tbuckley/cabot-search huggingface dataset:
Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity
Authors: Christoph F.A. Vogel, W.L. William Chang, Sarah Kado, Kelly McCulloh, Helena Vogel, Dalei Wu, Thomas Haarmann-Stemmann, GuoXiang Yang, Patrick S.C. Leung, Fumio Matsumura, M. Eric Gershwin
Journal: Environmental Health Perspectives (2016)

Background:The aryl hydrocarbon receptor repressor (AhRR) is known to repress aryl hydrocarbon receptor (AhR) signaling, but very little is known regarding the role of the AhRR in vivo.Objective:This study tested the role of AhRR in vivo in AhRR overexpressing mice on molecular and toxic end points mediated through a prototypical AhR ligand.Methods:We generated AhRR-transgenic mice (AhRR Tg) based on the genetic background of C57BL/6J wild type (wt) mice. We tested the effect of the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of cytochrome P450 (CYP)1A1 and cytokines in various tissues of mice. We next analyzed the infiltration of immune cells in adipose tissue of mice after treatment with TCDD using flow cytometry.Results:AhRR Tg mice express significantly higher levels of AhRR compared to wt mice. Activation of AhR by TCDD caused a significant increase of the inflammatory cytokines Interleukin (IL)-1β, IL-6 and IL-10, and CXCL chemokines in white epididymal adipose tissue from both wt and AhRR Tg mice. However, the expression of IL-1β, CXCL2 and CXCL3 were significantly lower in AhRR Tg versus wt mice following TCDD treatment. Exposure to TCDD caused a rapid accumulation of neutrophils and macrophages in white adipose tissue of wt and AhRR Tg mice. Furthermore we found that male AhRR Tg mice were protected from high-dose TCDD-induced lethality associated with a reduced inflammatory response and liver damage as indicated by lower levels of TCDD-induced alanine aminotransferase and hepatic triglycerides. Females from both wt and AhRR Tg mice were less sensitive than male mice to acute toxicity induced by TCDD.Conclusion:In conclusion, the current study identifies AhRR as a previously uncharacterized regulator of specific inflammatory cytokines, which may protect from acute toxicity induced by TCDD.Citation:Vogel CF, Chang WL, Kado S, McCulloh K, Vogel H, Wu D, Haarmann-Stemmann T, Yang GX, Leung PS, Matsumura F, Gershwin ME. 2016. Transgenic overexpression of aryl hydrocarbon receptor repressor (AhRR) and AhR-mediated induction of CYP1A1, cytokines, and acute toxicity. Environ Health Perspect 124:1071–1083; http://dx.doi.org/10.1289/ehp.1510194
PWE-427 The development of a national nurse / non-medical endoscopist course
Authors: H Watson, F Hibberts
Journal: Gut (2015)

