tbuckley/cabot-search huggingface dataset:
Abstract 259: Xenon-loaded Echogenic Liposomes Provide Cardioprotection in Acute Myocardial Infarction
Authors: Xing Yin, Yuping Ren, Melvin E Klegerman, Melanie R Moody, Tao Peng, Hyunggun Kim, David D McPherson, Shao-Ling Huang
Journal: Circulation Research (2015)

Background: Acute myocardial infarction (AMI) is a leading cause of sudden cardiac death. Following AMI, left ventricular (LV) remodeling plays an important pathophysiologic role in progression to heart failure (HF). Effective therapeutic approaches to decrease the size of MI can reduce progression to HF. Xenon (Xe), a non-toxic, easily diffusible, noble gas can provide cardiovascular protection. However, delivery of Xe is challenging. Carrier delivery of Xe may be an effective way to deliver this gas to the ischemic area. We have developed Xe-loaded echogenic liposomes (Xe-ELIP) for intravascular delivery of the bioactive gas to the infarct area. Here, we investigate the effect of Xe-ELIP on MI size and LV remodeling in an AMI model. Methods: Xe-ELIP were prepared by a pressurization-freeze method. Rats were randomly divided into 4 groups; sham, AMI control, empty ELIP, and Xe-ELIP at 45 minutes following AMI. AMI was induced by ligating the left anterior descending artery. Liposomes were intravenously administrated immediately after reperfusion. Cardiac function was evaluated by ultrasound at baseline, after AMI, and on day 7. Infarct size was evaluated by TTC staining. Results: Gas chromatography-mass spectrometry demonstrated that 1 mg lipid contains 190 μl Xe. Xe-ELIP treatment decreased end-systolic LV volume (Fig. 1A), improved cardiac output, and reduced infract volume (Fig. 1B, 1C). Conclusion: This novel carrier system allows a therapeutic dose of Xe to reach the ischemic myocardium with resultant all preservation. This methodology can be easily translated for intracoronary injection of Xe-ELIP at the time of coronary intervention at AMI for cellular protection.
05.17 An integrated chemoinformatics-aided pipeline for the discovery of small–molecule dual inhibitors of tnf and rankl
Authors: Dimitra Papadopoulou, Georgia Melagraki, Evangelos Ntougkos, Vagelis Rinotas, Eleni Douni, Antreas Afantitis, George Kollias
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> TNF deregulation plays a critical role in the pathogenesis of a range of immune-mediated diseases. On the other hand, RANKL, a member of the TNF family, regulates osteoclast formation and bone resorption. Inhibitors of these trimeric molecules have been used to treat patients suffering from chronic inflammatory diseases and osteoporosis, respectively. Our aim has been to create an integrated pipeline which through comprehensive computational and experimental methods would lead to the discovery of small molecule dual inhibitors of TNF and RANKL. <h3>Materials and methods</h3> Structure and ligand–based modelling as well as molecular dynamics were applied for the virtual screening and identification of small-molecules that act as dual inhibitors of TNF and RANKL via their shared trimerization interface. The highest ranking compounds were then tested <i>in vitro</i> in the L929 cell assay to assess their ability to inhibit the cytotoxic effect of TNF. Additionally, TNF-TNFRI binding inhibition was tested through ELISA. The successful compounds were also evaluated <i>ex vivo</i> in mouse bone marrow cells stimulated with RANKL and M-CSF to inhibit RANKL-dependent osteoclast differentiation. The cytotoxic effects of the compounds were also assessed. <h3>Results</h3> A consensus predictive model based on several known TNF inhibitors generated a priority list of 9 small molecules as candidates for TNF function inhibition. The model was made freely available through the Enalos Cloud platform. <i>In vitro</i> evaluation of the compounds led to the selection of two small molecules (T8 and T23) that inhibit TNF function, with IC50s similar to a previously-described inhibitor (SPD304), albeit displaying reduced toxicity. Both compounds were found to significantly inhibit RANKL in inducing the formation of osteoclasts. Further screening of compounds using the same approach led to identification of three additional nontoxic inhibitors of TNF that act at a nanomolar range. <h3>Conclusion</h3> Five new small molecule inhibitors of TNF have been identified. Two of them (T8 and T23) have been already confirmed as RANKL inhibitors. The compounds are currently under <i>in vivo</i> evaluation and their further optimisation may contribute to the development of novel dual inhibitor therapeutics.
