tbuckley/cabot-search huggingface dataset:
Abstract 73: A Novel Role of E2F1 in Stress-induced Cardiac Fibrosis
Authors: Dauren Biyashev, Chan Boriboun, Gangjian Qin
Journal: Circulation Research (2014)

Rationale: E2F1 transcription factor is best known as a cell cycle regulator. Recent reports indicate the importance of E2F1 in cardiovascular system, though its exact role is not clear. TGF-beta/Smad2,3 signaling pathway, on the other hand, has been long implicated in the regulation of cardiovascular health and numerous disease, including cardiac fibrosis. Interaction between these two major pathways has been reported in the cancer settings. Objective: To identify the possible interactions between E2F1 and TGF-beta/Smad2,3 signaling pathways in cardiovascular system and determine the functional outcome of these interactions in cardiac health. Methods and Results: E2F1-/- mice developed significantly higher degree of cardiac fibrosis than wild type mice in the Angiotensin II - induced cardiac fibrosis model. The levels of phosphorylated Smad2 and Smad3 were significantly higher in the hearts of E2F1-/- mice, as well as in mouse embryonic fibroblasts derived from E2F1-/- animals. Associated expression of collagen I was significantly increased in mouse embryonic fibroblasts derived from E2F1-/- animals, and treatment with TGF-beta resulted in higher collagen deposition compared to wild type fibroblasts. Treating animals with SB 431542, chemical inhibitor of Smad2,3 signaling, obliterated the difference in the degree of cardiac fibrosis between wild type and E2F1 knockout animals in the Ang II model. We discovered that levels of syndecan-4, heparan sulfate proteoglycan transmembrane protein implicated in fibrosis and known to interact with TGF-beta are significantly increased in both E2F1-/- fibroblasts and hearts. siRNA-mediated knockdown of syndecan-4 using siRNA resulted in decreased Smad2,3 phosphorylation in E2F1-/- MEFs. Similarly, down regulation of syndecan-4 in-vivo using morpholino lead to decreased cardiac fibrosis in E2F1-/- mice in Ang II model. Conclusions: E2F1 suppresses activation of TGF-beta/Smad 2,3 pathway. The E2F1-dependent suppression of cardiac fibrosis through TGF-beta/Smad 2,3 pathway is at least partially regulated by syndecan-4.
Treatment of Uncomplicated Acute Appendicitis
Authors: Maryam Alfa-Wali, Paul Toomey, Ash Gupta
Journal: JAMA (2015)

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PTSD among Israeli former prisoners of war and soldiers with combat stress reaction: a longitudinal study
Authors: Z Solomon, Y Neria, A Ohry, M Waysman, K Ginzburg
Journal: American Journal of Psychiatry (1994)

