Age of Child, More than HPV Type, Is Associated with Clinical Course in Recurrent Respiratory Papillomatosis

Background: RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Methodology/Principal Findings: Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fisher's exact p = 0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p = 0.014). Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. Conclusions/Significance Abstract: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

Gene silencing during development of in vitro-produced female bovine embryos

In early development, female embryos (XX) produce twice the transcripts of X-linked genes compared with male embryos (XY). During the course of development, inactivation of the X chromosome equilibrates gene dosage, making the development of female embryos viable. Moreover, the biotechnologies used for producing embryos in vitro seem to work better with male embryos, making it easier for them to reach the blastocyst stage and allow for complete gestation. We investigated the expression of three X-linked genes that are involved in development, XIST, G6PD, and HPRT, and of the transcript interferon-tau, in male and female bovine blastocysts produced by nuclear transfer (NT) and by in vitro fertilization (IVF). Oocytes that had been matured in vitro were enucleated and reconstructed with somatic cells from adult animals at 18 h post-maturation. After fusion (two pulses of 2.25 kv/cm) and chemical activation (5.0 mu M ionomycin for 5 min and 2.0 mM 6-DMAP for 3 h), the oocytesomatic cell units were cultivated in CR2 with a monolayer of granulosa cells at 38.8 degrees C, in a humidified 5% CO(2) atmosphere. IVF embryos were inseminated, after centrifugation in a Percoll gradient, with 2 x 10(6) sperm/mL TALP medium supplemented with BSA and PHE and cultivated under the same conditions as the cloned embryos. We used real-time PCR to analyze the gene expression of individual blastocysts compared to expression of the housekeeping gene, GAPDH. The gene XIST was expressed in female embryos and not in male embryos produced by IVF, though it was expressed at low levels in male embryos produced by NT. Unlike previous reports, we found lower levels of the transcript of G6PD in females than in males, suggesting double silencing or other mechanisms of control of this gene. Female embryos produced by IVF expressed the HPRT gene at a higher level than female embryos produced by NT, suggesting that gene silencing proceeds faster in NT-produced female embryos due to ""inactivation memory"" from the nucleus donor. In conclusion, male and female embryos express different levels of X-chromosome genes and failures of these genes that are essential for development could reduce the viability of females. Nuclear transfer can modify this relation, possibly due to epigenetic memory, leading to frequent failures in nuclear reprogramming.

Trypanosoma cruzi: The effects of zinc supplementation in the immune response during the course of experimental disease

Zinc is an essential nutritional component required for normal development and maintenance of immune functions. The possible effects of zinc in upregulating the host immune response during the acute and chronic phases of experimental Chagas` disease were evaluated. In young, infected and Zn-supplemented animals, higher concentrations of IFN-gamma and NO were observed. During the chronic phase, decreased concentrations of NO and IFN-gamma were found for older infected animals that received Zn supplementation. For young animals, hearts from Zn-supplemented groups displayed reduced inflammatory infiltrate, heart weight and number of amastigote burdens. For older, infected and Zn-supplemented animals amastigote nests were absent with reduced inflammatory cell infiltrate. This study identifies a potentially novel therapeutic approach that could control the parasite load during acute phase of disease, consequently preventing the deleterious, parasite-elicited responses observed during chronic phase. (C) 2008 Elsevier Inc. All rights reserved.

Closing the gap in curriculum development leadership

“Closing the gap in curriculum development leadership” is a Carrick-funded University of Queensland project which is designed to address two related gaps in current knowledge and in existing professional development programs for academic staff. The first gap is in our knowledge of curriculum and pedagogical issues as they arise in relation to multi-year sequences of study, such as majors in generalist degrees, or core programs in more structured degrees. While there is considerable knowledge of curriculum and pedagogy at the course or individual unit of study level (e.g. Philosophy I), there is very little properly conceptualised, empirically informed knowledge about student learning (and teaching) over, say, a three-year major sequence in a traditional Arts or Sciences subject. The Carrick-funded project aims to (begin to) fill this gap through bottom-up curriculum development projects across the range of UQ’s offerings. The second gap is in our professional development programs and, indeed, in our recognition and support for the people who are in charge of such multi-year sequences of study. The major convener or program coordinator is not as well supported, in Australian and overseas professional development programs, as the lecturer in charge of a single course (or unit of study). Nor is her work likely to be taken account of in workload calculations or for the purposes of promotion and career advancement more generally. The Carrick-funded project aims to fill this gap by developing, in consultation with crucial stakeholders, amendments to existing university policies and practices. The attached documents provide a useful introduction to the project. For more information, please contact Fred D’Agostino at f.dagostino@uq.edu.au.

