystals was found to increase the crystallinity of the hard segment by way of nucleation, which in turn improves the shape recovery considerably. The thermally activated shape-memory behavior of the synthesized bionancomposites is exploitable with a programming and release temperature of 60 °C. The materials display good in vitro cell response, as shown by short-term cytotoxicity assays, and therefore, the bionanocomposites appear to be potentially useful for biomedical applications.

Conditioned Medium from H2O2-Preconditioned Human Adipose-Derived Stem Cells Ameliorates UVB-Induced Damage to Human Dermal Fibroblasts.

Human skin exposure to ultraviolet B (UVB) radiation can result in acute photodamage through oxidative modifications of cellular components and biomolecules involved in the metabolism of dermal cells. Recently, the therapeutic potential of human adipose-derived stem cells (hASCs) has been investigated as a novel strategy for photoprotection due to their pro-angiogenic properties, protective activity against oxidative stress and paracrine effect on dermal cells. To enhance these therapeutic properties, hASCs can be preconditioned by exposing them to sublethal cellular stressors. In this study, we first analyzed response capacity against UVB-induced oxidative stress in H2O2-preconditioned hASCs (called HC016 cells); and second, we evaluated the photoprotective effect of HC016-conditioned medium (CM) in an in vitro UVB irradiation model in cultured human foreskin fibroblasts (hFFs). The results demonstrated that HC016 cells have a greater capacity to respond efficiently to UVB-induced oxidative stress, evidenced by higher Nrf2 antioxidant system activity and enhanced viability and migration capacity. Further, HC016-CM treatment increased viability, migratory capacity and collagen type I synthesis in hFFs exposed to UVB radiation, as well as reducing their cytotoxicity, apoptosis, senescence and IL-6 secretion. Collectively, these findings support the view that HC016 cells could protect against UVB-induced photodamage via paracrine mechanisms.

Learning How to Order Imaging Tests and Make Subsequent Clinical Decisions: a Randomized Study of the Effectiveness of a Virtual Learning Environment for Medical Students.

RATIONALE AND OBJECTIVES: Two critical skills that medical students must acquire during undergraduate education are the ability to order imaging tests and make clinical decisions based on their results. We implemented an e-learning course in Moodle specifically designed to teach these skills to medical students. The aim of this study was to assess the effectiveness of our course. MATERIAL AND METHODS: We randomized 26 undergraduate medical students to an experimental group that had access to the virtual learning environment and a control group that did not. Three weeks after the course, we evaluated its effectiveness through a blinded objective structured clinical examination. To avoid any bias in favor of the experimental group, the assessment considered scores on two pre-specified subscales: one related to the contents of the course and the other to new clinical scenarios. RESULTS: Students that completed the e-course performed better overall than controls (mean score ± standard deviation 59.3 ± 6.2 vs 41.8 ± 10.2, p = 0.0020). This better performance was observed in both types of skills assessed (ordering imaging tests, and making diagnostic and therapeutic decisions based on test results). More importantly, this better performance of the experimental group was observed consistently both with items related to the course content (1.7 times higher, p = 0.0034) and new scenarios (1.3 times higher, p = 0.0098). CONCLUSIONS: Through an ad - hoc e-course, undergraduate medical students learned effectively how to order imaging tests and make optimal subsequent decisions. Moreover, they were able to apply these skills to new clinical scenarios.

Partial hepatectomy enhances the growth of CC531 rat colorectal cancer cells both in vitro and in vivo.