Risk factors for uterine fibroids: reduced risk associated with oral contraceptives: Authors' reply
Authors: R K Ross, M P Vessey, M C Pike
Journal: BMJ (1986)

As far as we can ascertain the presence of  has not been regarded as a contraindication to oral contraceptive (OC) use in Britain although some authorities suggest that women   who are taking the pill should be kept under observation.  Caution is however also counselled about the use of IUDs in women   so any patient selection is likely to have operated in relation to this birth control method as well; as we noted in our paper there was no relationship  use of an IUD and  in our study.  Perhaps more importantly all women giving a history of  on recruitment to our study were excluded from the analysis (not just those  pathologically confirmed  as incorrectly stated in our paper).  2 further points seem worth making.  Firstly the fact that we found that the protective effect of OCs against  increased  duration of use argues against selection bias being the explanation.  Secondly a substantial number of women in our study 1st started to use OCs during the follow up period having switched from a diaphragm or an IUD.  We found no evidence to suggest that OCs are likely to provoke fibroid complications either in the early months of use or later.  In our view Dr. Ratners hypothesis does not offer an explanation for our findings.  We would like to take this opportunity to point out a number of typographical errors in the article as printed:  on page 360 column 2 line 4 from bottom of page should have read with either 0.25 mg or 0.15 mg levonorgestrel brands; in table 4 the drug name in the 2nd column should have been lynestrenol not lynestrol; and on page 361 column 1 line 5 from bottom of page should have read:  between cervicitis and fibroids not between urinary tract infections and fibroids.  (full text)
P224 Towards person-centred care: development of a patient support needs tool for patients with advanced chronic obstructive pulmonary disease (copd) in primary care
Authors: AC Gardener, G Ewing, M Farquhar
Journal: BMJ (2016)

Introduction  Patients with advanced COPD have difficulty articulating their support needs to clinicians, undermining person-centred care and support. A new approach, the Support Needs Approach for Patients (SNAP), informed by, and modelled on, the evidence-based Carer Support Needs Assessment Tool (CSNAT), may enable patients to identify and express their support needs and start person-centred conversations with clinicians. SNAP is underpinned by an evidence-based tool (a brief set of questions) to help patients consider and express their support needs. This study aimed to develop the SNAP tool, suitable for use in clinical practice.  Methods  Two-stage qualitative study. Stage 1: domains of support need in advanced COPD were identified through a rapid review of the literature, analysis of data from the Living with Breathlessness Study (n = 20 purposively sampled patients with advanced COPD) and patient focus groups. Stage 2: the draft SNAP tool was developed based on the identified domains of support need, then reviewed and refined in stakeholder workshops with patients, carers and clinicians (from primary, secondary and community care, including specialist respiratory care) to ensure acceptability and suitability for clinical practice.  Results  A comprehensive range of evidence-based domains of support need were identified in Stage 1 which were then formulated into questions for inclusion on the draft SNAP tool in Stage 2. The draft tool asks patients to consider whether they need more support in relation to 16 broad areas (domains) of support need such as practical help in the home, knowing what to expect in the future, understanding their condition, getting out and about, and support for their carer. Patients, carers and clinical stakeholders from community respiratory care endorsed the content and wording of the draft SNAP tool and the proposed Support Needs Approach for Patients which it underpins (forthcoming workshops with primary and secondary care clinicians will identify their views which will also be reported).  Discussion  The SNAP tool has the potential to help patients with advanced COPD identify and express their support needs to clinicians in order to enable delivery of person-centred care. Future work will test the tool’s validity and feasibility of use in everyday clinical practice.