Career development and systems theory: Connecting theory and practice

The Systems Theory Framework was developed to produce a metatheoretical framework through which the contribution of all theories to our understanding of career behaviour could be recognised. In addition it emphasises the individual as the site for the integration of theory and practice. Its utility has become more broadly acknowledged through its application to a range of cultural groups and settings, qualitative assessment processes, career counselling, and multicultural career counselling. For these reasons, the STF is a very valuable addition to the field of career theory. In viewing the field of career theory as a system, open to changes and developments from within itself and through constantly interrelating with other systems, the STF and this book is adding to the pattern of knowledge and relationships within the career field. The contents of this book will be integrated within the field as representative of a shift in understanding existing relationships within and between theories. In the same way, each reader will integrate the contents of the book within their existing views about the current state of career theory and within their current theory-practice relationship. This book should be required reading for anyone involved in career theory. It is also highly suitable as a text for an advanced career counselling or theory course.

The influence of glutathione modulators on the course of Leishmania major infection in susceptible and resistant mice

Glutathione (GSH) has an important dual role in parasite-host relationship in Leishmania major infection. Our previous studies showed that both antioxidant systems, glutathione and trypanothione/trypanothione reductase, participate in the protection of Leishmania against the toxic effect of nitrogen-derived reactive species. On the other hand, GSH also is very important to the modulation of the effective immune response, inducting NO production and leishmanicidal activity of macrophages. In the present study, we investigated the role of host GSH during the course of L. major infection, analysing the size of footpad lesions and parasite load from mice treated with two GSH modulators, N-acethyl-L-cysteine (NAC) and buthionine sulphoximine (BSO). Resistant mice treated with BSO, which depletes GSH develop exacerbated lesions, but only harbour higher parasite load in their lesions 2 weeks post-infection. Although the NAC treatment does not affect the footpad lesions development in susceptible BALB/c mice, it significantly reduced the tissue parasitism in the lesions throughout the course of infection. Interestingly, the treatment with BSO did not change the course of L. major infection on susceptible mice when compared with nontreated mice. These results suggest that GSH is an important antioxidant modulator during anti-Leishmania immune response in vivo.

Development of a platform for lean manufacturing simulation games

More than ever, the economic globalization is creating the need to increase business competitiveness. Lean manufacturing is a management philosophy oriented to the elimination of activities that do not create any type of value and are thus considered a waste. One of the main differences from other management philosophies is the shop-floor focus and the operators' involvement. Therefore, the training of all organization levels is crucial for the success of lean manufacturing. Universities should also participate actively in this process by developing students' lean management skills and promoting a better and faster integration of students into their future organizations. This paper proposes a single realistic manufacturing platform, involving production and assembly operations, to learn by playing many of the lean tools such as VSM, 5S, SMED, poke-yoke, line balance, TPM, Mizusumashi, plant layout, and JIT/kanban. This simulation game was built in tight cooperation with experienced lean companies under the international program “Lean Learning Academy,”http://www.leanlearningacademy.eu/ and its main aim is to make bachelor and master courses in applied sciences more attractive by integrating classic lectures with a simulated production environment that could result in more motivated students and higher study yields. The simulation game results show that our approach is efficient in providing a realistic platform for the effective learning of lean principles, tools, and mindset, which can be easily included in course classes of less than two hours.

Towards Active Course Marks for Autonomous Sailing Competitions

This paper describes the environmental monitoring / regatta beacon buoy under development at the Laboratory of Autonomous Systems (LSA) of the Polytechnic Institute of Porto. On the one hand, environmentalmonitoring of open water bodies in real or deferred time is essential to assess and make sensible decisions and, on the other hand, the broadcast in real time of position, water and wind related parameters allows autonomous boats to optimise their regatta performance. This proposal, rather than restraining the boats autonomy, fosters the development of intelligent behaviour by allowing the boats to focus on regatta strategy and tactics. The Nautical and Telemetric Application (NAUTA) buoy is a dual mode reconfigurable system that includes communications, control, data logging, sensing, storage and power subsystems. In environmental monitoring mode, the buoy gathers and stores data from several underwater and above water sensors and, in regatta mode, the buoy becomes an active course mark for the autonomous sailing boats in the vicinity. During a race, the buoy broadcasts its position, together with the wind and the water current local conditions, allowing autonomous boats to navigate towards and round the mark successfully. This project started with the specification of the requirements of the dual mode operation, followed by the design and building of the buoy structure. The research is currently focussed on the development of the modular, reconfigurable, open source-based control system. The NAUTA buoy is innovative, extensible and optimises the on board platform resources.

