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BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a multifactorial fatal motoneuron disease without a cure. Ten percent of ALS cases can be pointed to a clear genetic cause, while the remaining 90% is classified as sporadic. Our study was aimed to uncover new connections within the ALS network through a bioinformatic approach, by which we identified C13orf18, recently named Pacer, as a new component of the autophagic machinery and potentially involved in ALS pathogenesis. METHODS: Initially, we identified Pacer using a network-based bioinformatic analysis. Expression of Pacer was then investigated in vivo using spinal cord tissue from two ALS mouse models (SOD1G93A and TDP43A315T) and sporadic ALS patients. Mechanistic studies were performed in cell culture using the mouse motoneuron cell line NSC34. Loss of function of Pacer was achieved by knockdown using short-hairpin constructs. The effect of Pacer repression was investigated in the context of autophagy, SOD1 aggregation, and neuronal death. RESULTS: Using an unbiased network-based approach, we integrated all available ALS data to identify new functional interactions involved in ALS pathogenesis. We found that Pacer associates to an ALS-specific subnetwork composed of components of the autophagy pathway, one of the main cellular processes affected in the disease. Interestingly, we found that Pacer levels are significantly reduced in spinal cord tissue from sporadic ALS patients and in tissues from two ALS mouse models. In vitro, Pacer deficiency lead to impaired autophagy and accumulation of ALS-associated protein aggregates, which correlated with the induction of cell death. CONCLUSIONS: This study, therefore, identifies Pacer as a new regulator of proteostasis associated with ALS pathology.

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Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings.

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Desde los inicios de la cirugía de implantes orales, se ha recomendado excluir o limitar a ciertos pacientes con problemas de salud o hábitos de tabaquismo. Los enfermedades crónicas no transmisibles de salud, no son considerados una contraindicación absoluta para la utilización de implantes orales, pero si se debe evaluar con detalle el tipo de enfermedad presente, por ser un potencial riesgo que podría afectar el proceso de oseointegración. Hay ciertas condiciones sistémicas, como la osteoporosis, enfermedades cardiovasculares, diabetes mellitus, e hipotiroidismo, así como también, el hábito de fumar, que inciden sobre el éxito, la sobrevida o el fracaso de los implantes. El propósito de la investigación realizada, es determinar si existe asociación entre los fracasos de los implantes dentales y las enfermedades sistémicas en la población de pacientes sometidos a cirugía de implantes dentales del hospital San José de Santiago de Chile. Se realizó un estudio de tipo observacional de carácter retrospectivo y las variables estudiadas fueron las enfermedades sistémicas (osteoporosis, hipertensión, diabetes, e hipotiroidismo) y los criterios utilizados para la evaluación de salud de implantes fueron los del Congreso Internacional de Implantología Oral de Pisa, en donde fracaso es el término usado para los implantes que requieren el retiro o ya se han perdido. Estas variables se registraron desde la ficha clínica y durante un examen clínico, en una ficha de recolección de datos. Esto permitió, describir variables y su distribución, posteriormente analizar los datos obtenidos encontrando evidencias de asociación estadísticamente válidas. Para este estudio podemos concluir, que el análisis de cada una de las variables sistémicas como son la hipertensión, clasificación ASA II, presentan una asociación con el fracaso de implantes dentales, no así la osteoporosis, hipotiroidismo, diabetes, edad, estado nutricional, genero y el habito de fumar.

Since the beginning of oral implant surgery it has been recommended to exclude or limit certain patients with health issues or smoking habits. The chronic non-communicable diseases are not considered an absolute contraindication to the use of oral implants, but the type of disease should be evaluated in detail, as a potential risk that could affect the process of osseointegration. There are certain systemic conditions, such as osteoporosis, cardiovascular disease, diabetes mellitus, and hypothyroidism, as well as the habit of smoking, that affect the success, survival or failure of the implants. The purpose of the investigation is to determine whether there is an association between the failure of dental implants and systemic diseases in the population of patients undergoing dental implant surgery of San José de Santiago de Chile Hospital. We conducted a retrospective observational study and the variables studied were systemic diseases (osteoporosis, hypertension, diabetes, and hypothyroidism) and the criteria used to assess the health of implants were those of the International Congress of Oral Implantology of Pisa, where "failure" is the term used for implants requiring removal or that were already lost. These variables were recorded from the clinical record and during a clinical examination, in a data collection sheet. This allowed to describe variables and their distribution, and then to analyze the data to find statistically valid evidence. For this study we can conclude that the analysis of each of the variables such as systemic hypertension or ASA II, have an association with the failure of dental implants, but not osteoporosis, hypothyroidism, diabetes, age, nutritional status, gender and cigarette smoking.

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BACKGROUND AND OBJECTIVE: It has been suggested that chronic infections may predispose to cardiovascular disease. The relationship between periodontal disease and cardiovascular disease has been a subject of increasing research in recent years. The isolation and identification of periodontal bacteria from atheromatous plaque can contribute to our knowledge of this vascular disease. The aim of this study was to isolate and identify periodontal bacteria from the periodontal pockets of different patients and to compare them with the microorganisms detected in the atheromatous plaques obtained from the same patients. MATERIAL AND METHODS: Clinical isolates were obtained from 12 patients with periodontal wounds and atheromathous plaques. These samples were cultured in the appropriate bacteriological culture media and incubated in an anaerobic system. Periodontal bacteria were identified using polymerase chain reaction (PCR) assays. RESULTS: From the 12 patients studied, nine presented different periodontopathic bacterial species. In two, Actinobacillus actinomycetemcomitans was present in the periodontal pockets and the respective atheromatous plaques. CONCLUSION: The presence of A. actinomycetemcomitans in atheromatous plaques and the periodontal pockets of the same patients could indicate a role for periodontal pathogenic bacteria in the atherosclerosis disease process.

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