Determinants of CD4 cell count decline after treatment interruption

Patients who had started HAART (Highly Active Anti-Retroviral Treatment) under previous aggressive DHHS guidelines (1997) underwent a life-long continuous HAART that was associated with many short term as well as long term complications. Many interventions attempted to reduce those complications including intermittent treatment also called pulse therapy. Many studies were done to study the determinants of rate of fall in CD4 count after interruption as this data would help guide treatment interruptions. The data set used here was a part of a cohort study taking place at the Johns Hopkins AIDS service since January 1984, in which the data were collected both prospectively and retrospectively. The patients in this data set consisted of 47 patients receiving via pulse therapy with the aim of reducing the long-term complications. ^ The aim of this project was to study the impact of virologic and immunologic factors on the rate of CD4 loss after treatment interruption. The exposure variables under investigation included CD4 cell count and viral load at treatment initiation. The rates of change of CD4 cell count after treatment interruption was estimated from observed data using advanced longitudinal data analysis methods (i.e., linear mixed model). Using random effects accounted for repeated measures of CD4 per person after treatment interruption. The regression coefficient estimates from the model was then used to produce subject specific rates of CD4 change accounting for group trends in change. The exposure variables of interest were age, race, and gender, CD4 cell counts and HIV RNA levels at HAART initiation. ^ The rate of fall of CD4 count did not depend on CD4 cell count or viral load at initiation of treatment. Thus these factors may not be used to determine who can have a chance of successful treatment interruption. CD4 and viral load were again studied by t-tests and ANOVA test after grouping based on medians and quartiles to see any difference in means of rate of CD4 fall after interruption. There was no significant difference between the groups suggesting that there was no association between rate of fall of CD4 after treatment interruption and above mentioned exposure variables. ^

Jean-Martin Charcot - Neurologist by Avocation, Nephrologist by Yearning

In an age of medical advances and specialization, Jean-Martin Charcot (1825-1893) helped found the discipline of neurology and in 1882 was appointed the first professor of Diseases of the Nervous System in France. As an investigator with broad interests and vast knowledge Charcot contributed to several other disciplines. An early mentor and dominant figure in Charcot's formative years was Pierre Rayer (1793-1867), famous for his seminal contributions to the study of the kidney, who gifted Charcot with his passion for clinical pathological correlations and likely a yearning for the study of kidney diseases. Famous for the clarity and incisiveness of his formal teaching presentations, Charcot lectured on the kidney at the Faculty of Medicine in Paris in 1877. Translated into English and published as a book titled Lectures on Bright's Disease, they became widely accessible and quoted in the literature through the present. In addition, at a time that he was already concentrating on the study of neurological disorders, Charcot maintained his life-long interest in the kidney and published original studies on the pathological changes of the kidney in gout and experimental lead poisoning, as well as supporting a study of hysterical ischuria by his students.

Exploring the Impact of Decreased AMPK Pathway Activity on Brain Injury Outcome

Each year, 150 million people sustain a Traumatic Brain Injury (TBI). TBI results in life-long cognitive impairments for many survivors. One observed pathological alteration following TBI are changes in glucose metabolism. Altered glucose uptake occurs in the periphery as well as in the nervous system, with an acute increase in glucose uptake, followed by a prolonged metabolic suppression. Chronic, persistent suppression of brain glucose uptake occurs in TBI patients experiencing memory loss. Abberant post-injury activation of energy-sensing signaling cascades could result in perturbed cellular metabolism. AMP-activated kinase (AMPK) is a kinase that senses low ATP levels, and promotes efficient cell energy usage. AMPK promotes energy production through increasing glucose uptake via glucose transporter 4 (GLUT4). When AMPK is activated, it phosphorylates Akt Substrate of 160 kDa (AS160), a Rab GTPase activating protein that controls Glut4 translocation. Additionally, AMPK negatively regulates energy-consumption by inhibiting protein synthesis via the mechanistic Target of Rapamycin (mTOR) pathway. Given that metabolic suppression has been observed post-injury, we hypothesized that activity of the AMPK pathway is transiently decreased. As AMPK activation increases energy efficiency of the cell, we proposed that increasing AMPK activity to combat the post-injury energy crisis would improve cognitive outcome. Additionally, we expected that inhibiting AMPK targets would be detrimental. We first investigated the role of an existing state of hyperglycemia on TBI outcome, as hyperglycemia correlates with increased mortality and decreased cognitive outcome in clinical studies. Inducing hyperglycemia had no effect on outcome; however, we discovered that AMPK and AS160 phosphorylation were altered post-injury. We conducted vii work to characterize this period of AMPK suppression and found that AMPK phosphorylation was significantly decreased in the hippocampus and cortex between 24 hours and 3 days post-injury, and phosphorylation of its downstream targets was consistently altered. Based on this period of observed decreased AMPK activity, we administered an AMPK activator post-injury, and this improved cognitive outcome. Finally, to examine whether AMPK-regulated target Glut4 is involved in post-injury glucose metabolism, we applied an inhibitor and found this treatment impaired post-injury cognitive function. This work is significant, as AMPK activation may represent a new TBI therapeutic target.