<h3>Introduction</h3> The demand for Gastrointestinal (GI) endoscopy continues to rise. Demand is expected to supersede current provision of endoscopy capacity through existing models leading to a huge capacity-demand gap. Nurse Endoscopists (NE) can potentially meet this demand as the medical workforce struggles to. However there is a significant gap in the training provision for NE that means the potential to utilise this significant pool from the available workforce is not being maximised. The basic skills JAG training courses address the practical skills training but not the specific skills that relate to nurses taking on advanced roles. Acquisition of such skills ensures that these individuals flourish in the role. <h3>Method</h3> 2 experienced consultant nurse endoscopists with skills, training and experience in post-graduate education and endoscopy training, set up a National Nurse Endoscopist Course in November 2013. Affiliated with Kings College London as academic partners who provide an optional 30 credits at level 6 or 7 to course participants. Clear, well defined learning aims and objectives have been developed to ensure competency and quality assurance. The course consists of 6 taught days, split into 3, 2 day sessions over 6 months designed to run concurrently with the trainee's in house/Trust training lists. The course addresses all the issues specific to the transition in role from a nurse to an advanced practitioner within endoscopy. The course is interactive and dynamic with continuous support via a purpose made networking page. Students are assessed via a formal presentation and OSCE. A portfolio of practice and an essay forms the optional academic assessment. <h3>Results</h3> The 1st intake in November 2013 consisted of 15 trainee NE from across the UK. The 2<sup>nd</sup>cohort in June 2014 consisted of 16 trainees, this included 2 NE from Sweden. The 3rd intake in January 2015 has 14 students taking part. The 45 course participants so far range from trainee NE already in post to nurses applying to become trainee endoscopists as part of the Bowel Scope screening programme. The first 31 students successfully completed the course and would 'recommend the course to a colleague'. They all rated the course very good (4) or excellent (5) on an evaluation scoring of 0 to 5. The latest 14 students will complete in June 2015. <h3>Conclusion</h3> A course such as this is desperately required nationwide to help meet the increasing demands. The course template has been adopted by Health Education England, supported by JAG. This course equips the trainees with a holistic approach to becoming an endoscopist. It raises the profile of the nurse endoscopist role and helps address the current national workforce shortfall for endoscopists. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Maslekar S, <i>et al</i>. Patient satisfaction with GI endoscopy. Colorectal Dis. 2010;12 Richardson G, <i>et al</i>. MINuET. <i>BMJ</i>2009;338
SAT0568 Long-Term Work Productivity Improvement Associated with Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Pooled Analysis of 3 Phase 3 Studies
Authors: F. Zhang, Z. Clancy, S. Li
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. The Work Limitations Questionnaire (WLQ) is a reliable tool for assessing limitations on work productivity in patients with chronic health conditions. The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo in patients with active psoriatic arthritis (PsA) despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics. <h3>Objectives</h3> Assess the effect of APR on work productivity and work limitations over 52 weeks in a pooled analysis. <h3>Methods</h3> Patients were randomized (1:1:1) to receive placebo, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). Patients whose swollen and tender joint counts had not improved ≥20% at Week 16 were considered non-responders and were required to be re-randomized (1:1) to APR20 or APR30 if initially randomized to placebo, or continued on their initial APR dose. At Week 24, all patients remaining on placebo were re-randomized to APR20 or APR30. Treatment efficacy at Week 16 was analyzed based on the intent-to-treat population, and analyses at Week 52 and Week 104 were based on data as observed. The WLQ, a 25-item questionnaire that assesses the impact of chronic health conditions on work performance and productivity, was administered at baseline, Week 16, and Week 52. Work limitations were categorized into 4 domains: physical demands (PDS), mental demands (MDS), time management demands (TMS), and output demands (ODS), which were then used to calculate the WLQ index. <h3>Results</h3> For the patients who completed the WLQ, baseline work productivity and work limitations were similar across treatment groups. At Week 16, APR20 and APR30, vs. placebo, were associated with a greater mean change from baseline in PDS, MDS, TMS, and ODS, resulting in a greater mean improvement in the WLQ index (Table), which corresponds to a higher mean percent improvement of productivity loss. Productivity improvements in PDS, MDS, TMS, and ODS were also maintained among patients receiving APR20 and APR30 at Week 52 (Table). <h3>Conclusions</h3> APR20 and APR30 treatment increased work productivity and improved work limitations among patients with active PsA who were not adequately controlled with prior or concurrent conventional DMARDs and/or prior biologics. Improvements in productivity loss were maintained at Week 52 of treatment. <h3>Disclosure of Interest</h3> F. Zhang Employee of: Celgene Corporation, Z. Clancy Employee of: Celgene Corporation, S. Li Employee of: Celgene Corporation
Prospective Observational Study for Dpyd and Ugt1A1 Deficiency-Associated Toxicity in Patients with Metastatic Colorectal Cancer (Mcrc) Receiving Triplet Chemotherapy with Capecitabine, Irinotecan and Oxaliplatin (Coi)
Authors: F.S. Falvella, S. Cheli, C. Maggi, R. Iacovelli, M. Pierotti, M. Gariboldi, A. Martinetti, F.G.M. De Braud, I. Bossi, M. Di Bartolomeo, E. Sottotetti, F. Ricchini, E. Clementi, F. Pietrantonio
Journal: Annals of Oncology (2014)
Rate of psychiatric morbidity in a metropolitan county jail population
Authors: J Petrich
Journal: American Journal of Psychiatry (1976)

