TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial.

In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.

El conocimiento y cumplimiento de las normas de protección sobre la radiación ionizante en una clínica dental docente / Knowledge and compliance with ionizing radiation protection standards in a teaching dental clinic

Introducción: El uso de radiografías como elemento complementario para el diagnóstico es fundamental para la práctica profesional de todo cirujano dentista. Por tanto, es importante conocer no solo los beneficios de la radiología oral y los fundamentos de protección radiológica, sino también determinar su nivel de aplicación o la adherencia frente al cumplimiento de los aspectos normativos que regulan el uso de la radiación ionizante en odontología. Objetivo: Relacionar el conocimiento sobre los cuidados en radiología bucal, las ventajas y los peligros en la toma de radiografías con el cumplimiento de las normas de protección radiológica y radiación ionizante en estudiantes de odontología de una clínica dental docente. Métodos: La población de estudio estuvo constituida por 180 estudiantes del cuarto año de la carrera de odontología, que emplearon los equipos radiológicos en la clínica docente asistencial durante los años 2019 (segundo semestre) y 2020 (primer trimestre). Se tomó como muestra representativa a 104 estudiantes, incorporados al estudio mediante muestreo aleatorio simple. Se aplicaron dos instrumentos de recolección de datos, uno para evaluar el conocimiento (cuestionario) y otro para verificar el cumplimiento de normas (lista de chequeo) sobre la protección radiológica y el diagnóstico por imágenes en la práctica odontológica. Para el análisis estadístico se aplicó la prueba estadística chi cuadrado con un nivel de significancia del 95 %. Resultados: No se encontró relación estadísticamente significativa (p = 0,30) entre el conocimiento teórico sobre la protección radiológica y el diagnóstico por imágenes, respecto el cumplimiento de las normas que regulan su aplicación (p > 0,05). El 90 % de participantes tienen conocimientos entre regulares y excelentes. Sin embargo, solo el 32 % cumple las normas técnicas de protección sobre radiación ionizante en su práctica clínica. Conclusión: Los estudiantes de odontología tienen suficiente conocimiento sobre protección radiológica y diagnóstico por imágenes. Sin embargo, este conocimiento no se refleja en prácticas adheridas a las normas.

Introduction: The use of radiographs as a complementary element for diagnosis is fundamental to the professional practice of every dental surgeon. Therefore, it is important to know not only the benefits of oral radiology and the fundamentals of radiological protection, but also to determine their level of application or adherence to compliance with the regulatory aspects that regulate the use of ionizing radiation in dentistry. Objective: To relate the knowledge of oral radiology care, the advantages and dangers in taking radiographs with compliance with the norms of radiological protection and ionizing radiation in dental students of a dental teaching clinic. Methods: The study population consisted of 180 fourth year dental students who used the radiological equipment in the teaching dental clinic during 2019 (second semester) and 2020 (first quarter). A representative sample of 104 students was taken, incorporated into the study by simple random sampling. Two data collection instruments were applied, one to evaluate knowledge (questionnaire) and the other to verify compliance with standards (checklist) on radiological protection and diagnostic imaging in dental practice. For the statistical analysis the chi-square statistical test was applied with a significance level of 95 %. Results: No statistically significant relationship was found (p = 0.30) between theoretical knowledge of radiological protection and diagnostic imaging with respect to compliance with the norms that regulate its application (p > 0.05). Ninety percent of participants have fair to excellent knowledge. However, only 32 % comply with the technical norms of ionizing radiation protection in their clinical practice. Conclusion: Dental students have sufficient knowledge of radiation protection and diagnostic imaging. However, this knowledge is not reflected in practices that adhere to the standards.

Dendritic Cell Vaccination in Conjunction with a TLR Agonist Polarizes Interferon Immune Responses in Malignant Glioma Patients.

Autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination is a promising immunotherapy for patients with high grade gliomas, but responses have not been demonstrated in all patients. To determine the most effective combination of autologous tumor lysate-pulsed DC vaccination, with or without the adjuvant toll-like receptor (TLR) agonists poly-ICLC or resiquimod, we conducted a Phase 2 clinical trial in 23 patients with newly diagnosed or recurrent WHO Grade III-IV malignant gliomas. We then performed deep, high-dimensional immune profiling of these patients to better understand how TLR agonists may influence the systemic immune responses induced by ATL-DC vaccination. Bulk RNAseq data demonstrated highly significant upregulation of type 1 and type 2 interferon gene expression selectively in patients who received adjuvant a TLR agonist together with ATL-DC. CyTOF analysis of patient peripheral blood mononuclear cells (PBMCs) showed increased expression of PD-1 on CD4+ T-cells, decreases in CD38 and CD39 on CD8+ T cells and elevated proportion of monocytes after ATL-DC + TLR agonist administration. In addition, scRNA-seq demonstrated a higher expression fold change of IFN-induced genes with poly-ICLC treatment in both peripheral blood monocytes and T lymphocytes. Patients who had higher expression of interferon response genes lived significantly longer and had longer time to progression compared to those with lower expression. The results suggest that ATL-DC in conjunction with adjuvant poly-ICLC induces a polarized interferon response in circulating monocytes and specific activation of a CD8+ T cell population, which may represent an important blood biomarker for immunotherapy in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01204684.

