The Characterization of Alzheimer’s Disease and the Development of Early Detection Paradigms: Insights from Nosology, Biomarkers and Machine Learning

Alzheimer’s Disease (AD) is the only condition in the top ten leading causes of death for which we do not have an effective treatment that prevents, slows, or stops its progression. Our ability to design useful interventions relies on (a) increasing our understanding of the pathological process of AD and (b) improving our ability for its early detection. These goals are impeded by our current reliance on the clinical symptoms of AD for its diagnosis. This characterizations of AD often falsely assumes a unified, underlying AD-specific pathology for similar presentations of dementia that leads to inconsistent diagnoses. It also hinges on postmortem verification, and so is not a helpful method for identifying patients and research subjects in the beginning phases of the pathophysiological process. Instead, a new biomarker-based approach provides a more biological understanding of the disease and can detect pathological changes up to 20 years before the clinical symptoms emerge. Subjects are assigned a profile according to their biomarker measures of amyloidosis (A), tauopathy (T) and neurodegeneration (N) that reflects their underlying pathology in vivo. AD is confirmed as the underlying pathology when subjects have abnormal values of both amyloid and tauopathy biomarkers, and so have a biomarker profile of A+T+(N)- or A+T+(N)+. This new biomarker based characterization of AD can be combined with machine learning techniques in multimodal classification studies to shed light on the elements of the AD pathological process and develop early detection paradigms. A guiding research framework is proposed for the development of reliable, biologically-valid and interpretable multimodal classification models

PRÉ-ESFRIAMENTO E TEMPERATURA PARA GERMINAÇÃO DE SEMENTES DE CARQUEJA

The objective of this work was to evaluate the effect of pre-chilling and temperature on the germination of Baccharis trimera seeds. B. trimera is a medicinal plant that grows spontaneously in regions with cold winter, then the seeds germination can be affected by the low temperure before and during the germination process. The seeds were collected at the locality of Laranjeiras do Sul, Paraná State, in November of 2001, and carried to the Plant Physiology Laboratory of PUCPR at São José dos Pinhais. The pre-chilling periods at the temperatures of 2 to 7° C (0, 7, 14 and 21 days), the temperature of germination test (20 and 25° C) and the test duration (7, 14 and 21 days) were studied in a randomized block design in a factorial squeme (4 x 2 x 3) with four repetitions and 100 seeds per parcel. The pre-chilling during 14 and 21 days improved the seeds germination when the temperature of 20° C was used. Without the pre-chilling the germination percentage at 25°C (53,8%) was higher than at 20° C (10,1%). A germination percentage from 53 to 58 % was obtained when the prechilling was used. There was a significant increase of the seeds germination untill 21 days of test. The germination of B. trimera seeds is viable when the temperature of test is 25°C and the pre-chilling from 14 to 21 days is necessary when the temperature is 20° C.Este trabalho objetivou estudar o efeito do pré-esfriamento e da temperatura na germinação de sementes de carqueja. Formulouse a hipótese que sendo a carqueja originária de regiões com inverno frio então a germinação de suas sementes pode ser influenciada por diferentes temperaturas ocorridas antes ou durante a mesma. As sementes foram coletadas em Laranjeiras do Sul, Paraná, em novembro de 2001, e levadas ao Laboratório de Fisiologia Vegetal da PUCPR em São José dos Pinhais. Adotou-se o delineamento de blocos casualizados num esquema fatorial (4 x 2 x 3) em que foram analisados o pré-esfriamento em geladeira a 2 a 7° C (0, 7, 14 e 21 dias), a temperatura durante a germinação (20 e 25° C) e o tempo para germinação (7, 14 e 21 dias) com quatro repetições e 100 sementes por parcela. O pré-esfriamento com 14 e 21 dias proporcionou efeito benéfico para a germinação das sementes quando a temperatura de germinação foi de 20° C. Quando não aplicado o pré-esfriamento a germinação a 25° C (53,8 %) foi superior àquela a 20° C (10,1 %). As sementes pré-esfriadas apresentaram valores de germinação de 53 a 58%. Houve aumento significativo da porcentagem de sementes germinadas até os 21 dias após a instalação. Conclui-se que a germinação de sementes de carqueja a temperatura de 25° C é viável e quando utilizada temperatura de 20° C é necessário o pré-esfriamento pelo período de 14 a 21 dias

