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Find video protocols related to scientific articles indexed in Pubmed.
[Conservation and natural history around 1900: the contribution of the Sarasin cousins].
Gesnerus
PUBLISHED: 09-20-2014
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Some basic concepts for the creation of the Swiss National Park were derived from observations made in Sri Lanka, Indonesia and New Caledonia. European researchers feared that the study of "virgin nature" would no longer be possible, as various species would soon become extinct under the combined influences of colonial practices and profit-oriented capitalism. While the motives for protecting nature originated from experiences made in the southern hemisphere, their scientific concept of conservation was based on European natural history and the related theories of evolution. In the light of this approach, endangered zoological and botanical species as well as "primitive" varieties of man were appreciated as "documents" to be preserved within their original environment for future scientific reference and research. Museum collections and reservations (parks) were two types of repositories connected to each other by the same objective.
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Using an iconic language to improve access to electronic medical records in general medicine.
Stud Health Technol Inform
PUBLISHED: 08-28-2014
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Physicians have difficulties to access and analyse information in a medical record. In a previous work on drug databanks, we have shown that with an iconic language as VCM, an icon-based presentation can help physicians to access medical information. Our objective, herein, is to study whether VCM can be used in an electronic medical record for facilitating physician access in general practice. We identify the data and the functionalities of an electronic medical record that could benefit from VCM icons representing clinical findings, patient history, etc. We also present a preliminary evaluation of this new icon-focused interface. We conclude by discussing the results like the assessment of the user's satisfaction and pointing out the importance of coding data.
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Delayed presentation of deep penetrating trauma to the subaxial cervical spine.
Eur Spine J
PUBLISHED: 08-08-2014
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To present a rare case of deep penetrating neck trauma in which a retained foreign body in the cervical spine (a broken knife blade) resulted in delayed radicular injury. We describe the surgical management using a retrojugular approach.
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Use of combined suspension laryngoscopy and jet ventilation for Y-shaped airway stents delivery.
Ann. Thorac. Surg.
PUBLISHED: 06-03-2014
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Airway stenting is a common endoscopic procedure that is used to treat a variety of central airway lesions. Obstructions or fistulas involving the carina or nearby tracheobronchial structures require the use of specially designed stents, commonly referred to as Y-stents. Conventional methods of endobronchial Y-stent delivery are all characterized by a blind and apneic period during the procedure that carries the risk of stent misplacement or ventilation/oxygenation problems or both. Using combined suspension laryngoscopy, flexible bronchoscopy, and jet ventilation, we describe a technique that makes challenging bronchoscopic interventions--such as self-expandable Y-shaped airway stent delivery--easy, precise, and safe.
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Acute neurorehabilitation: does a neurosensory and coordinated interdisciplinary programme reduce tracheostomy weaning time and weaning failure?
NeuroRehabilitation
PUBLISHED: 05-03-2014
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A new coordinated interdisciplinary unit was created in the acute section of the department of clinical neurosciences, the Acute NeuroRehabilitation (NRA) unit. The objective was to evaluate the impact of the unit and its neurosensory programme on the management of tracheostomy patients in terms of reduction in the average time taken for weaning, weaning success rate and therapeutic efficiency.
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The Effect of Receiving Treatment Within a Clinical Trial Setting on Survival and Quality of Care Perception in Advanced Stage Non-Small Cell Lung Cancer.
Am. J. Clin. Oncol.
PUBLISHED: 03-18-2014
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Treatment outcomes of advanced stage (IIIB and IV) non-small cell lung cancer (NSCLC) are poor. In this study, we explore the survival outcomes and the perception of the quality of care delivered in stage IIIB and IV NSCLC patients treated within versus outside a clinical trial.
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Clinicobiological progression and prognosis of oral squamous cell carcinoma in relation to the tumor invasive front: impact on prognosis.
Acta Otolaryngol.
PUBLISHED: 03-18-2014
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There are several factors that influence the final outcome when treating oral squamous cell carcinoma (OSCC). Invasive front phenomena and more importantly their clinicopathological translation can have a direct impact on survival, and subsequently on the decision for an adjuvant treatment.
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Presynaptic Localization of Smn and hnRNP R in Axon Terminals of Embryonic and Postnatal Mouse Motoneurons.
PLoS ONE
PUBLISHED: 01-01-2014
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Spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motoneuron (SMN) protein. SMN is crucial component of a complex for the assembly of spliceosomal small nuclear ribonucleoprotein (snRNP) particles. Other cellular functions of SMN are less characterized so far. SMA predominantly affects lower motoneurons, but the cellular basis for this relative specificity is still unknown. In contrast to nonneuronal cells where the protein is mainly localized in perinuclear regions and the nucleus, Smn is also present in dendrites, axons and axonal growth cones of isolated motoneurons in vitro. However, this distribution has not been shown in vivo and it is not clear whether Smn and hnRNP R are also present in presynaptic axon terminals of motoneurons in postnatal mice. Smn also associates with components not included in the classical SMN complex like RNA-binding proteins FUS, TDP43, HuD and hnRNP R which are involved in RNA processing, subcellular localization and translation. We show here that Smn and hnRNP R are present in presynaptic compartments at neuromuscular endplates of embryonic and postnatal mice. Smn and hnRNP R are localized in close proximity to each other in axons and axon terminals both in vitro and in vivo. We also provide new evidence for a direct interaction of Smn and hnRNP R in vitro and in vivo, particularly in the cytosol of motoneurons. These data point to functions of SMN beyond snRNP assembly which could be crucial for recruitment and transport of RNA particles into axons and axon terminals, a mechanism which may contribute to SMA pathogenesis.
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Characterizing the human hematopoietic CDome.
Front Genet
PUBLISHED: 01-01-2014
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In this study, we performed extensive semi-automated data collection from the primary and secondary literature in an effort to characterize the expression of all membrane proteins within the CD scheme on hematopoietic cells. Utilizing over 6000 data points across 305 CD molecules on 206 cell types, we seek to give a preliminary characterization of the "human hematopoietic CDome." We encountered severe gaps in the knowledge of CD protein expression, mostly resulting from incomplete and unstructured data generation, which we argue inhibit both basic research as well as therapies seeking to target membrane proteins. We detail these shortcomings and propose strategies to overcome these issues. Analyzing the available data, we explore the functional characteristics of the CD molecules both individually and across the groups of hematopoietic cells on which they are expressed. We compare protein and mRNA data for a subset of CD molecules, and explore cell functions in the context of CD protein expression. We find that the presence and function of CD molecules serve as good indicators for the overall function of the cells that express them, suggesting that increasing our knowledge about the cellular CDome may serve to stratify cells on a more functional level.
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Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin - implications for cross-reactivity of neutralizing antibodies.