The author describes social-psychiatric characteristics of 122 jail inmates examined while awaiting trail, 80% of them on felony charges. The estimated overall rate of psychiatric illness was 4.6%. The patient sample was significantly older and contained significantly more minority group men than the jail population as a whole. Thirty-six percent of the patients diagnosed as schizophrenic were arrested on misdemeanor charges. Drug dependency was diagnosed in 51% of the men but in only 15% of the women. Psychosis was diagnosed more frequently and alcoholism, anxiety neurosis, and antisocial personality less frequently than in studies of prison populations using similar diagnostic criteria.
Six-Year Change in High-Sensitivity Cardiac Troponin T and Risk of Subsequent Coronary Heart Disease, Heart Failure, and Death
Authors: John W. McEvoy, Yuan Chen, Chiadi E. Ndumele, Scott D. Solomon, Vijay Nambi, Christie M. Ballantyne, Roger S. Blumenthal, Josef Coresh, Elizabeth Selvin
Journal: JAMA Cardiology (2016)

High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiovascular risk and could be approved in the United States for clinical use soon. However, data linking long-term temporal change in hs-cTnT to outcomes are limited, particularly in primary prevention settings.To examine the association of 6-year change in hs-cTnT with incident coronary heart disease (CHD), heart failure (HF), and all-cause mortality.This prospective observational cohort study, performed from January 1, 1990, to December 31, 2011, included 8838 participants with biracial representation from the Atherosclerosis Risk in Communities Study who were initially free of CHD and HF and who had hs-cTnT measured twice, 6 years apart. Data analysis was performed from October 28, 2014, to March 9, 2016.Risk factor and temporal hs-cTnT data were collected. Using Cox proportional hazards regression, we examined the association of hs-cTnT change with subsequent CHD, HF, and death during a maximum of 16 years. Improvement in discrimination was determined by the Harrell C statistic.Of the 8838 participants (mean age, 56 years; 5215 female [59.0%]; 1891 black [21.4%]) there were 1157 CHD events, 965 HF events, and 1813 deaths overall. Incident detectable hs-cTnT (baseline, <0.005 ng/mL; follow-up, ≥0.005 ng/mL) was independently associated with subsequent CHD (hazard ratio [HR], 1.4; 95% CI, 1.2-1.6), HF (HR, 2.0; 95% CI, 1.6-2.4), and death (HR, 1.5; 95% CI, 1.3-1.7), relative to an hs-cTnT level less than 0.005 ng/mL at both visits. In addition, HRs as high as 4 for CHD and death and 8 for HF were recorded among individuals with the most marked hs-cTnT increases (eg, baseline, < 0.005 ng/mL; follow-up, ≥0.014 ng/mL). Risk for subsequent outcomes was lower among those with relative hs-cTnT reductions greater than 50% from baseline. Furthermore, information on hs-cTnT change improved discrimination for HF and death when added to a model that included traditional risk factors, N-terminal pro-brain natriuretic peptide, and baseline hs-cTnT level. Among individuals with adjudicated HF hospitalizations, hs-cTnT change appeared to be similarly associated with HF with reduced and preserved ejection fraction.Temporal increases in hs-cTnT, suggestive of progressive myocardial damage, are independently associated with incident CHD, death, and, above all, HF. Serial determination of hs-cTnT trajectory adds clinically relevant information to baseline testing and may be useful in prognostic assessments and the targeting of prevention strategies to high-risk individuals, especially among persons with stage A or B HF.
AB1060 Diagnostic Utility of Ultrasonography in Carpal Tunnel Syndrome Complicated with RA
Authors: K. Fujikawa, A. Mizokami, S.-Y. Kawashiri, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) is one of the risk factors associated with carpal tunnel syndrome (CTS). Ultrasonography is a useful tool for the diagnosis of CTS, but the features of ultrasonography in RA patients complicated with CTS are not well known. <h3>Objectives</h3> To examine the utility of ultrasonography for the diagnosis of CTS complicated with RA. <h3>Methods</h3> Eighteen wrists from the 10 RA patients with CTS (CTS+RA group), 14 wrists from the 8 patients of CTS without RA (CTS group), 42 wrists from the 22 RA patients without CTS (RA group) and 26 wrists from 13 healthy subjects (control group) were assessed by ultrasonography. Diagnosis of CTS was made based on the guideline published from American Academy of Orthopaedic Surgeons (AAOS). Ultrasonography assessment was made according to the methods proposed from OMERACT. We also evaluated the maximum and minimum value of cross-sectional area (CSA) of the median nerves by ultrasonography. We have tried to investigate the characteristics found in ultrasonography of CTS+RA group. <h3>Results</h3> CSA of the median nerves were significantly higher in the CTS patients (CTS+RA and CTS groups) compared with the others (RA and control groups). Receiver operating characteristics (ROC) analysis revealed that maximum value of CSA 12mm<sup>2</sup> was the most powerful predictor toward CTS (CTS+RA and CTS groups) (AUC=0.93; sensitivity 87%, specificity 90% and accuracy 89%). Furthermore, the presence of PD signals (p&lt;0.001) and tenosynovitis (p&lt;0.001) of flexor tendon were significantly high in CTS+RA group as compared with RA group. <h3>Conclusions</h3> CSA measurement of median nerves and the presence of PD signals of median nerves as well as flexor tenosynovitis determined by ultrasonography are considered to be clinically useful indicators to diagnose the patients of CTS complicated with RA. <h3>Disclosure of Interest</h3> None declared
Oral Cholecystography
Authors: Joseph F. Linsman
Journal: JAMA (1974)