Partial hepatectomy (PHx) is the gold standard for the treatment of colorectal cancer liver metastases. However, after removing a substantial amount of hepatic tissue, growth factors are released to induce liver regeneration, which may promote the proliferation of liver micrometastases or circulating tumour cells still present in the patient. The aim of this study is to assess the effect of PHx on the growth of liver metastases induced by intrasplenic cell inoculation as well as on in vitro proliferation of the same cancer cell line. Liver tumours were induced in 18 WAG/RijHsd male rats, by seeding 250,000 syngeneic colorectal cancer cells (CC531) into the spleen. The left lateral lobe of the liver was mobilized and in half of the animals it was removed to achieve a 40% hepatectomy. Twenty-eight days after tumour induction, the animals were sacrificed and the liver was removed and sliced to assess the relative tumour surface area (RTSA%). CC531 cells were cultured in presence of foetal calf serum, non-hepatectomised (NRS) or hepatectomized rat serum (HRS), and their proliferation rate at 24, 48, and 72 h was measured. RTSA% was significantly higher in animals which had undergone PHx than in the controls (non-hepatectomised) (46.98 ± 8.76% vs. 18.73 ± 5.65%; p < 0.05). Analysing each lobe separately, this difference in favour of hepatectomized animals was relevant and statistically significant in the paramedian and caudate lobes. But in the right lobe the difference was scarce and not significant. In vitro, 2.5% HRS achieved stronger proliferative rates than the control cultures (10% FCS) or their equivalent of NRS. In this experimental model, a parallelism has been shown between the effect of PHx on the growth of colorectal cancer cells in the liver and the effect of the serum on those cells in vitro.

The role of cellulose nanocrystals in biocompatible starch-based clicked nanocomposite hydrogels.

Starch-based nanocomposite hydrogels were successfully prepared by the Diels-Alder click cross-linking reaction between furan-functionalized starch derivative and a water-soluble tetrafunctional maleimide compound, adding cellulose nanocrystals (CNC) as nanoreinforcement. The effect of increasing the CNC content on rheological and swelling properties as well as on the morphology of the hydrogels was analyzed. Besides, in order to evaluate the applicability of the as-prepared hydrogels as delivery systems, drug release measurements and in vitro cytotoxicity assays were also performed. It was found that the prepared nanocomposite hydrogels presented higher stiffness as the CNC content increased. The incorporation of the nanocrystals modified the internal porous microstructure of the hydrogels, affecting consequently both the swelling capacity and the drug-delivery kinetics. Moreover, the prepared nanocomposite hydrogels showed non-toxic behavior, demonstrating their potential applicability in the biomedical field, especially as sustained drug delivery systems.

H2O2-preconditioned human adipose-derived stem cells (HC016) increase their resistance to oxidative stress by overexpressing Nrf2 and bioenergetic adaptation.

BACKGROUND: Mesenchymal stem cells, including those derived from human adipose tissue (hASCs), are currently being widely investigated for cell therapy. However, when transplanted at the site of injury, the survival and engraftment rates of hASCs are low, mainly due to the harsh microenvironment they encounter, characterized by inflammation and oxidative stress. To overcome these therapeutic limitations, cell preconditioning with low-concentration of hydrogen peroxide (H2O2) has been proposed as a plausible strategy to increase their survival and adaptation to oxidative stress. Nonetheless, the underlying mechanisms of this approach are not yet fully understood. In this study, we analyzed molecular and bioenergetic changes that take place in H2O2 preconditioned hASCs. METHODS: Long-term exposure to a low concentration of H2O2 was applied to obtain preconditioned hASCs (named HC016), and then, their response to oxidative stress was analyzed. The effect of preconditioning on the expression of Nrf2 and its downstream antioxidant enzymes (HO-1, SOD-1, GPx-1, and CAT), and of NF-κB and its related inflammatory proteins (COX-2 and IL-1ß), were examined by Western blot. Finally, the Seahorse XF96 Flux analysis system was used to evaluate the mitochondrial respiration and glycolytic function, along with the total ATP production. RESULTS: We found that under oxidative conditions, HC016 cells increased the survival by (i) decreasing intracellular ROS levels through the overexpression of the transcription factor Nrf2 and its related antioxidant enzymes HO-1, SOD-1, GPx-1, and CAT; (ii) reducing the secretion of pro-inflammatory molecules COX-2 and IL-1ß through the attenuation of the expression of NF-κB; and (iii) increasing the total ATP production rate through the adaption of their metabolism to meet the energetic demand required to survive. CONCLUSIONS: H2O2 preconditioning enhances hASC survival under oxidative stress conditions by stimulating their antioxidant response and bioenergetic adaptation. Therefore, this preconditioning strategy might be considered an excellent tool for strengthening the resistance of hASCs to harmful oxidative stress.