Front Immunol
PUBLISHED: 01-01-2014
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Influenza viruses continue to cause substantial morbidity and mortality worldwide. Fast gene mutation on surface proteins of influenza virus result in increasing resistance to current vaccines and available antiviral drugs. Broadly neutralizing antibodies (bnAbs) represent targets for prophylactic and therapeutic treatments of influenza. We performed a systematic bioinformatics study of cross-reactivity of neutralizing antibodies (nAbs) against influenza virus surface glycoprotein hemagglutinin (HA). This study utilized the available crystal structures of HA complexed with the antibodies for the analysis of tens of thousands of HA sequences. The detailed description of B-cell epitopes, measurement of epitope area similarity among different strains, and estimation of antibody neutralizing coverage provide insights into cross-reactivity status of existing nAbs against influenza virus. We have developed a method to assess the likely cross-reactivity potential of bnAbs for influenza strains, either newly emerged or existing. Our method catalogs influenza strains by a new concept named discontinuous peptide, and then provide assessment of cross-reactivity. Potentially cross-reactive strains are those that share 100% identity with experimentally verified neutralized strains. By cataloging influenza strains and their B-cell epitopes for known bnAbs, our method provides guidance for selection of representative strains for further experimental design. The knowledge of sequences, their B-cell epitopes, and differences between historical influenza strains, we enhance our preparedness and the ability to respond to the emerging pandemic threats.
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Enrollment of patients with lung and colorectal cancers onto clinical trials.
J Oncol Pract
PUBLISHED: 07-02-2013
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Only 2% to 5% of adult patients with cancer enroll onto clinical trials. We assessed simultaneously characteristics of patients and their physicians that may be independently associated with participation.
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Cricotracheal resection for laryngeal invasion by thyroid carcinoma: our experience.
Eur Arch Otorhinolaryngol
PUBLISHED: 06-24-2013
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Invasion of the laryngeal framework by thyroid carcinoma requires specific surgical techniques and carries a higher rate of complications that deserve to be highlighted. We reviewed our data from 1995 to 2012 and found six patients with laryngotracheal invasion by thyroid carcinoma. All underwent total thyroidectomy and single-stage cricotracheal resection, plus anterolateral neck dissection. Three had airway obstruction that necessitated prior endoscopic debulking. None of the patients needed a tracheotomy. There were four cases of papillary carcinoma, and two cases of undifferentiated carcinoma. One patient died of complications of the procedure (anastomotic dehiscence and tracheo-innominate artery fistula). Another died 2 months after the procedure from local recurrence and aspiration pneumonia. One case presented recurrence at 15 months, which was managed by re-excision and adjuvant radiotherapy; after 26 months of follow-up, he has no evidence of locoregional recurrence. The three other patients are alive without evidence of disease at 6, 18 and 41 months, respectively. Cricotracheal resection for subglottic invasion by thyroid carcinoma is an effective procedure, but carries significant risks of complications. This could be attributed to the devascularisation of the tracheal wall due to the simultaneous neck dissection, sacrifice of the strap muscles or of a patch of oesophageal muscle layer. We advocate a sternocleidomastoid flap to cover the anastomosis. Cricotracheal resection for subglottic invasion can be curative with good functional outcomes, even for the advanced stages of thyroid cancer. Endoscopic debulking of the airway prior to the procedure avoids tracheotomy.
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Management of Pharyngeal Fistulas After Anterior Cervical Spine Surgery: A Treatment Algorithm for Severe Complications.
J Spinal Disord Tech
PUBLISHED: 05-24-2013
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Retrospective database- query to identify all anterior spinal approaches.
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BlockLogo: Visualization of peptide and sequence motif conservation.
J. Immunol. Methods
PUBLISHED: 04-23-2013
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BlockLogo is a web-server application for the visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, selection of motif positions, type of sequence, and output format definition. The output has BlockLogo along with the sequence logo, and a table of motif frequencies. We deployed BlockLogo as an online application and have demonstrated its utility through examples that show visualization of T-cell epitopes and B-cell epitopes (both continuous and discontinuous). Our additional example shows a visualization and analysis of structural motifs that determine the specificity of peptide binding to HLA-DR molecules. The BlockLogo server also employs selected experimentally validated prediction algorithms to enable on-the-fly prediction of MHC binding affinity to 15 common HLA class I and class II alleles as well as visual analysis of discontinuous epitopes from multiple sequence alignments. It enables the visualization and analysis of structural and functional motifs that are usually described as regular expressions. It provides a compact view of discontinuous motifs composed of distant positions within biological sequences. BlockLogo is available at: http://research4.dfci.harvard.edu/cvc/blocklogo/ and http://met-hilab.bu.edu/blocklogo/.
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The disclosure of incidental genomic findings: an "ethically important moment" in pediatric research and practice.
J Community Genet
PUBLISHED: 03-26-2013
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Although there are numerous position papers on the issues and challenges surrounding disclosure of incidental genomic findings involving children, there is very little research. To fill this gap, the purpose of this study was to explore the perspectives of multiple professional (N?=?103) and public (N?=?63) stakeholders using both interviews and focus groups. Using qualitative analysis, we identified one overarching theme, "Its hard for us; its hard for them," and three subthemes/questions: "What to disclose?," "Who gets the information?," and "What happens later?" Perspectives differed between professional (Institutional Review Board chairs, clinicians, and researchers) and public stakeholders. While professionals focused on the complexities of what to disclose, the lay public stated that parents should have all information laid out for them. Professionals pondered multiple parent and child situations, while the public identified parents as informational gatekeepers who know their children best. Professionals described the potential requirement for follow-up over time as a logistical "nightmare," while the public believed that parents have the responsibility for managing their childrens health information over time. However, the parent role as gatekeeper was seen as time limited and in need of professional support and backup. Our findings present a case for needed dialogue around what we propose as an "ethically important moment," with the goal of protecting and respecting the viewpoints of all stakeholders when policies regarding children are developed.
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Clinical and molecular characteristics of HNSCC patients with brain metastases: a retrospective study.
Eur Arch Otorhinolaryngol
PUBLISHED: 03-19-2013
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Among the metastasis patterns of head and neck squamous cell carcinoma (HNSCC), intracranial spread is a rare but dreaded event. To date only very few cases have been reported and clinical and molecular data are sparse. We screened our archives for HNSCC patients from 1992 to 2005 who were diagnosed with brain metastases (BM). For retrospective analysis, all clinico-pathological data including disease-free survival (DFS), local progression-free survival (LPFS), and overall survival (OS) were compiled. Additionally, we assessed the mutational status of the TP53 gene and the prevalence of HPV serotypes by PCR and Sanger sequencing. Immunohistochemistry was applied to detect p16INK4A expression levels as surrogate marker for HPV infection. The prevalence rate of BM in our cohort comprising 193 patients with advanced HNSCC was 5.7 %. Of 11 patients with BM, 3 were female and 9 were male. Seven of the primary tumors were of oropharyngeal origin (OPSCC). LPFS of the cohort was 11.8 months, DFS was 12.1 months and OS was 36.0 months. After the diagnosis of BM, survival was 10.5 months. Five tumors showed a mutation in the TP53 gene, while five of the seven OPSCC tumors had a positive HPV status displaying infection with serotype 16 in all cases. Compared with patients who harbored TP53wt/HPV-positive tumors, patients with TP53 mutations showed a poor prognosis. Compared with the whole cohort, the interval between diagnosis of the primary and the detection of BM was prolonged in the HPV-infected OPSCC subgroup (26.4 vs. 45.6 months). The prognosis of HNSCC patients with BM is poor. In our cohort, most tumors were OPSCC with the majority being HPV positive. Our study points toward a putatively unusual metastatic behavior of HPV-positive OPSCC.
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A closer look at the recommended criteria for disclosing genetic results: perspectives of medical genetic specialists, genomic researchers, and institutional review board chairs.