<h3>To the Editor.—</h3> I disagree with some remarks in Dr. Harold D. Rosenbaum's article, "An Evaluation of Oral Cholecystography" (229:76, 1974). He is of the opinion that a roentgenogram of the abdomen before the administration of iopanoic acid may provide information that makes cholecystography unnecessary. However, x-ray visualization of calculi in the right upper quadrant along the liver edge does not always mean gallstones, even when they are faceted or otherwise "typical" of gallstones. Confirmation by cholecystography is necessary. This will avoid embarrassment in diagnosis. The following items, in my personal experience, proved, to the embarrassment of surgeons who did not use cholecystography for confirmation, that all apparent gallstones were in fact not biliary: faceted calculi in an obstructed renal pelvis; appendicoliths; clustered calculi in the head of the pancreas in a patient with marked scoliosis of the thoracolumbar junction; peripherally calcified encysted oil droplets in a patient in whom
AB0978 Role of Bone Scan and MRI in the Detection of Bone Inflammation in Chronic Recurrent Multifocal Osteomyelitis (CRMO):
Authors: G. Buckley, M. Easty, S. Compeyrot-Lacassagne, L. Biassoni
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> CRMO is a rare inflammatory bone disorder presenting with relapsing and remitting episodes of bone pain. It affects predominantly females between the age of 9 and 14. Insidious onset of bone pain in one or multiple sites may be associated with localised swelling and warmth. <h3>Objectives</h3> To assess the value of bone scan (BS) and MRI in the detection of bone inflammation. To correlate the imaging findings with inflammatory markers and clinical symptoms/location of pain. <h3>Methods</h3> We performed a retrospective review of the clinical notes of children with a confirmed diagnosis of CRMO who had both bone scan and MRI between September 2009 to September 2014 and within 9 weeks of each other. We recorded for each patient: inflammatory markers at time of scans (ESR, CRP and WCC), clinical symptoms/location of pain. Patients were excluded if both scans were done more than 9 weeks apart or if there was any change to treatment in-between scans. We recorded for both bone scan and MRI the number and the location of lesions. <h3>Results</h3> We identified nine patients (7 females, 2 males) who had CRMO and both bone scan and MRI less than 9 weeks apart. Despite a retrospective design and a small data set, we could observe that inflammatory markers appear non-specific, pain is often associated with a bone lesion on imaging, there are many additional asymptomatic lesions, pain can be referred, MRI and BS are equivalent in 44% of cases, there is no false negatives with BS, MRI is consistently detecting more lesions, BS may be better at detecting lesions in ribs and MRI detects more lesions in the spine. <h3>Conclusions</h3> The nature of these additional lesions seen on MRI is questionable as it is known that bone marrow oedema can be seen in normal children. Specificity and clinical importance of the MRI-positive but bone scan-negative lesions are still contentious issues. High quality BS is essential, with spot view and the right level of reporter experience. BS remains more easily accessible than MRI and contributes to the diagnosis of CRMO. Further studies are needed to establish sensitivity and specificity of both imaging. <h3>Disclosure of Interest</h3> None declared
Mania associated with LSD ingestion
Authors: C R Lake, A L Stirba, R E Kinneman, B Carlson, H C Holloway
Journal: American Journal of Psychiatry (1981)

