Tooth loss and depression in Chilean participants of the National Health Survey 2016-2017: Oral and social functions mediation analysis.

BACKGROUND: Previous studies have indicated the association between poor oral health and depression in adults. This study evaluated oral and social functions contribution to the association between tooth loss and depressive symptoms in Chilean individuals. METHODS: We used data from the Chilean National Health Survey. The number of remaining teeth (≤19 versus ≥20 teeth) and anterior tooth losses were the exposure variables. Outcome was depression, measured through a self-report question and with the Composite International Diagnostic Interview - Short Form (CIDI SF). Mediating variables were determined by five questions, including problems regarding "speaking", "pain and suffering", "eating", "daily activities", and "social relationships". We performed logistic regression models adjusted by multiple confounders variables. Finally, we calculated indirect, direct effect, total effect, and the proportion mediated (PM). RESULTS: We included 5383 participants. The self-reported depression and suspected depression prevalence were 22,1 % and 14,0 % respectively. The total effect of fewer remaining teeth (≤19) on self-reported depression was 1.21 (95 % CI 1.02-1.44), and 1.09 (95 % CI 0.90-1.33) for suspected depression. All five variables of oral and social functions significantly mediated the association between tooth loss and depression. Feeling uncomfortable when speaking or eating discomfort were the most significant mediators. LIMITATIONS: The mediation analysis should be interpreted with caution due to the cross-sectional design. CONCLUSIONS: Deterioration of oral and social functions was a significant mediator in the association between tooth loss and depression, in particular feeling uncomfortable when speaking or eating. This mechanism should be considered in interventions to improve mental health.

Rasgos funcionales de frutos con importancia particular para los dispersores de semillas en el bosque seco tropical

Introducción: La frugivoría es un proceso ecológico determinante para la estructuración y regeneración de los bosques. En los trópicos, donde la diversidad de plantas y animales frugívoros es alta, las relaciones interespecíficas son complejas y requieren estudio. Objetivo: Identificar las especies de plantas ecológicamente importantes en dos redes de interacción, y el papel de los rasgos funcionales de los frutos en esas interacciones en un bosque seco. Métodos: Recolectamos 10 frutos por planta de 10 plantas de cada especie de interés en un bosque seco colombiano, calculamos el índice de importancia de las plantas a partir de la relevancia de aves y mamíferos frugívoros en la estructura de las redes. Esta relevancia se relaciona directamente con el potencial del animal como dispersor efectivo de semillas. Utilizamos modelos lineales generalizados para estimar el tamaño, color, estrato, y tipo de pulpa, en el índice. Resultados: Las plantas más importantes son especies de los géneros Miconia, Ficus, Cecropia, Bursera, Casearia y Trichilia, también identificadas como recursos importantes para los frugívoros de los trópicos en otros estudios. Las plantas con frutos carnosos, rojos y de menor tamaño son los mejores para dispersores de semillas. El índice de importancia de las plantas tiene alta variación; esto sugiere que un conjunto de especies frugívoras beneficiadas por cada especie de planta tiene una contribución diferenciada en procesos ecológicos derivados de la dispersión de semillas. Conclusiones: Programas de restauración para este tipo de bosque tropical seco debería incluir una variedad de plantas, incluyendo especies con frutos pequeños, rojos y carnosos.

Introduction: Frugivory is a pivotal ecological process for the structure and regeneration of forests. In the tropics, where the diversity of plants and frugivorous animals is high, interspecific relationships in the interaction networks are complex and need study. Objective: To identify ecologically important plant species in two interaction networks, and the role of functional fruit traits in those interactions in a dry forest. Methods: We collected 10 fruits per plant from 10 plants of each species of interest in a Colombian dry forest, we calculated the Plant Importance Index based on the bird and mammal frugivores relevance for network structure. This relevance is directly related to the animal's potential as effective seed dispersers. We used generalized linear models to estimate the effect of fruit size, color, stratum, and type of pulp, on the index. Results: The most important plants are species of the genera Miconia, Ficus, Cecropia, Bursera, Casearia and Trichilia, also identified as important resources for tropical frugivores in other studies. Plants with small, red, and fleshy fruits are the best for seed dispersers. The plant importance index has a high variation; this suggests that the set of frugivore species benefited by each plant species has a differential contribution to the ecological processes derived from seed dispersal. Conclusions: Restoration programs for this kind of tropical dry forest should include a variety of plants, including species with small, red, and fleshy fruits.