AB0792 Current status and unmet needs in the management of psoriatic arthritis with conventional synthetic and biological disease modifying anti-rheumatic drugs: taiwanese nationwide physicians' perspectives
Authors: T-H Li, C-C Lai, C-YT Tsai
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Psoriatic arthritis (PsA) contributes to enormous burden of disease and thus early correct diagnosis and adequate therapeutic management are essential for physicians in practice; however, There have been several studies highlighting the inadequate diagnosis and suboptimal therapies for PsA worldwide and physicians generally report difficulties in managing psoriasis. <h3>Objectives</h3> To analyze the real-world clinical practice of PsA in Taiwan, and assess physicians9 adopted methods and difficulties of diagnosis, therapeutic consideration and strategy, in addition to rationales for biologic agents and unmet needs. <h3>Methods</h3> A nationwide cross-sectional observational study in Taiwan was conducted by means of the face-to-face in depth interviews with the 80 physicians, composed of 50 rheumatologists and 30 dermatologists, from November 2014 to January 2015. <h3>Results</h3> The major adopted diagnostic examinations for PsA are arthritis performance, psoriasis and nail dystrophy, roentgenological studies, personal and family history; however, more dermatologists rely on RF for initial diagnosis (<i>p</i>&lt;0.05). The difficulties for diagnosis, considerations on therapeutic management and current prescription were reported and displayed some interdisciplinary difference. Rationales for biological agent selection were investigated and physicians generally favored etanercept in terms of milder symptoms or more conservative treatment. The main unmet needs for current biologic therapies for PsA included the aspects of better efficacy, safety, sustainability and oral administration. <h3>Conclusions</h3> The nationwide study is the first survey for real-world clinical practice of PsA in Asia and provides detailed messages about the diagnostic difficulties and therapeutic consideration, especially rationales and unmet needs on current biologic therapies, which may offer possible directions for new drug development. We also made interdisciplinary comparison, hence in order to improve comprehensive care. <h3>References</h3> Liu JT, Yeh HM, Liu SY, Chen KT. Psoriatic arthritis: Epidemiology, diagnosis, and treatment. World J Orthop 2014;5:537–43. van de Kerkhof PC, Reich K, Kavanaugh A, et al. Physician perspectives in the management of psoriasis and psoriatic arthritis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis survey. J Eur Acad Dermatol Venereol 2015;29:2002–10. <h3>Disclosure of Interest</h3> None declared
Rapid Virologic Response (RVR), IL28B Single Nucleotide Polymorphism (SNP) rs12980275 and HCV genotype are independent predictors of Sustained Virologic Response (SVR) in HIV/HCV coinfected patients treated with Pegylated Interferon and Ribavirin.
Authors: M. Puoti, L. Covolo, P. Nasta, F. Gatti, F. Suter, C. Mussini, R. Bruno, C. Ferrari, T. Santantonio, V. Di Marco, A. Craxì
Journal: Hepatology (2011)
The Relationship between Cardioembolic Stroke and Vascular Endothelial Dysfunction in Patients with Non-valvular Atrial Fibrillation
Authors: Matsumoto Yuki, Komatsu Takashi, Kunugita Fusanori, Ozawa Mahito, Yoshizawa Reisuke, Morino Yoshihiro, Nakamura Motoyuki
Journal: Circulation (2016)
PTU-081A Initial experience of a nurse-led irritable bowel syndrome clinic
Authors: M Neilson, L Caulfield, Allan J. Morris, Daniel R. Gaya, J W Winter, A Cahill, N Lachlan, Adrian J. Stanley, E H Forrest, R Gillespie, Stephen T. Barclay, Lyn A. Smith
Journal: Gut (2017)

Introduction  Irritable bowel syndrome (IBS) is a common indication for Gastroenterology referral.  We launched a “one-stop” nurse-led clinic for the diagnosis and management of patients with suspected IBS.  Method  With the assistance of a pump priming grant an IBS Clinical Nurse Specialist (CNS) was recruited and trained by the lead gastroenterologist and community dieticians.  GP referrals of patients under 50y with symptoms consistent with IBS without “red flag” symptoms were identified as suitable to be assessed in the clinic.  Three clinics per week were established with consultation times of 30 min per patient. A ‘Suspected IBS Protocol’ for investigation and management was followed.  Data on the final diagnosis, management and re-referral rates were collected prospectively.  Results  Initial analysis is of 18 months of the service. 389 patients were identified, 48 (12%) failed to attend.  