Lesiones en tejidos dentarios y trastornos de la salud bucal en el examen médico ocupacional de trabajadores del sector construcción de Lima, Perú / Lesions in dental tissues and oral health disorders in the occupational medical examination of workers in the construction sector in Lima, Peru / Lesões nos tecidos dentários e perturbações da saúde oral no exame médico ocupacional dos trabalhadores do sector da construção em Lima, Peru

RESUMEN Objetivo: Describir las lesiones en tejidos dentarios y trastornos de la salud bucal encontradas durante el examen médico ocupacional en trabajadores del sector construcción de Lima, Perú. Material y métodos: Estudio epidemiológico transversal realizado en 150 trabajadores del sector construcción, seleccionados mediante muestreo aleatorio simple. Se realizó una evaluación estomatológica mediante observación directa y se empleó un instrumento de evaluación odontológico-ocupacional con índices para caries dental, severidad de caries y traumatismos dentales e indicadores de consecuencias clínicas de caries no tratada (patología pulpar) y lesiones no cariosas. Resultados: La experiencia de caries de los operadores sin estudio superior (CPOD = 14,99) y con estudio superior (CPOD = 13,06) fue superior frente a los supervisores (CPOD = 8,23) y administrativos (CPOD = 5,08). Los trabajadores operadores sin estudio superior (SiC = 18,04) y con estudio superior (SiC = 17,17) presentaron peores indicadores de significancia de caries frente a los supervisores (SiC = 13,67) y administrativos (SiC = 8,25). Además, los operadores sin estudio superior presentaron mayor carga de consecuencias clínicas de caries no tratada (PUFA = 2,35; severidad = 9,2%) en comparación con los operativos con estudio superior (PUFA = 1,91; severidad = 8,4%), los supervisores (PUFA = 0,53; severidad = 2,1%) y los administrativos (PUFA = 0,46; severidad = 1,8%), así como mayor frecuencia de lesiones no cariosas (47,3 %) y traumatismos dentales (21,3 %). Conclusiones: La salud dental, sus consecuencias clínicas y la estructura de los tejidos dentarios de los trabajadores operativos de una empresa constructora se encuentran más afectadas en comparación con los otros grupos laborales de la misma empresa.

ABSTRACT Objective: To describe the lesions in dental tissues and oral health disorders found during the occupational medical examination of workers in the construction sector in Lima, Peru. Material and methods: A cross-sectional epidemiological study was carried out on 150 workers in the construction sector, selected by simple random sampling. A stomatological evaluation was carried out by direct observation, and a dental-occupational evaluation instrument was used with indexes for dental caries, caries severity and dental trauma, and indicators of clinical consequences of untreated caries (pulp pathology) and non-carious lesions. Results: The caries experience of operators without higher education (CPOD = 14.99) and with higher education (CPOD = 13.06) was higher than that of supervisors (CPOD = 8.23) and administrative workers (CPOD = 5.08). The operators without higher education (SiC = 18.04) and with higher education (SiC = 17.17) presented worse caries significance indicators compared to supervisors (SiC = 13.67) and administrative workers (SiC = 8.25). In addition, operators without higher education had a higher burden of clinical consequences of untreated caries (PUFA = 2.35; severity = 9.2%) compared to operators with higher education (PUFA = 1.91; severity = 8.4%), supervisors (PUFA = 0.53; severity = 2.1%) and administrators (PUFA = 0.46; severity = 1.8%), as well as a higher frequency of non-carious lesions (47.3%) and dental trauma (21.3%). Conclusions: Dental health, its clinical consequences, and the structure of the dental tissues of the operative workers of a construction company are more affected compared to the other labor groups of the same company.

RESUMO Objetivo: Descrever as lesões nos tecidos dentários e os distúrbios de saúde oral encontrados durante o exame médico ocupacional em trabalhadores do sector da construção em Lima, Peru. Material e métodos: Foi realizado um estudo epidemiológico transversal em 150 trabalhadores do sector da construção, selecionados por amostragem aleatória simples. Foi realizada uma avaliação de estomatologia por observação direta e foi utilizado um instrumento de avaliação dentária ocupacional com índices de cárie dentária, gravidade da cárie e traumatismo dentário e indicadores das consequências clínicas da cárie não tratada (patologia pulpar) e lesões não cariosas. Resultados: A experiência de cárie dos operadores sem ensino superior (CPOD = 14,99) e com ensino superior (CPOD = 13,06) foi maior em comparação com os supervisores (CPOD = 8,23) e trabalhadores administrativos (CPOD = 5,08). Os operadores sem ensino superior (SiC = 18,04) e com ensino superior (SiC = 17,17) apresentaram piores indicadores de significância da cárie quando comparados aos supervisores (SiC = 13,67) e aos funcionários administrativos (SiC = 8,25). Além disso, os operadores sem ensino superior apresentaram maior carga de consequências clínicas da cárie não tratada (PUFA = 2,35; severidade = 9,2%) em relação aos operadores com ensino superior (PUFA = 1,91; severidade = 8,4%), supervisores (PUFA = 0,53; severidade = 2,1%) e administradores (PUFA = 0,46; severidade = 1,8%), bem como maior frequência de lesões não cariosas (47,3%) e traumatismos dentários (21,3%). Conclusões: A saúde dentária, as suas consequências clínicas e a estrutura dos tecidos dentários dos operários de uma empresa de construção civil são mais afetadas em comparação com os outros grupos de trabalho da mesma empresa.

