26 research outputs found

    Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays

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    CpG island arrays represent a high-throughput epigenomic discovery platform to identify global disease-specific promoter hypermethylation candidates along bladder cancer progression. DNA obtained from 10 pairs of invasive bladder tumours were profiled vs their respective normal urothelium using differential methylation hybridisation on custom-made CpG arrays (n=12 288 clones). Promoter hypermethylation of 84 clones was simultaneously shown in at least 70% of the tumours. SOX9 was selected for further validation by bisulphite genomic sequencing and methylation-specific polymerase chain reaction in bladder cancer cells (n=11) and primary bladder tumours (n=101). Hypermethylation was observed in bladder cancer cells and associated with lack of gene expression, being restored in vitro by a demethylating agent. In primary bladder tumours, SOX9 hypermethylation was present in 56.4% of the cases. Moreover, SOX9 hypermethylation was significantly associated with tumour grade and overall survival. Thus, this high-throughput epigenomic strategy has served to identify novel hypermethylated candidates in bladder cancer. In vitro analyses supported the role of methylation in silencing SOX9 gene. The association of SOX9 hypermethylation with tumour progression and clinical outcome suggests its relevant clinical implications at stratifying patients affected with bladder cancer

    Developing a competency-based curriculum in HIV for nursing schools in Haiti

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    <p>Abstract</p> <p>Background</p> <p>Preparing health workers to confront the HIV/AIDS epidemic is an urgent challenge in Haiti, where the HIV prevalence rate is 2.2% and approximately 10 100 people are taking antiretroviral treatment. There is a critical shortage of doctors in Haiti, leaving nurses as the primary care providers for much of the population. Haiti's approximately 1000 nurses play a leading role in HIV/AIDS prevention, care and treatment. However, nurses do not receive sufficient training at the pre-service level to carry out this important work.</p> <p>Methods</p> <p>To address this issue, the Ministry of Health and Population collaborated with the International Training and Education Center on HIV over a period of 12 months to create a competency-based HIV/AIDS curriculum to be integrated into the 4-year baccalaureate programme of the four national schools of nursing.</p> <p>Results</p> <p>Using a review of the international health and education literature on HIV/AIDS competencies and various models of curriculum development, a Haiti-based curriculum committee developed expected HIV/AIDS competencies for graduating nurses and then drafted related learning objectives. The committee then mapped these learning objectives to current courses in the nursing curriculum and created an 'HIV/AIDS Teaching Guide' for faculty on how to integrate and achieve these objectives within their current courses. The curriculum committee also created an 'HIV/AIDS Reference Manual' that detailed the relevant HIV/AIDS content that should be taught for each course.</p> <p>Conclusion</p> <p>All nursing students will now need to demonstrate competency in HIV/AIDS-related knowledge, skills and attitudes during periodic assessment with direct observation of the student performing authentic tasks. Faculty will have the responsibility of developing exercises to address the required objectives and creating assessment tools to demonstrate that their graduates have met the objectives. This activity brought different administrators, nurse leaders and faculty from four geographically dispersed nursing schools to collaborate on a shared goal using a process that could be easily replicated to integrate any new topic in a resource-constrained pre-service institution. It is hoped that this experience provided stakeholders with the experience, skills and motivation to strengthen other domains of the pre-service nursing curriculum, improve the synchronization of didactic and practical training and develop standardized, competency-based examinations for nursing licensure in Haiti.</p

    Principal component analysis of ensemble recordings reveals cell assemblies at high temporal resolution

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    Simultaneous recordings of many single neurons reveals unique insights into network processing spanning the timescale from single spikes to global oscillations. Neurons dynamically self-organize in subgroups of coactivated elements referred to as cell assemblies. Furthermore, these cell assemblies are reactivated, or replayed, preferentially during subsequent rest or sleep episodes, a proposed mechanism for memory trace consolidation. Here we employ Principal Component Analysis to isolate such patterns of neural activity. In addition, a measure is developed to quantify the similarity of instantaneous activity with a template pattern, and we derive theoretical distributions for the null hypothesis of no correlation between spike trains, allowing one to evaluate the statistical significance of instantaneous coactivations. Hence, when applied in an epoch different from the one where the patterns were identified, (e.g. subsequent sleep) this measure allows to identify times and intensities of reactivation. The distribution of this measure provides information on the dynamics of reactivation events: in sleep these occur as transients rather than as a continuous process

    Disruption of the Lipid-Transporting LdMT-LdRos3 Complex in Leishmania donovani Affects Membrane Lipid Asymmetry but Not Host Cell Invasion

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    Maintenance and regulation of the asymmetric lipid distribution across eukaryotic plasma membranes is governed by the concerted action of specific membrane proteins controlling lipid movement across the bilayer. Here, we show that the miltefosine transporter (LdMT), a member of the P4-ATPase subfamily in Leishmania donovani, and the Cdc50-like protein LdRos3 form a stable complex that plays an essential role in maintaining phospholipid asymmetry in the parasite plasma membrane. Loss of either LdMT or LdRos3 abolishes ATP-dependent transport of NBD-labelled phosphatidylethanolamine (PE) and phosphatidylcholine from the outer to the inner plasma membrane leaflet and results in an increased cell surface exposure of endogenous PE. We also find that promastigotes of L. donovani lack any detectable amount of phosphatidylserine (PS) but retain their infectivity in THP-1-derived macrophages. Likewise, infectivity was unchanged for parasites without LdMT-LdRos3 complexes. We conclude that exposure of PS and PE to the exoplasmic leaflet is not crucial for the infectivity of L. donovani promastigotes

    Elastofibroma dorsi – differential diagnosis in chest wall tumours

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    BACKGROUND: Elastofibromas are benign soft tissue tumours mostly of the infrascapular region between the thoracic wall, the serratus anterior and the latissimus dorsi muscle with a prevalence of up to 24% in the elderly. The pathogenesis of the lesion is still unclear, but repetitive microtrauma by friction between the scapula and the thoracic wall may cause the reactive hyperproliferation of fibroelastic tissue. METHODS: We present a series of seven cases with elastofibroma dorsi with reference to clinical findings, further clinical course and functional results after resection, as well as recurrence. Data were obtained retrospectively by clinical examination, phone calls to the patients' general practitioners and charts review. Follow-up time ranged from four months to nine years and averaged 53 months. RESULTS: The patients presented with swelling of the infrascapular region or snapping scapula. In three cases, the lesion was painful. The ratio men/women was 2/5 with a mean age of 64 years. The tumor sizes ranged from 3 to 13 cm. The typical macroscopic aspect was characterized as poorly defined fibroelastic soft tissue lesion with a white and yellow cut surface caused by intermingled remnants of fatty tissue. Microscopically, the lesions consisted of broad collagenous strands and densely packed enlarged and fragmented elastic fibres with mostly round shapes. In all patients but one, postoperative seroma (which had to be punctuated) occurred after resection; however, at follow-up time, no patient reported any decrease of function or sensation at the shoulder or the arm of the operated side. None of the patients experienced a relapse. CONCLUSION: In differential diagnosis of soft tissue tumors located at this specific site, elastofibroma should be considered as likely diagnosis. Due to its benign behaviour, the tumor should be resected only in symptomatic patients
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