Introducing numerical analysis tools in engineering: a Scilab user case in electronics course

Software tools in education became popular since the widespread of personal computers. Engineering courses lead the way in this development and these tools became almost a standard. Engineering graduates are familiar with numerical analysis tools but also with simulators (e.g. electronic circuits), computer assisted design tools and others, depending on the degree. One of the main problems with these tools is when and how to start use them so that they can be beneficial to students and not mere substitutes for potentially difficult calculations or design. In this paper a software tool to be used by first year students in electronics/electricity courses is presented. The growing acknowledgement and acceptance of open source software lead to the choice of an open source software tool – Scilab, which is a numerical analysis tool – to develop a toolbox. The toolbox was developed to be used as standalone or integrated in an e-learning platform. The e-learning platform used was Moodle. The first approach was to assess the mathematical skills necessary to solve all the problems related to electronics and electricity courses. Analysing the existing circuit simulators software tools, it is clear that even though they are very helpful by showing the end result they are not so effective in the process of the students studying and self learning since they show results but not intermediate steps which are crucial in problems that involve derivatives or integrals. Also, they are not very effective in obtaining graphical results that could be used to elaborate reports and for an overall better comprehension of the results. The developed tool was based on the numerical analysis software Scilab and is a toolbox that gives their users the opportunity to obtain the end results of a circuit analysis but also the expressions obtained when derivative and integrals calculations, plot signals, obtain vector diagrams, etc. The toolbox runs entirely in the Moodle web platform and provides the same results as the standalone application. The students can use the toolbox through the web platform (in computers where they don't have installation privileges) or in their personal computers by installing both the Scilab software and the toolbox. This approach was designed for first year students from all engineering degrees that have electronics/electricity courses in their curricula.

Challenges in the creation and development of a mathematics MOOC

The fast development of distance learning tools such as Open Educational Resources (OER) and Massive Open Online Courses (MOOC or MOOCs) are indicators of a shift in the way in which digital teaching and learning are understood. MOOC are a new style of online classes that allow any person with web access, anywhere, usually free of charge, to participate through video lectures, computer graded tests and discussion forums. They have been capturing the attention of many higher education institutions around the world. This paper will give us an overview of the “Introduction to Differential Calculus” a MOOC Project, created by an engaged volunteer team of Mathematics lecturers from four schools of the Polytechnic Institute of Oporto (IPP). The MOOC theories and their popularity are presented and complemented by a discussion of some MOOC definitions and their inherent advantages and disadvantages. It will also explore what MOOC mean for Mathematics education. The Project development is revealed by focusing on used MOOC structure, as well as the quite a lot of types of course materials produced. It ends with a presentation of a short discussion about problems and challenges met throughout the development of the project. It is also our goal to contribute for a change in the way teaching and learning Mathematics is seen and practiced nowadays, trying to make education more accessible to as many people as possible and increase our institution (IPP) recognition.

A Communication Intervention for Training Southern European Oncologists to Recognize Psychosocial Morbidity in Cancer. I - Development of the Model and Preliminary Results on Physicians' Satisfaction

