Biocompatibilidad "in vitro" de nuevos productos de eliminación de caries químico-mecánicos en células madre de pulpa dental humana

Introducción: La caries dental en la dentición permanente es la afección más prevalente entre todas las enfermedades humanas y afecta a más de 2500 millones de personas. Una de las técnicas aplicadas en la odontología mínimamente invasiva incluye la remoción químico-mecánica de la caries. La utilización de los materiales de remoción química de caries ha demostrado reducir la ansiedad, el dolor y la necesidad de anestesia, y esto lo hace muy adecuado para el tratamiento de pacientes ansiosos o médicamente comprometidos. Objetivo: El objetivo de este estudio fue comparar las características biológicas de cuatro materiales de remoción químico-mecánica de caries para evaluar su biocompatibilidad usando células madre de pulpa de diente permanente. Material y Métodos: Los materiales analizados fueron Papacárie Duo®, BRIX3000®, Cariesolut y NATURAL-CARE. Los procedimientos para evaluar la biocompatibilidad de estos materiales fueron realizados sobre células madre de pulpa dental de diente permanente. En una cabina de Bioseguridad Tesltar nivel II se realizaron un total de siete experimentos: medición de la concentración inhibitoria media (IC50), medición de la actividad metabólica celular (MTT) (24, 48, 72 horas), experimento de migración celular (24, 48, 72 horas), experimento de inmunofluorescencia (72 horas), análisis de apoptosis y necrosis celular, análisis de producción de especies reactivas de oxígeno (ROS) y análisis del ciclo celular. Los análisis estadísticos se realizaron mediante ANOVA unidireccional y prueba post-hoc de Tukey (p<0,05). Resultados: En nuestros resultados se obtuvo que BRIX3000® mostró al 0,1% y 0,01% una citocompatibilidad equiparable a la del grupo control para todos los períodos de tiempo analizados. Papacárie Duo® presentó una citotoxicidad concentración-dependiente, mostrando una baja biocompatibilidad y viabilidad celular a altas concentraciones la cual mejoraba al diluir el material. NATURAL-CARE presentó un comportamiento similar al observado en Papacárie Duo®, llegando a alcanzar a bajas concentraciones (0,01%) resultados más favorables en los experimentos de migración celular y de inmunofluorescencia con respecto a dicho material y semejantes a los del control. Cariesolut fue el material que mayor citotoxicidad 4 TESIS DOCTORAL- NURIA PÉREZ GUZMÁN demostró en todos los casos. Los resultados sugieren que BRIX3000® a altas concentraciones es capaz de levantar las células cultivadas sin llegar a producir su apoptosis, permitiendo una viabilidad celular bastante aceptable a bajas concentraciones; Papacárie Duo® y NATURAL-CARE si llegan a producir muerte celular a altas concentraciones, mejorando su biocompatibilidad al disminuir su concentración. Conclusiones: Nuestros hallazgos sugieren que BRIX3000® sería el material más adecuado para realizar una remoción química de caries, siendo buenas opciones también Papacárie Duo® y NATURAL-CARE, y desaconsejando la utilización de Cariesolut debido a su baja biocompatibilidad sobre células de pulpa dental de diente permanente.Introduction: Dental caries in the permanent dentition is the most prevalent of all human diseases and affects more than 2.5 billion people. One of the techniques applied in minimally invasive dentistry includes chemical-mechanical caries removal. The use of chemical caries removal materials has been shown to reduce anxiety, pain and the need for anaesthesia, and this makes it well suited to the treatment of anxious or medically compromised patients. Objective: The aim of this study was to compare the biological characteristics of four chemical-mechanical caries removal materials to evaluate their biocompatibility using permanent tooth pulp stem cells. Material and Methods: The materials evaluated were Papacárie Duo®, BRIX3000®, Cariesolut and NATURAL-CARE. Procedures to evaluate the biocompatibility of these materials were performed on permanent tooth pulp stem cells. A total of seven experiments were performed in a Tesltar level II biosafety cabinet: measurement of the mean inhibitory concentration (IC50), measurement of cell metabolic activity (MTT) (24, 48, 72 hours), cell migration experiment (24, 48, 72 hours), immunofluorescence experiment (72 hours), cell apoptosis and necrosis analysis, reactive oxygen species (ROS) production analysis and cell cycle analysis. Statistical analyses were performed by one-way ANOVA and Tukey's post-hoc test (p<0.05). Results: In our results, BRIX3000® showed at 0.1% and 0.01% a cytocompatibility comparable to that of the control group for all time periods analysed. Papacárie Duo® presented a concentration-dependent cytotoxicity, showing low biocompatibility and cell viability at high concentrations which improved when the material was diluted. NATURAL-CARE showed a similar behaviour to that observed in Papacárie Duo®, reaching at low concentrations (0.01%) more favourable results in cell migration and immunofluorescence experiments with respect to that material and similar to those of the control. Cariesolut was the material that showed the highest cytotoxicity in all cases. The results suggest that BRIX3000® at high concentrations is capable of lifting the cultured cells without producing apoptosis, allowing a fairly acceptable cell viability at low concentrations; Papacárie Duo® and NATURAL-CARE do produce cell 8 TESIS DOCTORAL- NURIA PÉREZ GUZMÁN death at high concentrations, improving their biocompatibility by decreasing their concentration. Conclusions: Our findings suggest that BRIX3000® would be the most suitable material for chemical caries removal, with Papacárie Duo® and NATURAL-CARE also being good options, and discourage the use of Cariesolut due to its low biocompatibility on permanent tooth pulp cells