The attention/support to students in the socio-labor transition

In the present paper I intend to put forward some inquiries regarding the socio-labor guidance and transition of the young people in the co-ordinates of contemporary society. The outstanding paradox in which some young people are immersed when trying to get a first, second, third employment is also analyzed: "The job of looking for a job". This is a common experience shared by many young people when they try to find a place in the complex labor panorama. Looking for a job is a recurrent situation in contemporary society, given the high dose of precarious employment in which the productive world moves. Life-long jobs belong to the past and what is normal is that people strive to enter the competitive labor market repeatedly. Moreover, the paper offers the partial results of a larger research project that approaches tutorship, decision taking and expectations before the academic-labor future of the studentship in the last years of secondary school. Finally, I suggest some insights in the line that it is not longer feasible to work with old-fashioned guidance, trying to channel people's vocation and offering them information so that they get a job that provides them with the happiness of "doing what you like". Behind these ideas lay the normal biographies, the predictable itineraries. Labor market complexity makes the transition to working life very difficult. Once immersed in it, biographies and labor itineraries are constructed and reconstructed at the rhythm of the changing fortunes of times.

Theoretical frames for the new tasks in career guidance and counseling

Personal and career development interventions aim to help people find answers to personal and career development issues that stem from the societal context in which they live. Societal definitions of these career issues have a double consequence. On the one hand, these issues differ from one culture to another; and, on the other, they evolve along with the contexts in which they are expressed. Implementation of rigorous career development interventions requires, first, a scientific reconstruction of these societal issues and, second, a clear definition of these interventions' goals and ends. Our current view of the societal issues relating to personal and career development interventions may be phrased thus--"How can we help individuals direct their lives, in the (human) society where they interact?" It may be turned into the following scientific question: "What are the factors and processes of life-long self-construction?" An articulation of three major propositions (sociological, cognitive and dynamic) seems to be needed to answer this question. Such a theoretical frame does not allow for a definition of personal and career development interventions ends. In the world of today, the adoption by everyone of a personal ethic of responsibility towards all life on Earth (H. Jonas) could well be a fundamental end to these interventions.

The attention/support to students in the socio-labor transition

In the present paper I intend to put forward some inquiries regarding the socio-labor guidance and transition of the young people in the co-ordinates of contemporary society. The outstanding paradox in which some young people are immersed when trying to get a first, second, third employment is also analyzed: "The job of looking for a job". This is a common experience shared by many young people when they try to find a place in the complex labor panorama. Looking for a job is a recurrent situation in contemporary society, given the high dose of precarious employment in which the productive world moves. Life-long jobs belong to the past and what is normal is that people strive to enter the competitive labor market repeatedly. Moreover, the paper offers the partial results of a larger research project that approaches tutorship, decision taking and expectations before the academic-labor future of the studentship in the last years of secondary school. Finally, I suggest some insights in the line that it is not longer feasible to work with old-fashioned guidance, trying to channel people's vocation and offering them information so that they get a job that provides them with the happiness of "doing what you like". Behind these ideas lay the normal biographies, the predictable itineraries. Labor market complexity makes the transition to working life very difficult. Once immersed in it, biographies and labor itineraries are constructed and reconstructed at the rhythm of the changing fortunes of times.