J Genet Couns
PUBLISHED: 03-18-2013
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Next generation sequencing offers benefit of improved health through knowledge, but comes with challenges, such as inevitable incidental findings (IFs). The applicability of recommended criteria for disclosure of individual results when applied to disclosure of IFs is not well known. The purpose of this study was to examine how medical genetic specialists, genomic researchers, and Institutional Review Board (IRB) chairs perceive the importance of recommended criteria when applied to genetic/genomic IFs. We conducted telephone interviews with medical genetic specialists (genetic counselors, genetic nurses, medical geneticists, laboratory professionals), genomic researchers, and IRB chairs (N?=?103). Respondents rated and discussed the importance of nine recommended criteria regarding disclosure of genetic/genomic IFs. Stakeholders agreed the most important criteria for disclosure were: (1) the IF points to a life-threatening condition; (2) there is a treatment; (3) individuals indicate in writing they wanted to be informed of IFs. Criteria rated less important were: analytic validity, high penetrance, association with a young age of onset and relative risk more than 2.0. Respondents indicated that some technical criteria were confusing, and in need of context. Our findings suggest that development of guidelines regarding management of IF include multiple stakeholders perspectives and be based on a common language.
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Protecting participants, promoting progress: public perspectives on community advisory boards (CABs) in biobanking.
J Empir Res Hum Res Ethics
PUBLISHED: 09-21-2011
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Few studies have explored public perspectives on community advisory board (CAB) involvement in biobank-based research. This study held focus groups (n = 7) with 48 individuals residing in the catchment of an emerging comprehensive tissue and DNA biobank in the state of Iowa. Participants recognized benefits of bringing CABs into biobank oversight, including additional levels of protection they could afford research participants. Yet, CAB goals of protecting participants were also seen as potentially antithetical to research and medical progress. Participants expressed uncertainty about the relationship of CABs to IRBs, communities, and industry. Findings suggest members of the public are in principle supportive of CAB involvement in biobanking, yet anticipate a range of problems and concerns. These perceptions will need to be proactively addressed.
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Informed consent and genomic incidental findings: IRB chair perspectives.
J Empir Res Hum Res Ethics
PUBLISHED: 08-19-2011
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It is unclear how genomic incidental finding (GIF) prospects should be addressed in informed consent processes. An exploratory study on this topic was conducted with 34 purposively sampled Chairs of institutional review boards (IRBs) at centers conducting genome-wide association studies. Most Chairs (96%) reported no knowledge of local IRB requirements regarding GIFs and informed consent. Chairs suggested consent processes should address the prospect of, and study disclosure policy on, GIFs; GIF management and follow-up; potential clinical significance of GIFs; potential risks of GIF disclosure; an opportunity for participants to opt out of GIF disclosure; and duration of the researchers duty to disclose GIFs. Chairs were concerned about participant disclosure preferences changing over time; inherent limitations in determining the scope and accuracy of claims about GIFs; and making consent processes longer and more complex. IRB Chair and other stakeholder perspectives can help advance informed consent efforts to accommodate GIF prospects.
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Ion specific effects on the structure of molten AF-ZrF4 systems (A+ = Li+, Na+, and K+).
J Phys Chem B
PUBLISHED: 07-01-2011
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The structure of AF-ZrF(4) system (A(+) = Li(+), Na(+), K(+)) compounds in the liquid state is studied using an approach combining EXAFS spectroscopy with molecular dynamics simulations. A very good agreement is observed between the two techniques, which allows us to propose a quantitative description of the liquids. From the Zr(4+) solvation shell point of view, we observe a progressive stabilization of the 7-fold and then of the 6-fold coordinated complexes when passing from Li(+) to Na(+) and K(+) as a "counterion". Particular attention is given to the systems consisting of 35 mol % of ZrF(4). At that particular composition, the ZrF(6)(2-) complex predominates largely whatever the nature of the alkali. The calculated vibrational properties of this complex are in excellent agreement with a previous Raman spectroscopy experiment on molten KF-ZrF(4). The most important differences are observed for the lifetime of these octahedral units, which increases importantly with the size of the monovalent cation. On a larger scale, an intense first sharp diffraction peak is observed for the Zr(4+)-Zr(4+) partial structure factor, which can be attributed to the correlations between the octahedral units formed.
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Active choice but not too active: public perspectives on biobank consent models.
Genet. Med.
PUBLISHED: 05-11-2011
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Despite important recent work, US public attitudes toward specific biobank consent models are not well understood. Public opinion data can help shape efforts to develop ethically sound and publicly trusted mechanisms for informing and consenting prospective biobank donors. The purpose of this study was to explore public perspectives toward a range of consent models currently being used or considered for use among comprehensive US biobanks.
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Monitoring stress changes in a concrete bridge with coda wave interferometry.
J. Acoust. Soc. Am.
PUBLISHED: 04-12-2011
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Coda wave interferometry is a recent analysis method now widely used in seismology. It uses the increased sensitivity of multiply scattered elastic waves with long travel-times for monitoring weak changes in a medium. While its application for structural monitoring has been shown to work under laboratory conditions, the usability on a real structure with known material changes had yet to be proven. This article presents experiments on a concrete bridge during construction. The results show that small velocity perturbations induced by a changing stress state in the structure can be determined even under adverse conditions. Theoretical estimations based on the stress calculations by the structural engineers are in good agreement with the measured velocity variations.
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Community researchers conducting health disparities research: Ethical and other insights from fieldwork journaling.
Soc Sci Med
PUBLISHED: 03-31-2011
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Lay persons who are trained to conduct research in their own communities form an essential part of many research projects. However, the effects of conducting research in their own communities have not been adequately explored. This paper examines the experiences, perceptions, and challenges faced by a group of community researchers during their involvement in a research project that examined if, and how, the relationships between mothers and their adolescent daughters could be harnessed to develop a daughter-initiated cervical cancer intervention. Seven community researchers interviewed 157 mother-daughter pairs in Cape Town, South Africa. We examine the use of journaling as a tool to document the experiences of community researchers, and we consider how journaling may help the community-based researcher grapple with the research process, and, more broadly, what such journal content illustrates with respect to the nature and challenges of community-engaged health research. An analysis of the content of the journals provides a strong indication of how personal and intimate the research process can be for community researchers by virtue of the background that they bring into the process as well as the additional weight of the research process itself. The complexities of navigating dual and somewhat oppositional roles - the role of impartial scientist or researcher and the role of invested community person - has been both underestimated and insufficiently researched.
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Getting personal: ethics and identity in global health research.
Dev World Bioeth
PUBLISHED: 03-22-2011
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Researcher identity affects global health research in profound and complex ways. Anthropologists in particular have led the way in portraying the multiple, and sometimes tension-generating, identities that researchers ascribe to themselves, or have ascribed to them, in their places of research. However, the central importance of researcher identity in the ethical conduct of global health research has yet to be fully appreciated. The capacity of researchers to respond effectively to the ethical tensions surrounding their identities is hampered by lack of conceptual clarity, as to the nature and scope of the issues involved. This paper strives to provide some clarification of these ethical tensions by considering researcher identity from the perspective of (1) Guillemin and Heggens (2009) key distinction between procedural ethics and ethics in practice, and (2) our own distinction between perceptions of identity that are either symmetrical or asymmetrical, with the potential to shift research relationships toward greater or lesser ethical harmony. Discussion of these concepts is supported with ethnographic examples from relevant literature and from our own (United States (US) Government-funded) research in South Africa. A preliminary set of recommendations is provided in an effort to equip researchers with a greater sense of organization and control over the ethics of researcher identity. The paper concludes that the complex construction of researcher identity needs to be central among the ethical concerns of global health researchers, and that the conceptual tools discussed in the paper are a useful starting point for better organizing and acting on these ethical concerns.