Light-driven assembly of biocompatible fluorescent chitosan hydrogels with self-healing ability.

Nitrile imine-mediated tetrazole-ene cycloaddition (NITEC) was successfully used to cross-link complementary tetrazole and maleimide chitosan derivatives into hydrogel networks using irradiation. The photo-click reaction resulted in the formation of robust fluorescent hydrogels with an emission signal at around 530 nm. The degree of cross-linking and the resulting hydrogel properties such as pH sensitivity and swelling were influenced by the tetrazole/maleimide ratio and the length of irradiation. Interestingly, rheological studies demonstrated self-healing character of the novel hydrogels as indicated by instantaneous recovery of the storage modulus to the initial values under different oscillatory strains without any additional external trigger. Finally, in addition to their photo-tuneable and self-healing properties, the novel chitosan hydrogels were also found to be biocompatible and susceptible to in vitro enzymatic degradation, making them suitable for design of traceable biomaterials for biomedical applications.

Multifunctional nanofibrous patches composed of nanocellulose and lysozyme nanofibers for cutaneous wound healing.

Cutaneous wounds frequently require the use of patches to promote healing, nevertheless, most commercial products are fabricated with non-biodegradable synthetic substrates that pose environmental problems upon disposal. Herein, the partnership between two biobased nanofibrous polymers, namely a polysaccharide (nanofibrillated cellulose (NFC)) and a protein (lysozyme nanofibers (LNFs)), is explored to design sustainable fibrous patches with good mechanical performance and biological functionalities for wound healing applications. Two patches with different morphologies were prepared by vacuum filtration of a water-based suspension of both nanofibers and by sequential filtration of the separated suspensions (layered patch). The resultant freestanding patches exhibited high thermal stability (up to 250 °C), mechanical performance (Young's modulus ≥3.7 GPa), and UV-barrier properties. The combination of the bioactive LNFs with the mechanically robust NFC conveyed antioxidant activity (76-79% DPPH scavenging) and antimicrobial activity against Staphylococcus aureus (3.5-log CFU mL-1 reduction), which is a major benefit to prevent microbial wound infections. Moreover, these patches are biocompatible towards L929 fibroblast cells, and the in vitro wound healing assay evidenced a good migration capacity leading to an almost complete wound occlusion. Therefore, the partnership between the two naturally derived nanofibrous polymers represents a potential blueprint to engineer sustainable multifunctional patches for cutaneous wound healing.

Cryopreserved H2 O2 -preconditioned human adipose-derived stem cells exhibit fast post-thaw recovery and enhanced bioactivity against oxidative stress.

Human adipose-derived stem cells (ASCs), despite being one of the most attractive cell populations for tissue engineering and regenerative medicine, currently have certain limitations that reduce their therapeutic efficacy. One of the most serious problems is the poor engraftment of cryopreserved ASCs at injured tissue, attributed to the diminished biological activity of ASCs immediately post-thaw and their poor survival under harsh conditions of oxidative stress. Seeking to address these issues, we have developed a hormetic strategy to preadapt human ASCs to oxidative stress based on a new hydrogen peroxide preconditioning procedure, resulting in cells we call HC016. These cells rapidly recover their biological activity and functionality after cryopreservation while maintaining their mesenchymal stem cell status. Compared with non-preconditioned ASCs, HC016 cells showed (a) faster in vitro adhesion capacity and cell cycle progression immediately post-thaw, (b) enhanced cell survival under oxidative stress in a serum-free environment, and (c) heightened chemotaxis towards damage signals of oxidized glial cells. In addition, compared with ASC-conditioned medium, HC016-conditioned medium showed a greater cytoprotective and pro-recovery effect on oxidized fibroblasts under serum-free conditions. Consistent with these results, in HC016 cells exposed to oxidative stress, we observed markedly higher expression of insulin-like growth factor-1 (a key factor in cell survival and migration) and of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 and pyruvate dehydrogenase kinase isozyme 1 (essential enzymes to upregulate glycolysis and downregulate oxidative phosphorylation) along with lower basal mitochondrial activity. Taking into account all the aforementioned advantages, HC016 cells might be considered an important breakthrough in ASC-based cell therapies.