Theoretical frames for the new tasks in career guidance and counseling

Personal and career development interventions aim to help people find answers to personal and career development issues that stem from the societal context in which they live. Societal definitions of these career issues have a double consequence. On the one hand, these issues differ from one culture to another; and, on the other, they evolve along with the contexts in which they are expressed. Implementation of rigorous career development interventions requires, first, a scientific reconstruction of these societal issues and, second, a clear definition of these interventions' goals and ends. Our current view of the societal issues relating to personal and career development interventions may be phrased thus--"How can we help individuals direct their lives, in the (human) society where they interact?" It may be turned into the following scientific question: "What are the factors and processes of life-long self-construction?" An articulation of three major propositions (sociological, cognitive and dynamic) seems to be needed to answer this question. Such a theoretical frame does not allow for a definition of personal and career development interventions ends. In the world of today, the adoption by everyone of a personal ethic of responsibility towards all life on Earth (H. Jonas) could well be a fundamental end to these interventions.

The attention/support to students in the socio-labor transition

In the present paper I intend to put forward some inquiries regarding the socio-labor guidance and transition of the young people in the co-ordinates of contemporary society. The outstanding paradox in which some young people are immersed when trying to get a first, second, third employment is also analyzed: "The job of looking for a job". This is a common experience shared by many young people when they try to find a place in the complex labor panorama. Looking for a job is a recurrent situation in contemporary society, given the high dose of precarious employment in which the productive world moves. Life-long jobs belong to the past and what is normal is that people strive to enter the competitive labor market repeatedly. Moreover, the paper offers the partial results of a larger research project that approaches tutorship, decision taking and expectations before the academic-labor future of the studentship in the last years of secondary school. Finally, I suggest some insights in the line that it is not longer feasible to work with old-fashioned guidance, trying to channel people's vocation and offering them information so that they get a job that provides them with the happiness of "doing what you like". Behind these ideas lay the normal biographies, the predictable itineraries. Labor market complexity makes the transition to working life very difficult. Once immersed in it, biographies and labor itineraries are constructed and reconstructed at the rhythm of the changing fortunes of times.

Theoretical frames for the new tasks in career guidance and counseling

Personal and career development interventions aim to help people find answers to personal and career development issues that stem from the societal context in which they live. Societal definitions of these career issues have a double consequence. On the one hand, these issues differ from one culture to another; and, on the other, they evolve along with the contexts in which they are expressed. Implementation of rigorous career development interventions requires, first, a scientific reconstruction of these societal issues and, second, a clear definition of these interventions' goals and ends. Our current view of the societal issues relating to personal and career development interventions may be phrased thus--"How can we help individuals direct their lives, in the (human) society where they interact?" It may be turned into the following scientific question: "What are the factors and processes of life-long self-construction?" An articulation of three major propositions (sociological, cognitive and dynamic) seems to be needed to answer this question. Such a theoretical frame does not allow for a definition of personal and career development interventions ends. In the world of today, the adoption by everyone of a personal ethic of responsibility towards all life on Earth (H. Jonas) could well be a fundamental end to these interventions.

Ouida Sprye Tolbert

Ouida Tolbert began her career at Lincoln University in 1950 as a Supervisory teacher of English, French, Speech, and Drama in the Laboratory High School and as an Associate Professor in the Department of Education. She retired from Lincoln as an Associate Professor of English in 1993. Tolbert was a mentor, role model, and life-long educator. Her dedication to pedagogy and passionate attitude touched many of her students’ and colleagues’ lives. She still contributes to the educating community today.

Somatic mosaicism in Fanconi anemia: Evidence of genotypic reversion in lymphohematopoietic stem cells

