PTEN-regulated PI3K-p110 and AKT isoform plasticity controls metastatic prostate cancer progression.

PTEN loss, one of the most frequent mutations in prostate cancer (PC), is presumed to drive disease progression through AKT activation. However, two transgenic PC models with Akt activation plus Rb loss exhibited different metastatic development: Pten/RbPE:-/- mice produced systemic metastatic adenocarcinomas with high AKT2 activation, whereas RbPE:-/- mice deficient for the Src-scaffolding protein, Akap12, induced high-grade prostatic intraepithelial neoplasias and indolent lymph node dissemination, correlating with upregulated phosphotyrosyl PI3K-p85α. Using PC cells isogenic for PTEN, we show that PTEN-deficiency correlated with dependence on both p110ß and AKT2 for in vitro and in vivo parameters of metastatic growth or motility, and with downregulation of SMAD4, a known PC metastasis suppressor. In contrast, PTEN expression, which dampened these oncogenic behaviors, correlated with greater dependence on p110α plus AKT1. Our data suggest that metastatic PC aggressiveness is controlled by specific PI3K/AKT isoform combinations influenced by divergent Src activation or PTEN-loss pathways.

PTEN regulated PI3K-p110 and AKT isoform plasticity controls metastatic prostate cancer progression.

PTEN loss, one of the most frequent mutations in prostate cancer (PC), is presumed to drive disease progression through AKT activation. However, two transgenic PC models with Akt activation plus Rb loss exhibited different metastasis development: Pten/RbPE:-/- mice produced systemic metastatic adenocarcinomas with high AKT2 activation, whereas RbPE:-/- mice deficient for the Src-scaffolding protein, Akap12, induced high-grade prostatic intraepithelial neoplasias and indolent lymph node disseminations, correlating with upregulated phosphotyrosyl PI3K-p85α. Using PC cells isogenic for PTEN, we show that PTEN-deficiency correlated with dependence on both p110ß and AKT2 for in vitro and in vivo parameters of metastatic growth or motility, and with downregulation of SMAD4, a known PC metastasis suppressor. In contrast, PTEN expression, which dampened these oncogenic behaviors, correlated with greater dependence on p110α plus AKT1. Our data suggest that metastatic PC aggressiveness is controlled by specific PI3K/AKT isoform combinations influenced by divergent Src activation or PTEN-loss pathways.

Dimensión subjetiva de los procesos de trabajo en profesionales de salud en contexto de pandemia: un estudio exploratorio a partir del análisis de dispositivos de Apoyo a los Equipos de Salud en un municipio del Área Metropolitana de Buenos Aires (AMBA)

Resumen: Objetivo: caracterizar la dimensión subjetiva de los procesos de trabajo en el primer nivel de atención en contexto de pandemia, a través de la descripción y análisis de los discursos de los y las trabajadores/as producidos en el marco del dispositivo de Apoyo a los Equipos de Salud implementado en un municipio del área metropolitana de Buenos Aires. Metodología: investigación cualitativa, exploratoria y descriptiva. Estudio de caso único centrado en observación participante en 10 reuniones en centros de salud del Municipio de Tigre, durante los meses de abril y mayo de 2020. La sistematización del material se realizó siguiendo técnicas de análisis de contenido y generación de categorías. Resultados: el análisis permitió identificar cinco categorías emergentes: a) cambios en los escenarios de trabajo, b) emociones y actitudes frente a la tarea, c) vínculos al interior de los equipos, d) vínculos con las autoridades y e) vínculos con la comunidad. Discusión: la dimensión subjetiva contenida en las vivencias relatadas está caracterizada por sensaciones de incertidumbre, miedos, tensiones en la relación entre compañeros/as, con las instancias jerárquicas y con la población asistida, pero también por búsquedas activas de alternativas, apoyo entre compañeros/as, participación, motivación en los sentidos del trabajo, cuidados mutuos y acercamiento a la comunidad. De este modo se hacen visibles aspectos que preexistían a la situación de pandemia y aspectos que el contexto introduce. Finalmente, se arriba a algunas reflexiones sobre las implicancias de la inclusión de este dispositivo en el proceso de trabajo de equipos de salud durante la pandemia.