Hybrid and biocompatible cellulose/polyurethane nanocomposites with water-activated shape memory properties.

Water-activated shape memory bacterial cellulose/polyurethane nanocomposites were prepared by the immersion of bacterial cellulose (BC) wet membranes into waterborne polyurethane (WBPU) dispersions for different times. The high affinity between the hydrophilic BC and water stable polyurethane led to the coating and embedding of the BC membrane into the WBPU, facts that were confirmed by FTIR, SEM and mechanical testing of the nanocomposites. The mechanical performance of the nanocomposites resulted enhanced with respect to the neat WBPU, confirming the reinforcing effect of the BC membrane. An improvement of the shape fixity ability and faster recovery process with the presence of BC was observed. In 3 min, the nanocomposite with highest BC content recovered the 92.8 ± 6.3% of the original shape, while the neat WBPU only recovered the 33.4 ± 9.6%. The obtained results indicated that 5 min of impregnation time was enough to obtain nanocomposites with improved mechanical performance and fast shape recovery for potential biomedical applications. The present work provides an approach for developing environmentally friendly and biocompatible BC/polyurethane based materials with enhanced mechanical and shape memory properties.

Effect of liver resection on the progression and growth of rhabdomyosarcoma metastases in a rat model.

BACKGROUND/AIMS: To analyze the effect of liver resection on the progression of liver metastases in a rhabdomyosarcoma rat model. METHODS: Liver metastases were induced by intrasplenic injection of S4MH rhabdomyosarcoma cells in WAG/RijCrl rats. In a first experiment, rats were sequentially sacrificed until day 30 following tumor cell inoculation to establish the optimal day to evaluate liver and lung metastases. A second group of rats were hepatectomized or laparotomized 10 d after tumor inoculation, and on day 21 they were sacrificed to determine the size and number of liver and lung metastases. Also, in vitro proliferation rates of tumor cells in the presence of fetal calf serum or hepatectomized or laparotomized rat serum were assessed. RESULTS: Individual metastases could be optimally determined on day 21. In hepatectomized animals liver metastases reached greater size and their number was significantly increased (28.7 versus 9.3, P < 0.05). Moreover, the number of lung tumor foci in this group nearly doubled that in the control group (99.2 versus 28.5, P < 0.05). In vitro studies showed that hepatectomized rat serum increased cell proliferation when compared with laparotomized rat serum (2.0-fold) or fetal calf serum (1.4-fold). CONCLUSIONS: This tumor model shows the tumor-enhancing effect derived from hepatic resection, and may be useful to assess preventive therapeutic strategies.

The Neuroprotective Effect of Conditioned Medium from Human Adipose-Derived Mesenchymal Stem Cells is Impaired by N-acetyl Cysteine Supplementation.