Local Anaesthetics Combined with Vasoconstrictors in Controlled Hypertensive Patients Undergoing Dental Procedures: Systematic Review and Meta-Analysis / Uso de Anestésicos Locales con Vasoconstrictor en Pacientes con Hipertensión Controlada Durante la Atención Odontológica: Una Revisión Sistemática y Metaanálisis

The aim of this systematic review is to assess the safety of local anaesthetics (LA) combined with vasoconstrictors (VC) for patients with controlled hypertension undergoing dental procedures. A comprehensive search strategy were used to identify all relevant randomized controlled trials (RCTs) that evaluated the effect of LA combined with VC. All searches covered the period from 1990 to February 2021. We performed a meta-analysis using random-effect models and assessed overall certainty in evidence using GRADE approach. Our search strategy yielded 1262 references. Finally, seven randomised trials were included, but only three were included in the meta-analysis. The use of LA with VC may result in little to no difference in the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), but the certainty of the evidence was assessed as low. Death, stroke, acute myocardial infarction, need for hospitalization, pain and bleeding were not reported by the included studies. The hemodynamic changes using VC do not imply an increased risk of occurrence of adverse cardiovascular events. The use of VC could even be recommendable considering their multiple advantages.

El objetivo de esta revisión sistemática es evaluar la seguridad del uso de anestésicos locales (AL) combinados con vasoconstrictor (VC) en pacientes con hipertensión controlada durante procedimientos dentales. Se realizó una estrategia de búsqueda para identificar todos los estudios clínicos aleatorizados (ECA) relevantes que evaluaban el efecto del AL combinado con VC. Todos los estudios fueron del periodo entre 1990 a febrero del 2021. Se realizó un meta-análisis usando modelos de efecto aleatorizado y una revisión de la certeza de la evidencia usando el método GRADE. Nuestra estrategia de búsqueda arrojó 1262 referencias. Finalmente, siete estudios clínicos aleatorizados fueron incluidos, de los cuales tres fueron incluidos en el meta-análisis. El uso de AL con VC produce una pequeña a ninguna diferencia en el pulso cardiaco, presión sistólica y diastólica, pero la certeza de la evidencia fue baja. Muerte, infarto agudo al miocardio, accidente cerebrovascular, necesidad de hospitalización, dolor y hemorragia no fueron reportados en los estudios incluidos. Los cambios hemodinámicos en el uso de VC no implican un aumento de riesgo de ocurrencia de efectos adversos cardiovasculares. El uso de VC puede ser recomendable considerando sus múltiples ventajas.

Antiviral activity of red algae phycocolloids against herpes simplex virus type 2 in vitro.

Herpes simplex virus type 2 (HSV-2) is a human infectious agent with significant impact on public health due to its high prevalence in the population and its ability to elicit a wide range of diseases, from mild to severe. Although several antiviral drugs, such as acyclovir, are currently available to treat HSV-2-related clinical manifestations, their effectiveness is poor. Therefore, the identification and development of new antiviral drugs against HSV-2 is necessary. Seaweeds are attractive candidates for such purposes because they are a vast source of natural products due to their highly diverse compounds, many with demonstrated biological activity. In this study, we evaluated the in vitro antiviral potential of red algae extracts obtained from Agarophyton chilense, Mazzaella laminarioides, Porphyridium cruentum, and Porphyridium purpureum against HSV-2. The phycocolloids agar and carrageenan obtained from the macroalgae dry biomass of A. chilense and M. laminarioides and the exopolysaccharides from P. cruentum and P. purpureum were evaluated. The cytotoxicity of these extracts and the surpluses obtained in the extraction process of the agar and carrageenans were evaluated in human epithelial cells (HeLa cells) in addition to their antiviral activity against HSV-2, which were used to calculate selectivity indexes (SIs). Several compounds displayed antiviral activity against HSV-2, but carrageenans were not considered as a potential antiviral therapeutic agent when compared to the other algae extracts with a SI of 23.3. Future assays in vivo models for HSV-2 infection should reveal the therapeutic potential of these algae compounds as new antivirals against this virus.

Systematic Mapping Review of Orthognathic Surgery (Protocol).

Study Design: This document details the planning phase of a systematic mapping review. Objective: The objective of this mapping review is to identify, describe, and organize evidence currently available from systematic reviews and primary studies regarding different co-interventions and surgical modalities used in orthognathic surgery (OS) and their outcomes. Methods: Systematic reviews (SRs), randomized controlled trials (RCTs), and observational studies that evaluate perioperative OS co-interventions and surgical modalities will be identified in an exhaustive search of MEDLINE, EMBASE, Epistemonikos, Lilacs, Web of Science, and CENTRAL. Grey literature will also be screened. Results: Expected results include identification of all PICO questions available in the evidence regarding OS and generation of evidence bubble maps, involving a matrix of all identified co-interventions, surgical modalities, and outcomes presented in the studies. This will achieve identification of research gaps and prioritization of new research questions. Conclusions: The significance of this review will result in a systematic identification and characterization of the available evidence, leading to a reduction in research waste and a guidance of future efforts in developing studies for unsolved questions.