The aim of this study was to assess the long-term impact of war captivity and combat stress reaction on rates of posttraumatic stress disorder (PTSD) in Israeli veterans of the 1973 Yom Kippur war.One hundred sixty-four former prisoners of war (POWs), 112 veterans who had had combat stress reaction, and 184 combat veteran comparison subjects filled out the PTSD Inventory, a self-report scale based on the DSM-III-R criteria for PTSD. The inventory diagnoses past and present PTSD, assesses its intensity, and provides a symptom profile.Thirty-seven percent of the veterans who had had combat stress reaction, 23% of the former POWs, and 14% of the comparison subjects had had diagnosable PTSD at some time in the past. The current rates were 13%, 13%, and 3%, respectively. The results showed different recovery rates over time: almost two-thirds of the veterans with combat stress reaction who had had PTSD in the past recovered, while less than one-half of the POW group showed this improvement.These findings indicate that small but significant proportions of the POWs and veterans with combat stress reaction were still suffering from PTSD almost two decades after the war. The different recovery rates in the two groups may reflect the differences in duration and severity of stressors, the impact of immediate intervention on long-term adjustment, or both.
Comparison of disk diffusion, Etest and VITEK2 for detection of carbapenemase‐producing Klebsiella pneumoniae with the EUCAST and CLSI breakpoint systems
Authors: M. Vading, Ø. Samuelsen, B. Haldorsen, A.S. Sundsfjord, C.G. Giske
Journal: Clinical Microbiology and Infection (2010)
Characteristics and Outcome of Children With Beckwith-Wiedemann Syndrome and Wilms’ Tumor: A Report From the National Wilms Tumor Study Group
Authors: Matthew H. Porteus, Patricia Narkool, Donna Neuberg, Katherine Guthrie, Norman Breslow, Daniel M. Green, Lisa Diller
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Children with Beckwith-Wiedemann syndrome (BWS) are at increased risk for developing Wilms’ tumor (WT). We reviewed the National Wilms Tumor Study Group (NWTSG) records to assess clinical characteristics and outcome of patients with WT and BWS. METHODS: In the NWTSG, treating clinicians were asked to report, for each enrolled patient, whether the patient had BWS. Between 1980 and 1995, 4,669 patients were treated on two consecutive NWTSG protocols (NWTS 3 and NWTS 4). We retrospectively reviewed the clinical characteristics and treatment outcomes of BWS patients compared with patients with WT without BWS. RESULTS: Fifty-three children enrolled onto NWTS 3 and 4 were reported to have BWS. BWS patients were more likely to present with lower-stage tumors (P = .0001), with more than half (27 of 53) presenting with stage I disease. The overall treatment outcomes for the BWS patients were nearly identical to those without BWS, with overall survival at 4 years from diagnosis at 89% and 90%, respectively. Overall, 21% of the patients with BWS had bilateral disease, either at diagnosis (nine of 53) or as metachronous contralateral recurrence (two of 53). BWS patients enrolled onto NWTS 4 had smaller tumors than those enrolled onto NWTS 3 (P = .02), a trend not seen in the non-BWS patients. CONCLUSION: Like children without BWS, children with BWS and WT have an excellent prognosis with modern treatment regimens. There is a high risk of bilateral disease, and increasingly smaller tumors are being detected. This suggests that a national trial assessing the role of ultrasound screening followed by nephron-sparing surgery for some patients may be appropriate.
Predictors of costs from the hospital perspective of primary pulmonary embolism
Authors: Serge Motte, Christian Mélot, Lionel Di Pierdomenico, Dimitri Martins, Pol Leclercq, Magali Pirson
Journal: European Respiratory Journal (2015)

The objective of this study was to estimate the total hospital cost per patient admitted through the emergency department with a primary diagnosis of pulmonary embolism (PE), and to identify the main components and predictors of costs.Actual costs of care of 652 consecutive patients hospitalised in 10 general hospitals in Belgium, including 31 outlier patients in terms of length of stay (4.8%), were obtained by aggregating all cost components contributing to care of each patient.In both inlier and outlier patients, the mean total cost per patient increased linearly with the degree of severity of illness classes related to the All Patient Refined Diagnosis Related Group (p<0.0001). Medical procedures, nursing activities and hospitalisation accommodation were the main cost components. We identified six independent predictors of costs in inliers: age group, chronic pulmonary heart disease, heart failure, admission to intensive care unit, initial thrombolysis treatment and type of hospital. There was a statistically significant linear trend between age groups and costs (p<0.0001).An increasing burden of comorbid illness was strongly associated with increasing actual cost for caring hospitalised patients for PE. Increasing age was associated with an increase in all main cost components.
Abstract 6001: Two Years Clinical Registry Follow Up of Endothelial Progenitor Cell Capture Stent versus Sirolimus-Eluting Bioabsorbable Polymer-Coated Stent versus Bare Metal Stents in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction
Authors: Eric Chong, Liang Shen, Chao Y Soon, Hean Y Ong, Kian K Poh, Swee G Teo, Ronald C Lee, Adrian Low, Huay C Tan
Journal: Circulation (2008)