Abstract: Objective: characterize the subjective dimension of the work processes at the first level of care in the context of a pandemic, through the description and analysis of the speeches of the workers produced within the framework of the Health Team Support device implemented in a municipality in the metropolitan area of Buenos Aires. Methodology: qualitative, exploratory and descriptive research. Single case study focused on participant observation in 10 meetings in health centers of the Municipality of Tigre, during the months of April and May 2020. The systematization of the material was carried out following techniques of content analysis and category generation. Results: the analysis identified five emerging categories: a) changes in work settings, b) emotions and attitudes towards the task, c) ties within teams, d) ties with authorities, and e) ties with the community. Discussion: the subjective dimension contained in the experiences reported are characterized by feelings of uncertainty, fears, tensions in the relationship between colleagues, with hierarchical instances and with the assisted population, but also by active searches for alternatives, support among colleagues, participation, motivation in the sense of work, mutual care and approach to the community. In this way, aspects that pre-existed the pandemic situation and aspects that the context introduce are made visible. Finally, we come up with some reflections on the implications of the inclusion of this device in the work process of health teams during the pandemic.

Resumo: Objetivo: caracterizar a dimensão subjetiva dos processos de trabalho em primeiro nível de atenção em contexto de pandemia, por meio da descrição e análise das falas dos trabalhadores produzidos no âmbito do dispositivo de Apoio à Equipe de Saúde implantado em município da região metropolitana de Buenos Aires. Metodologia: pesquisa qualitativa, exploratória e descritiva. Estudo de caso único com foco na observação participante em 10 encontros em centros de saúde do Município de Tigre, durante os meses de abril e maio de 2020. A sistematização do material foi realizada seguindo técnicas de análise de conteúdo e geração de categorias. Resultados: a análise identificou cinco categorias emergentes: a) mudanças nos ambientes de trabalho, b) emoções e atitudes em relação à tarefa, c) vínculos dentro das equipes, d) vínculos com autoridades e e) vínculos com a comunidade. Discussão: a dimensão subjetiva contida nas vivências relatadas é caracterizada por sentimentos de incerteza, medos, tensões na relação entre colegas, com instâncias hierárquicas e com a população assistida, mas também por buscas ativas de alternativas, apoio entre colegas, participação, motivação no sentido de trabalho, cuidado mútuo e aproximação com a comunidade. Desta forma, tornam-se visíveis os aspectos prévios à situação pandémica e os que o contexto introduz. Por fim, são feitas algumas reflexões sobre as implicações da inclusão desse dispositivo no processo de trabalho das equipes de saúde durante a pandemia.

Apoyo Equipos de Salud en Contexto de Pandemia Covid-19 / Support Health Teams in the Context of the Covid-19 Pandemic

INTRODUCCIÓN El contexto de pandemia ha impuesto a los sistemas de salud una exigencia de trabajo inédita. Desde el punto de vista de la salud mental, los equipos de salud se encuentran expuestos a situaciones de tensión que pueden generar sufrimiento psíquico. Por ello el trabajo de apoyo a los equipos es considerado una acción prioritaria en este contexto. OBJETIVO Caracterizar la dimensión subjetiva de los procesos de trabajo en el primer nivel de atención en contexto de pandemia, a través de la descripción y análisis de los discursos de los y las trabajadores/as producidos en el marco del Dispositivo de Apoyo a los Equipos de Salud implementado en un municipio del área metropolitana de Buenos Aires. METODOLOGÍA Investigación cualitativa, exploratoria y descriptiva. Estudio de caso único centrado en observación participante en reuniones de equipo y entrevistas realizadas en centros de salud del Municipio de Tigre. La sistematización del material se realizó siguiendo técnicas de análisis de contenido y generación de categorías. RESULTADOS El análisis permitió identificar cinco categorías emergentes 1. Cambios en los escenarios de trabajo, 2. Emociones y actitudes frente a la tarea, 3. Vínculos al interior de los equipos, 4. Vínculos con las autoridades y 5. Vínculos con la comunidad. DISCUSIÓN La dimensión subjetiva contenida en las vivencias relatadas está caracterizada por sensaciones de incertidumbre, miedos, tensiones en la relación entre compañeros/as, con las instancias jerárquicas y con la población asistida, pero también por búsquedas activas de alternativas, apoyo entre compañeros/as, participación, 4 motivación en los sentidos del trabajo, cuidados mutuos y acercamiento a la comunidad. De este modo se hacen visibles aspectos que preexistían a la situación de pandemia y aspectos que el contexto introduce. Se evidencia que ha sido muy positiva la apertura de espacios de conversación coordinados por psicólogos/as como práctica de cuidado en salud mental.