Systematic mapping review of interventions to prevent blood loss, infection and relapse in orthognathic surgery

Background: This systematic mapping review aims to identify, describe, and organize the currently available evidence in systematic reviews (SR) and primary studies regarding orthognathic surgery (OS) co-interventions and surgical modalities, focusing on the outcomes blood loss, infection and relapse. Material and methods: A comprehensive search strategy was performed to identify all SRs, randomized controlled trials and observational studies that evaluate surgical modalities and perioperative co-interventions in OS that evaluate the outcomes blood loss, infection and relapse, regardless of language or publication date. Searches were conducted in MEDLINE, EMBASE, Epistemonikos, Lilacs, Web of Science, and CENTRAL. In addition, grey literature was screened. Results: 27 SRs and 150 primary studies fulfilled the inclusion criteria, 91 from SRs, and 59 from our search strategy. Overall, the quality of the SRs was graded as "Critically low," and only two SRs were rated as "High" quality. 11 PICO questions were extracted from SRs and 31 from primary studies, which focused on osteosynthesis methods, surgical cutting devices, use of antibiotics, and induced hypotension. In addition, evidence bubble maps for each outcome were created to analyze in a visual manner the existing evidence. Conclusions: Future primary and secondary high-quality research should be addressed focused on the eight knowledge gaps identified in this mapping review. We concluded that the evidence mapping approach is a practical methodology for organizing the current evidence and identifying knowledge gaps in OS, helping to reduce research waste and canalize future efforts in developing studies for unsolved questions. (AU)

In Vitro Effect of Mitochondria-Targeted Triphenylphosphonium-Based Compounds (Honokiol, Lonidamine, and Atovaquone) on the Platelet Function and Cytotoxic Activity.

Introduction: Obtaining triphenylphosphonium salts derived from anticancer compounds to inhibit mitochondrial metabolism is of major interest due to their pivotal role in reactive oxygen species (ROS) production, calcium homeostasis, apoptosis, and cell proliferation. However, the use of this type of antitumor compound presents a risk of bleeding since the platelet activation is especially dependent on the mitochondrial function. In this study, we evaluated the in vitro effect of three triphenylphosphonium-based compounds, honokiol (HNK), lonidamine (LDN), and atovaquone (ATO), on the platelet function linked to the triphenylphosphonium cation by a lineal 10-carbon alkyl chain and also the decyltriphenylphosphonium salt (decylphos). Methods: Platelets obtained by phlebotomy from healthy donors were exposed in vitro to different concentrations (0.1-10 µM) of the three compounds; cellular viability, exposure of phosphatidylserine, the mitochondrial membrane potential (∆Ψm), intracellular calcium release, and intracellular ROS generation were measured. Platelet activation and aggregation were induced by agonists (adenosine diphosphate, thrombin receptor-activating peptide-6, convulxin, or phorbol-12-myristate-13-acetate) and were evaluated by flow cytometry and light transmission, respectively. Results: The three compounds showed a slight cytotoxic effect from 1 µM, and this was concomitant with a decrease in ∆Ψm and intracellular calcium increase. Only ATO produced a modest but significant increase in intra-platelet ROS. Also, the three compounds increased the exposure to phosphatidylserine in platelets expressed in platelets positive for annexin V. None of the compounds had an inhibitory effect on the aggregation or activation markers of platelets stimulated with three different agonists. Similar results were obtained with decylphos. Conclusion: Triphenylphosphonium derivatives showed slight platelet toxicity below 1 µM, probably associated with their effect on ∆Ψm and exposure to phosphatidylserine, but no significant effect on platelet activation and aggregation, making them an antitumoral alternative with a low risk of bleeding. However, future assays on animal models and human trials are required to evaluate if their effects with a low risk for hemostasis are replicated in vivo.

Systematic mapping review of orthognathic surgery.

STUDY DESIGN: Systematic mapping review AIM AND SCOPE: The objective of this mapping review was to identify, describe, and organize clinical research currently available from systematic reviews and primary studies regarding co-interventions and different surgical modalities used in orthognathic surgery (OS) and their outcomes. METHODS: Systematic reviews (SRs), randomized controlled trials, and observational studies that evaluated perioperative OS co-interventions and surgical modalities were identified in an exhaustive search of MEDLINE, EMBASE, Epistemonikos, Lilacs, Web of Science, and CENTRAL. Grey literature was also screened. RESULTS: Included were 35 SRs and 253 primary studies, 103 from SRs, and another 150 identified in our search. Overall, SR quality was rated as critically low, with only two SRs rated as of high quality. 19 questions on population, interventions, comparisons, and outcomes (PICO) extracted from the SRs focused on osteosynthesis methods, surgical cutting devices, and use of antibiotics, corticosteroids, and induced hypotension. Also identified were 15 research gaps. Evidence bubble maps were created to graphically depict the available evidence. CONCLUSION: Future high-quality research, both primary and secondary, is needed to address the knowledge gaps identified in this systematic mapping review.

