Ex Vivo Generation and Characterization of Human Hyaline and Elastic Cartilaginous Microtissues for Tissue Engineering Applications

This study was supported by grants FIS PI17/0393 and PI20/0318 from the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III); grants PI-0257-2017 and PE-0395- 2019 from Consejería de Salud y Familias, Junta de Andalucía, España; grant P18-RT-5059 from Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía, España; grant A-CTS-498-UGR18 from the University of Granada and Junta de Andalucía, España. It was co-funded by FEDER-ERDF funds.Authors are grateful to Fabiola Bermejo Casares for the technical histological assistance. Special thanks to Ariane Ruyffelaert for her critical review and proofreading service. This work forms part of the doctoral thesis conducted by David Sánchez Porras (Doctoral Program in Biomedicine, Doctoral School, University of Granada, Spain).Considering the high prevalence of cartilage-associated pathologies, low self-repair capacity and limitations of current repair techniques, tissue engineering (TE) strategies have emerged as a promising alternative in this field. Three-dimensional culture techniques have gained attention in recent years, showing their ability to provide the most biomimetic environment for the cells under culture conditions, enabling the cells to fabricate natural, 3D functional microtissues (MTs). In this sense, the aim of this study was to generate, characterize and compare scaffold-free human hyaline and elastic cartilage-derived MTs (HC-MTs and EC-MTs, respectively) under expansion (EM) and chondrogenic media (CM). MTs were generated by using agarose microchips and evaluated ex vivo for 28 days. The MTs generated were subjected to morphometric assessment and cell viability, metabolic activity and histological analyses. Results suggest that the use of CM improves the biomimicry of the MTs obtained in terms of morphology, viability and extracellular matrix (ECM) synthesis with respect to the use of EM. Moreover, the overall results indicate a faster and more sensitive response of the EC-derived cells to the use of CM as compared to HC chondrocytes. Finally, future preclinical in vivo studies are still needed to determine the potential clinical usefulness of these novel advanced therapy products.Instituto de Salud Carlos III Spanish Government FIS PI17/0393 PI20/0318Junta de Andalucia PI-0257-2017 PE-03952019Junta de Andalucia P18-RT-5059University of Granada A-CTS-498-UGR18Junta de Andalucia A-CTS-498-UGR18FEDER-ERDF fund

Use of bone scintigraphy in the early diagnosis of bisphosphonate related osteonecrosis of the jaw. Case report and review of the literature

The main aim of the present report is to show the potential utility of bone scintigraphy for the diagnosis of jaw osteonecrosis. We report the history of a 62-year-old woman underwent breast cancer surgery in 2010. Moreover, patient received postoperative radiotherapy and chemotherapy. Intravenous bisphosphonates were also added to the treatment strategy to reduce the risk of bone metastasis. However, a hypermetabolic focus on left hemimandible was evidenced with a bone scintigraphy during follow up. After a careful study, the diagnosis of Bisphosphonate Related Ostneonecrosis of the Jaw (BRONJ) was carried out. This case highlights that bone scintigraphy may be extremely helpful for the early detection of BRONJ in high risk patient

Multiple oral fibropapillomatosis as an initial manifestation of Cowden Syndrome : case report

El síndrome de Cowden es una infrecuente enfermedad hereditaria englobada dentro de las poliposis gastrointestinales de tipo hamartomatoso. Se caracteriza por asociar anomalías cutaneomucosas y por la extraordinaria tendencia a desarrollar neoplasias malignas, principalmente de mama y tiroides. La importancia de un diagnóstico precoz del síndrome y de un adecuado screening tumoral en pacientes con lesiones papilomatosas cutaneomucosas, nos va a permitir adelantarnos en el diagnóstico de patologías con enorme morbimortalidad asociada en caso de una detección tardía. Presentamos el caso de una paciente diagnosticada de síndrome de Cowden tras consultar por lesiones papilomatosas labiales de largo tiempo de evolución y tratada posteriormente de cáncer de mama y riñón en estadios iniciales. El correcto diagnóstico de una patología banal de mucosa oral, nos ha permitido actuar de manera muy precoz frente a la patología neoplásica asociada a dicha enfermedad

In vitro characterization of a novel magnetic fibrin-agarose hydrogel for cartilage tissue engineering

