1,774 research outputs found

    Melanosis coli: Harmless pigmentation? A case-control retrospective study of 657 cases

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    Primary omental fibromatosis presenting as an incarcerated inguinal hernia: Case report from a single institution over 20 years

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    This paper has been presented in 12th International Congress of Asia-Pacific Hernia Society in Tokyo, Japan during period of 27th–28th October, 2016

    A network medicine approach to quantify distance between hereditary disease modules on the interactome

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    We introduce a MeSH-based method that accurately quantifies similarity between heritable diseases at molecular level. This method effectively brings together the existing information about diseases that is scattered across the vast corpus of biomedical literature. We prove that sets of MeSH terms provide a highly descriptive representation of heritable disease and that the structure of MeSH provides a natural way of combining individual MeSH vocabularies. We show that our measure can be used effectively in the prediction of candidate disease genes. We developed a web application to query more than 28.5 million relationships between 7,574 hereditary diseases (96% of OMIM) based on our similarity measure

    An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

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    ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

    Isometric muscle training of the spine musculature in patients with spinal bony metastases under radiation therapy

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    <p/> <p>Background</p> <p>Osseous metastatic involvement of the spinal column affects many patients with a primary tumour disease of all entities. The consequences are pain both at rest and under exertion, impairments in going about day-to-day activities, diminished performance, the risk of pathological fractures, and neurological deficits. Palliative percutaneous radiotherapy is one of the therapeutical options available in this connection. The aim of this explorative study is to investigate the feasibility of muscle-training exercises and to evaluate the progression- and fracture-free survival time and the improvement of bone density, as well as to assess other clinical parameters such as pain, quality of life, and fatigue as secondary endpoints.</p> <p>Methods/Design</p> <p>This study is a prospective, randomized, monocentre, controlled explorative intervention study in the parallel-group design to determine the multidimensional effects of a course of exercises at first under physiotherapeutic instruction and subsequently performed by the patients independently for strengthening the paravertebral muscles of patients with metastases of the vertebral column parallel to their percutaneous radiotherapy. On the days of radiation treatment the patients in the control group shall be given physical treatment in the form of respiratory therapy and the so-called "hot roll". The patients will be randomized into one of the two groups: differentiated muscle training or physiotherapy with thirty patients in each group.</p> <p>Discussion</p> <p>The aim of the study is to evaluate the feasibility of the training programme described here. Progression-free and fracture-free survival, improved response to radiotherapy by means of bone density, and clinical parameters such as pain, quality of life, and fatigue constitute secondary study objectives.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01409720">NCT01409720</a></p

    Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

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    The decay channel ψ′→π+π−J/ψ(J/ψ→γppˉ)\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) is studied using a sample of 1.06×1081.06\times 10^8 ψ′\psi^\prime events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the ppˉp\bar{p} invariant mass spectrum. The enhancement can be fit with an SS-wave Breit-Wigner resonance function with a resulting peak mass of M=1861−13+6(stat)−26+7(syst)MeV/c2M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2 and a narrow width that is Γ<38MeV/c2\Gamma<38 {\rm MeV/}c^2 at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

    Compare the differences of synonymous codon usage between the two species within cardiovirus

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    <p>Abstract</p> <p>Background</p> <p>Cardioviruses are positive-strand RNA viruses in the Picornaviridae family that can cause enteric infection in rodents and also been detected at lower frequencies in other mammals such as pigs and human beings. The Cardiovirus genus consists two distinct species: Encephalomyocarditis virus (EMCV) and Theilovirus (ThV). There are a lot differences between the two species. In this study, the differences of codon usage in EMCV and ThV were compared.</p> <p>Results</p> <p>The mean ENC values of EMCV and ThV are 54.86 and 51.08 respectively, higher than 40.And there are correlations between (C+G)<sub>12</sub>% and (C+G)<sub>3</sub>% for both EMCV and ThV (r = -0.736;r = 0.986, P < 0.01, repectively). For ThV the (C+G)<sub>12</sub>%, (C+G)<sub>3</sub>%, axis <it>f</it>'<sub>1 </sub>and axis <it>f</it>'<sub>2 </sub>had a significant correlations respectively but not for EMCV. According to the RSCU values, the EMCV species seemed to prefer U, G and C ending codon, while the ThV spice seemed to like using U and A ending codon. However, in both genus AGA for Arg, AUU for Ile, UCU for Ser, and GGA for Gly were chosen preferentially. Correspondence analysis detected one major trend in the first axis (<it>f</it>'<sub>1</sub>) which accounted for 22.89% of the total variation, and another major trend in the second axis (<it>f</it>'<sub>2</sub>) which accounted for 17.64% of the total variation. And the plots of the same serotype seemed at the same region at the coordinate.</p> <p>Conclusion</p> <p>The overall extents of codon usage bias in both EMCV and ThV are low. The mutational pressure is the main factor that determines the codon usage bias, but the (C+G) content plays a more important role in codon usage bias for ThV than for EMCV. The synonymous codon usage pattern in both EMCV and ThV genes is gene function and geography specific, but not host specific. Maybe the serotype is one factor effected the codon bias for ThV, and location has no significant effect on the variations of synonymous codon usage in these virus genes.</p

    Retrieval practice, with or without Mind Mapping, Boosts Fact Learning in Primary School Children

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    Retrieval practice is a method of study in which testing is incorporated into the learning process. This method is known to facilitate recall for facts in adults and in secondary-school-age children, but existing studies in younger children are somewhat limited in their practical applicability. In two studies of primary school-age children of 8-12 years, we tested retrieval practice along with another study technique, mind mapping, which is more widely-used, but less well-evidenced. Children studied novel geographical facts, with or without retrieval practice and with or without mind mapping, in a crossed-factorial between-subjects design. In Experiment 1, children in the retrieval practice condition recalled significantly more facts four days later. In Experiment 2, this benefit was replicated at one and five weeks in a different, larger sample of schoolchildren. No consistent effects of mind mapping were observed. These results underline the effectiveness of retrieval practice for fact learning in young children

    Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

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    The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

    Combination of RAD001 (everolimus) and docetaxel reduces prostate and breast cancer cell VEGF production and tumour vascularisation independently of sphingosine-kinase-1

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    Resistance to docetaxel is a key problem in current prostate and breast cancer management. We have recently discovered a new molecular mechanism of prostate cancer docetaxel chemoresistance mediated by the mammalian target of rapamycin (mTOR)/sphingosine-kinase-1 (SK1) pathway. Here we investigated the influence of this pathway on vascular endothelial growth factor (VEGF) production and tumour vascularisation in hormone resistant prostate and breast cancer models. Immunofluorescent staining of tumour sections from human oestrogen receptor (ER)-negative breast cancer patients showed a strong correlation between phosphorylated P70S6 kinase (mTOR downstream target), VEGF and SK1 protein expression. In hormone-insensitive prostate (PC3) and breast (MDA-MB-231 and BT-549) cancer cell lines the mTOR inhibitor RAD001 (everolimus) has significantly inhibited SK1 and VEGF expression, while low dose (5 nM) docetaxel had no significant effect. In these cell lines, SK1 overexpression slightly increased the basal levels of VEGF, but did not block the inhibitory effect of RAD001 on VEGF. In a human prostate xenograft model established in nude mice, RAD001 alone or in combination with docetaxel has suppressed tumour growth, VEGF expression and decreased tumour vasculature. Overall, our data demonstrate a new mechanism of an independent regulation of SK1 and VEGF by mTOR in hormone-insensitive prostate and breast cancers
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