BACKGROUND: The detection of psychosocial distress is a significant communication problem in Southern Europe and other countries. Work in this area is hampered by a lack of data. Because not much is known about training aimed at improving the recognition of psychosocial disorders in cancer patients, we developed a basic course model for medical oncology professionals. METHODS: A specific educational and experiential model (12 hours divided into 2 modules) involving formal teaching (ie, journal articles, large-group presentations), practice in small groups (ie, small-group exercises and role playing), and discussion in large groups was developed with the aim of improving the ability of oncologists to detect emotional disturbances in cancer patients (ie, depression, anxiety, and adjustment disorders). RESULTS: A total of 30 oncologists from 3 Southern European countries (Italy, Portugal, and Spain) participated in the workshop. The training course was well accepted by most participants who expressed general satisfaction and a positive subjective perception of the utility of the course for clinical practice. Of the total participants, 28 physicians (93.3%) thought that had they been exposed to this material sooner, they would have incorporated the techniques received in the workshop into their practices; 2 participants stated they would likely have done so. Half of the doctors (n = 15) believed that their clinical communication techniques were improved by participating in the workshop, and the remaining half thought that their abilities to communicate with cancer patients had improved. CONCLUSIONS: This model is a feasible approach for oncologists and is easily applicable to various oncology settings. Further studies will demonstrate the effectiveness of this method for improving oncologists skills in recognizing emotional disorders in their patients with cancer.

The Support Role in Clinical Supervision of Nursing Students: Determinant in the Development of Emotional Skills

The problematic situation faced by clients, associated to the processes of health and disease, is expressed through emotions that nursing students have to deal with in the course of care and their formative experiences in clinical teaching. Students have learning needs not only to manage emotions in the context of customer care, but also in terms of their own internal world, emotional conflicts, emotional stress and burn-out. With the present literature review, we intend to explore existing evidence regarding the ways in which the nurse supervisor's support towards nursing students potentiates the development of their competences for the performance of emotional labour. These skills prove to be the key in the ability to manage the emotionally intense situations of care practice and the support function of the nursing supervisor contributes to the development of such competences.

Reduction of spleen size in a child with Hyperreactive Malarious Splenomegaly (HMS) treated outside the Brazilian endemic area of malaria with only one course of quinine

We report the clinical picture, treatment and evolution of a child with hyperreactive malarious splenomegaly treated outside the endemic area of malaria. The patient presented gross splenomegaly, proceeded from an area where malaria is endemic, showed increased immunoglobulins levels, high antimalarial antibody titres and hepatic sinusoidal lymphocytosis. The child did not return to an area where malaria is endemic and showed a favorable response to only one course of quinine. The response of this patient to limited antimalarial therapy suggests the importance of reinfection with malaria in the development and maintenance of this syndrome.

Interaction of malaria parasites with host late endocytic and autophagic pathways is essential for Plasmodium liver stage development