The encapsulation of cells into biopolymer matrices enables the preparation of engineered substitute tissues. Here we report the generation of novel 3D magnetic biomaterials by encapsulation of magnetic nanoparticles and human hyaline chondrocytes within fibrin-agarose hydrogels, with potential use as articular hyaline cartilagelike tissues. By rheological measurements we observed that, (i) the incorporation of magnetic nanoparticles resulted in increased values of the storage and loss moduli for the different times of cell culture; and (ii) the incorporation of human hyaline chondrocytes into nonmagnetic and magnetic fibrin-agarose biomaterials produced a control of their swelling capacity in comparison with acellular nonmagnetic and magnetic fibrin-agarose biomaterials. Interestingly, the in vitro viability and proliferation results showed that the inclusion of magnetic nanoparticles did not affect the cytocompatibility of the biomaterials. What is more, immunohistochemistry showed that the inclusion of magnetic nanoparticles did not negatively affect the expression of type II collagen of the human hyaline chondrocytes. Summarizing, our results suggest that the generation of engineered hyaline cartilage-like tissues by using magnetic fibrin-agarose hydrogels is feasible. The resulting artificial tissues combine a stronger and stable mechanical response, with promising in vitro cytocompatibility. Further research would be required to elucidate if for longer culture times additional features typical of the extracellular matrix of cartilage could be expressed by human hyaline chondrocytes within magnetic fibrin-agarose hydrogels.This study was supported by projects FIS2013-41821-R (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía, Industria y Competitividad, MINECO Spain, cofunded by Fondo Europeo de Desarrollo Regional, FEDER, European Union), FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, and Agencia Estatal de Investigación, AEI, Spain, cofunded by Fondo Europeo de Desarrollo Regional, FEDER, European Union), and by the Consejería de Salud y Familias, Junta de Andalucía, Spain, Grant SAS CS PI-0257-2017

Effectiveness of 1% versus 0.2% chlorhexidine gels in reducing alveolar osteitis from mandibular third molar surgery: a randomiz, double-blind clinical trial

Purpose: Alveolar osteitis (AO) is the most common postoperative complication of dental extractions. The purpose of this study was to compare the effectiveness of 1% versus 0.2% chlorhexidine (CHX) gel in reducing postoperative AO after surgical extraction of mandibular third molars, and assess the impact of treatment on the Oral HealthRelated Quality of Life (OHRQoL). Material and Methods: This clinical study was a randomized, double-blind clinical trial. Eighty eight patients underwent surgical extraction of one retained mandibular third molar with the intra-alveolar application of 0.2% CHX gel. Afterwards, they were assigned to one of two groups: 1% CHX gel (n=42) or 0.2% CHX gel (n=46). The patients applied the gel twice a day to the wound for one week. All patients were evaluated for AO. Results: In the 0.2% CHX gel group, 13% of AO incidence was found, while in the 1% CHX gel group, AO incidence was 7%, a difference that was not statistically significant. Variables such as sensation of pain and inflammation at baseline and during one week, as well as OHRQoL of the patients at 24 hours and 7 days post-extraction, gave no statistically significant differences. Conclusions: There are no significant differences in AO after surgical extraction of mandibular third molars, when comparing applying 1% CHX gel twice a day for 7 days with 0.2% CHX gel

Efeitos ansiolíticos do Atenolol injetado no núcleo accumbens septi em ratos após restrição de estresse no teste do labirinto em cruz elevado

