tbuckley/cabot-search huggingface dataset:
Self-esteem in patients with rheumatic diseases : The role of body-self unity
Authors: C. Bode, A. van der Heij, E. Taal, M.A.F.J. van de Laar
Journal: Annals of the Rheumatic Diseases (2008)

Background: Maintaining positive self-esteem is one of the challenges for patients with chronic diseases. Limitations in physical functioning, often associated with having a rheumatic disease, can influence the perception of the body as belonging to the person (or as detached from the self) and might thereby finally affect the self-esteem of patients. The concept of body-self unity has been investigated in a phenomenological research tradition that works with qualitative methodology and small samples. Objectives: To develop a questionnaire to measure body-self unity quantitatively and to investigate the predictive value of body-self unity for self-esteem in patients with rheumatic diseases. Methods: The Body Experience Questionnaire was developed for the measurement of body-self unity. Besides this questionnaire, illness cognitions, pain intensity, functional limitations and self-esteem were measured via computers with touchscreen. 168 patients (mean age = 54,2 years, 62% female) with a rheumatic disease participated in this study consecutive visiting the rheumatology clinic. To analyse predictors of self-esteem, hierarchical regression analyses were employed (first step demographic characteristics, second step disease related variables (disease duration, functional limitations, pain), final step psychological constructs (body-self unity, illness cognitions)). Results: The Body Experience Questionnaire revealed a two factor structure with good reliability (subscale harmony, Cronbachs alpha=.76; subscale alienation, Cronbachs alpha = 0.84). The final model of the hierarchical regression analyses showed that self-esteem can be predicted by helplessness, acceptance, harmony of body and self and most strongly by the alienation of body and self. R2 of the final model was 0.50 (delta R for psychological variables in the final step was 0.28). The relation between functional limitations and self-esteem was fully mediated by the psychological constructs body self unity and illness cognitions. Conclusion: This study showed the importance of psychological characteristics and particularly the experience of the body for self-esteem in patients with a rheumatic disease. Further research should explore therapies to increase the body-self unity.
Abstract 19153: Morphine Delays and Attenuates Ticagrelor Exposure and Action in Patients With Myocardial Infarction: The Randomized, Double-blind, Placebo-controlled Impression Trial
Authors: Jacek Kubica, Piotr Adamski, Malgorzata Ostrowska, Joanna Sikora, Julia M Kubica, Wiktor Sroka, Katarzyna Stankowska, Katarzyna Buszko, Eliano P Navarese, Bernd Jilma, Jolanta M Siller-Matula, Danuta Rosc, Michal Marszall, Marek Kozinski
Journal: Circulation (2015)

Introduction: The currently available data from observational studies and a randomized trial on clopidogrel conducted in healthy volunteers suggest existence of drug-drug interactions between morphine and oral P2Y12 inhibitors, when administered together. Hypothesis: We aimed to test the hypothesis that morfine administered intravenously excerts the negative impact on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with myocardial infarction. Methods: In a single center, randomized, double-blind trial, participants were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry, while ticagrelor antiplatelet effect was measured with up to 3 different platelet function tests: vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, multiple electrode aggregometry and VerifyNow P2Y12. Results: The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine administration lowered the total exposure to ticagrelor and its active metabolite by 35.6% (AUC(0-12): 6307 vs. 9791 ng·h/mL; p=0.003) and 37.1% (AUC(0-12): 1503 vs. 2388 ng·h/mL; p=0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; p=0.002) and AR-C124910XX (6 vs. 4 h; p=0.03) in morphine-treated patients. Multiple regression analysis showed that lower AUC(0-12) values for ticagrelor were associated with morphine administration (p=0.003) and the presence of ST-segment elevation myocardial infarction (p=0.010). All three methods of platelet reactivity assessment consistently showed a stronger antiplatelet effect of ticagrelor in the placebo group as reflected by a higher prevalence of high platelet reactivity in patients receiving morphine. Conclusions: Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction.