Noncommunicable diseases in the Americas: a review of the Pan American Health Organization's 25-year program of work.

This article describes progress in tackling noncommunicable diseases (NCDs) in the Americas since the Pan American Health Organization (PAHO) started its NCD program 25 years ago. Changes in the epidemiology of NCDs, NCD policies, health service capacity, and surveillance are discussed. PAHO's NCD program is guided by regional plans of action on specific NCDs and risk factors, as well as a comprehensive NCD plan. Its work involves implementing evidence-based World Health Organization technical packages on NCDs and their risk factors with the aim of achieving the Sustainable Development Goal target of a one third reduction in premature mortality caused by NCDs by 2030. Important advances have been made in the past 25 years in implementation of: policies on NCD risk factors; interventions to improve NCD diagnosis and treatment; and NCD surveillance. Premature mortality from NCDs decreased by 1.7% a year between 2000 and 2011 and 0.77% a year between 2011 and 2019. However, policies on risk factor prevention and health promotion need to be strengthened to ensure more countries are on track to achieving the NCD-related health goals of the Sustainable Development Goals by 2030. Actions are recommended for governments to raise the priority of NCDs by: making NCDs a core pillar of primary care services, using revenues from health taxes to invest more in NCD prevention and control; and implementing policies, laws, and regulations to reduce the demand for and availability of tobacco, alcohol, and ultra-processed food products.

En este artículo se describe el progreso en la lucha contra las enfermedades no transmisibles (ENT) en la Región de las Américas desde que la Organización Panamericana de la Salud (OPS) iniciara su programa contra las ENT hace 25 años. Se abordan los cambios en las características epidemiológicas, las políticas, la capacidad de los servicios de salud y la vigilancia de estas enfermedades. Este programa de la OPS se rige por planes regionales de acción sobre enfermedades y factores de riesgo específicos, así como por un plan integral de ENT. Su labor consiste en poner en práctica paquetes técnicos de la Organización Mundial de la Salud basados en la evidencia sobre las ENT y sus factores de riesgo con el objetivo de alcanzar la meta de los Objetivos de Desarrollo Sostenible (ODS) de reducir en un tercio la mortalidad prematura causada por las ENT para el 2030. En los últimos 25 años se han logrado importantes avances en la ejecución de políticas sobre los factores de riesgo de estas enfermedades, en las intervenciones para mejorar su diagnóstico y tratamiento, y en la vigilancia. La mortalidad prematura por ENT disminuyó 1,7% anual entre el 2000 y el 2011 y 0,77% anual entre los años 2011 y 2019. Sin embargo, es necesario fortalecer las políticas de prevención de factores de riesgo y promoción de la salud para garantizar que más países estén bien encaminados para lograr las metas de salud de los ODS relacionadas con las ENT para el 2030. Se recomiendan medidas para que los gobiernos prioricen más las ENT y las conviertan en un pilar central de los servicios de atención primaria, al usar los ingresos generados por los impuestos en el sector de la salud para incrementar las inversiones en la prevención y control de las ENT, y ejecutar políticas, leyes y regulaciones para reducir la demanda y la disponibilidad de tabaco, alcohol y alimentos ultraprocesados.

Este artigo descreve o progresso no combate às doenças não transmissíveis (DNTs) nas Américas desde que a Organização Pan-Americana da Saúde (OPAS) iniciou seu programa para essas doenças há 25 anos. Discute-se como evoluíram a epidemiologia das DNTs, as políticas contra essas doenças, a capacidade dos serviços de saúde e a vigilância. O programa da OPAS para as DNTs é orientado por planos de ação regionais sobre DNTs específicas e fatores de risco, bem como por um plano integral contra essas doenças. O trabalho envolve a implementação de pacotes técnicos da Organização Mundial da Saúde baseados em evidências sobre as DNTs e seus fatores de risco, no intuito de alcançar a meta do Objetivo de Desenvolvimento Sustentável de reduzir em um terço a mortalidade prematura causada pelas DNTs até 2030. Avanços importantes foram obtidos nos últimos 25 anos na implementação de políticas sobre fatores de risco das DNTs, intervenções para melhorar o diagnóstico e o tratamento das DNTs, e vigilância das DNTs. A mortalidade prematura causada pelas DNTs diminuiu 1,7% ao ano entre 2000 e 2011 e 0,77% ao ano entre 2011 e 2019. Contudo, as políticas sobre a prevenção dos fatores de risco e a promoção da saúde precisam ser fortalecidas para que mais países estejam no rumo certo para alcançar as metas de saúde relacionadas a essas doenças, no âmbito dos Objetivos de Desenvolvimento Sustentável até 2030. São recomendadas medidas para que os governos elevem a prioridade das DNTs ao torná-las um pilar central dos serviços de atenção primária, usando a receita dos tributos saudáveis para investir mais na prevenção e no controle das DNTs, e ao implementar políticas, leis e regulamentos para reduzir a demanda e a disponibilidade de álcool, tabaco e produtos alimentícios ultraprocessados.