Toxina Botulínica tipo A para el bruxismo del sueño en adultos / Botulinum toxin type A for sleep bruxism in adults

RESUMEN: Introducción: El bruxismo del sueño es un comportamiento que se caracteriza por la actividad repetitiva de los músculos masticadores. Varias terapias para el manejo del bruxismo del sueño se centran en la relajación de los músculos involucrados, incluyendo la inyección intramuscular de Toxina Botulínica tipo A (BoNTA). A pesar de que se ha comprobado la efectividad de esta terapia frente al dolor subjetivo, cuando se asocia a bruxismo del sueño, es necesario determinarla frente a desenlaces objetivos, tanto a nivel craneofacial como sistémico. Además, se debe evaluar también la seguridad de esta intervención frente a eventos adversos tales como afecciones estéticas, debilidad masticatoria y pérdida ósea mandibular, entre otros. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta-análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos 11 revisiones sistemáticas que en conjunto incluyeron 9 estudios primarios, de los cuales, 8 corresponden a ensayos aleatorizados. Concluimos que la inyección intramuscular de toxina botulínica tipo A podría disminuir el dolor en reposo, presentar poca o nula diferencia en dolor durante la masticación y mejorar la autoevaluación del bruxismo, pero la certeza de la evidencia es baja. Por otra parte, no es posible establecer con claridad si el uso de Toxina Botulínica Tipo A disminuye el número de eventos de bruxismo, ya que la certeza de la evidencia ha sido evaluada como muy baja. Finalmente y a pesar de la evidencia existente respecto de los potenciales eventos adversos producto de la intervención con Toxina Botulínica Tipo A en los músculos masticatorios, los ensayos clínicos fallan en evaluarlos y reportarlos.

ABSTRACT: Introduction: The sleep bruxism is a behavior that impacts the craniofacial musculoskeletal system characterized by repetitive activity of the masticatory muscles. Several management strategies for sleep bruxism are focused of the relaxation of the involved masticatory muscles, including the intramuscular injection of botulinum toxin type A (BoNTA). Although the effectiveness of BoNTA for myofascial pain, when related with the sleep bruxism in adult patients, it is necessary to determine its effectiveness using objective outcomes at both craniofacial and systemic levels. In addition, it is necessary to determine the safety of this intervention in the context of adverse events such as aesthetic alterations, reduced masticatory function, mandibular bone loss among others. Methods: A search was performed using Epistemonikos, the biggest database for systematic reviews in health, with is maintained by screening of multiple sources of information, including MEDLINE, EMBASE, Cochrane, among others. Data from systematic reviews were extracted, and analysis of the primary studies was performed, including a meta-analysis and a summary of findings table using GRADE assessment. Results and conclusions: 11 systematic reviews were identified, and 9 primary studies were included. 8 out of these 9 studies corresponded to randomized clinical trials. We conclude that the intramuscular injection of BoNTA may reduce the pain during rest and results in either little or none difference in pain during mastication, when pain is associated with sleep bruxism in adult patients. Also, low evidence is determined for auto-report and subjective evaluation of sleep bruxism among adult patients. Additionally, it is not possible to determine if the BoNTA intervention is effective to reduce the bruxism events due to the low evidence. Finally, although evidence regarding adverse events such as mandibular bone loss after BoNTA intervention in masticatory muscles has been published at preclinical and clinical levels, the clinical trials fail to consider and to report these outcomes.

La declinación de la autoridad docente en la contemporaneidad: una perspectiva psicoanalítica / The fall of the Teaching Tuthority in the Contemporary: a Psychoanalytic Perspective

Resumen Este artículo presenta una reflexión sobre la autoridad docente en el contexto de la cultura actual, marcada por los discursos del capitalismo y de la ciencia, de los cuales surge una nueva subjetividad. El objetivo de este trabajo es discurrir sobre la incidencia de los discursos del capitalismo y de la ciencia en la declinación de la autoridad docente. En un primer momento, se aborda el proyecto y la subjetividad moderna fundados en los productos de la razón; posteriormente, se indica cómo dicho proyecto entra en una fase de sospecha, por sus efectos en el siglo XX y por la crítica realizada por los maestros de la sospecha. Luego se desarrolla la declinación de la función del padre por la incidencia del discurso del capitalismo, continuando con las consecuencias subjetivas de la declinación de la autoridad docente que genera una nueva subjetividad basada en los derechos individuales hedonistas, para finalizar con la declinación de la autoridad docente, entendida desde dos perspectivas: empresarial y epistémica, que tienen por consecuencia la forclusión de la singularidad. Se concluye que el lugar de la autoridad docente es afectado por dos elementos: primero, por el discurso del capitalismo en su relación con el discurso de la ciencia porque borra la disimetría del lazo social, donde el vínculo docente-estudiante se torna simétrico marcado por el valor de laigualdad; y segundo, por el empuje al Uno de la estandarización del conocimiento dado por políticas educativas internacionales en las que el docente es un instrumento.

