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61.
Kim Brandes Phyllis N. Butow Martin H.N. Tattersall Josephine M. Clayton Patricia M. Davidson Jane Young Ronald M. Epstein Adam Walczak 《Patient education and counseling》2014
Objective
The objective of this study was to provide insight into how advanced cancer patients and their caregivers use a Question Prompt List (QPL) during a consultation and for preparation for future consultations.Methods
Audiotaped consultations and follow-up phone calls of 28 advanced cancer patients were coded and content analyzed. Questions asked and concerns expressed in consultations were coded for initiator, content, inclusion in the QPL and exact wording. Patients’ reported and future use of the QPL were coded from the phone calls.Results
The majority of patients reported that they used the QPL. Questions asked by patients and caregivers predominately coincided with questions from the prognosis section of the QPL. Questions were rarely asked literally from the QPL, instead questions were tailored to patients’ own circumstances.Conclusion
QPLs are useful to stimulate discussion on prognosis among advanced cancer patients and caregivers. Patients tailored questions from the QPL to their own circumstances which may suggest high involvement and engagement. The development of more specific tailored communication interventions for advanced cancer patients is warranted.Practice implications
Implementation of QPLs in the advanced cancer setting may be beneficial for patients, caregivers and healthcare providers to facilitate discussion of topics such as prognosis. 相似文献62.
High resolution SNP array profiling identifies variability in retinoblastoma genome stability
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Berber M. Mol Maarten P. G. Massink Annemarie H. van der Hout Charlotte J. Dommering Johannes M. A. Zaman Machteld I. Bosscha Wijnanda A. Kors Hanne E. Meijers‐Heijboer Gertjan J. L. Kaspers Hein te Riele Annette C. Moll Jacqueline Cloos Josephine C. Dorsman 《Genes, chromosomes & cancer》2014,53(1):1-14
Both hereditary and nonhereditary retinoblastoma (Rb) are commonly initiated by loss of both copies of the retinoblastoma tumor suppressor gene (RB1), while additional genomic changes are required for tumor initiation and progression. Our aim was to determine whether there is genomic heterogeneity between different clinical Rb subtypes. Therefore, 21 Rb tumors from 11 hereditary patients and 10 nonhereditary Rb patients were analyzed using high‐resolution single nucleotide polymorphism (SNP) arrays and gene losses and gains were validated with Multiplex Ligation‐dependent Probe Amplification. In these tumors only a few focal aberrations were detected. The most frequent was a focal gain on chromosome 2p24.3, the minimal region of gain encompassing the oncogene MYCN. The genes BAZ1A, OTX2, FUT8, and AKT1 were detected in four focal regions on chromosome 14 in one nonhereditary Rb. There was a large difference in number of copy number aberrations between tumors. A subset of nonhereditary Rbs turned out to be the most genomic unstable, while especially very young patients with hereditary Rb display stable genomes. Established Rb copy number aberrations, including gain of chromosome arm 1q and loss of chromosome arm 16q, turned out to be preferentially associated with the nonhereditary Rbs with later age of diagnosis. In contrast, copy number neutral loss of heterozygosity was detected mainly on chromosome 13, where RB1 resides, irrespective of hereditary status or age. Focal amplifications and deletions and copy number neutral loss of heterozygosity besides chromosome 13 appear to be rare events in retinoblastoma. © 2013 Wiley Periodicals, Inc. 相似文献
63.
Josephine Skat‐Rrdam David Hjland Ipsen Jens Lykkesfeldt Pernille Tveden‐Nyborg 《Basic & clinical pharmacology & toxicology》2019,124(5):528-537
Non‐alcoholic fatty liver disease is becoming a major health burden, as prevalence increases and there are no approved treatment options. Thiazolidinediones target the nuclear receptor peroxisome proliferator‐activated receptor γ (PPARγ) and have been investigated in several clinical trials for their potential in treating non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH). PPARγ has specialized roles in distinct tissues and cell types, and although the primary function of PPARγ is in adipose tissue, where the highest expression levels are observed, hepatic expression levels of PPARγ are significantly increased in patients with NAFLD. Thus, NAFLD patients receiving treatment with PPARγ agonists might have a liver response apart from the one in adipose tissue. Owing to the different roles of PPARγ, new treatment strategies include development of compounds harnessing the beneficial effects of PPARγ while restricting PPARγ unwanted effects such as adipogenesis resulting in weight gain. Furthermore, dual or pan agonists targeting two or more of the PPARs have shown promising results in pre‐clinical research and some are currently proceeding to clinical trials. This MiniReview explores adipose‐ and liver‐specific actions of PPARγ, and how this knowledge may contribute in the search for new treatment modalities in NAFLD/NASH. 相似文献
64.
Blanca Scheijen Josephine T. Tauer Christina Nowasz Edwin Sonneveld Geertruida H. de Bock Tiny G. J. Meeuwsen‐de Boer Simon van Reijmersdal Roland P. Kuiper Jutta Bradtke Frank N. van Leeuwen 《British journal of haematology》2014,166(2):250-253
Early recognition of children with chronic phase chronic myeloid leukaemia (CML‐CP) at risk for developing a lymphoid blast crisis (LyBC) is desirable, because therapy options in CML‐LyBC are limited. We used Multiplex Ligation‐dependent Probe Amplification to determine whether B‐cell lymphoid leukaemia‐specific copy number alterations (CNAs) (e.g. IKZF1, PAX5, CDKN2A deletions) could be detected in CML‐CP and may be used to predict disease progression to LyBC. CNAs were detected in all patients with CML‐LyBC, but in none of the 77 patients with CML‐CP. Based on this study we conclude that CNAs remain a hallmark of disease progression. 相似文献
65.