The authors report a patient who suffered a full-blown manic attack after ingesting LSD or an LSD analogue. The patient experienced acute symptoms of LSD intoxication, which resolved but were followed in about 3 weeks by a typical manic episode of psychotic magnitude. The mania cleared with lithium therapy.
Studies of Survival of Unicellular Species. I. Variations in Life Expectancy of a Paramecium Under Laboratory Conditions
Authors: Spencer, R. R., Melroy, M. B.
Journal: JNCI Journal of the National Cancer Institute (1949)

Journal Article Studies of Survival of Unicellular Species. I. Variations in Life Expectancy of a Paramecium Under Laboratory Conditions Get access R. R. Spencer, R. R. Spencer National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. B. Melroy M. B. Melroy National Cancer Institute, National Institutes of Health, Public Health Service, Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 1, August 1949, Pages 1–10, https://doi.org/10.1093/jnci/10.1.1 Published: 01 August 1949 Article history Received: 10 January 1949 Published: 01 August 1949
PTH-140 Dual modality endoscopic therapy for barrett’s-associated oesophageal dysplasia in a tertiary referral centre: completing the audit cycle
Authors: M Almond, C Florance, O Old, ZC Oliphant, H Barr
Journal: Gut (2015)

<h3>Introduction</h3> The efficacy of dual modality endotherapy with endoscopic resection and mucosal ablation is now well documented in the treatment of Barrett’s-associated early neoplasia. This strategy was supported by a consensus survey of international experts in 2011 with the aim of achieving high rates of complete eradication of dysplasia and intestinal metaplasia (CE-D and CE-IM).<sup>1</sup> This re-audit of clinical practice in a single tertiary oesophagogastric unit aimed to assess whether patients with Barrett’s-associated early neoplasia received dual modality endoscopic therapy in order to achieve CE-D and CE-IM. <h3>Method</h3> In 2011 an audit standard was defined recommending that patients with early glandular neoplasia (high-grade dysplasia (HGD) +/- intramucosal cancer (IMC)) should receive dual modality endoscopic therapy aiming for CE-IM. In the initial audit phase a prospectively maintained database was interrogated between 2004–2011 in order to assess current practice. Changes in practice were implemented following in-house presentation to the oesophagogastric MDT in 2011, and practice and outcomes between 2012–2014 were re-audited. <h3>Results</h3> The initial audit included 72 patients with a median follow-up of 38 months treated by ER +/- ablative therapy with curative intent for HGD (88%) or IMC (12%). The re-audit included 43 patients: LGD 2 (5%), HGD 31 (72%) and IMC 10 (23%), with a median follow-up was 21 months. The use of ablation therapy post-ER was higher in the re-audit group (86% vs 60%; p = 0.003). Rates of CE-D and CE-IM were also higher in the re-audit group (79% vs. 29%; p &lt; 0.001) and (28% vs. 1%; p &lt; 0.001) respectively. Disease progression to invasive cancer (at least T1b) appeared lower in the re-audit group although did not achieve statistical significance (2% Vs. 11%; p = 0.150). <h3>Conclusion</h3> This completed audit cycle demonstrated that use of dual modality endoscopic therapy has increased since 2011. This was associated with higher CE-IM and CE-D rates. Regular audit and re-audit can improve outcomes in patients receiving endoscopic therapy for early Barrett’s-associated neoplasia. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Bennett C, Vakil N, Bergman J, <i>et al</i>. Consensus statements for management of Barrett’s dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process. Gastroenterology. 2012;143(2):336–46
Targeted Cancer Therapy: Correlative Light‐Electron Microscopy Shows RGD‐Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity (Adv. Healthcare Mater. 11/2016)
Authors: Basmah A. Othman, Christina Greenwood, Ayman F. Abuelela, Anil A. Bharath, Shu Chen, Ioannis Theodorou, Trevor Douglas, Maskai Uchida, Mary Ryan, Jasmeen S. Merzaban, Alexandra E. Porter
Journal: Advanced Healthcare Materials (2016)

On page 1310 J. S. Merzaban, A. E. Porter, and co-workers present fluorescently labeled RGD-targeted ZnO nanoparticles (NPs; green) for the targeted delivery of cytotoxic ZnO to integrin αvβ3 receptors expressed on triple negative breast cancer cells. Correlative light-electron microscopy shows that NPs dissolve into ionic Zn2+ (blue) upon uptake and cause apoptosis (red) with intra-tumor heterogeneity, thereby providing a possible strategy for targeted breast cancer therapy. Cover design by Ivan Gromicho.