1,548 research outputs found

    A review of tertiary BIM education for advanced engineering communication with visualization

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    SPECT with Tc-99m-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasoclilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on the changes in blood flow are lacking in SPECT but can be provided by PET. The aim of the present study was to use PET to evaluate whether nitrate administration increases blood flow to chronically dysfunctional but viable myocardium. Methods: N-13-Ammonia PET was used to quantitatively assess blood flow, and F-18-FDG PET was used as the gold standard to detect viable myocardium. Twenty-five patients with chronic ischemic left ventricular dysfunction underwent N-13-ammonia PET at rest and after nitrate administration. Results: A significant increase in nitrate-enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68 +/- 0.24 mL/min/g, P <0.05). No statistically significant change in blood flow was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal detection of viable myocardium, yielding a sensitivity of 82% with a specificity of 100%. Conclusion: N-13-Ammonia PET showed a significant increase in nitrate-enhanced blood flow in viable myocardium, whereas blood flow remained unchanged after nitrate administration in nonviable myocardium. Nitrate use during myocardial perfusion imaging will lead to improved assessment of myocardial viability

    Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

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    The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

    Daptomycin in experimental murine pneumococcal meningitis

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    <p>Abstract</p> <p>Background</p> <p>Daptomycin, a lipopeptide antibiotic, could be an alternative to vancomycin for treatment of pneumococcal meningitis. We determined the activity of daptomycin versus vancomycin, with dexamethasone as an adjuvant, in a murine model of pneumococcal meningitis.</p> <p>Methods</p> <p>Ninety-six 25–30 gram mice were inoculated intracisternally with serotype 3 <it>Streptococcus pneumoniae </it>modified by the integration of a luminescent <it>lux </it>operon. All mice were treated with either dexamethasone 1 mg/kg intraperitoneally every 6 hours alone or in combination with either vancomycin or daptomycin, also administered intraperitoneally. Serum antimicrobial concentrations were selected to approximate those achieved in humans. Following treatment, bioluminescence and cerebrospinal fluid (CSF) bacterial concentrations were determined. Caspase-3 staining was used to assess apoptosis on brain histopathology.</p> <p>Results</p> <p>Sixteen hours post intracisternal inoculation, bacterial titers in CSF were 6.8 log<sub>10 </sub>cfu/ml. Amongst the animals given no antibiotic, vancomycin 50 mg/kg at 16 and 20 hours or daptomycin 25 mg/kg at 16 hours, CSF titers were 7.6, 3.4, and 3.9 log<sub>10 </sub>cfu/ml, respectively, at 24 hours post infection (p-value, < 0.001 for both vancomycin or daptomycin versus no antibiotic); there was no significant difference in bactericidal activity between the vancomycin and daptomycin groups (p-value, 0.18). CSF bioluminescence correlated with bacterial titer (Pearson regression coefficient, 0.75). The amount of apoptosis of brain parenchymal cells was equivalent among treatment groups.</p> <p>Conclusion</p> <p>Daptomycin or vancomycin, when given in combination with dexamethasone, is active in the treatment of experimental pneumococcal meningitis.</p

    VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor

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    Vascular endothelial growth factor (VEGF) and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF

    The impact of health system governance and policy processes on health services in Iraqi Kurdistan

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    BACKGROUND: Relative to the amount of global attention and media coverage since the first and second Gulf Wars, very little has been published in the health services research literature regarding the state of health services in Iraq, and particularly on the semi-autonomous region of Kurdistan. Building on findings from a field visit, this paper describes the state of health services in Kurdistan, analyzes their underlying governance structures and policy processes, and their overall impact on the quality, accessibility and cost of the health system, while stressing the importance of reinvesting in public health and community-based primary care. DISCUSSION: Very little validated, research-based data exists relating to the state of population health and health services in Kurdistan. What little evidence exists, points to a region experiencing an epidemiological polarization, with different segments of the population experiencing rapidly-diverging rates of morbidity and mortality related to different etiological patterns of communicable, non-communicable, acute and chronic illness and disease. Simply put, the rural poor suffer from malnutrition and cholera, while the urban middle and upper classes deal with issues of obesity and Type 2 diabetes. The inequity is exacerbated by a poorly governed, fragmented, unregulated, specialized and heavily privatized system, that not only leads to poor quality of care and catastrophic health expenditures, but also threatens the economic and political stability of the region. There is an urgent need to revisit and clearly define the core values and goals of a future health system, and to develop an inclusive governance and policy framework for change, towards a more equitable and effective primary care-based health system, with attention to broader social determinants of health and salutogenesis. SUMMARY: This paper not only frames the situation in Kurdistan in terms of a human rights or special political issue of a minority population, but provides important generalizable lessons for other constituencies, highlighting the need for political action before effective public health policies can be implemented - as embodied by Rudolf Virchow, the father of European public health and pathology, in his famous quote "politics is nothing but medicine at a larger scale"