What is the NCD service capacity and disruptions due to COVID-19? Results from the WHO non-communicable disease country capacity survey in the Americas region.

OBJECTIVE: This article presents the Americas regional results of the WHO non-communicable diseases (NCDs) Country Capacity Survey from 2019 to 2021, on NCD service capacity and disruptions from the COVID-19 pandemic. SETTING: Information on public sector primary care services for NCDs, and related technical inputs from 35 countries in the Americas region are provided. PARTICIPANTS: All Ministry of Health officials managing a national NCD programme, from a WHO Member State in the Americas region, were included throughout this study. Government health officials from countries that are not WHO Member States were excluded. OUTCOME MEASURES: The availability of evidence-based NCD guidelines, essential NCD medicines and basic technologies in primary care, cardiovascular disease risk stratification, cancer screening and palliative care services were measured in 2019, 2020 and 2021. NCD service interruptions, reassignments of NCD staff during the COVID-19 pandemic and mitigation strategies to reduce disruptions for NCD services were measured in 2020 and 2021. RESULTS: More than 50% of countries reported a lack of comprehensive package of NCD guidelines, essential medicines and related service inputs. Extensive disruptions in NCD services resulted from the pandemic, with only 12/35 countries (34%), reporting that outpatient NCD services were functioning normally. Ministry of Health staff were largely redirected to work on the COVID-19 response, either full time or partially, reducing the human resources available for NCD services. Six of 24 countries (25%) reported stock out of essential NCD medicines and/or diagnostics at health facilities which affected service continuity. Mitigation strategies to ensure continuity of care for people with NCDs were deployed in many countries and included triaging patients, telemedicine and teleconsultations, and electronic prescriptions and other novel prescribing practices. CONCLUSIONS: The findings from this regional survey suggest significant and sustained disruptions, affecting all countries regardless of the country's level of investments in healthcare or NCD burden.

Noncommunicable diseases in the Americas: a review of the Pan American Health Organization's 25-year program of work / Enfermedades no transmisibles en la Región de las Américas: revisión del programa de trabajo de la Organización Panamericana de la Salud tras 25 años de actividades / Doenças não transmissíveis nas Américas: uma revisão do programa de trabalho de 25 anos da Organização Pan-Americana da Saúde

ABSTRACT This article describes progress in tackling noncommunicable diseases (NCDs) in the Americas since the Pan American Health Organization (PAHO) started its NCD program 25 years ago. Changes in the epidemiology of NCDs, NCD policies, health service capacity, and surveillance are discussed. PAHO's NCD program is guided by regional plans of action on specific NCDs and risk factors, as well as a comprehensive NCD plan. Its work involves implementing evidence-based World Health Organization technical packages on NCDs and their risk factors with the aim of achieving the Sustainable Development Goal target of a one third reduction in premature mortality caused by NCDs by 2030. Important advances have been made in the past 25 years in implementation of: policies on NCD risk factors; interventions to improve NCD diagnosis and treatment; and NCD surveillance. Premature mortality from NCDs decreased by 1.7% a year between 2000 and 2011 and 0.77% a year between 2011 and 2019. However, policies on risk factor prevention and health promotion need to be strengthened to ensure more countries are on track to achieving the NCD-related health goals of the Sustainable Development Goals by 2030. Actions are recommended for governments to raise the priority of NCDs by: making NCDs a core pillar of primary care services, using revenues from health taxes to invest more in NCD prevention and control; and implementing policies, laws, and regulations to reduce the demand for and availability of tobacco, alcohol, and ultra-processed food products.

RESUMEN En este artículo se describe el progreso en la lucha contra las enfermedades no transmisibles (ENT) en la Región de las Américas desde que la Organización Panamericana de la Salud (OPS) iniciara su programa contra las ENT hace 25 años. Se abordan los cambios en las características epidemiológicas, las políticas, la capacidad de los servicios de salud y la vigilancia de estas enfermedades. Este programa de la OPS se rige por planes regionales de acción sobre enfermedades y factores de riesgo específicos, así como por un plan integral de ENT. Su labor consiste en poner en práctica paquetes técnicos de la Organización Mundial de la Salud basados en la evidencia sobre las ENT y sus factores de riesgo con el objetivo de alcanzar la meta de los Objetivos de Desarrollo Sostenible (ODS) de reducir en un tercio la mortalidad prematura causada por las ENT para el 2030. En los últimos 25 años se han logrado importantes avances en la ejecución de políticas sobre los factores de riesgo de estas enfermedades, en las intervenciones para mejorar su diagnóstico y tratamiento, y en la vigilancia. La mortalidad prematura por ENT disminuyó 1,7% anual entre el 2000 y el 2011 y 0,77% anual entre los años 2011 y 2019. Sin embargo, es necesario fortalecer las políticas de prevención de factores de riesgo y promoción de la salud para garantizar que más países estén bien encaminados para lograr las metas de salud de los ODS relacionadas con las ENT para el 2030. Se recomiendan medidas para que los gobiernos prioricen más las ENT y las conviertan en un pilar central de los servicios de atención primaria, al usar los ingresos generados por los impuestos en el sector de la salud para incrementar las inversiones en la prevención y control de las ENT, y ejecutar políticas, leyes y regulaciones para reducir la demanda y la disponibilidad de tabaco, alcohol y alimentos ultraprocesados.