Abstract This article reflects on the teaching authority in the context of current culture, marked by the discourses of capitalism and science, from which a new subjectivity emerges from these discourses. The objective to be developed is the incidence of the discourses of capitalism and science in the decline of teaching authority. At first, the project and the modern subjectivity based on the products of reason are approached, later it is indicated how this project is under an initial phase of suspicion, due to its effects in the 20th century and the criticism exerted by the masters of the suspicion. To end with the decline of the teaching authority, understood from two perspectives: business and epistemic that result in the foreclosure of the singularity. It is concluded that the place of teaching authority is affected by two elements: first, by the discourse of capitalism in its relationship with the discourse of science because it erases the dissymmetry of the social bond, where teacher-student bond becomes symmetrical marked by the value of equality; and second, by the push to One of the standardization of knowledge given by international educational policies in which the teacher is an instrument.

Análisis descriptivo del concurso de ingreso al ciclo de destinación y formación de cirujanos dentistas entre los años 2009 y 2018 / Descriptive analysis of the admission process to the destination and training cycle of dental surgeons between 2009 and 2018

RESUMEN: Introducción. Desde 1955 existe en Chile una estrategia de recursos humanos destinada a llevar profesionales de la salud a zonas rurales o de difícil acceso, denominada ciclo de destinación y formación (ex generales de zona). Existe poca información sobre las características de los postulantes a él. Esta investigación tiene como objetivo describir las postulaciones para el ingreso al ciclo entre los años 2009 al 2018. Metodología: Se obtuvieron los datos del ciclo desde la web del Ministerio de Salud, los que fueron completados con datos de la Superintendencia de Salud y web del Ministerio de Educación. Los datos se analizaron utilizando el software SPSS. Resultados: Se analizaron 10 concursos de ingreso al ciclo con un total de 1.689 postulantes, que representan 13,8% de cirujanos dentistas recién titulados entre años 2009-2018. El 60% de los postulantes son mujeres, pero las postulaciones de hombres son más efectivas (p=0,038). 5 universidades concentran 63% de las postulaciones y el 86% de las plazas (p<0,001). El offset se ha mantenido constante. Discusión: Existe poca investigación del tema y resulta de interés analizar las diferencias entre la efectividad de las postulaciones según sexo y universidad de origen, así como las motivaciones para postular.

ABSTRACT: Introduction. Since 1955, a human resources strategy has existed in Chile aiming to insert health professionals into rural or difficult-to-reach areas, called the EDF destination and training cycle (formerly, zone generals). There is little information regarding recent graduates entering this cycle and the factors conditioning their application. Therefore, this study aims to describe the cohorts that entered the EDF cycle between 2009 and 2018. Methodology: Data from the EDF application processes were obtained from the website of the Ministry of Health and completed with the records from the Superintendence of Health. Information on the total number of graduates from each Chilean university was obtained from the Ministry of Education website. The data were analyzed using the SPSS IBM Statistic v24 software. Results: Ten application processes for entering the EDF cycle were analyzed, encompassing a total of 1,689 applicants, representing 13.8% of the newly registered dental surgeons between 2009-2018. Even though 60% of the applicants are female, the applications from men are more effective (p=0,038). Five universities concentrate 63% of the applications and 86% of the places (p <0.001). The offset has remained constant. Discussion: There is little research on this subject and it would be interesting to analyze the reasons behind the differences between the effectiveness of the applications according to sex and university of origin, as well as the motivations of the applicants to apply.

Silver diamine fluoride compared to atraumatic restorative technique for the treatment of caries in primary and mixed first phase dentition. / Fluoruro diamino de plata comparado con técnica de restauración atraumática para el tratamiento de caries cavitadas en dentición primaria y mixta primera fase.

INTRODUCTION: Cavitated carious lesions in primary and mixed dentition require prompt treatment to control caries progression. Silver diamine fluoride has emerged as an alternative to the atraumatic restorative technique due to its easy application. However, there is still uncertainty regarding its effectiveness and safety. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a metanalysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified ten systematic reviews, including two studies overall, which are randomized trials. We concluded that silver diamine fluoride compared to the atraumatic restorative technique may increase the arrest of caries in primary and mixed first phase dentition, however, the certainty of the evidence has been assessed as low. On the other hand, treatment with silver diamine fluoride compared to the atraumatic restorative technique (ART) probably increases the risk of adverse events.