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Sensitive quantification of Escherichia coli O157:H7, Salmonella enterica , and Campylobacter jejuni by combining stopped polymerase chain reaction with chemiluminescence flow-through DNA microarray analysis.
Anal. Chem.
PUBLISHED: 03-21-2011
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Rapid analysis of pathogenic bacteria is essential for food and water control to preserve the public health. Therefore, we report on a chemiluminescence (CL) flow-through DNA microarray assay for the rapid and sensitive quantification of the pathogenic bacteria Escherichia coli O157:H7, Salmonella enterica , and Campylobacter jejuni in water. Using the stopped polymerase chain reaction (PCR) strategy, the amount of amplified target DNA was strongly dependent on the applied cell concentration. The amplification was stopped at the logarithmic phase of the PCR to quantify the DNA products on the DNA microarray chip. The generation of single-stranded DNA sequences is essential for DNA hybridization assays on microarrays. Therefore, the DNA strands of the PCR products were separated by streptavidin-conjugated magnetic nanoparticles. This was achieved by introducing a reverse primer labeled with biotin together with a digoxigenin labeled forward primer for CL microarray imaging. A conjugate of an antidigoxigenin antibody and horseradish peroxidase recognized the digoxigenin-labeled antistrands bound to the probes on the microarray surface and catalyzed the reaction of luminol and hydrogen peroxide. The generated light emission was recorded by a sensitive charge-coupled device (CCD) camera. The quantification was conducted by a flow-through CL microarray readout system. The DNA microarrays were based on an NHS-activated poly(ethylene glycol)-modified glass substrate. The DNA probes which have the same DNA sequence as the reverse primer were immobilized on this surface. The full assay was characterized by spiking experiments with heat-inactivated bacteria in water. The total assay time was 3.5 h, and the detection limits determined on CL microarrays were for E. coli O157:H7, S. enterica , and C. jejuni 136, 500, and 1 cell/mL, respectively. The results of the DNA microarray assay were comparable to the SYBR green-based assays analyzed with a real-time PCR device. The advantage of the new microarray analysis method is seen in the ability of a high multiplex degree on DNA microarrays, the high specificity of DNA hybridization on DNA microarrays, and the possibility to get quantitative results on an automated CL flow-through microarray analysis system.
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Assessment of peri- and postoperative complications and Karnofsky-performance status in head and neck cancer patients after radiation or chemoradiation that underwent surgery with regional or free-flap reconstruction for salvage, palliation, or to improve
Radiat Oncol
PUBLISHED: 03-09-2011
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Surgery after (chemo)radiation (RCTX/RTX) is felt to be plagued with a high incidence of wound healing complications reported to be as high as 70%. The additional use of vascularized flaps may help to decrease this high rate of complications. Therefore, we examined within a retrospective single-institutional study the peri--and postoperative complications in patients who underwent surgery for salvage, palliation or functional rehabilitation after (chemo)radiation with regional and free flaps. As a second study end point the Karnofsky performance status (KPS) was determined preoperatively and 3 months postoperatively to assess the impact of such extensive procedures on the overall performance status of this heavily pretreated patient population.
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Optical basicity scales in protic solvents: water, hydrogen fluoride, ammonia and their mixtures.
Phys Chem Chem Phys
PUBLISHED: 03-01-2011
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In an inorganic material, a measure of the Lewis basicity of a solvent is commonly provided by the optical basicity, i.e. the ability of the solvent molecules to donate their electrons to an acidic species. This quantity is known to vary with the polarizability of the Lewis base. In protic solvents, the Lewis definition of basicity is barely used; it is replaced by the more purpose-built Brønsted-Lowry scale, and its generalized variant proposed by Hammett. In this study, individual molecular polarizabilities were computed from first-principles for a series of protic solvents: pure water, hydrogen fluoride, ammonia and their mixtures. From these calculations optical basicity scales were set up for each Lewis base. It was shown that these scales correlate with the Hammett acidity. It is therefore possible to build a common optical basicity scale, in which any material (protic solvents, inorganic materials) can unambiguously be classified.
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Risk and uncertainty: shifting decision making for aneuploidy screening to the first trimester of pregnancy.
Genet. Med.
PUBLISHED: 02-05-2011
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The clinical introduction of first trimester aneuploidy screening uniquely challenges the informed consent process for both patients and providers. This study investigated key aspects of the decision-making process for this new form of prenatal genetic screening.
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Long-term outcome and patterns of failure in patients with advanced head and neck cancer.
Radiat Oncol
PUBLISHED: 01-19-2011
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To access the long-time outcome and patterns of failure in patients with advanced head and neck squamous cell carcinoma (HNSCC).
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Indoline-3-carboxylic acid derived organocatalysts for the anti-Mannich reaction.
Chemistry
PUBLISHED: 11-26-2010
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Mannich type reactions of a preformed aldimine with various carbonyl compounds were investigated with a series of functionalised indoline derivatives as catalysts: indoline-3-carboxylic acid, the diphenylcarbinol analogue and O-protected silyl ether analogues. All compounds were readily prepared in enantiopure form by using an enzymatic kinetic resolution as a key step (E?100). The alcohol and ether catalysts failed to induce complete chirality transfer but did afford the Mannich bases in good yields and high diastereomeric ratios, whereas the acid catalyst gave the products in a highly diastereo- and enantioselective manner. The absolute configuration of the products was determined by a syn-anti isomerisation protocol, initiated by the sterically demanding base 1,8-diazabicyclo[5.4.0]undec-7-ene.
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Towards iconic language for patient records, drug monographs, guidelines and medical search engines.
Stud Health Technol Inform
PUBLISHED: 09-16-2010
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Practicing physicians have limited time for consulting medical knowledge and records. We have previously shown that using icons instead of text to present drug monographs may allow contraindications and adverse effects to be identified more rapidly and more accurately. These findings were based on the use of an iconic language designed for drug knowledge, providing icons for many medical concepts, including diseases, antecedents, drug classes and tests. In this paper, we describe a new project aimed at extending this iconic language, and exploring the possible applications of these icons in medicine. Based on evaluators comments, focus groups of physicians and opinions of academic, industrial and associative partners, we propose iconic applications related to patient records, for example summarizing patient conditions, searching for specific clinical documents and helping to code structured data. Other applications involve the presentation of clinical practice guidelines and improving the interface of medical search engines. These new applications could use the same iconic language that was designed for drug knowledge, with a few additional items that respect the logic of the language.
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Cancer perceptions of South African mothers and daughters: implications for health promotion programs.
Health Care Women Int
PUBLISHED: 08-03-2010
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Cancer is one of the leading causes of death worldwide. A major reason why women do not obtain cancer screening procedures relates to the high levels of fear associated with cancer. In this study, we explored South African mothers and daughters reaction to the word "cancer" specifically. The study sample included 157 randomly selected mother and adolescent daughter pairs from an urban community in Cape Town, South Africa. Mothers and their adolescent daughters had very similar responses to the term "cancer." We found that most South African mothers and daughters had a fear-based attitude toward the illness. When we asked mothers what they immediately thought of upon hearing "cancer," a majority of women (69%) thought of death, and another 43% thought of suffering and the detrimental consequences of the illness. Similarly, 50% of the daughters also thought of death, and 42% thought of the detrimental aspects of cancer. Fatalistic attitudes and negative emotional reactions have important implications in cancer prevention and need to be addressed within a public health context.
