83 research outputs found

    Breaking tolerance in transgenic mice expressing the human TSH receptor A-subunit: thyroiditis, epitope spreading and adjuvant as a 'double edged sword'.

    Get PDF
    Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice. Our present goal was to determine if thyroiditis could be induced in Hi-expressor transgenics using a more potent immunization protocol: Treg depletion, priming with Complete Freund's Adjuvant (CFA) + A-subunit protein and further Treg depletions before two boosts with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type mice were primed with CFA+ mouse thyroglobulin (Tg) or CFA alone before A-sub-Ad boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice) were resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis was associated with the development of antibodies to the mouse TSHR downstream of the A-subunit. Unexpectedly, we observed that the effect of bacterial products on the immune system is a "double-edged sword". On the one hand, priming with CFA (mycobacteria emulsified in oil) plus A-subunit protein broke tolerance to the A-subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the other hand, prior treatment with CFA in the absence of A-subunit protein inhibited responses to subsequent immunization with A-sub-Ad. Consequently, adjuvant activity arising in vivo after bacterial infections combined with a protein autoantigen can break self-tolerance but in the absence of the autoantigen, adjuvant activity can inhibit the induction of immunity to autoantigens (like the TSHR) displaying strong self-tolerance

    Impact of Pooling Samples on Analytic Sensitivity of a Real-Time Reverse Transcriptase PCR Assay for SARS CoV-2

    Get PDF
    During the COVID-19 pandemic, laboratories experienced periods of shortages for certain critical materials required to meet the high demand for SARS-CoV-2 testing. The U.S. Food & Drug Administration provided a template for molecular diagnostic testing, including guidance for a specimen pooling process in order to evaluate performance of the SARS-CoV-2 nucleic acid amplification assay. This study aimed to evaluate the testing of pooled specimens consisting of four nasopharyngeal swab specimens using the Luminex ARIES® nucleic acid amplification platform. Results indicated that there was a loss of analytic sensitivity with pooled nasopharyngeal swab samples, demonstrating that this approach should be balanced against material shortages and the clinical utility of a less sensitive assay

    Development of a real-time Reverse-Transcription PCR for SARS CoV-2 on the Luminex ARIES® Platform

    Get PDF
    The University of Louisville Infectious Diseases Laboratory followed the US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) guidance for developing a molecular diagnostic test for SARS CoV-2 to help address the novel coronavirus pandemic. As a Clinical Laboratory Improvement Amendment ‘88 (CLIA) certified, high-complexity clinical laboratory, the Infectious Diseases Laboratory chose to use the Luminex ARIES® platform to evaluate a laboratory developed test. This instrument was already familiar to the Infectious Diseases Laboratory and in use for molecular diagnostic testing for pathogens causing atypical pneumonia and two tick-borne pathogens. The FDA EUA guidance for molecular diagnostic tests recommended limit of detection studies, inclusivity and exclusivity (specificity) analysis, and validation with clinical samples to ensure the performance of the assay was acceptable for use as a molecular diagnostic tool. Data obtained from these experiments demonstrated acceptable performance per FDA guidance, as well as for CLIA requirements. Thus, the real-time Reverse Transcription PCR assay was implemented for diagnostic use on March 27, 2020 and was a great benefit to the local community in responding to the pandemic.

    Use of Cina 30 CH on Diarrhea Caused by Coccidiaon Backyard Hog Litters.

    Get PDF
    The action of Cina 30 CH on diarrhea caused by Coccidiato 140 backyard hog litters was assessed in Camagüey, Cuba. The animals were distributed in two groups, each of 70 individuals. Each group had animals of 10 days of age and 3 kg of initial mean weight. Group 1 was given Cina 30 CH, five sublingual drops every 12 h, until the tenth day; group 2 received Metronidazole (250 mg) orally, ½ tablet (25 mg/kg) every 12 h, for seven days. Upon assess-ing clinical evolution, significant differences were observed between the two groups. White cells (leukocytes and lymphocytes) were assessed, before and after the treatment. Comparison of weight at weaning (ANOVA), and hema-tological parameters by t-Student for samples related within the same group produced a significant difference of P < 0.05; as well as improved behavior in animals treated homeopathically corroborated that the homeopathic technique tested was effective