Of the 341 patients reviewed 252 (74%) were female and 89 (26%) male. Median age was 32. 67 patients (20%) required further investigation in the form of colonoscopy/flexible sigmoidoscopy/upper GI endoscopy  The final diagnosis was IBS in 264 patients (77%); of which  153 (58%) had IBS-D; 61 (23%) had IBS-C; 46 (17%) had IBS-M and 4 (2%) had post infectious IBS. 52 (15%) of patients had alternative diagnosis made: functional abdominal pain 15 (4.4%); Helicobacter Pylori 7 (2.1%); chronic constipation 6 (1.8%); bile salt malabsorption 4 (1.2%), diverticulosis 3 (0.9%); Crohn’s colitis 2 (0.6%); Colonic schistosomiasis 1 (0.3%); small bowel Crohn’s 1 (0.3%); lactose intolerance 1 (0.3%); gastritis 1 (0.3%), ovarian carcinoma 1 (0.3%); renal carcinoma 1 (0.3%); lymphocytic colitis 1 (0.3%); functional dyspepsia 1 (0.3%); non-coeliac gluten intolerance 1 (0.3%); inappropriate vetting 3 (0.9%). Two (0.6%) patients symptoms had resolved completely prior to review and 1 (0.3%) patient refused consultation. 12 (3.5%) patients defaulted from colonoscopy and have an unclear final diagnosis, 9 (2.6%) of patients failed to supply a stool sample for faecal calprotectin analysis therefore have an unclear final diagnosis. Dietary and lifestyle advice was provided to all patients. Medications were suggested in 140 patients (41%). 4 (1.1%) patients are awaiting investigation. 4 patients (1.1%) have been referred back to the IBS clinic by GP with unresolved symptoms.  Conclusion  The service has been successful in confirming the diagnosis of IBS in the majority of patients. Only a small number have needed referral back to the service.  The advantages of this service are that patients see a specially trained individual with the expertise and time required to manage them and facilitate discharge back to primary care.  Diverting these patients to a CNS clinic can help reduce waiting times for consultant clinics.  Disclosure of Interest  None Declared
PRE-PARTICIPATION CARDIOVASCULAR SCREENING OF ELITE GEORGIAN ADOLESCENT ATHLETES: CLINICAL SIGNIFICANCE AND OUTCOMES
Authors: Lela Maskhulia, Valeri Akhalkatsi, Kakhaber Chelidze, Zurab Kakhabrishvili, Marina Matiashvili, Tamar Chutkerashvili, Ana Gogelia
Journal: British Journal of Sports Medicine (2017)

Background A variety of cardiovascular abnormalities have been found to be responsible for sudden cardiac death(SCD) in competitive athletes. The lesions responsible for athletic field deaths differ with regard to age and vast majority of SCD occur in athletes aged &lt;18 yrs. Appropriate pre-participation screening (PPS) of young competitive athletes can reduce their risk for SCD. Objective To analyse cardiovascular findings obtained in the pre-participation screening of elite Georgian adolescent athletes. Design Observational follow-up study. Setting Sports Medicine and Rehabilitation Clinical Centre. Patients 227 asymptomatic elite adolescent athletes (83% males), age 15,4±1,6 years, representatives of national teams of 9 sporting disciplines. Interventions The participants underwent cardiovascular(CV) evaluation with medical history, physical examination, 12-lead resting and exercise ECG, and transthoracic echocardiography (TTE) in 2013–2015. Main Outcome Measurements The participants were followed prospectively until July 2015 with respect to clinically significant cardiovascular abnormalities, and until July 2016 with respect to safe return to sport. Results Resting ECG revealed common/training–related ECG alterations in 70 (31%) athletes, as well as uncommon/training-unrelated changes in 5 (2,2%). TTE revealed mitral valve prolapse in 8(3,5%) athletes, bicuspid aortic valve in 1(0,4%), and signs consistent with anomalous origin of left coronary artery from the pulmonary artery(ALCAPA) in 1 (0,4%) athlete. Stress test revealed decreased exercise tolerance and negative T-waves in V4-V6 in this athlete. Athlete was directed to further CV investigation and CT angiography led to the diagnosis of ALCAPA. Coronary artery bypass grafting was performed. After treatment athlete underwent cardiac rehabilitation program and risk-stratification before entering sports activity. As subendocardial ischemic pattern still existed, the athlete was advised against current participation in competitive sports. Follow-up over a longer period has been planned. Conclusions PPS is significant tool to identify adolescent athletes at risk for exercise-induced SCD. As coronary anomalies are among the common reasons for SCD in young athletes, timely identification and appropriate clinical management, including considerations regarding safe return to sport are necessary.