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Influence of HPV16 E2 and its localisation on the expression of matrix metalloproteinase-9.
Int. J. Oncol.
PUBLISHED: 07-03-2010
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Infection with the high-risk HPV types 16 and 18 is the major cause of cervical cancer and plays a role in the development of certain head and neck and skin cancers. We have previously demonstrated that the Early Protein 2 of the Cottontail Rabbit papillomavirus (CRPV), required for skin carcinogenesis in a rabbit model, is able to induce the expression of a matrix metalloproteinase (MMP-9); a protease known to play a key role in invasion and metastasis. However, as of now we do not understand the underlying mechanism of activation nor relevance for the human system. Here, we report that high-risk human papillomavirus HPV16 E2 similar to our previously reported results on CRPV E2 activates the human MMP-9 promoter predominantly via the MEK1-ERK1/2-AP-1-signaling pathway. In addition this activation is associated with a nuclear sub-localisation of HPV16-E2 suggesting a nuclear protein-protein or protein-DNA interaction of E2 as the underlying mechanism of activation.
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Potential-induced ordering transition of the adsorbed layer at the ionic liquid/electrified metal interface.
J Phys Chem B
PUBLISHED: 06-10-2010
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The potential-driven ordering transition of a LiCl layer adsorbed on the (100) surface of a metallic aluminum electrode is studied by molecular dynamics simulations. The transition causes a sharp peak in the potential dependence of the differential capacitance of the interface. This result is in qualitative agreement with recently reported experimental work on the interface between a room temperature ionic liquid and a well-defined Au(100) surface. In the LiCl/Al simulations, the transition occurs when the interaction model includes the induction of dipoles on the ions of the liquid by their mutual interaction and their interaction with the electrode surface as well as the polarization of the metal by the charges and dipoles on the ions ("image" interactions). When the electrode or ion polarization effects are not included, the transition is no longer observed. The interaction between the induced charges on the metal atoms and the induced dipoles on the ions creates an additional screening, which stabilizes the formation of a crystalline layer at the anode. When the crystallographic plane of the metal is changed to (110) instead of (100), the two first adsorbed layer are crystalline on both the anode and the cathode, but the structure is different: the crystal is formed through an epitaxial mechanism to adapt to the electrode surface structure. In the case of the (110) crystallographic plane, the charging of the adsorbed layer occurs through the formation of nonstoichiometric crystalline layers.
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How to translate therapeutic recommendations in clinical practice guidelines into rules for critiquing physician prescriptions? Methods and application to five guidelines.
BMC Med Inform Decis Mak
PUBLISHED: 05-28-2010
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Clinical practice guidelines give recommendations about what to do in various medical situations, including therapeutical recommendations for drug prescription. An effective way to computerize these recommendations is to design critiquing decision support systems, i.e. systems that criticize the physicians prescription when it does not conform to the guidelines. These systems are commonly based on a list of "if conditions then criticism" rules. However, writing these rules from the guidelines is not a trivial task. The objective of this article is to propose methods that (1) simplify the implementation of guidelines therapeutical recommendations in critiquing systems by automatically translating structured therapeutical recommendations into a list of "if conditions then criticize" rules, and (2) can generate an appropriate textual label to explain to the physician why his/her prescription is not recommended.
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Treatment of locally advanced carcinomas of head and neck with intensity-modulated radiation therapy (IMRT) in combination with cetuximab and chemotherapy: the REACH protocol.
BMC Cancer
PUBLISHED: 05-22-2010
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Primary treatment of carcinoma of the oro-/hypopharynx or larynx may consist of combined platinum-containing chemoradiotherapy. In order to improve clinical outcome (i.e. local control/overall survival), combined therapy is intensified by the addition of the EGFR inhibitor cetuximab (Erbitux®). Radiation therapy (RT) is carried out as intensity-modulated RT (IMRT) to avoid higher grade acute and late toxicity by sparing of surrounding normal tissues.
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In situ experimental evidence for a nonmonotonous structural evolution with composition in the molten LiF-ZrF4 system.
J Phys Chem B
PUBLISHED: 04-29-2010
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We propose in this paper an original approach to study the structure of the molten LiF-ZrF(4) system up to 50 mol % ZrF(4), combining high-temperature nuclear magnetic resonance (NMR) and extended X-ray absorption fine structure (EXAFS) experiments with molecular dynamics (MD) calculations. (91)Zr high-temperature NMR experiments give an average coordination of 7 for the zirconium ion on all domains of composition. MD simulations, in agreement with EXAFS experiments at the K-edge of Zr, provide evidence for the coexistence of three different Zr-based complexes, [ZrF(6)](2-), [ZrF(7)](3-), and [ZrF(8)](4-), in the melt; the evolution of the concentration of these species upon addition of ZrF(4) is quantified. Smooth variations are observed, apart from a given composition at 35 mol % ZrF(4), for which an anomalous point is observed. Concerning the anion coordination, we observe a predominance of free fluorides at low concentrations in ZrF(4), and an increase of the number of bridging fluoride ions between complexes with addition of ZrF(4).
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Biocompatible protein nanocontainers for controlled drugs release.
ACS Nano
PUBLISHED: 04-17-2010
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We designed a biocompatible carrier for controlled release of hydrophobic drugs. The designed carrier was prepared by sonicating oil in a protein aqueous solution forming a protein nanocontainer composed of an inner gel core and an outer protein shell. Two model drugs were loaded into the designed nanocontainers by dissolving drugs in the oil phase before sonication. The loading capacity was up to 0.9 mg/mL for the amphiphilic drug rifampicin, while it reached to 19 mg/mL for the hydrophobic drug indomethacin. The encapsulated drugs were released at different temperatures. At 37 degrees C, only less than 20% of the drug was released due to the protection by the gel core. Increasing temperature to 40 degrees C led to a completely release of the remaining drug. The drug release showed drastic temperature dependence. The biocompatibility of the protein nanocontainers was evaluated by incubating the nanocontainers in the 3T3 cell and B-LCL cell lines. Both experiments indicated an excellent biocompatibility of the designed nanocontainers.
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Accuracy to 2nd International HIV-1 RNA WHO Standard: assessment of three generations of quantitative HIV-1 RNA nucleic acid amplification tests.
J. Clin. Virol.
PUBLISHED: 04-11-2010
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Standardization of quantitative HIV-1 tests to a global primary standard is required by regulatory authorities to ensure comparability of test results across different assays and platforms of different manufacturers.
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Pharmacogenomic identification of c-Myc/Max-regulated genes associated with cytotoxicity of artesunate towards human colon, ovarian and lung cancer cell lines.