Burden and Profile of Somatic Mutation in Duodenal Adenomas from Patients with Familial Adenomatous- and <i>MUTYH</i>-associated Polyposis
Authors: Laura E. Thomas, Joanna J. Hurley, Elena Meuser, Sian Jose, Kevin E. Ashelford, Matthew Mort, Shelley Idziaszczyk, Julie Maynard, Helena Leon Brito, Manon Harry, Angharad Walters, Meera Raja, Sarah-Jane Walton, Sunil Dolwani, Geraint T. Williams, Meleri Morgan, Morgan Moorghen, Susan K. Clark, Julian R. Sampson
Journal: Clinical Cancer Research (2017)

Purpose: Duodenal polyposis and cancer are important causes of morbidity and mortality in familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). This study aimed to comprehensively characterize somatic genetic changes in FAP and MAP duodenal adenomas to better understand duodenal tumorigenesis in these disorders.Experimental Design: Sixty-nine adenomas were biopsied during endoscopy in 16 FAP and 10 MAP patients with duodenal polyposis. Ten FAP and 10 MAP adenomas and matched blood DNA samples were exome sequenced, 42 further adenomas underwent targeted sequencing, and 47 were studied by array comparative genomic hybridization. Findings in FAP and MAP duodenal adenomas were compared with each other and to the reported mutational landscape in FAP and MAP colorectal adenomas.Results: MAP duodenal adenomas had significantly more protein-changing somatic mutations (P = 0.018), truncating mutations (P = 0.006), and copy number variants (P = 0.005) than FAP duodenal adenomas, even though MAP patients had lower Spigelman stage duodenal polyposis. Fifteen genes were significantly recurrently mutated. Targeted sequencing of APC, KRAS, PTCHD2, and PLCL1 identified further mutations in each of these genes in additional duodenal adenomas. In contrast to MAP and FAP colorectal adenomas, neither exome nor targeted sequencing identified WTX mutations (P = 0.0017).Conclusions: The mutational landscapes in FAP and MAP duodenal adenomas overlapped with, but had significant differences to those reported in colorectal adenomas. The significantly higher burden of somatic mutations in MAP than FAP duodenal adenomas despite lower Spigelman stage disease could increase cancer risk in the context of apparently less severe benign disease. Clin Cancer Res; 23(21); 6721-32. ©2017 AACR.
Possibilities of Improved Therapy for Cancer Patients&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1941)

It is indeed an honor to have been invited by Dr. Cowdry and the Board of the Barnard Free Skin and Cancer Hospital to give the second Barnard Hospital Lecture, particularly because St. Louis is one of the oldest and most important centers of experimental and clinical cancer research in the country.  Since I am a laboratory worker, it was with some misgiving that I agreed to speak to you on the possibilities of improved therapy for cancer patients. However, I shall deal mainly with fundamental principles of therapy, and these are essentially the same, whether they arise in the clinic or in the experimental laboratory. It is my aim to discuss, briefly and as objectively as possible, various points which to my mind may lead to improvements in cancer therapy. These may be grouped into two broad classes: first, the more widespread application of known methods and their improvements;
02.49 Does biological therapy play any role on cardiovascular risk in rheumatoid arthritis?
Authors: Raquel Hernández, Julia Uceda, Carmen Almeida, Jose L. Marenco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Although there are conflicting data on the subject, it seems that there is a higher incidence of cardiovascular events (CVE) in Rheumatoid Arthritis (RA) compared to population control. Apart from classical cardiovascular risk factors (CV), we must consider the severity of the inflammatory process plays an essential role in accelerated atherosclerosis in this pathology. On the long term security of biological therapies, we find heterogeneous data in different studies and registries. Has observed a decrease in CV risk in RA patients treated with anti-TNF-α agents. <h3>Objectives</h3> The main aim was to evaluate the CV risk and prevalence of CVD in RA treated with biological teraphies versus RA treated with classics disease modifying drugs (DMARDs). <h3>Methods</h3> Retrospective cohort study over the CV risk and prevalence of cardiovascular events in RA patients treated with biological therapies. We reviewed a cohort of 260 patients diagnosed with RA (ACR 1987). We recorded sociodemographic variables, classics CV risk factors (smoking history, cholesterol levels, hypertension, diabetes mellitus), immunological profile (presence of RF and/or ACPA), treatment (DMARDs or biological therapy) at the time of the study. The CV risk was measured by the estimated SCORE of atherosclerotic cardiovascular mortality risk in 10 years, for specific values of systolic blood pressure and total cholesterol, according to smoking history, gender and age, calibrated to Spain. Also checked all cardiovascular events occurred since the beginning of RA until time of the study. <h3>Results</h3> 72% were women, with a current average age of 58.5 years. 48% were receiving biological therapy with or without concomitant DMARDs. Among the classic CV risk factors highlighted: 38% overweight and obesity in 32% of patients, 14% had diabetes mellitus and 39% hypertension; 51% had dyslipidemia and 18% were smokers. Regarding the immune profile had ACPA+61% and 65% FR +. 13% of patients who did not realise biological therapy treatment showed a high Score (5–10) versus 3.7% of patients with biological therapy treatment, this difference was statistically significant. Regarding the prevalence of cardiovascular events we found no difference between groups, 13% and 15% respectively. <h3>Conclusions</h3> patients treated with biological therapy have lower cardiovascular risk than patients treated with DMARs. WE dont found differences in the prevalence of CVE between groups. Probably the reduction of inflammation with TB has direct relation with cardiovascular risk reduction in patients with RA.