RESUMO Este artigo descreve o progresso no combate às doenças não transmissíveis (DNTs) nas Américas desde que a Organização Pan-Americana da Saúde (OPAS) iniciou seu programa para essas doenças há 25 anos. Discute-se como evoluíram a epidemiologia das DNTs, as políticas contra essas doenças, a capacidade dos serviços de saúde e a vigilância. O programa da OPAS para as DNTs é orientado por planos de ação regionais sobre DNTs específicas e fatores de risco, bem como por um plano integral contra essas doenças. O trabalho envolve a implementação de pacotes técnicos da Organização Mundial da Saúde baseados em evidências sobre as DNTs e seus fatores de risco, no intuito de alcançar a meta do Objetivo de Desenvolvimento Sustentável de reduzir em um terço a mortalidade prematura causada pelas DNTs até 2030. Avanços importantes foram obtidos nos últimos 25 anos na implementação de políticas sobre fatores de risco das DNTs, intervenções para melhorar o diagnóstico e o tratamento das DNTs, e vigilância das DNTs. A mortalidade prematura causada pelas DNTs diminuiu 1,7% ao ano entre 2000 e 2011 e 0,77% ao ano entre 2011 e 2019. Contudo, as políticas sobre a prevenção dos fatores de risco e a promoção da saúde precisam ser fortalecidas para que mais países estejam no rumo certo para alcançar as metas de saúde relacionadas a essas doenças, no âmbito dos Objetivos de Desenvolvimento Sustentável até 2030. São recomendadas medidas para que os governos elevem a prioridade das DNTs ao torná-las um pilar central dos serviços de atenção primária, usando a receita dos tributos saudáveis para investir mais na prevenção e no controle das DNTs, e ao implementar políticas, leis e regulamentos para reduzir a demanda e a disponibilidade de álcool, tabaco e produtos alimentícios ultraprocessados.

Seguridad del paciente y eventos adversos en la práctica odontológica en una clínica dental docente / Patient safety and adverse events in dental practice in a Teaching Dental Clinic

RESUMEN Objetivo: Evaluar la frecuencia y distribución de eventos adversos que se presentan en el desarrollo de los tratamientos odontológicos ejecutados por operadores clínicos de una Clínica Dental Docente durante el 2015. Material y Métodos: Se realizó un estudio observacional y descriptivo de corte longitudinal y prospectivo para evaluar la frecuencia de eventos adversos en la práctica odontológica de estudiantes de Odontología, para lo cual se implementó un Sistema de Registro y Notificación de Eventos Adversos en Odontología dirigido a 110 operadores clínicos en las áreas de Odontología Restauradora, Cirugía Bucal, Endodoncia y Rehabilitación Oral durante el 2015. Resultados: Se reportaron 167 eventos adversos que representan un 10.18% del total de tratamientos realizados durante el periodo de seguimiento y evaluación Los eventos más frecuentes, según campo clínico, fueron la "Hipersensibilidad post tratamiento restaurador" (operatoria dental), "Sobreobturación o subobturación con sintomatología" (endodoncia), "Alveolitis dental post-extracción" (cirugía bucal) y "Sensibilidad post-tallado para prótesis fija (pilares)" (rehabilitación oral). Conclusiones: La implementación de un sistema de registro y notificación es el punto de partida para la identificación de eventos adversos más frecuentes en la práctica odontológico, el cual es útil para definir procedimientos a seguir, elaborar protocolos y formular lineamientos para la atención segura y de calidad.

ABSTRACT Objective: To evaluate the frequency and distribution of adverse events that occur in the development of dental treatments performed by clinical operators of a Teaching Dental Clinic during 2015. Material and Methods: An observational and descriptive longitudinal and prospective study was carried out to evaluate the frequency of adverse events in the dental practice of Dentistry students, for which a System for the Registration and Notification of Adverse Events in Dentistry was implemented aimed at 110 clinical operators in the areas of Restorative Dentistry, Oral Surgery, Endodontics and Oral Rehabilitation during 2015. Results: 167 adverse events were reported, representing 10.18% of the total treatments performed during the monitoring and evaluation period. Common, depending on the clinical field, were "Post-restorative treatment hypersensitivity" (restorative dentistry), "Over-filling or under-filling with symptoms" (endodontics), "Post-extraction dental alveolitis" (oral surgery) and "Post-carving sensitivity for fixed prostheses (pillars)" (oral rehabilitation). Conclusions: The implementation of a registration and notification system is the starting point for the identification of the most frequent adverse events in dental practice, which is useful for defining procedures to be followed, developing protocols, and formulating guidelines for healthcare quality and safety.

The ecological roles of microbial lipopeptides: Where are we going?