Shares of the search for respiratory symptoms of tuberculosis according to the professionals' view of a Family Health Unit

Analyze in accordance with the professional's view of a Family Health Team the practice of Search for respiratory symptoms of Tuberculosis in daily activities identifying difficulties in developing this action. Qualitative, with content analysis, thematic, through semi-structured interviews applied to five professionals that form a family health team of a health unit (clinic) in a medium-sized city in southern Brazil. The statements reveal that shares of the search for respiratory symptoms of tuberculosis have the community as the main scenario and the Family Health Strategy has the potential to intensify actions to control TB in this medium. The role of the Community Health Agent is deployed in these shares and also the insecurity of health professionals with the risk of contagion of the disease. The search for respiratory symptoms of TB is a program developed by the professionals of the FHS. However, difficulties are identified in the continuity of health care necessary to diagnose the disease because of quantitative weaknesses (lack of human resources) and qualitative (unprepared professionals) with implications for tuberculosis contro

Ações de busca de sintomáticos respiratórios de tuberculose na visão dos profissionais de uma unidade saúde da família

O objetivo da pesquisa foi analisar na visão dos profissionais de uma Equipe Saúde da Família a prática da Busca dos Sintomáticos Respiratórios (BSR) da Tuberculose (TB) em suas atividades diárias identificando dificuldade no desenvolvimento desta ação. Trata-se de uma pesquisa de abordagem qualitativa, a análise foi de conteúdo, modalidade temática, por meio de entrevistas semi-estruturadas aplicadas a 5 profissionais que conformam uma equipe de saúde da família de uma unidade de saúde de um município de médio porte no sul do Brasil. Os depoimentos revelam que as ações de BSR têm como cenário principal a comunidade e que Estratégia Saúde da Família (ESF), tem potencial para intensificar as ações de controle da TB neste meio. Destaca-se o protagonismo do Agente Comunitário de Saúde (ACS) nestas ações e a insegurança do profissional de saúde diante do risco de contagio da doença. A BSR é uma ação desenvolvida pelos profissionais da ESF. Contudo, identificam-se dificuldades na continuidade das ações de saúde necessárias ao diagnóstico da doença devido às fragilidades quantitativas (falta de recursos humanos) e qualitativas (despreparo dos profissionais) com implicações para controle da tuberculose

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Florence Nightingale: the impact of her contributions in the contemporary world of nursing