INTRODUCCIÓN: Las lesiones de caries cavitadas en dentición primaria y mixta requieren un tratamiento oportuno, para evitar así la progresión de la caries. El fluoruro diamino de plata ha surgido como una alternativa a la técnica de restauración atraumática debido a su fácil aplicación. Sin embargo, aún existe incertidumbre en relación a su efectividad y seguridad. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos diez revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, ambos ensayos aleatorizados. Concluimos que el fluoruro diamino de plata en comparación a la técnica de restauración atraumática podría aumentar el arresto de caries en dentición primaria y mixta primera fase, pero la certeza de la evidencia ha sido evaluada como baja. Por otra parte, el tratamiento con fluoruro diamino de plata comparado con la técnica de restauración atraumática (ART) probablemente aumenta el riesgo de eventos adversos.

Number of Remaining Teeth and Its Association with Educational Level in Chilean Adults: Data from the National Health Survey 2016-2017.

INTRODUCTION: Several population studies have addressed oral health inequalities. Edentulism, functional dentition, and number of remaining teeth have been associated with different socioeconomic level measurements. The aim of this study was to evaluate the association between educational level and tooth loss in the Chilean population aged 15 years and above, based on the 2016-2017 National Health Survey (ENS 2016-2017). Material and Methods. The sample for this cross-sectional study comprised 5473 subjects. The main independent variable was educational level (LEL: low, MEL: medium, and HEL: high). To measure tooth loss, we considered the variables number of remaining teeth, edentulism, and functional dentition. We used logistic regressions to assess the condition of dentition according to the subject's EL. As to the number of teeth variable, linear regressions were conducted. The analyses were carried out considering the complex sampling design in SPSS 24.0. RESULTS: When comparing LEL subjects with HEL subjects, the adjusted difference in number of remaining teeth was 3.11 for the maxilla and 1.72 for the mandible. An individual with LEL had a 7.51 [3.50-16.10] and 6.06 [2.68-13.68] times higher risk of upper edentulism and lower edentulism than a HEL individual, respectively. Regarding functional dentition, the adjusted OR in HEL subjects was 13.33 [8.02-22.15] and in MEL subjects was 2.81 [2.03-3.87], compared to LEL results. CONCLUSIONS: LEL was associated with a significant tooth loss in the Chilean population. Subjects with LEL obtained a lower mean of number of remaining teeth and higher prevalence of edentulism and nonfunctional dentition.

An acylhydroquinone derivative produces OXPHOS uncoupling and sensitization to BH3 mimetic ABT-199 (Venetoclax) in human promyelocytic leukemia cells.

Since cancer cells have different mitochondrial bioenergetic requirements than non-cancerous cells, therapeutic inhibition of its mitochondrial functionality continues to be an important target for anticancer drug discovery. In this study, a series of acylhydroquinones with different acyl-chain length, and their chlorinated derivatives, in the aromatic ring, synthesized by Fries rearrangement under microwave irradiation, were evaluated for their anticancer activity in two leukemia cell lines. Findings from the primary and secondary screening of the 18 acylhydroquinones, tested at 5 µM on acute promyelocytic leukemia HL-60 and acute lymphoblastic leukemia CEM cells lines, identified an acylchlorohydroquinone (12) with a highly selective anti-proliferative effect toward HL-60 cells. This compound induced S-phase arrest in the cell cycle progression of HL-60 cells with insignificant toxicity on leukemic CEM cells and non-cancerous Hs27 cells. In HL-60 leukemic cells, 12 triggered increased mitochondrial NADH oxidation, increased respiration in presence of oligomycin (state 4o), mitochondrial depolarization, and ROS production, suggesting an uncoupling of OXPHOS. This provoked a metabolic adaptation dependent on AMPK/ACC/autophagy axis, having the mitochondrial ß-oxidation a pro-survival role since the combination of 12 and etomoxir, a carnitine palmitoyl-transferase (CPT) inhibitor promoted extensive HL-60 cell death. Finally, 12-induced metabolic stress sensitized to HL-60 cells to cell death by the FDA-approved anti-leukemic drug ABT-199, a BH3 mimetic. Therefore, our results suggest that acylchlorohydroquinone is a promising scaffold in anti-promyelocytic leukemia drug research.

Synthesis of antiplatelet ortho-carbonyl hydroquinones with differential action on platelet aggregation stimulated by collagen or TRAP-6.

Cardiovascular diseases are the leading cause of death in the world. Platelets have a major role in cardiovascular events as they bind to the damaged endothelium activating and forming thrombi. Although some hydroquinone scaffold-containing compounds have known antiplatelet activities, currently there is a lack of evidence on the antiplatelet activity of hydroquinones carrying electron attractor groups. In this work, we evaluate the antiplatelet effect of a series of ortho-carbonyl hydroquinone derivatives on cytotoxicity and function of human platelets, using collagen and thrombin receptor activator peptide 6 (TRAP-6) as agonists. Our structure-activity relationship study shows that gem-diethyl/methyl substitutions and the addition/modifications of the third ring of ortho-carbonyl hydroquinone scaffold influence on the selective index (IC50 TRAP-6/IC50 Collagen) and the inhibitory capacity of platelet aggregation. Compounds 3 and 8 inhibit agonist-induced platelet aggregation in a non-competitive manner with IC50 values of 1.77 ± 2.09 µM (collagen) and 11.88 ± 4.59 µM (TRAP-6), respectively and show no cytotoxicity. Both compounds do not affect intracellular calcium levels and mitochondrial bioenergetics. Consistently, they reduce the expression of P-selectin, activation of glycoprotein IIb/IIIa, and release of adenosine triphosphate and CD63 from platelet. Our findings may be used for further development of new drugs in platelet-related thrombosis diseases.