Clinical Characteristics of Localized Aggressive Periodontitis in Primary Dentition.

OBJECTIVES: Due to the low prevalence of localized aggressive periodontitis (LAP), clinical characteristics of LAP in primary dentition are derived from a few case reports/series in the literature. The goal of this study was to determine common clinical characteristics such as bone and root resorption patterns, in a series of cases with LAP in primary dentition. We hypothesize these cases present aggressive periodontal bone destruction starting mostly around first primary molars and atypical root resorption patterns. STUDY DESIGN: We have evaluated 33 LAP cases in primary dentition for pattern of bone destruction, root resorption and early exfoliation. RESULTS: Cases evaluated were aged 5-12 (mean=8.7 years). Thirty cases presented more severe bone loss on first than second molars, with relatively fast progression to second molars, altered pattern of root resorption, mostly external (n=16) and early exfoliation of primary teeth due to periodontal bone loss, rather than physiologic root resorption (n=11). CONCLUSIONS: This study showed common clinical characteristics found in LAP in primary molars, including possible initiation on first primary molars and abnormal root resorption patterns. These characteristics are important to be early identified and treated in order to prevent possible progression into the permanent dentition.

Long-term clinical response to treatment and maintenance of localized aggressive periodontitis: a cohort study.

AIM: To evaluate long-term clinical response to periodontal therapy and maintenance in localized aggressive periodontitis (LAP). MATERIALS AND METHODS: One hundred forty-one African Americans diagnosed with LAP, aged 5-25 years, were enrolled. Patients underwent periodontal mechanical debridement plus 1 week of amoxicillin/metronidazole. Mechanical therapy was repeated as needed and clinical parameters were recorded at baseline, 3, 6, 12, 18 and 24 months, and two additional annual follow-up visits after treatment. Radiographs from primary dentition of patients with LAP in permanent dentition, and additional healthy siblings (HS) were analysed retrospectively. RESULTS: Periodontal therapy significantly improved probing depth and clinical attachment level up to 4 years (mean reductions: 2.18 ± 1.03 and 2.80 ± 1.43 mm, respectively). Percentage of affected sites was reduced at all time points and maintained up to 4 years. Non-compliance with antibiotics/appointments negatively affected the treatment response. Ninety per cent of LAP patients in permanent dentition and 32% of HS presented radiographic bone loss in primary dentition. CONCLUSIONS: Mechanical debridement with 1 week of systemic antibiotics along with proper periodontal maintenance was effective in the treatment and successful maintenance of LAP for up to 4 years. LAP in permanent dentition may be preceded in the primary dentition. Clinicaltrials.gov #NCT01330719.

Oral, radiographical, and clinical findings in Weaver syndrome: a case report.

Weaver syndrome is a rare condition characterized by accelerated growth, advanced osseous maturation, and distinct craniofacial features that can occur in both males and females. Etiology is unknown and no definitive oral characteristics have been established. The objective of this case report is to describe the oral and radiographic findings of a 14-year-old male with Weaver syndrome. A comprehensive dental examination was performed under general anesthesia. The clinical findings were: severe generalized heavy plaque with subgingival calculus, gingival edema, malocclusion and maxillary atresia, mild micrognathia of the mandible, enlarged tongue, and bifid uvula. Clinical and radiographic caries were not found. Out of over 40 possible cases of Weaver syndrome previously reported in the literature, only two were related to the oral cavity. Bifida uvula was not mentioned until now as clinical findings associated with the syndrome. Autism, macroglossia, and cleft palate were seldom mentioned. The oral manifestations in Weaver syndrome are not yet well known. Future studies will be required to improve the subject matter.