El papel de la atención es parte de la existencia humana y se relaciona con la imagen de la mujer, que buscó, a través de esta práctica, una forma de supervivencia que se ha desarrollado en ámbitos más amplios, como la promoción y el mantenimiento de la salud. Objetivo: Reflexionar sobre las contribuciones de Florence Nightingale para el ejercicio del cuidado en la actualidad. Metodología: Se trata de un estudio reflexivo con perspectiva histórica, estructurada por temas, cuyas fuentes de recolección de datos fueron artículos de periodicos publicados, libros y obras de crítica presentados en la Maestria Académica en Enfermería. Resultados: Florence Nightingale se convirtió en el personaje que representa a la profesión de enfermería a través de su visión del mundo, convirtiéndose en un punto de referencia de la vida y la práctica profesional en esta área de la salud. Conclusiones: Se encontró que su visión teórica contribuyó para la desmitificación de las disparidades relacionadas con el género, favoreciendo el ejercicio de la capacidad intelectual de las mujeres en la sociedad. Ella ha recibido esta distinción a través de sus conocimientos científicos, dando un carácter organizado a la clase de la Enfermería. Su atención se recomendó a los seres humanos directamente vinculados a su entorno, las expresiones de una obra integral, pre-anunciando una definición que incluye la totalidad de los individuos en el ámbito de la enfermería.The role of caring is part of human existence and is related to the woman's image that has sought, through this practice, a form of survival that has evolved into broader areas such as promotion and health maintenance. Objective: To reflect on the contributions of Florence Nightingale for the care exercise in the current days. Methodology: It is a reflective study with historical perspective, structured by themes, whose sources of data collection were journal articles, books, and critical works approached in the Nursing Academic Master. Results: Florence Nightingale became the character that retracts the nursing profession through their worldview, becoming a benchmark of life and professional practice in this area of health. Conclusions: We found that her theoretical vision contributed to the demystification of disparities related to gender, favoring the exercise of the intellectual capacity of women in society. She has received this merit through her scientific knowledge, giving an organized profile to the class. Her care was recommended to the human being and directly associated to his environment, expressions of a holistic work, pre-announcing the definition that includes the individual totality in the field of nursing.O papel de cuidar faz parte da existência humana e está relacionado à imagem da mulher, que buscava, através dessa práxis, uma forma de sobrevivência que evoluiu para âmbitos mais abrangentes, como a promoção e manutenção da saúde. Objetivo: Refletir sobre as contribuições de Florence Nightingale para o exercício do cuidado na atualidade. Metodologia: É um estudo reflexivo com perspectiva histórica, estruturado por temáticas, cujas fontes de obtenção dos dados foram artigos de periódicos publicados, livros, e trabalhos críticos abordados no Mestrado Acadêmico de Enfermagem. Resultados: Florence Nightingale passou a ser a personagem que retrata a profissão de enfermagem através da sua visão de mundo, tornando-se um referencial de vida e de prática profissional para esta área da saúde. Conclusões: Constatou-se que a sua visão teórica contribuiu para a desmistificação de disparidades relacionadas ao gênero, favorecendo o exercício da capacidade intelectual da mulher na sociedade. Ela recebeu esse mérito por meio de seu conhecimento científico, conferindo um caráter organizado à categoria. Seu cuidado era preconizado ao ser humano e associado diretamente ao seu meio ambiente, expressões de um trabalho holístico, pré-anunciando a definição que contempla a totalidade do indivíduo no campo da enfermagem

Molecular mechanism of pdxr - a transcriptional activator involved in the regulation of vitamin b biosynthesis in the probiotic bacterium Bacillus clausii

Pyridoxal 5'-phosphate (PLP), the well-known active form of vitamin B6 , is an essential enzyme cofactor involved in a large number of metabolic processes. PLP levels need to be finely tuned in response to cell requirements; however, little is known about the regulation of PLP biosynthesis and recycling pathways. The transcriptional regulator PdxR activates transcription of the pdxST genes encoding PLP synthase. It is characterized by an N-terminal helix-turn-helix motif that binds DNA and an effector-binding C-terminal domain homologous to PLP-dependent enzymes. Although it is known that PLP acts as an anti-activator, the mechanism of action of PdxR is unknown. In the present study, we analyzed the biochemical and DNA-binding properties of PdxR from the probiotic Bacillus clausii. Spectroscopic measurements showed that PLP is the only B6 vitamer that acts as an effector molecule of PdxR. Binding of PLP to PdxR determines a protein conformational change, as detected by gel filtration chromatography and limited proteolysis experiments. We showed that two direct repeats and one inverted repeat are present in the DNA promoter region and PdxR is able to bind DNA fragments containing any combination of two of them. However, when PLP binds to PdxR, it modifies the DNA-binding properties of the protein, making it selective for inverted repeats. A molecular mechanism is proposed in which the two different DNA binding modalities of PdxR determined by the presence or absence of PLP are responsible for the control of pdxST transcription