    Performance of a SARS-CoV-2 RT-PCR Assay with Non-Traditional Specimen Types

    Get PDF
    During the first two years of the coronavirus disease 2019 (COVID-19) pandemic, nasopharyngeal (NP) specimens were the gold standard for clinical diagnostic testing. As information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the pandemic continued to be shared, it was clear that the virus could be detected in other specimen types during an active infection. The University of Louisville Infectious Diseases Laboratory accepted non-traditional specimen types, most without a paired, positive NP result, for research purposes only to support local epidemiology efforts. A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay originally validated for NP specimens was used for non-traditional specimen types using a variety of specimen preparation methods. Limit of detection (LOD) studies allowed for direct comparison between NP, sputum, and breast milk specimen types. The primary aim of the study was to determine whether SARS-CoV-2 RNA could be detected in different human specimen types. The results showed that the non-traditional specimens were not inherently inhibitory since SARS-CoV-2 RNA was detected in 36 (14.5%) out of 249 non-traditional specimens, and the limit of detection for SARS-CoV-2 in breast milk and sputum was the same as for NP specimens. SARS-CoV-2 was not detected in 15 breast milk specimens from mothers with positive SARS-CoV-2 NP results. In addition, a direct comparison study showed that NP specimens performed better than paired nasal specimens. In conclusion, by analyzing real-time RT-PCR test results for these non-traditional specimen types, two benefits were realized. Health care providers gained additional epidemiologic information (since information was not to be used for managing or treating patients), and the laboratory gathered important information about specimen types for which complete method validation studies could be pursued in the future

    LAS FUENTES DEL CONOCIMIENTO HISTÓRICO: EL VALOR INELUDIBLE DE LAS FUENTES ORALES

    Get PDF
    El artículo aborda lo limitado que era el empleo de las fuentes orales desde la historiografía; muestra la importancia que tienen las fuentes del conocimiento histórico, y dentro de ellas, las antes mencionadas; se exponen las potencialidades de las fuentes orales en el proceso de enseñanza aprendizaje de la Historia, así como su clasificación y definición desde la didáctica de la Historia. Se propone integrar el empleo de las fuentes orales al proceso de enseñanza aprendizaje de la Historia en la secundaria básica, dicha propuesta didáctico-metodológica en los programas escolares permite ampliar los límites del conocimiento, específicamente, en el campo de la historia social, porque el estudiante en el rescate y escritura de las leyendas, los testimonios e historias de vida, recupera elementos de su propia identidad, lo mismo que tradiciones o creencias de su ámbito social; descubre fuentes vivas y se involucra con ellas, y no estudia solamente aquella historia que que se encuentra en los libros. Se especifica cómo los profesores deben dar tratamiento correcto a las fuentes orales para lograr una educación histórica en los adolescentes. ABSTRACT The article offers the limited that was the employ of oral sources since the historiography; it also shows the importance of the sources of the historical knowledge and inside them those before mentioned, as well as their classification and definition since History didactics. Besides prosecute how the professors should give correct treatment to the oral sources, giving him their value and showing the potentialities of these in the History teaching-learning, to achieve a historical education in the adolescents from Junior High School. KEY WORDS: Orality, oral sources, oral history, historical education

    LA EVOLUCIÓN HISTÓRICA DE LAS FUENTES ORALES EN EL PROCESO DE ENSEÑANZA-APRENDIZAJE DE LA HISTORIA

    Get PDF
    En este artículo se presentan las ideas esenciales relacionadas con las características del proceso de enseñanza-aprendizaje de la Historia en la Educación Secundaria Básica, y una valoración crítica del estado del tratamiento de las fuentes orales por los docentes, teniendo determinado valor para la didáctica, lo que facilitó caracterizar su estado histórico tendencial y metodológicamente orientar la investigación por un camino científico. Para realizar esta evolución histórica de las fuentes orales en el proceso de enseñanza-aprendizaje de la Historia se hizo la consulta de resultados investigativos que tienen relación con el objeto y campo, la revisión de programas de la asignatura en la Educación Secundaria Básica, de orientaciones metodológicas, planes de clases de los profesores de historia, así como entrevistas a docentes que impartieron la asignatura en su momento. ABSTRACT In this work the essential ideas are related to the characteristics of the teaching-learning process of History in Junior Education, and is carried out a critical evaluation of the state of the treatment of the oral sources made by teachers, having certain value for didactics, this eased to characterize their historical state and methodologically to guide the investigation scientifically. To carry out this historical evolution of the oral sources in the teaching-learning process of the History, it was necessary to consult investigative results which are related to the object of investigation and the scope of action, the revision of syllabus of the subject in Junior High, the methodological guide lines, the lesson plans of the history teachers, as well as the interview of teachers who taught the subject at a moment. KEY WORDS: teaching-learning, History, oral sources, Oral History, historical education