Background: Endothelial progenitor cell (EPC) capture stent (Genous ™ , OrbusNeich), is designed to promote rapid endothelization and healing and is potentially useful in patients undergoing primary percutaneous coronary intervention (PPCI) for acute ST-segment elevation myocardial infarction (STEMI). We compare its clinical efficacy and safety with a sirolimus-eluting (SES) bioabsorbable polymer-coated stent (Cura ™ , OrbusNeich) and a bare metal stent (BMS) (Liberte ™ , Boston scientific) in patients presenting with STEMI. Methods: All patients presented to our center with STEMI and received PPCI with either EPC, SES or BMS stents between Jan 2004 and June 2006 were enrolled in the cohort study. The study endpoints were major adverse cardiac events (MACE) defined as composite end point of death, myocardial infarction (MI) and target vessel revascularization (TVR) at 2 years as well as acute, subacute and late stent thrombosis. Results: A total of 366 patients (EPC=95, SES=53, BMS 218) were enrolled. Baseline demographics in terms of age, gender, diabetes mellitus, baseline renal impairment, pre-discharge left ventricular ejection fraction, cardiogenic shock were comparable among the 3 groups. Procedural success rate was high at a mean of 99.5%. Post-procedural TIMI 3 flow was achieved in EPC 91.6%, SES 96.2% and BMS 88.5%. The MACE and stent thrombosis results at 2 years are shown in the table . Conclusion: The MACE rates among patients who underwent PPCI were similar in all 3 stent groups at 2 years follow-up. There was no difference in TVR rate and stent thrombosis remains a low event occurrence. None of the patients in the EPC stent group developed late stent thrombosis at 2 years follow up.
Evolutionary transfer of ORF-containing group I introns between different subcellular compartments (chloroplast and mitochondrion).
Authors: M Turmel, V Côté, C Otis, J P Mercier, M W Gray, K M Lonergan, C Lemieux
Journal: Molecular Biology and Evolution (1995)

We describe here a case of homologous introns containing homologous open reading frames (ORFs) that are inserted at the same site in the large subunit (LSU) rRNA gene of different organelles in distantly related organisms. We show that the chloroplast LSU rRNA gene of the green alga Chlamydomonas pallidostigmatica contains a group I intron (CpLSU.2) encoding a site-specific endonuclease (I-CpaI). This intron is inserted at the identical site (corresponding to position 1931-1932 of the Escherichia coli 23S rRNA sequence) as a group I intron (AcLSU.m1) in the mitochondrial LSU rRNA gene of the amoeboid protozoon Acanthamoeba castellanii. The CpLSU.2 intron displays a remarkable degree of nucleotide similarity in both primary sequence and secondary structure to the AcLSU.m1 intron; moreover, the Acanthamoeba intron contains an ORF in the same location within its secondary structure as the CpLSU.2 ORF and shares with it a strikingly high level of amino acid similarity (65%; 42% identity). A comprehensive survey of intron distribution at site 1931 of the chloroplast LSU rRNA gene reveals a rather restricted occurrence within the polyphyletic genus Chlamydomonas, with no evidence of this intron among a number of non-Chlamydomonad green algae surveyed, nor in land plants. A parallel survey of homologues of a previously described and similar intron/ORF pair (C. reinhardtii chloroplast CrLSU/A. castellanii mitochondrial AcLSU.m3) also shows a restricted occurrence of this intron (site 2593) among chloroplasts, although the intron distribution is somewhat broader than that observed at site 1931, with site-2593 introns appearing in several green algal branches outside of the Chlamydomonas lineage. The available data, while not definitive, are most consistent with a relatively recent horizontal transfer of both site-1931 and site-2593 introns (and their contained ORFs) between the chloroplast of a Chlamydomonas-type organism and the mitochondrion of an Acanthamoeba-like organism, probably in the direction chloroplast to mitochondrion. The data also suggest that both introns could have been acquired in a single event.
Flutamide Versus Prednisone in Patients With Prostate Cancer Symptomatically Progressing After Androgen-Ablative Therapy: A Phase III Study of the European Organization for Research and Treatment of Cancer Genitourinary Group
Authors: S. D. Fosså, P. H.Th. Slee, M. Brausi, S. Horenblas, R. R. Hall, J. W. Hetherington, N. Aaronson, L. de Prijck, L. Collette
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Time to progression (TTP), overall survival, and quality of life (QL) were compared in patients with hormone-resistant prostate cancer (HRPC) treated with prednisone (5 mg orally, four times a day) or flutamide (250 mg orally, three times a day). PATIENTS AND METHODS: Symptomatic patients were randomized to receive either prednisone (101 patients) or flutamide (100 patients). Subjective response was assessed based on performance status, the use of analgesics, and the need to apply alternative palliative treatment. Prostate-specific antigen (PSA)–based biochemical response (≥ 50% reduction of baseline PSA) was recorded. At baseline and at 6-week intervals during follow-up, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. RESULTS: There was no difference between the groups in median TTP (prednisone, 3.4 months; flutamide, 2.3 months) or overall survival (prednisone, 10.6 months; flutamide, 11.2 months). In the prednisone group, 56% of the patients experienced a subjective response, compared with 45% in the flutamide group (P = .18). The median response duration was 4.8 months for prednisone and 4.2 months for flutamide. A biochemical response was observed in 21% and 23% of the prednisone and flutamide groups, respectively. Gastrointestinal toxicity was the reason for trial discontinuation in seven patients receiving flutamide and two patients receiving prednisone. The QL assessment parameters favored the use of prednisone with statistically significant differences in pain, fatigue, role functioning, appetite loss, gastrointestinal distress, and overall QL. CONCLUSION: In symptomatic HRPC, treatment with prednisone or flutamide leads to similar rates of TTP and overall survival and no difference in subjective or biochemical response. The QL results favor the use of low-cost prednisone in patients with HRPC.
The public health burden of acute lung injury.
Authors: L Camporota
Journal: Thorax (2006)