Fluoruro diamino de plata comparado con técnica de restauración atraumática para el tratamiento de caries cavitadas en dentición primaria y mixta primera fase / Silver diamine fluoride compared to atraumatic restorative technique for the treatment of caries in primary and mixed first phase dentition

INTRODUCCIÓN: Las lesiones de caries cavitadas en dentición primaria y mixta requieren un tratamiento oportuno, para evitar así la progresión de la caries. El fluoruro diamino de plata ha surgido como una alternativa a la técnica de restauración atraumática debido a su fácil aplicación. Sin embargo, aún existe incertidumbre en relación a su efectividad y seguridad. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos diez revisiones sistemáticas que en conjunto incluyeron dos estudios primarios, ambos ensayos aleatorizados. Concluimos que el fluoruro diamino de plata en comparación a la técnica de restauración atraumática podría aumentar el arresto de caries en dentición primaria y mixta primera fase, pero la certeza de la evidencia ha sido evaluada como baja. Por otra parte, el tratamiento con fluoruro diamino de plata comparado con la técnica de restauración atraumática (ART) probablemente aumenta el riesgo de eventos adversos

INTRODUCTION: Cavitated carious lesions in primary and mixed dentition require prompt treatment to control caries progression. Silver diamine fluoride has emerged as an alternative to the atraumatic restorative technique due to its easy application. However, there is still uncertainty regarding its effectiveness and safety. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a metanalysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified ten systematic reviews, including two studies overall, which are randomized trials. We concluded that silver diamine fluoride compared to the atraumatic restorative technique may increase the arrest of caries in primary and mixed first phase dentition, however, the certainty of the evidence has been assessed as low. On the other hand, treatment with silver diamine fluoride compared to the atraumatic restorative technique (ART) probably increases the risk of adverse events.

Assessing Parameter Suitability for the Strength Evaluation of Intramolecular Resonance Assisted Hydrogen Bonding in o-Carbonyl Hydroquinones.

Intramolecular hydrogen bond (IMHB) interactions have attracted considerable attention due to their central role in molecular structure, chemical reactivity, and interactions of biologically active molecules. Precise correlations of the strength of IMHB's with experimental parameters are a key goal in order to model compounds for drug discovery. In this work, we carry out an experimental (NMR) and theoretical (DFT) study of the IMHB in a series of structurally similar o-carbonyl hydroquinones. Geometrical parameters, as well as Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) parameters for IMHB were compared with experimental NMR data. Three DFT functionals were employed to calculated theoretical parameters: B3LYP, M06-2X, and ωB97XD. O…H distance is the most suitable geometrical parameter to distinguish among similar IMHBs. Second order stabilization energies ΔEij(2) from NBO analysis and hydrogen bond energy (EHB) obtained from QTAIM analysis also properly distinguishes the order in strength of the studied IMHB. ΔEij(2) from NBO give values for the IMHB below 30 kcal/mol, while EHB from QTAIM analysis give values above 30 kcal/mol. In all cases, the calculated parameters using ωB97XD give the best correlations with experimental ¹H-NMR chemical shifts for the IMHB, with R² values around 0.89. Although the results show that these parameters correctly reflect the strength of the IMHB, when the weakest one is removed from the analysis, arguing experimental considerations, correlations improve significantly to values around 0.95 for R².

FR58P1a; a new uncoupler of OXPHOS that inhibits migration in triple-negative breast cancer cells via Sirt1/AMPK/ß1-integrin pathway.

Highly malignant triple-negative breast cancer (TNBC) cells rely mostly on glycolysis to maintain cellular homeostasis; however, mitochondria are still required for migration and metastasis. Taking advantage of the metabolic flexibility of TNBC MDA-MB-231 cells to generate subpopulations with glycolytic or oxidative phenotypes, we screened phenolic compounds containing an ortho-carbonyl group with mitochondrial activity and identified a bromoalkyl-ester of hydroquinone named FR58P1a, as a mitochondrial metabolism-affecting compound that uncouples OXPHOS through a protonophoric mechanism. In contrast to well-known protonophore uncoupler FCCP, FR58P1a does not depolarize the plasma membrane and its effect on the mitochondrial membrane potential and bioenergetics is moderate suggesting a mild uncoupling of OXPHOS. FR58P1a activates AMPK in a Sirt1-dependent fashion. Although the activation of Sirt1/AMPK axis by FR58P1a has a cyto-protective role, selectively inhibits fibronectin-dependent adhesion and migration in TNBC cells but not in non-tumoral MCF10A cells by decreasing ß1-integrin at the cell surface. Prolonged exposure to FR58P1a triggers a metabolic reprograming in TNBC cells characterized by down-regulation of OXPHOS-related genes that promote cell survival but comprise their ability to migrate. Taken together, our results show that TNBC cell migration is susceptible to mitochondrial alterations induced by small molecules as FR58P1a, which may have therapeutic implications.