Lipopeptides (LPs) are secondary metabolites produced by a diversity of bacteria and fungi. Their unique chemical structure comprises both a peptide and a lipid moiety. LPs are of major biotechnological interest owing to their emulsification, antitumor, immunomodulatory, and antimicrobial activities. To date, these versatile compounds have been applied across multiple industries, from pharmaceuticals through to food processing, cosmetics, agriculture, heavy metal, and hydrocarbon bioremediation. The variety of LP structures and the diversity of the environments from which LP-producing microorganisms have been isolated suggest important functions in their natural environment. However, our understanding of the ecological role of LPs is limited. In this review, the mode of action and the role of LPs in motility, antimicrobial activity, heavy metals removal and biofilm formation are addressed. We include discussion on the need to characterise LPs from a diversity of microorganisms, with a focus on taxa inhabiting 'extreme' environments. We introduce the use of computational target fishing and molecular dynamics simulations as powerful tools to investigate the process of interaction between LPs and cell membranes. Together, these advances will provide new understanding of the mechanism of action of novel LPs, providing greater insights into the roles of LPs in the natural environment.

Antarctic desert soil bacteria exhibit high novel natural product potential, evaluated through long-read genome sequencing and comparative genomics.

Actinobacteria and Proteobacteria are important producers of bioactive natural products (NP), and these phyla dominate in the arid soils of Antarctica, where metabolic adaptations influence survival under harsh conditions. Biosynthetic gene clusters (BGCs) which encode NPs, are typically long and repetitious high G + C regions difficult to sequence with short-read technologies. We sequenced 17 Antarctic soil bacteria from multi-genome libraries, employing the long-read PacBio platform, to optimize capture of BGCs and to facilitate a comprehensive analysis of their NP capacity. We report 13 complete bacterial genomes of high quality and contiguity, representing 10 different cold-adapted genera including novel species. Antarctic BGCs exhibited low similarity to known compound BGCs (av. 31%), with an abundance of terpene, non-ribosomal peptide and polyketide-encoding clusters. Comparative genome analysis was used to map BGC variation between closely related strains from geographically distant environments. Results showed the greatest biosynthetic differences to be in a psychrotolerant Streptomyces strain, as well as a rare Actinobacteria genus, Kribbella, while two other Streptomyces spp. were surprisingly similar to known genomes. Streptomyces and Kribbella BGCs were predicted to encode antitumour, antifungal, antibacterial and biosurfactant-like compounds, and the synthesis of NPs with antibacterial, antifungal and surfactant properties was confirmed through bioactivity assays.

The Mi-2 nucleosome remodeler and the Rpd3 histone deacetylase are involved in piRNA-guided heterochromatin formation.

In eukaryotes, trimethylation of lysine 9 on histone H3 (H3K9) is associated with transcriptional silencing of transposable elements (TEs). In drosophila ovaries, this heterochromatic repressive mark is thought to be deposited by SetDB1 on TE genomic loci after the initial recognition of nascent transcripts by PIWI-interacting RNAs (piRNAs) loaded on the Piwi protein. Here, we show that the nucleosome remodeler Mi-2, in complex with its partner MEP-1, forms a subunit that is transiently associated, in a MEP-1 C-terminus-dependent manner, with known Piwi interactors, including a recently reported SUMO ligase, Su(var)2-10. Together with the histone deacetylase Rpd3, this module is involved in the piRNA-dependent TE silencing, correlated with H3K9 deacetylation and trimethylation. Therefore, drosophila piRNA-mediated transcriptional silencing involves three epigenetic effectors, a remodeler, Mi-2, an eraser, Rpd3 and a writer, SetDB1, in addition to the Su(var)2-10 SUMO ligase.

The effect of angiotensin AT1A inactivation on innate and learned fear responses in mice and its relationship to blood pressure.

Angiotensin AT1 receptors are implicated in behavioral and physiological processes associated with fear and stress. However, the precise role of AT1 receptors in modulating fear-related behavior and its relation to their physiological effects remains unclear. Here, we examined innate and learned fear responses and their relationship to cardiovascular arousal in AT1A receptor knockout (AT1A-/-) mice. Using synchronized video and blood pressure telemetry, we found that, in a novel test environment, AT1A-/- mice showed reduced neophobia but a similar rise in blood pressure, as compared to AT1A+/+ mice. In response to a discrete threat, footshock, both flight behavior and cardiovascular arousal were decreased in AT1A-/- mice. Reduced flight behavior was also observed in AT1A-/- mice in the elevated T-maze test. During fear conditioning, the immediate freezing response to the first shock, but not the rate of freezing acquisition was decreased in AT1A-/- mice. Likewise, AT1A-/- mice showed reduced freezing and pressor responses to the first re-exposure, but normal rate of freezing extinction over subsequent trials. Similarly, in the elevated T-maze, the rates of avoidance acquisition and escape learning remained unchanged in AT1A-/- mice. Finally, after re-exposure, AT1A-/- mice displayed altered c-Fos expression, compared to AT1A+/+ mice, in the hypothalamus and periaqueductal gray but not in fear-related limbic-cortical areas, nor in medullary nuclei that convey visceral afferent information. We conclude that AT1A receptor knockout reduces innate fear responses, without affecting learning efficiency in mice. These effects are dissociable from cardiovascular effects and likely reflect altered neurotransmission in hypothalamic-midbrain defense regions.