Oxidative stress is a common feature in neurodegenerative diseases associated with neuroinflammation, and therefore, has been proposed as a key target for novel therapies for these diseases. Recently, adipose-derived stem cell (ASC)-based cell therapy has emerged as a novel strategy for neuroprotection. In this study, we evaluate the therapeutic role of ASC-conditioned medium (ASC-CM) against H2O2-induced neurotoxicity in a new in vitro model of ec23/brain-derived neurotrophic factor (BDNF)-differentiated human SH-SY5Y neuron-like cells (SH-SY5Yd). In the presence of ASC-CM, stressed SH-SY5Yd cells recover normal axonal morphology (with an almost complete absence of H2O2-induced axonal beading), electrophysiological features, and cell viability. This beneficial effect of ASC-CM was associated with its antioxidant capacity and the presence of growth factors, namely, BDNF, glial cell line-derived neurotrophic factor, and transforming growth factor ß1. Moreover, the neuroprotective effect of ASC-CM was very similar to that obtained from treatment with BDNF, an essential factor for SH-SY5Yd cell survival. Importantly, we also found that the addition of the antioxidant agent N-acetyl cysteine to ASC-CM abolished its restorative effect; this was associated with a strong reduction in reactive oxygen species (ROS), in contrast to the moderate decrease in ROS produced by ASC-CM alone. These results suggest that neuronal restorative effect of ASC-CM is associated with not only the release of essential neurotrophic factors, but also the maintenance of an appropriate redox state to preserve neuronal function.

Desarrollo de un plan integral para la adquisición de la competencia de comunicación en el grado en Odontología de la Universidad del País Vasco: un reto institucional / Development of a comprehensive plan for the acquisition of communication skills in the degree in dentistry at the University of the Basque Country: an institutional challenge

INTRODUCCIÓN: La praxis de la odontología requiere el desarrollo adecuado de las habilidades de comunicación, competencia transversal que ha de estar garantizada durante los estudios de grado. Esto supone un reto institucional, por cuanto las facultades han de poner los mecanismos académicos para evaluar el nivel de desarrollo de dichas habilidades. MÉTODOS: Se plantea un plan integral de carácter colaborativo para el desarrollo de las habilidades comunicativas en el grado en Odontología de la Universidad del País Vasco/Euskal Herriko Unibertsitatea, que contempla cuatro fases: a) recogida y socialización de la información sobre el desarrollo de la competencia; b) diseño de desarrollo trasversal y vertical de la competencia; c) implementación y análisis de resultados; y d) recogida de evidencias del proceso y divulgación de los resultados. RESULTADOS: Tras la detección de las fortalezas y debilidades, se definieron 40 habilidades comunicacionales, estructuradas en cinco bloques (comunicación oral con pacientes/familiares, comunicación oral con otros profesionales, comunicación escrita con pacientes/familiares, comunicación escrita con otros profesionales sanitarios y técnicas de comunicación odontólogo-paciente) y tres niveles de desempeño (identificación de la información, desempeño con alta supervisión y desempeño autónomo con moderada supervisión). Para su desarrollo, se diseñaron 19 actividades formativas y de evaluación, actualmente en implementación. CONCLUSIÓN: El plan se está desarrollando con éxito, y las evidencias del proceso, recogidas en un portafolio, servirán para el seguimiento de la titulación

INTRODUCTION: The practice of dentistry requires the proper development of communication skills, which must be guaranteed during undergraduate studies. This is an institutional challenge, because the schools have to put the academic mechanisms to evaluate the level of development of these skills. METHODS: The University of the Basque Country (UPV/EHU) is developing a comprehensive collaborative plan that includes four phases: a) collection and socialization of information on the current situation of the development of communication skills; b) design of a training plan to improve these skills, c) training plan implementation and results assessment, and d) gathering evidence of the process and dissemination of the results. RESULTS: After the detection of strengths and weaknesses in communication, we defined a total of 40 communication skills, structured in five blocks (oral communication with patients/family members; oral communication with other professionals; written communication with patients/family members; written communication with other health professionals, and dentist-patient communication techniques) and three levels of performance (identifying information, performance with high supervision, autonomous with moderate supervision). For its development, 19 training and evaluation activities were designed, currently being implemented. CONCLUSION: The plan is being developed successfully and the evidence of the process, collected in a portfolio, will be used to monitor the degree