Periodontite agressiva localizada: considerações sobre etiopatogenia e tratamento / Localized aggressive periodontitis: aspects of etiopathogenesis and treatment

A periodontite agressiva localizada (PAL) é uma doença caracterizada pela destruição periodontal agressiva em dentes específicos, de agregação familiar, geralmente afetando a população jovem, principalmente os afrodescendentes. Apesar da baixa prevalência, o diagnóstico precoce desta doença é difícil, especialmente na dentição decídua, o que geralmente resulta em sua rápida progressão e eventual perda precoce de importantes dentes da cavidade oral. Até o presente momento, a maior parte dos estudos realizados tem envolvido populações pequenas, devido à dificuldade em se obter grandes populações com esta doença. Entretanto, há evidências científicas de espécies bacterianas e vírus associados à PAL, bem como de respostas imunológicas específicas associadas com indivíduos ou famílias de indivíduos afetados pela doença. Há evidências, ainda, da efetividade de antibióticos associados ao debridamento mecânico, quando se compara com a terapia mecânica isolada em PAL. No entanto, mais estudos são necessários para esclarecer mecanismos específicos relacionados à PAL, a participação de outros fatores na patogênese da doença e a estabilidade, a longo prazo, dos dentes com destruição periodontal inicialmente severa.

Prevalência microbiana e quantificação da arginase na saúde e doença periodontal / Microbial prevalence and arginase quantification in health and periodontal disease

A arginase salivar está aumentada em processos inflamatórios e infecciosos da cavidade bucal. O objetivo do presente estudo foi avaliar a atividade de arginase salivar, correlacionando-a a parâmetros clínicos e microbiológicos em diferentes condições periodontais. Foram avaliados os seguintes parâmetros clínicos: índice de placa, índice de sangramento, profundidade de sondagem e nível de inserção clínica. Foi avaliada ainda a presença dos periodontopatógenos Campylobacter rectus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tanerella forsythia, Treponema denticola e Prevotella intermedia por meio da reação em cadeia da polimerase (PCR). Finalmente, a presença salivar de arginase — por meio de espectrofotometria —também foi considerada. O tratamento estatístico dos dados foi realizado pelos testes Qui-quadrado e Kruskal-Wallis, adotando-se significância estatística quando p<0,05. Foram alocados no presente estudo 78 indivíduos assim caracterizados: 26 periodontalmente saudáveis (S), 26 com gengivite(G) e 26 com periodontite crônica (P). P. gingivalis, P. intermedia e T. denticola estavam mais prevalentes significativamente em P do que em G e S (p<0,05). A. actinomycetemcomitans foi significativamente mais prevalente (p<0,05) em P e G do que em S. C. rectus apresentou distribuição similar nos três grupos (p>0,05). Com relação aos níveis de atividade de arginase, os indivíduos portadores de periodontite crônica apresentaram maiores níveis (p<0,05) em comparação aos com gengivite ou periodontalmente saudáveis. A expressão da arginase salivar parece acompanhar a mudança dos sinais clínicos e a alteração do perfil microbiológico das diferentes condições periodontais

The salivary arginase is increased in inflammatory and infectious processes of the oral cavity. The aim of this study was to evaluate the salivary arginase activity, correlating it to clinical and microbiological parameters in different periodontal conditions. We evaluated the following parameters: plaque index, bleeding index, probing depth and clinical attachment level. It also assessed the presence of periodontopathogens Campylobacter rectus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tanerellaforsythia, Treponema denticola, and Prevotella intermedia by polymerase chain reaction (PCR). Finally, presence of salivary arginase - by spectrophotometry - was also considered. Statistical treatment of data was performed by chi-square and Kruskal-Wallis, adopting statistical significance at p <0.05. Eighty-nine individuals were allocated in this study:26 periodontally healthy (S), 26 with gingivitis (G) and 26 with chronic periodontitis (P). P. gingivalis, P. intermedia and T. denticola were significantly more prevalent in P-group than G- and S-group (p <0.05). A. actinomycetemcomitans was significantly more prevalent (p <0.05) in P- and G-group than in S-group. C. rectus showed a similar distribution in the three groups (p> 0.05). With respect to the levels of arginase activity, individuals with chronic periodontitis had higher levels (p <0.05) than those with gingivitis or periodontally healthy. Expression of the salivary arginase seems to followthe changes of clinical signs and microbiological profile in different periodontal conditions.