Calidad técnica y percibida del servicio de operatoria dental en una clínica dental docente / Technical and perceived quality of dental operative service in a teaching dental clinic

Objetivos: Evaluar la calidad técnica de los tratamientos realizados por los operadores y la calidad percibida por los pacientes del Servicio de Operatoria Dental en una Clínica Dental Docente durante el año 2014. Material y métodos: Participaron 216 pacientes de manera voluntaria y aleatoria a quienes se les aplicó una encuesta para medir la calidad percibida del servicio. Posteriormente, se evaluaron los tratamientos de operatoria que les fueron realizados para determinar la calidad técnica a través de la comparación con los protocolos de atención. Resultados: En relación con la calidad percibida, el 74,8% de los participantes percibe la calidad de atención como "Regular", seguido de un 15,3% de pacientes que la perciben como "Malo" y un solo un 5% como "Muy malo". Sólo un 4,3% la percibe como "Bueno" y un 0,6% la percibe como "Muy bueno". En relación con la calidad técnica, se cumple en el 99% de los tratamientos evaluados, ya que se encuentran adheridos a los protocolos de atención clínica. Conclusiones: La calidad percibida por el paciente es en su mayoría negativa o neutral, sin embargo, los resultados de la calidad técnica de los tratamientos describen que éstos se encuentran altamente adheridos a los protocolos de atención.

Objectives: To evaluate the technical quality of the treatments performed by the operators and the quality perceived by the patients of the Dental Operative Service in a Teaching Dental Clinic during the year 2014. Material and methods: 216 patients participated voluntarily and randomly in a survey to measure the perceived quality of the service as well as evaluate the operative treatments that were performed to determine the technical quality.Results: Regarding perceived quality, 74.8% of the participants perceived the quality of care as "Ordinary", followed by 15.3% of patients perceiving it as "Poor" and only 5% as "Very bad". Only 4.3% perceive it as "Good" and 0.6% perceive it as "Very good". Concerning technical quality, 99% of the evaluated treatments are fulfilled since they adhere to the clinical care protocols. Conclusions: The quality perceived by the patient is mostly negative or neutral, however, the results of the technical quality of the treatments describe that they are highly adhered to the care protocols.

ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity.

Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health.

Botulinum neurotoxin type B uses a distinct entry pathway mediated by CDC42 into intestinal cells versus neuronal cells.

Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. BoNT type B (BoNT/B) most often induces mild forms of botulism with predominant dysautonomic symptoms. In food borne botulism and botulism by intestinal colonisation such as infant botulism, which are the most frequent naturally acquired forms of botulism, the digestive tract is the main entry route of BoNTs into the organism. We previously showed that BoNT/B translocates through mouse intestinal barrier by an endocytosis-dependent mechanism and subsequently targets neuronal cells, mainly cholinergic neurons, in the intestinal mucosa and musculosa. Here, we investigated the entry pathway of BoNT/B using fluorescent C-terminal domain of the heavy chain (HcB), which is involved in the binding to specific receptor(s) and entry process into target cells. While the combination of gangliosides GD1a /GD1b /GT1b and synaptotagmin I and to a greater extent synaptotagmin II constitutes the functional HcB receptor on NG108-15 neuronal cells, HcB only uses the gangliosides GD1a /GD1b /GT1b to efficiently bind to m-ICcl2 intestinal cells. HcB enters both cell types by a dynamin-dependent endocytosis, which is efficiently prevented by Dynasore, a dynamin inhibitor, and reaches a common early endosomal compartment labeled by early endosome antigen (EEA1). In contrast to neuronal cells, HcB uses a Cdc42-dependent pathway to enter intestinal cells. Then, HcB is transported to late endosomes in neuronal cells, whereas it exploits a nonacidified pathway from apical to basal lateral side of m-ICcl2 cells supporting a transcytotic route in epithelial intestinal cells.

Impairment of lysophospholipid metabolism in obesity: altered plasma profile and desensitization to the modulatory properties of n-3 polyunsaturated fatty acids in a randomized controlled trial.

BACKGROUND: Plasma lysophospholipids have emerged as signaling molecules with important effects on inflammation, insulin resistance, and fatty liver disease, each of which is linked closely to obesity. Dietary n-3 (ω-3) polyunsaturated fatty acids (PUFAs) may be able to improve these conditions. OBJECTIVE: The objective of this study was to assess the response of plasma lysophospholipids to obesity, n-3 PUFA consumption, and a high-fat meal challenge to better understand the role of lysophospholipid metabolism in the progression of obesity-related disorders. DESIGN: We determined the concentrations of 8 lysophosphatidylcholines, 11 lysophosphatidylethanolamines, and 7 lysophosphatidylinositols in the plasma of 34 normal-weight and 38 obese subjects randomly assigned to consume corn oil (control) or n-3 PUFA-rich fish oil (3 g/d; n = 15-19/group) for 90 d. Blood samples were collected on the last day of the study under fasting conditions and 6 h after a high-fat meal (1135 kcal, 86 g fat) challenge. The profile of secreted lysophospholipids was studied in HepG2 cells under palmitate-induced steatosis. RESULTS: Obese and normal-weight subjects had different profiles of plasma lysophospholipids. A multivariate combination of the 26 lysophospholipids could discriminate between normal-weight and obese subjects with an accuracy of 98%. The high-fat meal challenge altered the concentration of plasma lysophosphatidylcholines in an oil treatment-dependent manner in normal-weight but not obese subjects, suggesting that obesity impairs the sensitivity of lysophospholipid metabolism to n-3 PUFAs. Noncytotoxic steatosis in HepG2 cells affected the secretion pattern of lysophospholipids, partially resembling the changes observed in the plasma of obese subjects. CONCLUSIONS: Obesity has a substantial impact on lysophospholipid metabolism, altering the plasma lysophospholipid profile and abolishing its sensitivity to dietary n-3 PUFAs. These effects could contribute to the onset or progression of alterations associated with obesity, such as inflammation, insulin resistance, and fatty liver disease. This trial was registered at www.controlled-trials.com as ISRCTN96712688.