Mika Skeppholm Paul Hjemdahl Jovan P. Antovic Josephine Muhrbeck Jaak Eintrei Yuko Rönquist-Nii Anton Pohanka Olof Beck Rickard E. Malmström 《Thrombosis research》2014
Introduction
The oral direct thrombin inhibitor dabigatran is increasingly used to prevent thromboembolic stroke in patients with atrial fibrillation (AF). Routine laboratory monitoring is currently not recommended, but measurements of dabigatran and/or its effect are desirable in certain situations. We studied dabigatran exposure and compared different tests for monitoring of dabigatran in a real-life cohort of AF patients.Material and methods
Ninety AF patients (68 ± 9 years, 67% men, mean CHADS2 score 1.5) were treated with dabigatran 150 (n = 73) or 110 mg BID (n = 17). Trough plasma concentrations of total and free dabigatran by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to indirect measurements by Hemoclot thrombin inhibitors (HTI) and Ecarin clotting assay (ECA), as well as PT-INR and aPTT.Results
Total plasma dabigatran varied 20-fold (12–237 ng/mL with 150 mg BID) and correlated well with free dabigatran (r2 = 0.93). There were strong correlations between LC-MS/MS and HTI or ECA (p < 0.001) but these assays were less accurate with dabigatran below 50 ng/mL. The aPTT assay was not dependable and PT-INR not useful at all. There were weak correlations between creatinine clearance (Cockcroft-Gault) and LC-MS/MS, HTI and ECA (p < 0.001 for all). A high body weight with normal kidney function was associated with low dabigatran levels.Conclusions
HTI and ECA reflect the intensity of dabigatran anticoagulation, but LC-MS/MS is required to quantify low levels or infer absence of dabigatran. Most real life patients with a normal creatinine clearance had low dabigatran levels suggesting a low risk of bleeding but possibly limited protection against stroke. 相似文献66.
67.
Chua JJ Butkevich E Worseck JM Kittelmann M Grønborg M Behrmann E Stelzl U Pavlos NJ Lalowski MM Eimer S Wanker EE Klopfenstein DR Jahn R 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(15):5862-5867
Presynaptic nerve terminals are formed from preassembled vesicles that are delivered to the prospective synapse by kinesin-mediated axonal transport. However, precisely how the various cargoes are linked to the motor proteins remains unclear. Here, we report a transport complex linking syntaxin 1a (Stx) and Munc18, two proteins functioning in synaptic vesicle exocytosis at the presynaptic plasma membrane, to the motor protein Kinesin-1 via the kinesin adaptor FEZ1. Mutation of the FEZ1 ortholog UNC-76 in Caenorhabditis elegans causes defects in the axonal transport of Stx. We also show that binding of FEZ1 to Kinesin-1 and Munc18 is regulated by phosphorylation, with a conserved site (serine 58) being essential for binding. When expressed in C. elegans, wild-type but not phosphorylation-deficient FEZ1 (S58A) restored axonal transport of Stx. We conclude that FEZ1 operates as a kinesin adaptor for the transport of Stx, with cargo loading and unloading being regulated by protein kinases. 相似文献
68.
Yan KS Chia LA Li X Ootani A Su J Lee JY Su N Luo Y Heilshorn SC Amieva MR Sangiorgi E Capecchi MR Kuo CJ 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(2):466-471
The small intestine epithelium undergoes rapid and continuous regeneration supported by crypt intestinal stem cells (ISCs). Bmi1 and Lgr5 have been independently identified to mark long-lived multipotent ISCs by lineage tracing in mice; however, the functional distinctions between these two populations remain undefined. Here, we demonstrate that Bmi1 and Lgr5 mark two functionally distinct ISCs in vivo. Lgr5 marks mitotically active ISCs that exhibit exquisite sensitivity to canonical Wnt modulation, contribute robustly to homeostatic regeneration, and are quantitatively ablated by irradiation. In contrast, Bmi1 marks quiescent ISCs that are insensitive to Wnt perturbations, contribute weakly to homeostatic regeneration, and are resistant to high-dose radiation injury. After irradiation, however, the normally quiescent Bmi1(+) ISCs dramatically proliferate to clonally repopulate multiple contiguous crypts and villi. Clonogenic culture of isolated single Bmi1(+) ISCs yields long-lived self-renewing spheroids of intestinal epithelium that produce Lgr5-expressing cells, thereby establishing a lineage relationship between these two populations in vitro. Taken together, these data provide direct evidence that Bmi1 marks quiescent, injury-inducible reserve ISCs that exhibit striking functional distinctions from Lgr5(+) ISCs and support a model whereby distinct ISC populations facilitate homeostatic vs. injury-induced regeneration. 相似文献
69.
70.
Shin YK Cong WN Cai H Kim W Maudsley S Egan JM Martin B 《The journals of gerontology. Series A, Biological sciences and medical sciences》2012,67(4):336-344
Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact. 相似文献