PTEN Deletion in Adult Mice Induces Hypoinsulinemia With Concomitant Low Glucose Levels

The PI3K/AKT pathway, negatively regulated by PTEN, plays a paramount role in glucose metabolism regulation due to its activation by the insulin receptor signaling pathway. We generated a PTEN-KO mouse to evaluate the systemic effect of the overactivation of the PI3K/AKT pathway in insulin signaling and glucose homeostasis. Our results demonstrate that PTEN-KO mice show very low glucose levels in the fasted state, which poorly respond to glucose and pyruvate administration. Insulinemia decreased without alterations in pancreatic islets. Among the possible reasons, we uncover the deregulation of the expression of proximal tubule glucose transporter and consequent glycosuria. Moreover, we evidence an altered activation of hepatic gluconeogenesis-related genes. In addition, the expression of several genes related to β-oxidation showed a delayed or even absent response to fasting, suggesting that the lack of PTEN not only impairs glucose metabolism but also slows down the use of lipids as a metabolic fuel. We conclude that the inducible full PTEN-KO mice could be a good model to study the metabolic interactions between glycidic and lipidic metabolism in hypoinsulinemic hypoglycemia and that PTEN could be an important mediator in the disease and/or a potential drug target

Conocimiento del profesorado sobre las dificultades específicas de aprendizaje en lectura y escritura

Specific Learning Disabilities (SLD) have generated much interest from educators and recent legislative reform has led to changes in this concept. The role of teachers in the prevention, detection and intervention of these disorders requires specific knowledge. This study analyses preschool and primary school teacher knowledge of general information, symptoms/diagnoses and interventions on reading and writing SLD (SLD-R and W) and its relationship with initial training and general or specific teaching experience. A sample of 149 teachers completed a survey including demographic questions (11) and a scale of knowledge on SLD-R and W (38 items). Results of the survey reveal that teachers have a greater degree of knowledge regarding intervention, erroneous conceptions of symptoms/diagnoses and knowledge gaps regarding general information. No relationship was found between training and experience and this knowledge. Conclusions reached highlight some practical repercussions: erroneous conceptions of symptoms may negatively affect the identification of SLD-R and W students, attention to risk factors and early intervention. It may also increase the risk of inappropriate counselor referrals and ineffective interventions.El objetivo de este estudio fue analizar los conocimientos, concepciones erróneas y lagunas de conocimiento de los tutores de las primeras etapas de escolaridad sobre las Dificultades Específicas de Aprendizaje en lectura y escritura. Una muestra de 149 profesores de 15 centros de la isla de Tenerife respondió una escala de 38 ítems agrupados en tres dimensiones: Síntomas/diagnósticos, Información General e Intervención, con 3 alternativas de respuesta (verdadero, falso y no sé). Se obtuvo un porcentaje medio de respuestas correctas superior al 50% en las tres áreas. Los contrastes mostraron que los tutores tienen un porcentaje significativamente mayor de conocimientos en el área de Intervención, más concepciones erróneas en la de Síntomas/diagnósticos y más lagunas de conocimientos en la de Información General

Effectiveness and acceptability of targeted text message reminders in colorectal cancer screening:a randomised controlled trial (M-TICS study)

Background:Mobile phone text message reminders to increase colorectal cancer (CRC) screening participation have shown moderate effects.Objective:This study assessed effectiveness and acceptability of targeted text message reminders for those who picked up but did not return their screening kit at pharmacy within 14 days in a CRC screening program in Catalonia, SpainMethods:We performed a randomised control trial in the screening hub of the metropolitan area of Barcelona that covers 502,348 adults aged 50-69 years. In total, 9,369 individuals were randomised in a 1:1 ratio to receive either a text message reminder or no reminder. Main primary outcome was FIT completion rate within 126 days from FIT kit pick-up (intention-to-treat-analysis). A telephone survey assessed acceptability and appropriateness of the intervention. Cost-effectiveness of adding a text message reminder to FIT completion was also performed.Results:FIT completion rate was 77.7% in control arm and 82.6% in text message arm. Higher participation rates in intervention arm were reported independent of sex, age, socioeconomic level, and screening profiles. 89.2% of interviewees considered it important and useful to receive text message reminders to FIT completion, and 93.4% preferred text messages to postal letters.Conclusions:Adding text message reminders to the standard procedure significantly increased FIT kit return rates and was considered acceptable and appropriate. The SMS plus letter reminder to complete and return the FIT kit was a cost-effective strategy. Clinical Trial: Registration Number NCT04343950 (04/09/2020) at clinicaltrials.go

Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves’ disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial

Background: Currently, both the American Thyroid Association and the European Thyroid Association recom mend preoperative preparation with Lugol's Solution (LS) for patients undergoing thyroidectomy for Graves’ Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to pro vide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidec tomy for GD. Methods: A multicenter randomized controlled trial will be performed. Patients ≥18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery. Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoper ative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS. Conclusions: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this set ting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations. Trial registration: ClinicalTrials.gov identifier: NCT03980132

The clinical and molecular cardiometabolic fingerprint of an exploratory psoriatic arthritis cohort is associated with the disease activity and differentially modulated by methotrexate and apremilast

Objectives: (1) To evaluate clinical and molecular cardiovascular disease (CVD) signs and their relationship with psoriatic arthritis (PsA) features and (2) to identify a clinical patient profile susceptible to benefit from methotrexate (MTX) and/or apremilast regarding CVD risk. Methods: This cross-sectional study included 100 patients with PsA and 100 age-matched healthy donors. In addition, an exploratory cohort of 45 biologically naïve patients treated for 6 months with apremilast, MTX or combined therapy according to routine clinical practice was recruited. Extensive clinical and metabolic profiles were obtained. Ninety-nine surrogate CVD-related molecules were analysed in plasma and peripheral blood mononuclear cells (PBMCs). Hard cluster analysis was performed to identify the clinical and molecular phenotypes. Mechanistic studies were performed on adipocytes. Results: Cardiometabolic comorbidities were associated with disease activity and long-term inflammatory status. Thirty-five CVD-related proteins were altered in the plasma and PBMCs of PsA patients and were associated with the key clinical features of the disease. Plasma levels of some of the CVD-related molecules might distinguish insulin-resistant patients (MMP-3, CD163, FABP-4), high disease activity (GAL-3 and FABP-4) and poor therapy outcomes (CD-163, LTBR and CNTN-1). Hard cluster analysis identified two phenotypes of patients according to the rates of cardiometabolic comorbidities with distinctive clinical and molecular responses to each treatment. Conclusions: (1) Novel CVD-related proteins associated with clinical features could be emerging therapeutic targets in the context of PsA and (2) the pleiotropic action of apremilast could make it an excellent choice for the management of PsA patients with high CVD risk, targeting metabolic alterations and CVD-related molecules

Cardiac electrical defects in progeroid mice and Hutchinson-Gilford progeria syndrome patients with nuclear lamina alterations

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by defective prelamin A processing, leading to nuclear lamina alterations, severe cardiovascular pathology, and premature death. Prelamin A alterations also occur in physiological aging. It remains unknown how defective prelamin A processing affects the cardiac rhythm. We show age-dependent cardiac repolarization abnormalities in HGPS patients that are also present in the Zmpste24−/− mouse model of HGPS. Challenge of Zmpste24−/− mice with the β-adrenergic agonist isoproterenol did not trigger ventricular arrhythmia but caused bradycardia-related premature ventricular complexes and slow-rate polymorphic ventricular rhythms during recovery. Patch-clamping in Zmpste24−/− cardiomyocytes revealed prolonged calcium-transient duration and reduced sarcoplasmic reticulum calcium loading and release, consistent with the absence of isoproterenol-induced ventricular arrhythmia. Zmpste24−/− progeroid mice also developed severe fibrosis-unrelated bradycardia and PQ interval and QRS complex prolongation. These conduction defects were accompanied by overt mislocalization of the gap junction protein connexin43 (Cx43). Remarkably, Cx43 mislocalization was also evident in autopsied left ventricle tissue from HGPS patients, suggesting intercellular connectivity alterations at late stages of the disease. The similarities between HGPS patients and progeroid mice reported here strongly suggest that defective cardiac repolarization and cardiomyocyte connectivity are important abnormalities in the HGPS pathogenesis that increase the risk of arrhythmia and premature death

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

PhDAY 2020 -FOO (Facultad de Óptica y Optometría)

Por cuarto año consecutivo los doctorandos de la Facultad de Óptica y Optometría de la Universidad Complutense de Madrid cuentan con un congreso propio organizado por y para ellos, el 4º PhDAY- FOO. Se trata de un congreso gratuito abierto en la que estos jóvenes científicos podrán presentar sus investigaciones al resto de sus compañeros predoctorales y a toda la comunidad universitaria que quiera disfrutar de este evento. Apunta en tu agenda: el 15 de octubre de 2020. En esta ocasión será un Congreso On-line para evitar que la incertidumbre asociada a la pandemia Covid-19 pudiera condicionar su celebración