Molecules
PUBLISHED: 03-26-2010
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Development of novel therapy strategies is one of the major pressing topics of clinical oncology to overcome drug resistance of tumors. Artesunate (ART) is an anti-malarial drug, which also exerts profound cytotoxic activity towards cancer cells. We applied a gene-hunting approach using microarray-based transcriptome-wide mRNA expression profiling and COMPARE analyses. We identified a set of genes, whose expression was associated either with high IC50 values or low IC50 values for ART. Therefore, these genes may function as resistance or sensitivity factors for response of tumor cells towards ART. This viewpoint is conceivable for genes involved in ribosomal activity, drug transport, cellular antioxidant defense, apoptosis, cell proliferation, cell cycle progression etc. An investigation of underlying signal transduction by pathway analysis suggested a role of the signaling pathways related to tumor necrosis factor (TNF) and the tumor suppressor p53. On the other hand, there were genes without obvious functional link to cellular response to ART, such as genes involved in the survival of cochlear outer and inner hair cells etc. We proved the hypothesis that ART influences the activity of transcription factors regulating downstream genes involved or not involved in response of cancer cells towards ART. This would explain the identification of genes with and without obvious relation to the cytotoxic activity of ART by microarray and COMPARE analyses. By analysis of the binding motifs for the transcription factors c-Myc and Max, we indeed found that 53 of 56 genes contained one or more binding sites for c-Myc/Max upstream of the gene-location. We conclude that c-Myc and Max-mediated transcriptional control of gene expression might contribute to the therapeutic effects of ART in cancer cells, but may also confer unwanted side effects by affecting therapy-unrelated genes.
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Community members as recruiters of human subjects: ethical considerations.
Am J Bioeth
PUBLISHED: 03-16-2010
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Few studies have considered in detail the ethical issues surrounding research in which investigators ask community members to engage in research subject recruitment within their own communities. Peer-driven recruitment (PDR) and its variants are useful for accessing and including certain populations in research, but also have the potential to undermine the ethical and scientific integrity of community-based research. This paper examines the ethical implications of utilizing community members as recruiters of human subjects in the context of PDR, as well as the authors experience with a variant of PDR in a research project in South Africa. The importance of situating PDR in a comprehensive community engagement process that is responsive to the constraints of science and local needs and interests is emphasized. The paper will have relevance to bioethicists, health researchers, and research regulators concerned about the appropriate use of peer-driven recruitment strategies in health research.
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Improved HIV-1 RNA quantitation by COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 using a novel dual-target approach.
J. Clin. Virol.
PUBLISHED: 03-10-2010
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HIV-1 RNA viral load is a key parameter for reliable treatment monitoring of HIV-1 infection. Accurate HIV-1 RNA quantitation can be impaired by primer and probe sequence polymorphisms as a result of tremendous genetic diversity and ongoing evolution of HIV-1. A novel dual HIV-1 target amplification approach was realized in the quantitative COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 (HIV-1 TaqMan test v2.0) to cope with the high genetic diversity of the virus.
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Development of an oral cancer recurrence mouse model after surgical resection.
Int. J. Oncol.
PUBLISHED: 03-04-2010
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Oral squamous cell carcinomas (OSCC) are frequent epithelial malignancies and afflicted with a poor prognosis. The majority of these cancers are treated with surgical resection and local recurrences are predominantly responsible for a fatal outcome. In order to provide a better understanding of the development of these local recurrences after surgical ablation, we developed an orthotopic floor-of-mouth squamous cell carcinoma murine model, in which local recurrences occur at a high frequency (55%, 8 out of 15 mice) within 6-21 days after microsurgical removal of the primary. Expression of the enhanced green fluorescent protein (eGFP) in the cancer cells allows in this new model to confirm complete surgical resection under the microscope and helps to track repopulating primary tumor cells in the local recurrence by optical imaging. In addition the model resembles all typical features of invasive head and neck cancers including the formation of lymph node metastasis and local infiltration.
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Patient internet use surrounding cancer clinical trials: clinician perceptions and responses.
Contemp Clin Trials
PUBLISHED: 02-17-2010
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Clinician perceptions of patient internet use related to clinical trials are not well documented. This exploratory study surveyed how cancer care providers at one NCI-designated cancer center viewed patient internet use surrounding cancer trials, including whether it affected patient decision making regarding trial enrollment. The sample included 20 oncologists (59%) and 14 (41%) nurses (n=34). Most clinicians (n=26; 76%) perceived the internet as having an effect on whether or not patients decided to enroll in a cancer trial. Two thirds (n=17; 65%) felt that this effect was positive, including in terms of enhancing patient knowledge of, access to, and enrollment in trials. Clinicians were asked if they ever discussed with their patients the topic of going online to find out more about cancer trials. Over half (n=18; 58%) who responded (n=31) to this item said yes; the rest (n=13; 42%) said no. The majority (n=10; 77%) in the "no" category were among those who reported that the internet had an effect on patient decision making. These data provisionally suggest that clinicians may see the internet as having mostly a positive effect on patient decision making about cancer trials, but that their communication efforts with patients do not always logically follow from this perception. Provider-patient discussion about internet use may be an opportunity for clinicians to contribute to improved patient knowledge of and enrollment in cancer trials. More research is needed to confirm and explain the gap between clinician perception and communication regarding trial-related internet use by cancer patients.
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A novel transmembrane domain mediating retention of a highly motile herpesvirus glycoprotein in the endoplasmic reticulum.
J. Gen. Virol.
PUBLISHED: 02-10-2010
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Gene m164 of murine cytomegalovirus belongs to the large group of private genes that show no homology to those of other cytomegalovirus species and are thought to represent host adaptation genes involved in virus-host interaction. Previous interest in the m164 gene product was based on the presence of an immunodominant CD8 T-cell epitope presented at the surface of infected cells, despite interference by viral immune-evasion proteins. Here, we provide data to reveal that the m164 gene product shows unusual features in its cell biology. A novel strategy of mass-spectrometric analysis was employed to map the N terminus of the mature protein, 107 aa downstream of the start site of the predicted open reading frame. The resulting 36.5 kDa m164 gene product is identified here as an integral type-I membrane glycoprotein with exceptional intracellular trafficking dynamics, moving within the endoplasmic reticulum (ER) and outer nuclear membrane with an outstandingly high lateral membrane motility, actually 100 times higher than those published for cellular ER-resident proteins. Notably, gp36.5/m164 does not contain any typical ER-retention/retrieval signals, such as the C-terminal motifs KKXX or KXKXX, and does not pass the Golgi apparatus. Instead, it belongs to the rare group of viral glycoproteins in which the transmembrane domain (TMD) itself mediates direct ER retention. This is the first report relating TMD usage of an ER-resident transmembrane protein to its lateral membrane motility as a paradigm in cell biology. We propose that TMD usage for ER retention facilitates free and fast floating in ER-related membranes and between ER subdomains.
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From localized orbitals to material properties: building classical force fields for nonmetallic condensed matter systems.
Phys. Rev. Lett.
PUBLISHED: 02-09-2010
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The reliability of force fields is one of todays major challenges in atomic scale computer simulations. We show how to generate predictive force fields from ab initio simulations in the condensed phase, using maximally localized Wannier orbitals (WO). We derive separately all interaction terms (electrostatic, exchange repulsion, dispersion, and induction) from these localized WOs. We demonstrate the excellent quality of the resulting force field for two different materials: molten salts and liquid water. This reinforces the usefulness of chemical concepts such as Lewis pairs. The localized WOs provide the missing link between electronic structure in condensed-phase and material properties.
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Ciliary neurotrophic factor-induced sprouting preserves motor function in a mouse model of mild spinal muscular atrophy.
Hum. Mol. Genet.