Restauraciones de lesiones cervicales no cariosas: un protocolo de revisión sistemática para la práctica clínica / Restorations of non-carious cervical lesions: a review protocol systematic for clinical practice

Las lesiones cervicales no cariosas son condiciones patológicas no bacterianas localizadas en el límite amelocementario de los dientes. Los principales biomateriales descritos para el tratamiento restaurador de estas lesiones son: vidrios ionómeros, vidrios ionómeros modificados con resinas, compómeros y resinas compuestas. El objetivo de este protocolo, consiste en establecer los elementos metodológicos de una revisión sistemática que evaluará el comportamiento clínico de restauraciones cervicales realizadas con estos biomateriales. Métodos: El protocolo fue diseñado, y será reportado, en línea con Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P 2015). Se realizará una búsqueda sensible en MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials y ClinicalTrials.gov, sin restricción por lenguaje o publicación, para identificar ensayos controlados aleatorizados que comparen dos o más tratamientos restauradores en lesiones cervicales no cariosas. Los desenlaces a evaluar serán la retención de las restauraciones y caries secundaria, según criterios RYGE/USPHS. Al menos dos investigadores realizarán de manera independiente la selección de los ensayos y la extracción de los datos. El riesgo de sesgo será evaluado utilizando la herramienta recomendada por la colaboración Cochrane. Si es posible, se realizará un metanálisis y los datos serán presentados en tablas de resúmenes de resultados mediante el método Grading of Recommendations Assesment, Development and Evaluation (GRADE). Fortalezas y debilidades: Esta revisión sistemática entregará evidencia actualizada sobre el comportamiento de cuatro biomateriales en el tratamiento de lesiones cervicales no cariosas. La principal limitación proviene de la baja cantidad o deficiencias metodológicas de los estudios primarios. Número de registro (PROSPERO): CRD42017071114.(AU)

Non-carious cervical lesions constitute a group of non-bacterial pathological conditions of the dental structure located at amelocementary junction. The main dental materials that have been described for the restorative treatment of these lesions are: ionomer glass, resin modified ionomer glass, compomers and composite resins. The objective of this protocol, is to establish the methodological elements of a systematic review, that will evaluate the clinical behavior of cervical restorations performed with four dental biomaterials. Methods: The protocol was designed, and will be reported, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P 2015). We will conduct a sensitive search in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov, without language or publication restrictions, in order to identify randomized controlled trials comparing two or more restorative treatments in non-carious cervical lesions. The evaluated outcomes will be retention of restorations and secondary caries, according to RYGE/USPHS criteria. At least two reviewers will independently select studies and extract data. The risk of bias will be assessed using the tool recommended by the Cochrane Collaboration. If possible, a meta-analysis will be performed and the data will be presented in summary tables of results using the Grading of Recommendations Assesment, Development and Evaluation (GRADE) approach. Strength and Limitations: This systematic review will provide updated evidence on the behavior of four different dental biomaterials in the treatment of non-carious cervical lesions. The main limitation might arise from the low number or methodological limitations of primary studies. Register number (PROSPERO): CRD42017071114.(AU)

Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation.

Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cell line. Our results indicate that these structural changes modify the effect on OXPHOS, obtaining compounds with three alternative actions: inhibitors of complex I-dependent respiration, uncoupler of OXPHOS and compounds with both actions. To confirm this, the effect of a bicyclic hydroquinone (9) was evaluated in isolated mitochondria. Hydroquinone 9 increased mitochondrial respiration in state 4o without effects on the ADP-stimulated respiration (state 3ADP), decreasing the complexes I and II-dependent respiratory control ratio. The effect on mitochondrial respiration was reversed by 6-ketocholestanol addition, indicating that this hydroquinone is a protonophoric uncoupling agent. In intact TA3/Ha cells, hydroquinone 9 caused mitochondrial depolarization, decreasing intracellular ATP and NAD(P)H levels and GSH/GSSG ratio, and slightly increasing the ROS levels. Moreover, it exhibited selective NAD(P)H availability-dependent anti-proliferative effect on cancer cells. Therefore, our results indicate that the ortho-carbonyl hydroquinone scaffold offers the possibility to design compounds with specific actions on OXPHOS of cancer cells.