▴ Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med2005;353:1685–93

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



The public health burden of acute lung injury (ALI/ARDS) in terms of morbidity, mortality, length of hospitalisation, and need for rehabilitation is poorly appreciated. This study reports the results of a prospective, population based, cohort study conducted in 21 hospitals in and around King County, Washington, USA to determine the …

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Multivalent glibenclamide to generate islet specific imaging probes
Authors: Andrej Babič, Smaragda Lamprianou, Laurent Vinet, Nathalie Stransky-Heilkron, Celine Xayaphoummine, Marino A. Campo, Heiner Glombik, Anke Schulte, Hans-Paul Juretschke, Xavier Montet, Paolo Meda, Norbert Lange
Journal: Biomaterials (2015)
What is newsworthy?
Authors: Lesley Fallowfield
Journal: BMJ (2002)

Editor—The article by Bartlett et al highlighting the apparent unwillingness of newspaper reporters or their editors to headline good news stories made unsurprising but disappointing reading.1 It mirrored my own impressions and experiences of television and radio reporting about doctors' communication skills. I have lost count of the mumber of times my group is contacted by reporters wanting examples of poor rather than good doctor-patient communication.

The worst example of this was a press release in February this year about a randomised controlled trial we had published in the Lancet.2 The paper showed the efficacy of a communication skills course for oncologists in 34 cancer centres throughout the United Kingdom involving over 2400 patients. I was invited to appear on BBC breakfast television to discuss the exciting beneficial findings and the intention of the Department of Health to implement the findings as part of the NHS cancer plan—or so I thought.

Instead, the interview was completely hijacked by a lengthy report about a patient with a brain tumour who had received bad news insensitively. I was asked to comment on his sorry experiences and given no opportunity to talk about the study and its highly positive findings.

Throughout the day, of the six interviews with radio stations only one, BBC Southern Counties, and an evening television news report on BBC South East (both local programmes) provided any opportunity to make positive comments about doctors and their skills, let alone report the findings of the study.