Objetives: Previously, we observed that the injection of glutamate antagonists injected within the Nucleus Accumbens Septi (NAS) produced an anxiolytic-like effect in the elevated plus maze (EPM) test in basal non-disturbed state rats. The effect of metoprolol, a specific Beta-1 Adrenoreceptor antagonist in the EPM, was studied previously in a resting condition in male rats bilaterally cannulated in the NAS. Methods: Rats were previously submitted to restrain stress and divided into four groups. They received bilaterally 1 μl injections of saline (n=13) or atenolol in different doses within the NAS: 0.75 (n=15), 1 (n=13) and 2 µg/1 µl (n=13), 15 min before testing. Rats were maintained under restrain between injection and test. Results: Time Spent in the Open Arm (TSOA) was modified by treatment (F = 4.239, p = 0.0096, df = 3) and increased by the medium dose group when it was compared with the saline group (p<0.05) and the lowest dose group (p<0.01). Open arms entries (OAE) were modified by treatment (F = 3.461, p = 0.0231, df = 3). This parameter was increased by the medium dose of atenolol (p<0.05) when compared to saline and the lowest dose. No significant differences were observed in other parameters studied. Conclusion: We conclude that atenolol beta-1 receptor blockade within the NAS after restraint leads to an anxiolytic-like effect related to an increase in the Time Spent in the Open Arm (TSOA), and behavioural disinhibition, evidenced in the increase in the Open Arm Entries (OAE), showing a specific behavioural pattern.Objetivos: Anteriormente, observamos que a injeção de antagonistas de glutamato injetados dentro do Nucleus Accumbens Septi (NAS) produziu um efeito ansiolítico no teste do labirinto em cruz elevado (LCE) em ratos em estado basal não perturbado. O efeito do metoprolol, um antagonista específico do receptor beta-1 adrenérgico no LCE, foi estudado anteriormente em condição de repouso em ratos machos canulados bilateralmente no NAS. Métodos: Os ratos foram previamente submetidos ao estresse de contenção e divididos em quatro grupos. Eles receberam injeções bilaterais de 1 μl de solução salina (n=13) ou atenolol em diferentes doses dentro do NAS: 0,75 (n=15), 1 (n=13) e 2 μg/1 μl (n=13), 15 min antes do teste. Os ratos foram mantidos sob controle entre a injeção e o teste. Resultados: O tempo gasto no braço aberto (TSOA) foi modificado pelo tratamento (F = 4,239, p = 0,0096, df = 3) e aumentado pelo grupo de dose média quando comparado com o grupo de solução salina (p<0,05) e o grupo de dose média e grupo de dose mais baixa (p<0,01). As entradas de braços abertos (EOA) foram modificadas pelo tratamento (F = 3,461, p = 0,0231, gl = 3). Esse parâmetro foi aumentado pela dose média de atenolol (p<0,05) quando comparado ao soro fisiológico e à dose mais baixa. Não foram observadas diferenças significativas nos demais parâmetros estudados. Conclusão: Concluímos que o bloqueio do receptor beta-1 pelo atenolol dentro do NAS após a contenção leva a um efeito do tipo ansiolítico relacionado ao aumento do Tempo Passado no Braço Aberto (TSOA), e à desinibição comportamental, evidenciada no aumento de Entradas de Braço Aberto (EOA), mostrando um padrão comportamental específico.Fil: Llano López, Luis Hernán. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Departamento de Neurociencias; Argentina. Gobierno de la Provincia de Mendoza. Hospital Pediátrico Humberto Notti; ArgentinaFil: Fraile, Miriam Debora. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Departamento de Neurociencias; ArgentinaFil: Landa, Adriana Inés. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Departamento de Neurociencias; ArgentinaFil: López Velásquez, Norman Darío. Universidad Santo Tomás;Fil: Guevara, Manuel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Departamento de Neurociencias; ArgentinaFil: Lafuente Sánchez, José Vicente. Universidad del País Vasco; EspañaFil: Gargiulo, Pascual Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Departamento de Neurociencias; Argentin

Sun exposure practices, attitudes and knowledge among students and teachers at a University School of Health Sciences in Ecuador

Skin cancer incidence is increasing worldwide. Late adolescence and young adulthood are fundamental stages of life to acquire good sun exposure practices, regarding both personal involvement in skin cancer prevention and being a role model for others, especially in a health education environment. This descriptive cross-sectional study is based on the validated CHACES questionnaire to study sun exposure and photoprotection behavior among students and teachers at the School of Health Sciences in the National University of Chimborazo, Riobamba (Ecuador). University members (814 students (89.8 %) and 93 teachers (10.2 %)) were studied, with a predominance of females and light-skin phototypes in both groups. Similar results were obtained regarding sun exposure, with higher recreative exposure in the teachers' group and higher occupational exposure in students. However, students significantly showed lower avoiding midday sun (41.9 % vs 60.9 %), and lower use of sunglasses (10.1 % vs. 41.6 %). Attitudes towards the sun and photoprotection knowledge issues were also equivalent between students and teachers (6.1/10 vs 6.2/10). Students' sunburn rate last year reaches 88.4 % and 52.7 % in teachers (p < 0.001). Using a multivariable logistic regression model, we identified risk factors associated with a greater risk of sunburn in our population. This study highlights areas to be improved regarding knowledge, attitudes and, especially, practices of photoprotection, among students and teachers at the University of Chimborazo. These results point out that awareness-raising campaigns should be implemented to reduce sunburns, morbidity and mortality of skin cancer in this environment.Proyecto Distintivo Soludable Ecuador: Certificación del Distintivo Saludable sobre Fotoprotección y Prevención del Cáncer, y Fortalecimiento de la Línea Estratégica de Seguridad del Paciente en la Facultad de Ciencias de la Salud de Riobamba. Proyecto financiado por la Agencia Andaluza de Cooperación Internacional al Desarrollo (AACID) en 2020. El Número de Expediente del Proyecto Distintivo Soludable Ecuador es 2020UI007. Investigador principal: Jacobo Cambil Martín. Investigadores colaboradores: Salvador Arias Santiago, Magdalena de Troya Martín, Nuria Blázquez Sánchez. Financiación: 47250 euros

A novel mobile phone and tablet application for automatized calculation of pain extent.