PUBLISHED: 12-18-2009
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Proximal spinal muscular atrophy (SMA) is caused by homozygous loss or mutation of the SMN1 gene on human chromosome 5. Depending on the levels of SMN protein produced from a second SMN gene (SMN2), different forms of the disease are distinguished. In patients with milder forms of the disease, type III or type IV SMA that normally reach adulthood, enlargement of motor units is regularly observed. However, the underlying mechanisms are not understood. Smn(+/-) mice, a mouse model of type III/IV SMA, reveal progressive loss of motor neurons and denervation of motor endplates starting at 4 weeks of age. Loss of spinal motor neurons between 1 month and 12 months reaches 40%, whereas muscle strength is not reduced. In these animals, amplitude of single motor unit action potentials in the gastrocnemic muscle is increased more than 2-fold. Confocal analysis reveals pronounced sprouting of innervating motor axons. As ciliary neurotrophic factor (CNTF) is highly expressed in Schwann cells, we investigated its role for a compensatory sprouting response and maintenance of muscle strength in this mouse model. Genetic ablation of CNTF results in reduced sprouting and decline of muscle strength in Smn(+/-) mice. These findings indicate that CNTF is necessary for a sprouting response and thus enhances the size of motor units in skeletal muscles of Smn(+/-) mice. This compensatory mechanism could guide the way to new therapies for this motor neuron disease.
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Diffusion coefficients and local structure in basic molten fluorides: in situ NMR measurements and molecular dynamics simulations.
Phys Chem Chem Phys
PUBLISHED: 10-20-2009
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The local structure and the dynamics of molten LiF-KF mixtures have been studied by nuclear magnetic resonance (NMR) and molecular dynamics simulations. We have measured and calculated the self-diffusion coefficients of fluorine, lithium and potassium across the full composition range around the liquidus temperature and at 1123 K. Close to the liquidus temperature, D(F), D(Li) and D(K) change with composition in a way that mimics the phase diagram shape. At 1123 K D(F), D(Li) and D(K) depend linearly on the LiF molar fraction. These results show that the composition affects the self-diffusion of anions and cations more weakly than the temperature. The activation energy for diffusion was also determined and its value can be correlated with the strength of the anion-cation interaction in molten fluoride salts.
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Additional use of acupuncture to NSAID effectively reduces post-tonsillectomy pain.
Eur Arch Otorhinolaryngol
PUBLISHED: 08-06-2009
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Post-tonsillectomy swallowing pain is a common and distressing side effect after tonsillectomy and thus of great clinical interest. Up until now, there is no randomized controlled patient- and observer-blinded study evaluating the efficacy of acupuncture against swallowing pain after tonsillectomy. We therefore compared the potency of specific verum acupuncture points related to a Chinese medical diagnosis in reducing postoperative swallowing pain with non-specific control points on the body as well as a non-acupuncture group who received standard medication only. The standardized pain therapy after tonsillectomy was orally administered nonsteroidal anti-inflammatory drugs (NSAID) (diclofenac 3 x 50 mg oral). The patients (n = 123) treated with NSAID were asked about their acute pain after taking a sip of water between the first and fifth postoperative day. Participants pain was assessed using visual analog (VAS) [zero (0) for no pain up to ten (10) for the acute reported outset pain] before and 20 min, 1, 2 and 3 h after acupuncture treatment or standard pain medication, respectively. The functional assessment of diagnosis and treatment point-combination occurred by means of the "Heidelberg Model" of Traditional Chinese Medicine (TCM). Verum acupuncture lead to a significant additional pain relief. In comparison to the acupuncture, they also reported an average of 3 h duration of adequate pain-relief past taking the NSAID. This trial strongly supports a specific acupuncture scheme for the treatment of postoperative swallowing pain after tonsillectomy. It may particularly serve as an alternative pain treatment in case of NSAID intolerances.
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Immune evasion proteins enhance cytomegalovirus latency in the lungs.
J. Virol.
PUBLISHED: 07-15-2009
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CD8 T cells control cytomegalovirus (CMV) infection in bone marrow transplantation recipients and persist in latently infected lungs as effector memory cells for continuous sensing of reactivated viral gene expression. Here we have addressed the question of whether viral immunoevasins, glycoproteins that specifically interfere with antigen presentation to CD8 T cells, have an impact on viral latency in the murine model. The data show that deletion of immunoevasin genes in murine CMV accelerates the clearance of productive infection during hematopoietic reconstitution and leads to a reduced latent viral genome load, reduced latency-associated viral transcription, and a lower incidence of recurrence in lung explants.
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Synergism between the components of the bipartite major immediate-early transcriptional enhancer of murine cytomegalovirus does not accelerate virus replication in cell culture and host tissues.
J. Gen. Virol.
PUBLISHED: 06-24-2009
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Major immediate-early (MIE) transcriptional enhancers of cytomegaloviruses are key regulators that are regarded as determinants of virus replicative fitness and pathogenicity. The MIE locus of murine cytomegalovirus (mCMV) shows bidirectional gene-pair architecture, with a bipartite enhancer flanked by divergent core promoters. Here, we have constructed recombinant viruses mCMV-DeltaEnh1 and mCMV-DeltaEnh2 to study the impact of either enhancer component on bidirectional MIE gene transcription and on virus replication in cell culture and various host tissues that are relevant to CMV disease. The data revealed that the two unipartite enhancers can operate independently, but synergize in enhancing MIE gene expression early after infection. Kick-start transcription facilitated by the bipartite enhancer configuration, however, did not ultimately result in accelerated virus replication. We conclude that virus replication, once triggered, proceeds with a fixed speed and we propose that synergism between the components of the bipartite enhancer may rather increase the probability for transcription initiation.
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Cutaneous human papillomavirus in head and neck squamous cell carcinomas.
Cancer Invest.
PUBLISHED: 06-11-2009
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To evaluate the prevalence and meaning of cutaneous human papillomavirus (HPV) types in HNSCC 51 patients were analyzed for the prevalence of cutaneous as well as mucosal HPV. HPV DNA was demonstrated in 18 (35%) of 51 tumors. The majority of these HPV types belong to so-called cutaneous HPV types, whereas only HPV 6 and HPV 16 were from the mucosal HPV types. A possible role for cutaneous HPV types as co-factors in the oncogenesis of HNSCC remains to be elucidated and may be relevant for future strategies of cancer prevention.
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P90 Ribosomal s6 kinase 2 negatively regulates axon growth in motoneurons.
Mol. Cell. Neurosci.
PUBLISHED: 06-07-2009
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Mutations in Ribosomal s6 kinase 2 (Rsk2) are associated with severe neuronal dysfunction in Coffin-Lowry syndrome (CLS) patients, flies and mice. So far, the mechanisms of how Rsk2 regulates development, maintenance and activity of neurons are not understood. We have investigated the consequences of Rsk2 deficiency in mouse spinal motoneurons. Survival of isolated Rsk2 deficient motoneurons is not reduced, but these cells grow significantly longer neurites. Conversely, overexpression of a constitutively active form of Rsk2 leads to reduced axon growth. Increased axon growth in Rsk2 deficient neurons was accompanied by higher Erk 1/2 phosphorylation, and the knockout phenotype could be rescued by pharmacological inhibition of MAPK/Erk kinase (Mek). These data indicate that Rsk2 negatively regulates axon elongation via the MAPK pathway. Thus, the functional defects observed in the nervous system of CLS patients and animal models with Rsk2 deficiency might be caused by dysregulated neurite growth rather than primary neurodegeneration.