骨再生のための絹に基づく異方3次元生体衣服【Powered by NICT】
Authors: P Ribeiro Viviana, Silva-Correia Joana, I Nascimento Ana, da Silva Morais Alain, P Marques Alexandra, S Ribeiro Ana, J Silva Carla, Bonifacio Graca, A Sousa Rui, M Oliveira Joaquim, L Oliveira Ana, L Reis Rui
Journal: Biomaterials (2017)
03.24 Effect of tocilizumab therapy on il-6 signalling pathway in early rheumatoid arthritis patients
Authors: Lylia Ouboussad, Chi Wong, Laura Hunt, Paul Emery, Michael F McDermott, Aamir Aslam, Maya H Buch
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> We previously reported increased constitutive but unchanged induced CD4+ p-STAT3 in established RA versus healthy control (HC).<sup>1</sup> This study aims to evaluate in early RA (ERA) (i) cell-subset constitutive and Cis (IL-6) and Trans (IL-6/sIL6R)-induced IL-6 signalling (ii) effect of tocilizumab (TCZ; +/-MTX) (iii) for an association between baseline phosphorylation intensities and TCZ (+/- MTX) response. <h3>Materials and methods</h3> Multiparameter phosphoflow cytometry was performed on 20 treatment-naïve, ERA patients randomised to TCZ monotherapy or TCZ-MTX to determine STAT3, Akt and Erk phosphorylation intensities. PBMCs were isolated and cryopreserved at baseline, and weeks 24 and 48 post-TCZ. HC samples (n=10) were also obtained. PBMCs were unmodulated, stimulated with IL-6 or soluble IL-6 receptor (sIL-6R) and median fluorescence intensities (MFI) were measured. <h3>Results</h3> <b>Baseline data, HC and ERA</b> Constitutive CD4+ p-STAT3 was numerically higher in ERA compared to HC, with non-significant increase following stimulation in both groups. There was no significant difference in constitutive monocyte p-STAT3 in HC vs ERA. Stimulation did not induce further increase in monocyte p-STAT3 in ERA. Constitutive CD4+ p-Akt was significantly higher in ERA versus HC (p=0.01), with no change post-stimulation. <b>Pre/Post TCZ in ERA</b> Constitutive CD4+ pSTAT3 expression did not alter following TCZ exposure. Statistically significant decreases in IL-6 stimulated CD4+ pSTAT3 expression from baseline to weeks 24 and 48 were observed (p=0.005 and 0.01 respectively); and similarly using IL-6/sIL-6R at week 48 (p=0.01). Constitutive monocyte p-STAT3 expression appeared to increase at week 24 compared to baseline (p=0.03); similar observation following stimulation with IL-6/sIL-6R at both weeks 24 and 48 was observed (p=0.01) TCZ led to non-significant decrease in constitutive and IL6-stimulated CD4+ p-Akt expression weeks 24 and 48. TCZ otherwise had no significant effect on p-Akt and p-Erk in other studied cell subsets. <h3>Conclusions</h3> TCZ reduced induced IL-6 signalling via CD4+ STAT3. This preliminary analysis also suggests importance of monocyte subset and relevance of Akt in IL-6 signalling. Complete analysis of these data will clarify the relative roles and impact of IL-6R targeting further. <h3>References</h3> Ouboussad L, Wong C, Hunt L, Emery P, McDermott MF, Buch MF. Investigating IL-6 pathway signalling kinetics in peripheral blood single cell subsets with tocilizumab therapy in patients with early rheumatoid arthritis. Ann Rheum Dis2016;75(Suppl 1):A31.2-A31.