    The NOD mouse beyond autoimmune diabetes

    Get PDF
    Autoimmune diabetes arises spontaneously in Non-Obese Diabetic (NOD) mice, and the pathophysiology of this disease shares many similarities with human type 1 diabetes. Since its generation in 1980, the NOD mouse, derived from the Cataract Shinogi strain, has represented the gold standard of spontaneous disease models, allowing to investigate autoimmune diabetes disease progression and susceptibility traits, as well as to test a wide array of potential treatments and therapies. Beyond autoimmune diabetes, NOD mice also exhibit polyautoimmunity, presenting with a low incidence of autoimmune thyroiditis and Sjögren’s syndrome. Genetic manipulation of the NOD strain has led to the generation of new mouse models facilitating the study of these and other autoimmune pathologies. For instance, following deletion of specific genes or via insertion of resistance alleles at genetic loci, NOD mice can become fully resistant to autoimmune diabetes; yet the newly generated diabetes-resistant NOD strains often show a high incidence of other autoimmune diseases. This suggests that the NOD genetic background is highly autoimmune-prone and that genetic manipulations can shift the autoimmune response from the pancreas to other organs. Overall, multiple NOD variant strains have become invaluable tools for understanding the pathophysiology of and for dissecting the genetic susceptibility of organ-specific autoimmune diseases. An interesting commonality to all autoimmune diseases developing in variant strains of the NOD mice is the presence of autoantibodies. This review will present the NOD mouse as a model for studying autoimmune diseases beyond autoimmune diabetes

    Stray dog population of the municipality of Camagüey, Cuba

    Get PDF
    Con el objetivo de estimar la población de perros callejeros en Camagüey, Cuba, se realizó un censo de la población canina callejera en cuatro barrios de la ciudad de Camagüey durante los meses de septiembre a diciembre de 2015. Se recopilaron datos sobre sexo del perro, presencia de ectoparásitos (garrapatas y pulgas) y enfermedades dermatológicas. Asimismo, se recolectó material fecal encontrado en calles y centros públicos. El promedio de perros por barrio varió entre 45 y 75, donde el 62% de las observaciones correspondieron a perros con lesiones en piel o con presencia de ectoparásitos. El 61.7% de las muestras fecales fue positiva a huevos de parásitos gastrointestinales, mayormente de los géneros Ancylostoma y Toxocara.In order to estimate the population of dogs in the streets of Camaguey, Cuba a field survey was carried out on stray dogs in four neighbourhoods of the Camagüey city during September to December 2015. Data related to sex of the dog, presence of ectoparasites (ticks and fleas) and skin diseases was collected. Besides, faecal material was collected from roads and public places. The number of stray dogs per neighborhood ranged from 45 to 75. Furthermore, 62% of the observations corresponded to dogs with skin lesions or presence of ectoparasites and 61.7% of the fecal samples were positive for eggs of gastrointestinal parasites, mostly of the genera Ancylostoma and Toxocara

    EL USO EDUCATIVO DE INTERNET EN LA FORMACIÓN INICIAL PROFESIONAL DE LA EDUCACIÓN A TRAVÉS DE LAS REDES SOCIALES DE INTERNET

    Get PDF
    La investigación va dirigida al perfeccionamiento continuo de la formación inicial del profesional de la Educación en la Universidad de Las Tunas, prestando especial atención a las Redes Sociales de Internet (RSI), las cuales se han convertido en un espacio para el aprendizaje colaborativo. En el presente material se exponen argumentos de las RSI más significativas de corte educativo, las potencialidades y debilidades que presentan en este contexto y el papel del profesor al convertir estas plataformas en espacios de aprendizaje, para lograrlo se ofrecen acciones para lograr su integración. Se utilizó el método de proyectos para incidir favorablemente con este propósito, los resultados obtenidos en la valoración final nos demuestran que los actores de este proceso pueden utilizar las ventajas que ofrecen estas plataformas en aras de favorecer el proceso de enseñanza-aprendizaje del contexto universitario
    corecore