Background: Pain drawings (PDs) are used for assessing pain extent as a complementary outcome to other pain measurements, consisting of shading a body chart template to report the location and extent of pain. However, the accuracy and reliability of digital PDs remain controversial due to the heterogeneity of methods used. This study aimed to develop an easy-to-use application for assessing its diagnostic accuracy in comparison with the classic paper-and-pencil method. Methods: A test-retest reliability study was conducted, recruiting 95 patients with musculoskeletal pain symptoms. Participants shaded 2 sets of 3 different PDs (paper-and-pencil PD, digital PD using the finger and digital PD using the digital stylus). Intraclass correlation coefficients (ICC), standard error of measurement and minimal detectable changes (MDC) were calculated for each method. Finally, repeated measure analysis of variance assessed the mean differences between trials and methods and the convergent validity between methods was calculated using Pearson’s correlation coefficients. Results: All methods were excellently reliable (all, ICC>0.94). However, digital PDs obtained higher ICCs (ICC≥0.970) and greater accuracy to detect whether changes reflect a real change and are not due to a measurement errors (MDC = 0.72%– 0.80 % for digital PDs versus MDC = 1.13 % for paper-and-Pencil PDs). No significant score differences were found among the instruments for assessing pain extent (p > 0.05). Finally, the PAIN EXTENT app showed adequate convergent validity (r > 0.850). Conclusion: The PAIN EXTENT app is a fast and easy-to-use instrument compatible with operative systems and devices commonly used for assessing and monitoring pain extent in the clinical and research settings.post-print2,22 M

A vision based aerial rbot solution for the IARC 2014 by the Technical University of Madrid

The IARC competitions aim at making the state of the art in UAV progress. The 2014 challenge deals mainly with GPS/Laser denied navigation, Robot-Robot interaction and Obstacle avoidance in the setting of a ground robot herding problem. We present in this paper a drone which will take part in this competition. The platform and hardware it is composed of and the software we designed are introduced. This software has three main components: the visual information acquisition, the mapping algorithm and the Aritificial Intelligence mission planner. A statement of the safety measures integrated in the drone and of our efforts to ensure field testing in conditions as close as possible to the challenge?s is also included

How should we analyze and present mortality in our patients?: A multicentre GCDP experience

There are different strategies to analyse mortality in peritoneal dialysis (PD) with different definitions for case, event, time at risk, and statistical tests. A common method for the different registries would enable proper comparison to better understand the actual differences in mortality of our patients. Methods: We review and describe the analysis strategies of regional, national and international registries. We include actuarial survival, Kaplan-Meier (KM) and competitive risk (CR) analyses. We apply different approaches to the same database (GCDP), which show apparent differences with each method. Results: A total of 1,890 incident patients in PD from 2003-2013 were included (55 years; men 64.2%), with initial RRF of 7 ml/min; 25% had diabetes and a Charlson index of 3 [2-4]; 261 patients died, 380 changed to haemodialysis (HD) and 682 received a transplant. Annual mortality rates varied up to 20% in relative numbers (6.4 vs. 5.2%) depending on the system applied. The estimated probability of mortality measured by CR progressively differs from the KM over the years: 3.6 vs. 4.0% the first year, then 9.0 vs. 11.9%, 15.6 vs. 28.3%, and 18.5 vs. 43.3% the following years. Conclusions: Although each method may be correct in themselves and express different approaches, the final impression left on the reader is a number that under/overestimates mortality. The CR model better expresses the reality of PD, where the number of patients lost to follow-up (transplant, transfer to HD) it is 4 times more than deceased patients and only a quarter remain on PD at the end of follow up.Existen distintas estrategias para analizar la mortalidad en diálisis peritoneal (DP), con diferentes definiciones de caso, evento, tiempo en riesgo y análisis estadístico. Un método común entre los distintos registros permitiría compararlos adecuadamente y entender mejor las diferencias reales de mortalidad de nuestros pacientes. Métodos: Revisamos y describimos las estrategias de análisis de los registros autonómicos, nacional e internacionales. Incluimos análisis de supervivencia actuarial, Kaplan-Meier (KM) y riesgos-competitivos (RC). Aplicamos los diferentes enfoques a la misma base de datos (GCDP), lo que permite mostrar las diferencias aparentes con cada método. Resultados: Se incluyeron 1.890 pacientes incidentes en DP en el periodo 2003-2013 (55 años; 64,2% varones), con FRR inicial de 7 ml/min; el 25% presentaba diabetes y un índice de Charlson de 3 [2–4]. Fallecieron 261 pacientes, 380 pasaron a hemodiálisis (HD) y 682 recibieron trasplante. Las tasas de mortalidad anual llegan a variar hasta un 20% en números relativos (6,4 vs. 5,2%) según el sistema aplicado. La estimación de probabilidad de mortalidad por RC es inferior a KM en todos los años: 3,6 vs. 4,0% el 1.er año; 9,0 vs. 11,9%; 15,6 vs. 28,3% y 18,5 vs. 43,3% los siguiente