Treatment outcome and lung toxicities of volumetric modulated arc therapy in the treatment of inoperable non-small-cell lung cancer patients.
Authors: Congying Xie, Baochai Lin, Xiance Jin
Journal: Journal of Clinical Oncology (2017)

e20046 Background: Volumetric-modulated arc therapy (VMAT) has demonstrated the ability to deliver radiation dose precisely and accurately with a shorter delivery time and less MU compared to conventional intensity-modulated fixed-field treatment (IMRT) in the treatment of inoperable non–small-cell lung cancer (NSCLC). However, published data on clinical outcome and lung toxicities of VMAT in the treatment of NSCLC are scarce. Methods: The clinical outcome, acute and late pulmonary toxicities of 134 consecutive inoperable NSCLC patients treated by VMAT with or without concurrent chemotherapy were retrospectively reviewed. Univariate and multivariate analysis on the dosimetric and characteristic factors associated with acute radiation pnuemonitis (RP) and pulmonary fibrosis were evaluated. Results: The average prescriptions dose to these patients were 5736.38±649.11 cGy (range from 5200 to 6400 cGy) with a median follow-up of 18.6 months (range, 2–45 months) for the enrolled 134 patients. The two-year progression-free survival (PFS) and overall survival (OS) for all patients was 18.2% and 38.4% with a median PFS and OS of 7.6 months and 18.6 months, respectively. There were 14 and 12 out of 134 patients experienced grade III/higher RP (10.45%) and pulmonary fibrosis (8.95%), respectively. Age, chemotherapy exposure, dose prescription, V10, V13, V20 and V30 were significantly associated with acute RP. Dose prescription was related to pulmonary fibrosis. Only V13 (p = 0.02) and age (p = 0.02) were independently associated with acute RP according to multivariate analysis. Based on regression analysis, the threshold for lung dosimetric metrics V10,V13,V20 andV30 were 50%,40%,28% and 18% in VMAT treatment of NSCLC to limit the RP rate &lt; 10%. Conclusions: VMAT can be delivered safely with acceptable acute and late toxicities for NSCLC. Lung dosimetric metrics were valuable in predicting acute RP. A threshold of 40% of Lung V13 in VMAT treatment of NSCLC was helpful to limit the RP rate &lt; 10%.
アビラテロン,エプレレノン,プレドニゾロンと野生型および変異型のアンドロゲン受容体との相互作用: アビラテロン曝露増大またはMDV3100との結合を追求する合理的理由
Authors: Richards Juliet, Lim Ai Chiin, W Hay Colin, E Taylor Angela, Wingate Anna, Nowakowska Karolina, Pezaro Carmel, Carreira Suzanne, Goodall Jane, Arlt Wiebke, J Mcewan Iain, S De Bono Johann, Attard Gerhardt
Journal: Cancer Research (2012)
Chromosomal Changes in Epidermal Carcinogenesis&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: J. J. Biesele, E. V. Cowdry
Journal: JNCI Journal of the National Cancer Institute (1944)

Chromosomal Changes in Epidermal Carcinogenesis Get access J. J. Biesele, J. J. Biesele fellow of The International Cancer Research Foundation Barnard Free Skin and Cancer Hospital, and the Anatomical Laboratory, Washington University, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar E. V. Cowdry E. V. Cowdry director of research Barnard Free Skin and Cancer Hospital, and the Anatomical Laboratory, Washington University, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 4, February 1944, Pages 373–384, https://doi.org/10.1093/jnci/4.4.373 Published: 01 February 1944
Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease
Authors: Daniel Lindholm, Johan Lindbäck, Paul W. Armstrong, Andrzej Budaj, Christopher P. Cannon, Christopher B. Granger, Emil Hagström, Claes Held, Wolfgang Koenig, Ollie Östlund, Ralph A.H. Stewart, Joseph Soffer, Harvey D. White, Robbert J. de Winter, Philippe Gabriel Steg, Agneta Siegbahn, Marcus E. Kleber, Alexander Dressel, Tanja B. Grammer, Winfried März, Lars Wallentin
Journal: Journal of the American College of Cardiology (2017)
02.47 Strong age-dependent effects of dopamine on synovial fibroblast migration in rheumatoid arthritis and osteoarthritis patients
Authors: Lina van Nie, Stefan Rehart, Elena Neumann, Ulf Müller-Ladner, Silvia Capellino