Somatic mosaicism has been observed previously in the lymphocyte population of patients with Fanconi anemia (FA). To identify the cellular origin of the genotypic reversion, we examined each lymphohematopoietic and stromal cell lineage in an FA patient with a 2815–2816ins19 mutation in FANCA and known lymphocyte somatic mosaicism. DNA extracted from individually plucked peripheral blood T cell colonies and marrow colony-forming unit granulocyte–macrophage and burst-forming unit erythroid cells revealed absence of the maternal FANCA exon 29 mutation in 74.0%, 80.3%, and 86.2% of colonies, respectively. These data, together with the absence of the FANCA exon 29 mutation in Epstein–Barr virus-transformed B cells and its presence in fibroblasts, indicate that genotypic reversion, most likely because of back mutation, originated in a lymphohematopoietic stem cell and not solely in a lymphocyte population. Contrary to a predicted increase in marrow cellularity resulting from reversion in a hematopoietic stem cell, pancytopenia was progressive. Additional evaluations revealed a partial deletion of 11q in 3 of 20 bone marrow metaphase cells. By using interphase fluorescence in situ hybridization with an MLL gene probe mapped to band 11q23 to identify colony-forming unit granulocyte–macrophage and burst-forming unit erythroid cells with the 11q deletion, the abnormal clone was exclusive to colonies with the FANCA exon 29 mutation. Thus, we demonstrate the spontaneous genotypic reversion in a lymphohematopoietic stem cell. The subsequent development of a clonal cytogenetic abnormality in nonrevertant cells suggests that ex vivo correction of hematopoietic stem cells by gene transfer may not be sufficient for providing life-long stable hematopoiesis in patients with FA.

Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype.

Athymic mice grafted at birth with allogeneic thymic epithelium (TE) from day 10 embryos before hematopoietic cell colonization reconstitute normal numbers of T cells and exhibit full life-long tolerance to skin grafts of the TE haplotype. Intravenous transfers of splenic cells, from these animals to adult syngeneic athymic recipients, reconstitute T-cell compartments and the ability to reject third-party skin grafts. The transfer of specific tolerance to skin grafts of the TE donor strain, however, is not observed in all reconstituted recipients, and the fraction of nontolerant recipients increases with decreasing numbers of cells transferred. Furthermore, transfers of high numbers of total or CD4+ T cells from TE chimeras to T-cell receptor-anti-H-Y antigen transgenic immunocompetent syngeneic hosts specifically hinder the rejection of skin grafts of the TE haplotype that normally occurs in such recipients. These observations demonstrate (i) that mice tolerized by allogeneic TE and bearing healthy skin grafts harbor peripheral immunocompetent T cells capable of rejecting this very same graft; and (ii) that TE selects for regulatory T cells that can inhibit effector activities of graft-reactive cells.

Intervenções de enfermagem na prevenção da pneumonia associada à ventilação mecânica

Relatório de Trabalho de Projeto apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Enfermagem Médico-cirúrgica

Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model.

The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.

Transition bei angeborenen Herzfehlern in der Schweiz

Die Chance, mit einem angeborenen Herzfehler erwachsen zu werden, liegt mittlerweile bei über 90 %. Trotz aller Erfolge der Medizin können Herzfehler auch nach erfolgreicher Korrektur nicht als geheilt betrachtet werden. Langzeitkomplikationen im Sinn von Herzrhythmusstörungen, Herzinsuffizienz, embolischen Ereignissen, Endokarditis, oder Reoperationen aufgrund residualer Befunde oder Klappendegenerationen sind häufig. Aus diesem Grund wird für eine Vielzahl angeborener Herzfehler eine lebenslange spezialisierte Betreuung empfohlen. Jugendliche mit Herzfehlern müssen darauf vorbereitet werden, im Erwachsenenalter Eigenverantwortung zu übernehmen. Dazu ist eine strukturierte Transition ein entscheidender Vorteil. Dadurch werden einerseits Jugendliche selbst auf ihre Erwachsenenrolle vorbereitet und andererseits kann ein adäquater Transfer der Betreuung vom Kinder- zum Erwachsenenmediziner gewährleistet werden. Jugendliche ohne Transfer und ohne spezialisierte Betreuung im Erwachsenenalter haben ein erhöhtes Risiko, kardiovaskuläre Komplikationen zu erleiden. Es wurde gezeigt, dass die Mortalität bei angeborenen Herzfehlern bei Erwachsenen mit spezialisierter Betreuung geringer ist als bei Patienten ohne entsprechende Betreuung. Am Beispiel des Zentrums für angeborene Herzfehler in Bern wird aufgezeigt, wie eine pflegegeleitete Transitionssprechstunde aufgebaut und erfolgreich umgesetzt werden kann.