    Current challenges in software solutions for mass spectrometry-based quantitative proteomics

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    This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

    Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

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    Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

    The Arab world's contribution to solid waste literature: a bibliometric analysis

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    BACKGROUND: Environmental and health-related effects of solid waste material are considered worldwide problems. The aim of this study was to assess the volume and impact of Arab scientific output published in journals indexed in the Science Citation Index (SCI) on solid waste. METHODS: We included all the documents within the SCI whose topic was solid waste from all previous years up to 31 December 2012. In this bibliometric analysis we sought to evaluate research that originated from Arab countries in the field of solid waste, as well as its relative growth rate, collaborative measures, productivity at the institutional level, and the most prolific journals. RESULTS: A total of 382 (2.35 % of the overall global research output in the field of solid waste) documents were retrieved from the Arab countries. The annual number of documents published in the past three decades (1982–2012) indicated that research productivity demonstrated a noticeable rise during the last decade. The highest number of articles associated with solid waste was that of Egypt (22.8 %), followed by Tunisia (19.6), and Jordan (13.4 %). the total number of citations over the analysed years at the date of data collection was 4,097, with an average of 10.7 citations per document. The h-index of the citing articles was 31. Environmental science was the most researched topic, represented by 175 (45.8 %) articles. Waste Management was the top active journal. The study recognized 139 (36.4 %) documents from collaborations with 25 non-Arab countries. Arab authors mainly collaborated with countries in Europe (22.5 %), especially France, followed by countries in the Americas (9.4 %), especially the USA. The most productive institution was the American University of Beirut, Lebanon, with 6.3 % of total publications. CONCLUSIONS: Despite the expected increase in solid waste production from Arab world, research activity about solid waste is still low. Governments must invest more in solid waste research to avoid future unexpected problems. Finally, since solid waste is a multidisciplinary science, research teams in engineering, health, toxicology, environment, geology and others must be formulated to produce research in solid waste from different scientific aspects

    Case management in oncology rehabilitation (CAMON): The effect of case management on the quality of life in patients with cancer after one year of ambulant rehabilitation. A study protocol for a randomized controlled clinical trial in oncology rehabilitation

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    Background Cancer diseases and their therapies have negative effects on the quality of life. The aim of this study is to assess the effectiveness of case management in a sample of oncological outpatients with the intent of rehabilitation after cancer treatment. Case management wants to support the complex information needs of the patients in addition to the segmented structure of the health care system. Emphasis is put on support for self-management in order to enhance health - conscious behaviour, learning to deal with the burden of the illness and providing the opportunity for regular contacts with care providers. We present a study protocol to investigate the efficacy of a case management in patients following oncology rehabilitation after cancer treatment. Methods The trial is a multicentre, two-arm randomised controlled study. Patients are randomised parallel in either 'usual care' plus case management or 'usual care' alone. Patients with all types of cancer can be included in the study, if they have completed the therapy with chemo- and/or radiotherapy/surgery with curative intention and are expected to have a survival time >1 year. To determine the health-related quality of life the general questionnaire FACT G is used. The direct correlation between self-management and perceived self-efficacy is measured with the Jerusalem & Schwarzer questionnaire. Patients satisfaction with the care received is measured using the Patient Assessment of Chronic Illness Care 5 As (PACIC-5A). Data are collected at the beginning of the trial and after 3, 6 and 12 months. The power analysis revealed a sample size of 102 patients. The recruitment of the centres began in 2009. The inclusion of patients began in May 2010. Discussion Case management has proved to be effective regarding quality of life of patients with chronic diseases. When it comes to oncology, case management is mainly used in cancer treatment, but it is not yet common in the rehabilitation of cancer patients. Case management in oncology rehabilitation is not well-established in Switzerland. A major challenge of the study will therefore probably be the recruitment of the patients due to the physicians' and patients' scarcely existing awareness of this issue
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