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> To keep synovial fibroblasts (SF) from migrating into the adjacent cartilage is a desirable therapeutic target in rheumatoid arthritis (RA). Using this approach, both joint destruction and disability could be prevented. Moreover, our previous studies could show a significant decrease of IL-6 and IL-8 in RASF under dopamine receptor activation (<i>Capellino S et al, Arthritis Rheumatol 2014</i>). Based on these results, we suggest a potential impact of RASF on joint invasion and destruction in RA. <h3>Materials and methods</h3> RA and osteoarthritis (OA) SF were obtained from patients undergoing knee joint replacement surgery (mean age: OA: 74.3±11.3 years; RA: 73.7±10.3 years).In order to investigate the dopamine receptor (DR) distribution in the synovium, we performed immunohistochemistry and evaluated all DR 5 receptor subtypes. Here, the DR-expression in the lining layer and especially in the invasion zone between was of special interest. SF migration and motility assays as well as ELISAs for MMP3 and proMMP1 were performed under D1-like (D1DR and D5DR) and D2-like (D2DR, D3DR and D4DR) receptor stimulation, each in different concentrations, respectively. <h3>Results</h3> D1DR, D4DR and D5DR were higher expressed on SF nearby the invasion zone. Also, migration of RASF and OASF were found to be correlated with age of the patient at surgery. While younger patients (≤75 years) showed an increase in migration up to 78%, the older patients (≥75 years) show a reduced migration of less than 50% (p=0.0009; r=0.69, OA n=8; RA n=7). No difference could be observed between RA and OA patients and between the D1-like and D2-like receptor stimulation. The same impact on the RASF and OASF could be seen in the motility assay (OA n=6; RA n=6). MMP3 and proMMP1 level were altered in both directions under DR activation (OA n=3; RA n=3). <h3>Conclusion</h3> DRs are highly expressed in the invasion zone, which suggests a direct role for dopamine on the aggressive phenotype of the synovial fibroblasts, as confirmed in the <i>in vitro</i> assays. As RASF migration is significantly altered under DR activation, the synovial dopamine pathway can be regarded as a potential therapeutic target of RA.
National and State Estimates of the Numbers of Adults and Children with Active Epilepsy — United States, 2015
Authors: Matthew M. Zack, Rosemarie Kobau
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Epilepsy, a brain disorder leading to recurring seizures, has garnered increased public health focus because persons with epilepsy experience pronounced and persistent health and socioeconomic disparities despite treatment advances, public awareness programs, and expanded rights for persons with disabilities (1,2).For almost all states, epilepsy prevalence estimates do not exist.CDC used national data sources including the 2015 National Health Interview Survey (NHIS) for adults (aged ≥18 years), the 2011-2012 National Survey of Children's Health (NSCH), and the 2015 Current Population Survey data, describing 2014 income levels, to estimate prevalent cases of active epilepsy, overall and by state, to provide information for state public health planning.In 2015, 1.2% of the U.S. population (3.4 million persons: 3 million adults and 470,000 children) reported active epilepsy (self-reported doctor-diagnosed epilepsy and under treatment or with recent seizures within 12 months of interview) or current epilepsy (parent-reported doctor-diagnosed epilepsy and current epilepsy).Estimated numbers of persons with active epilepsy, after accounting for income and age differences by state, ranged from 5,900 in Wyoming to 427,700 in California.NHIS data from 2010-2015 indicate increases in the number of persons with active epilepsy, probably because of population growth.This study provides updated national and modeled state-specific numbers of active epilepsy cases.Public health practitioners, health care providers, policy makers, epilepsy researchers, and other epilepsy stakeholders, including family members and people with epilepsy, can use these findings to ensure that evidence-based programs meet the complex needs of adults and children with epilepsy and reduce the disparities resulting from it.