BIOMECHANICAL CHANGES WITH FIFA11+ UTILIZATION OVER MULTIPLE SOCCER SEASONS
Authors: Amelia Arundale, Holly Silvers-Granelli, Adam Marmon, Ryan Zarzycki, Celeste Dix, Lynn Snyder-Mackler
Journal: British Journal of Sports Medicine (2017)

Background The FIFA11+ is a dynamic warm-up injury prevention program. Previous studies have examined its efficacy in reducing injuries, however no information is available on whether it changes targeted movement patterns. Objective The purpose of this study was to examine the changes in peak knee abduction moment (PKAM) over two soccer seasons using the FIFA11+. We hypothesized that athletes will have decreased PKAM over the first season, no changes in the off-season, and further decreases over the second season. Design Prospective non-randomized intervention study (control team data currently being collected). Setting Elite collegiate women's soccer. Patients (or Participants) First season N=83, off-season N=68, second season N=59. Interventions The FIFA11+ program was initiated during the preseason and completed throughout two consecutive soccer seasons as a warm-up prior to training sessions and games at least 3x/week. Researchers did not influence the training during the off-season. Main Outcome Measurements PKAM measured during motion analysis of a drop jump at pre- and postseason of two consecutive seasons. Repeated measures ANCOVAs were used to analyse the change over each season and the off-season, with baseline PKAM included in each model as a covariate. Results There was a significant main effect of time over the first season (preseason 0.24±0.01, postseason 0.23±0.01, p=0.02). PKAM was a significant covariate (p&lt;0.01). There no main effect of time over the off-season (p=0.40), however, PKAM was a significant covariate (p&lt;0.01). There was also no main effect of time over the second season (p=0.29), with PKAM again a significant covariate (p&lt;0.01). Conclusions The FIFA11+ is effective in preventing injuries, however its mechanism is unknown. The preliminary results of this study indicate this injury reduction may not be occurring as a result of a decrease in PKAM in all athletes.
Inducible Activation of MyD88 and CD40 in CAR T Cells Results in Controllable and Potent Antitumor Activity in Preclinical Solid Tumor Models
Authors: Melinda Mata, Claudia Gerken, Phuong Nguyen, Giedre Krenciute, David M. Spencer, Stephen Gottschalk
Journal: Cancer Discovery (2017)

Adoptive immunotherapy with T cells expressing chimeric antigen receptors (CAR) has had limited success for solid tumors in early-phase clinical studies. We reasoned that introducing into CAR T cells an inducible costimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets in vitro relative to HER2ζ.iCO T cells without CID and T cells expressing HER2-CAR.CD28ζ. HER2ζ.iCO T cells with CID also significantly improved survival in vivo in two xenograft models. Repeat injections of CID were able to further increase the antitumor activity of HER2ζ.iCO T cells in vivo Thus, expressing MyD88/CD40-based iCO molecules in CAR T cells has the potential to improve the efficacy of CAR T-cell therapy approaches for solid tumors.Significance: Inducible activation of MyD88 and CD40 in CAR T cells with a small-molecule drug not only enhances their effector function, resulting in potent antitumor activity in preclinical solid tumors, but also enables their remote control post infusion. Cancer Discov; 7(11); 1306-19. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1201.