Translocation and dissemination to target neurons of botulinum neurotoxin type B in the mouse intestinal wall.

Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis (botulism), which in most cases enter the organism via the digestive tract and then disseminate into the blood or lymph circulation to target autonomic and motor nerve endings. The passage way of BoNTs alone or in complex forms with associated nontoxic proteins through the epithelial barrier of the digestive tract still remains unclear. Here, we show using an in vivo model of mouse ligated intestinal loop that BoNT/B alone or the BoNT/B C-terminal domain of the heavy chain (HCcB), which interacts with cell surface receptors, translocates across the intestinal barrier. The BoNT/B or HCcB translocation through the intestinal barrier occurred via an endocytosis-dependent mechanism within 10-20 min, because Dynasore, a potent endocytosis inhibitor, significantly prevented BoNT/B as well as HCcB translocation. We also show that HCcB or BoNT/B specifically targets neuronal cells and neuronal extensions in the intestinal submucosa and musculosa expressing synaptotagmin, preferentially cholinergic neurons and to a lower extent other neuronal cell types, notably serotonergic neurons. Interestingly, rare intestinal epithelial cells accumulated HCcB suggesting that distinct cell types of the intestinal epithelium, still undefined, might mediate efficient translocation of BoNT/B.

Nitric oxide participates in the toxicity of Bacillus thuringiensis Cry1Ab toxin to kill Manduca sexta larvae.

Nitric oxide (NO) produced by the nitric oxide synthase (NOS) enzyme is a reactive oxygen molecule widely considered as important participant in the immune system of different organisms to confront microbial infections. In insects the NO molecule has also been implicated in immune response against microbial pathogens. Bacillus thuringiensis (Bt) is an insect-pathogenic bacterium that produces insecticidal proteins such as Cry toxins. These proteins kill insects because they form pores in the larval-midgut cells. Here we show that intoxication of Manduca sexta larvae with Cry1Ab activates expression of NOS with a corresponding increase in NO. This effect is not observed with a non-toxic mutant toxin Cry1Ab-E129K that is affected in pore formation. The increased production of NO triggered by intoxication with LC50 dose of Cry1Ab toxin is not associated with higher expression of antimicrobial peptides. NO participates in Cry1Ab toxicity since inhibition of NOS by selective l-NAME inhibitor prevented NO production and resulted in reduced mortality of the larvae. The fact that mortality was not completely abolished by L-NAME indicates that other processes participate in toxin action and induction of NO production upon Cry1Ab toxin administration accounts only for a part of the toxicity of this protein to M. sexta larvae.

Evaluación de la calidad de los registros empleando la auditoría odontológica en una clínica dental docente / Quality evaluation of the records using dental audit in a teaching dental clinic

Objetivo: Evaluar la calidad de registro o llenado de historias clínicas de pacientes nuevos atendidos en una Clínica Dental Docente durante el período de enero a julio de 2012 empleando la auditoría odontológica como herramienta sistematizada. Material y métodos: Se tomaron como muestra 140 historias clínicas de pacientes nuevos de las cuales se evaluó la frecuencia y porcentaje de registro de los diferentes aspectos que componen la historia clínica. Resultados: Se encontró que el 78% de las historias no tenían completo el registro en los diferentes aspectos evaluados, encontrando que de los diecisiete aspectos evaluados, nueve registran entre 11% y 29%, quedando entre un 89% y un 71% de historias que no registran estos aspectos. Se identificaron tres aspectos que se registran entre 84% y 86% (número de historias, cuestionario de salud y examen estomatológico), cuatro aspectos resgistran entre 94% y 98% (fecha de ingreso, asignación de operador, odontograma y filiación) y sólo un aspecto se registra al 100% (evolución del tratamiento) del total de historias clínicas auditadas. conclusiones: más del 45% de las historias clínicas auditadas en la presente investigación tenían deficiencias en el registro o llenado de los datos que la historia clínica requiere como información de documento médico-legal.

Introduction: To assess the quality of registration or filling histories of new patients treated at a Teaching Dental Clinic during the period January to July 2012 using the Dental Audit as a tool systematized. Material and methods: Was sampled 140 medical records of new patients which assessed the frequency and percentage of recording various aspects that make up the medical record. Results: We found that 78% of the medical records do not have full registration in the different aspects evaluated, fi nding that of the seventeen aspects evaluated, nine recordedbetween 11% and 29 %, remaining between 89% and 71% of medical records that not record these aspects. Weidentifi ed three aspects that are recorded between 84% and 86% (medical record number, health questionnaire and dental examination), four points recorded between 94% and 98% (date of entry, operator assignment, odontogram and fi liation) and only one side is recorded 100% (treatment outcome) of the total audited medical records. Conclusions: Over 45% of medical records audited in this investigation are impaired in the registry or data fi lling medical history required as medico-legal document.