It has jaundiced my view of anything reported in the lay media, but how can we as doctors refuse to give press briefings or talk to journalists?
Enhanced antitumor activity of rapamycin and genipin, a UCP-2 inhibitor, in lung cancer.
Authors: Wen-Pin Su, Jang-Yang Chang, Hungjiun Liaw, Ching-Chuan Kuo, Wu-Chou Su
Journal: Journal of Clinical Oncology (2015)

e13595 Background: mTOR is constitutively activated in lung cancer. Deletion of TOR1 increases expression of OXPHOS proteins, and mitochondrial uncoupling proteins 2 (UCP-2) expression promotes chemoresistance. Therefore, we evaluated whether adding genipin, a UCP-2 inhibitor, to rapamycin has better antitumor effect in lung cancer. Methods: We combined the treatment of genipin and rapamycin in human lung cancer A549, H460 and CL1-0 cells. Then we treated the cancer cells with rapamycin, everolimus and BGT226 (a dual PI3K/mTOR inhibitor), and detected p62 and NrF2 activation, the downstream antioxidant signaling and UCP-2 expression and mRNA level. The NrF2 activation was confirmed by luciferase assay. Their relationship was verified by intracellular ROS measurement, and mitochondrial membrane potential. We used seahorse to examine the change in mitochondrial function of lung cancer cells after rapamycin treatment. Finally, we validated our results in animal model. Results: Combined with genipin and rapamycin have a synergistic effect with more cellular apoptosis in A549, H460 and CL1-0 cells. It's said that NrF2 may affect UCP-2 expression. We found NrF2 was activated in lung cancer A549, H460 and CL1-0 cells treated with rapamycin. Another mTOR inhibitor, everolimus and dual PI3K/mTOR inhibitor, BGT226, also induced NrF2 nuclear translocation in these lung cancer cells. Ishimura R et al. reported p62 activates NrF2 through P62 Ser351-phosphorylation under oxidant stress. We found that rapamycin induced ROS generation, p62 serine phosphorylation and NrF2 downstream mRNA and protein expression, including UCP-2. ROS inhibitor, NAC, and down-regulation of p62 by siRNA suppressed rapamycin-induced UCP-2 expression. Overexpression of p62 by cDNA transfection enhanced NrF2 activation and then UCP-2 expression in lung cancer cells. Moreover, Rapamycin-induced enhanced UCP-2 expression, leading to decreased mitochondrial membrane potential and mild increased oxygen consumption rate. Finally in A549 subcutaneous tumor from nude mice, combined genipin and everolimus demonstrated the greatest antitumor activity. Conclusions: Inhibition UCP-2 by genipin enhances anticancer effect of rapamycin in lung cancer.
Telomere length in a bronchial epithelial cell line after 2 week exposure to particulate matter
Authors: Lee Chern Koh, Naseem Mushtaq, Jonathan Grigg
Journal: European Respiratory Journal (2014)

Background: The effect of inhaled particulate matter (PM) on cell telomere length (TL) is unclear. Epidemiological studies report an association between blood cell TL and exposure to fossil-fuel derived PM (average up to 10 days) with a decrease in blood telomere (1) .  Aim: We sought to assess changes in TL  in vitro  in a human bronchial epithelial cell line (BEAS-2B) after a 2 wk exposure to urban PM.  Methods: Urban PM 10  was extracted from tapered element oscillating microbalance (TEOM) filters and suspended in phosphate buffered saline (PBS). The concentration was indexed to known concentrations of an ultrafine carbon black suspension. Bronchial epithelial cells were seeded at a density of 1x10 5  cells per well, and cultured with or without PM 10  (10µg/ml and 25µg/ml) for 2 wks. DNA was then extracted and the telomere length (T) measured by monochrome multiplex quantitative PCR. Relative fluorescence of the telomere and single copy gene (S) products were determined by the T/S ratio. The relative telomere length (RTL) was obtained by comparison to a reference sample. Statistical analysis was carried out by one way ANOVA, and p  Results: There was no significant difference in RTL between cells cultured with PM 10  at 10µg/ml or 25µg/ml concentrations, and the PBS control for 2 wk (p=0.9837, ANOVA).[figure1]Conclusion: A two week exposure of PM 10  to BEAS-2B cells  in vitro  is not associated with an alteration in RTL.  1. Hou L. Wang S, Dou C, et al. Air pollution exposure and telomere length in highly exposed subjects in Beijing, China: a repeated-measure study. Environ Int 2012; 48C:71-7.