RESUMO: A Malária é causada por parasitas do género Plasmodium, sendo a doença parasitária mais fatal para o ser humano. Apesar de, durante o século passado, o desenvolvimento económico e a implementação de diversas medidas de controlo, tenham permitido erradicar a doença em muitos países, a Malária continua a ser um problema de saúde grave, em particular nos países em desenvolvimento. A Malária é transmitida através da picada de uma fêmea de mosquito do género Anopheles. Durante a picada, os esporozoítos são injetados na pele do hospedeiro, seguindo-se a fase hepática e obrigatória do ciclo de vida. No fígado, os esporozoítos infetam os hepatócitos onde se replicam, dentro de um vacúolo parasitário (VP) e de uma forma imunitária silenciosa, em centenas de merozoitos. Estas novas formas do parasita são as responsáveis por infetar os eritrócitos, iniciando a fase sanguínea da doença, onde se os primeiros sintomas se manifestam, tais como a característica febre cíclica. A fase hepática da doença é a menos estudada e compreendida. Mais ainda, as interações entre o VP e os organelos da células hospedeira estão ainda pouco caracterizados. Assim, neste estudo, as interações entre os organelos endocíticos e autofágicos da célula hospedeira e o VP foram dissecados, observando-se que os anfisomas, que são organelos resultantes da intersecção do dois processos de tráfego intracelular, interagem com o parasita. Descobrimos que a autofagia tem também uma importante função imunitária durante a fase hepática inicial, ao passo, que durante o desenvolvimento do parasita, já numa fase mais tardia, o parasita depende da interação com os endossomas tardios e anfisomas para crescer. Vesiculas de BSA, EGF e LC3, foram, também, observadas dentro do VP, sugerindo que os parasitas são capazes de internalizar material endocítico e autofágico do hospedeiro. Mais ainda, mostramos que esta interação depende da cinase PIKfyve, responsável pela conversão do fosfoinositidio-3-fosfato no fosfoinositidio-3,5-bifosfato, uma vez que inibindo esta cinase o parasita não é capaz de crescer normalmente. Finalmente, mostramos que a proteína TRPML1, uma proteína efetora do fosfoinositidio-3,5-bifosfato, e envolvida no processo de fusão das membranas dos organelos endocíticos e autofágicos, também é necessária para o crescimento do parasita. Desta forma, o nosso estudo sugere que a membrana do VP funde com vesiculas endocíticas e autofágicas tardias, de uma forma dependente do fositidio-3,5-bifosfato e do seu effetor TRPML1, permitindo a troca de material com a célula hospedeira. Concluindo, os nossos resultados evidenciam que o processo autofágico que ocorre na célula hospedeira tem um papel duplo durante a fase hepática da malaria. Enquanto numa fase inicial os hepatócitos usam o processo autofágico como forma de defesa contra o parasita, já durante a fase de replicação o VP funde com vesiculas autofágicas e endocíticas de forma a obter os nutrientes necessários ao seu desenvolvimento.--------- ABSTRACT: Malaria, which is caused by parasites of the genus Plasmodium, is the most deadly parasitic infection in humans. Although economic development and the implementation of control measures during the last century have erradicated the disease from many areas of the world, it remains a serious human health issue, particularly in developing countries. Malaria is transmitted by female mosquitoes of the genus Anopheles. During the mosquito blood meal, Plasmodium spp. sporozoites are injected into the skin dermis of the vertebrate host, followed by an obligatory liver stage. Upon entering the liver, Plasmodium parasites infect hepatocytes and silently replicate inside a host cell-derived parasitophorous vacuole (PV) into thousands of merozoites. These new parasite forms can infect red blood cells initiating the the blood stage of the disease which shows the characteristic febrile malaria episodes. The liver stage is the least characterized step of the malaria infection. Moreover, the interactions between the Plasmodium spp. PV and the host cell trafficking pathways are poorly understood. We dissected the interaction between Plasmodium parasites and the host cell endocytic and autophagic pathways and we found that both pathways intersect and interconnect in the close vicinity of the parasite PV, where amphisomes are formed and accumulate. Interestingly, we observed a clearance function for autophagy in hepatocytes infected with Plasmodium berghei parasites at early infection times, whereas during late liver stage development late endosomes and amphisomes are required for parasite growth. Moreover, we found the presence of internalized BSA, EGF and LC3 inside parasite vacuoles, suggesting that the parasites uptake endocytic and autophagic cargo. Furthermore, we showed that the interaction between the PV and host traffic pathways is dependent on the kinase PIKfyve, which converts the phosphoinositide PI(3)P into PI(3,5)P2, since PIKfyve inhibition caused a reduction in parasite growth. Finally, we showed that the PI(3,5)P2 effector protein TRPML1, which is involved in late endocytic and autophagic membrane fusion, is also required for parasite development. Thus, our studies suggest that the parasite parasitophorous vacuole membrane (PVM) is able to fuse with late endocytic and autophagic vesicles in a PI(3,5)P2- and TRPML1-dependent manner, allowing the exchange of material between the host cell and the parasites, necessary for the rapid development of the latter that is seen during the liver stage of infection. In conclusion, we present evidence supporting a specific and essential dual role of host autophagy during the course of Plasmodium liver infection. Whereas in the initial hours of infection the host cell uses autophagy as a cell survival mechanism to fight the infection, during the replicative phase the PV fuses with host autophagic and endocytic vesicles to obtain nutrients required for parasite growth.

Longitudinal evaluation, acceptability and long-term retention of knowledge on a horizontally integrated organic and functional systems course

Undergraduate medical education is moving from traditional disciplinary basic science courses into more integrated curricula. Integration models based on organ systems originated in the 1950s, but few longitudinal studies have evaluated their effectiveness. This article outlines the development and implementation of the Organic and Functional Systems (OFS) courses at the University of Minho in Portugal, using evidence collected over 10 years. It describes the organization of content, student academic performance and acceptability of the courses, the evaluation of preparedness for future courses and the retention of knowledge on basic sciences. Students consistently rated the OFS courses highly. Physician tutors in subsequent clinical attachments considered that students were appropriately prepared. Performance in the International Foundations of Medicine examination of a self-selected sample of students revealed similar performances in basic science items after the last OFS course and 4 years later, at the moment of graduation. In conclusion, the organizational and pedagogical approaches of the OFS courses achieve high acceptability by students and result in positive outcomes in terms of preparedness for subsequent training and long-term retention of basic science knowledge.