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Cervical cancer attitudes and beliefs-a Cape Town community responds on World Cancer Day.
J Cancer Educ
PUBLISHED: 05-12-2009
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Attitudes and beliefs affect womens cervical cancer screening behavior. Methods. We surveyed 228 women in Cape Town, South Africa about their screening history, knowledge, beliefs, and access barriers regarding Papanicolaou (Pap) smears and cervical cancer.
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AP-1 and ERK1 but not p38 nor JNK is required for CRPV early protein 2-dependent MMP-9 promoter activation in rabbit epithelial cells.
Virus Res.
PUBLISHED: 03-18-2009
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Human papillomaviruses (HPV) are the known cause for a variety of cancers including cervical and epithelial cancers. The cottontail-rabbit papillomavirus (CRPV) serves as a suitable animal model to study the development of these cancers in vivo. We have previously demonstrated that CRPV-induced skin carcinomas express high levels of MMP-9, a metalloproteinase contributing to cancer progression by extracellular matrix remodelling. Based on our previously reported finding that CRPV early protein 2 can activate a truncated human 670bp MMP-9 promoter fragment, we hypothesized that MMP-9 expression in the rabbit carcinomas is a consequence of activation of the rabbit MMP-9 promoter in-trans by CRPV early protein 2. Further elucidation of the mechanism revealed the requirement for both a proximal and distal AP-1 transcription factor binding site in the rabbit MMP-9 promoter and the AP-1 complex as demonstrated by the inhibitory effect of TAM67, a trans-activation deficient c-jun mutant. The characterization of signal-transduction requirements revealed predominantly ERK1 to be required for CRPV early protein 2-dependent MMP-9 promoter activation, but not JNK nor p38. In summary CRPV early protein 2 activates the expression of MMP-9 in-trans through AP-1 and ERK1 and may contribute to cancer development and progression via this mechanism within the animal model.
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Acquired form of angioedema of the head and neck related to a deficiency in c1-inhibitor: a case report with a review of the literature.
Case Rep Otolaryngol
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Angioedema related to a deficiency in the C1-inhibitor protein is characterized by its lack of response to therapies including antihistamine, steroids, and epinephrine. In the case of laryngeal edema, mortality rate is approximately 30 percent. The first case of the acquired form of angioedema related to a deficiency in C1-inhibitor was published in 1972. In our paper, we present a case of an acquired form of angioedema of the oropharyngeal region secondary to the simultaneous occurrence of two causative factors: neutralization of C1-inhibitor by an autoantibody and the use of an angiotensin convertin enzyme inhibitor.
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Genetics specialists perspectives on disclosure of genomic incidental findings in the clinical setting.
Patient Educ Couns
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Evidence documenting management of incidental findings (IFs) from clinical genomic testing is limited. The aim of this study was to examine genetics specialists perspectives regarding current and preferred disclosure of clinical genomic IFs.
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Viral latency drives memory inflation: a unifying hypothesis linking two hallmarks of cytomegalovirus infection.
Med. Microbiol. Immunol.
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Low public awareness of cytomegalovirus (CMV) results from the only mild and transient symptoms that it causes in the healthy immunocompetent host, so that primary infection usually goes unnoticed. The virus is not cleared, however, but stays for the lifetime of the host in a non-infectious, replicatively dormant state known as viral latency. Medical interest in CMV results from the fact that latent virus can reactivate to cytopathogenic, tissue-destructive infection causing life-threatening end-organ disease in immunocompromised recipients of solid organ transplantation (SOT) or hematopoietic cell transplantation (HCT). It is becoming increasingly clear that CMV latency is not a static state in which the viral genome is silenced at all its genetic loci making the latent virus immunologically invisible, but rather is a dynamic state characterized by stochastic episodes of transient viral gene desilencing. This gene expression can lead to the presentation of antigenic peptides encoded by antigenicity-determining transcripts expressed in latency (ADTELs) sensed by tissue-patrolling effector-memory CD8 T cells for immune surveillance of latency [In Reddehase et al., Murine model of cytomegalovirus latency and reactivation, Current Topics in Microbiology and Immunology, vol 325. Springer, Berlin, pp 315-331, 2008]. A hallmark of the CD8 T cell response to CMV is the observation that with increasing time during latency, CD8 T cells specific for certain viral epitopes increase in numbers, a phenomenon that has gained much attention in recent years and is known under the catchphrase memory inflation. Here, we provide a unifying hypothesis linking stochastic viral gene desilencing during latency to memory inflation.
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Dynamic kinetic resolution of 2,3-dihydrobenzo[b]furans: chemoenzymatic synthesis of analgesic agent BRL 37959.
Chemistry
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An efficient asymmetric synthesis of (S)-2,3-dihydrobenzo[b]furan-3-carboxylic acid (8 a) and (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (8 b) was established. Key to the success was the highly stereoselective enzymatic kinetic resolution of the corresponding methyl or ethyl esters that was further developed into a dynamic process. As a reliable and fast tool for analysing the enantiomeric excess, HPLC coupled with a CD detector was utilized. The route was completed by a Friedel-Crafts acylation of ethyl (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylate (7 c) followed by saponification leading to (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (2), an analgesic agent.
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Unmasked: when a clinically malignant disease turns out infectious. A rare case of tularemia.
Int. J. Surg. Pathol.
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This article reports on a 62-year-old man, who presented with cervical mass and rather nonspecific symptoms. The medical history and clinical workup initially favored a malignant disease such as a carcinoma of unknown primary as the underlying cause. Eventually, the patient was diagnosed with a granulomatous lymphadenitis caused by Francisella tularensis subsp holarctica. Tularemia is a rare disease in Western Europe and can present in multiple ways encompassing almost asymptomatic infections and fatal disease. A rapid diagnosis is often hampered by nonspecific symptoms and the generally low prevalence and incidence of this disease in endemic countries. This case report also provides a comprehensive review of the literature on cervical tularemia and discusses the differential diagnoses.
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Radiochemoimmunotherapy with intensity-modulated concomitant boost: interim analysis of the REACH trial.
Radiat Oncol
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To evaluate efficacy and toxicity clinical in the intensified treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) with the combination of chemotherapy, the EGFR antibody cetuximab, and intensity-modulated radiation therapy (IMRT) in a concomitant boost concept.
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Individual genetic and genomic research results and the tradition of informed consent: exploring US review board guidance.
J Med Ethics
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Genomic research is challenging the tradition of informed consent. Genomic researchers in the USA, Canada and parts of Europe are encouraged to use informed consent to address the prospect of disclosing individual research results (IRRs) to study participants. In the USA, no national policy exists to direct this use of informed consent, and it is unclear how local institutional review boards (IRBs) may want researchers to respond.
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Researcher and institutional review board chair perspectives on incidental findings in genomic research.
Genet Test Mol Biomarkers
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Genomic research can produce findings unrelated to a studys aims. The purpose of this study was to examine researcher and Institutional Review Board (IRB) chair perspectives on genomic incidental findings (GIFs).
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Opposing function of MYBBP1A in proliferation and migration of head and neck squamous cell carcinoma cells.
BMC Cancer
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Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and lethal cancers worldwide and mortality mostly results from loco-regional recurrence and metastasis. Despite its significance, our knowledge on molecular, cellular and environmental mechanisms that drive disease pathogenesis remains largely elusive, and there are limited therapeutic options, with only negligible clinical benefit.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.