tbuckley/cabot-search huggingface dataset:
Concern of underdiagnosing asthma–COPD overlap syndrome if age limit of 40 years for asthma is used
Authors: Minna Tommola, Pinja Ilmarinen, Leena E. Tuomisto, Hannu Kankaanranta
Journal: European Respiratory Journal (2017)

In a recent issue of the European Respiratory Journal , Sin et al . [1] presented recommendations on the definition of asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS). The presented conclusions, based on a round table discussion, are very important and notable, especially considering the current lack of specific clinical criteria for ACOS. One of the key recommendations is that asthma or atopy should be diagnosed before age of 40 years (or patients should have very large airway reversibility) in order to fulfil the criteria of ACOS. However, the scientific basis of using the 40-year cut-off remains debatable. In addition, the proposal raises a major concern of underdiagnosing adult-onset asthma and ACOS if the suggested age limit is used. The suggested asthma-onset age limit of 40 as a criterion for ACOS may lead to severe underdiagnosis of ACOS <http://ow.ly/rVSk30ckrOq> We thank senior statistical analyser Timo Partio from the Social Insurance Institution of Finland for providing the data.
08.03 Il-17 and tnf-α induce in synergy an inflammatory response in hepatocytes through il-6-dependent and –independent pathways
Authors: Audrey Beringer, Ndieme Thiam, Jennifer Molle, Birke Bartosch, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-17A (IL-17A) and tumour necrosis factor-alpha (TNF-α) are involved in many autoimmune and inflammatory diseases including rheumatoid arthritis (RA). Many markers produced in response to inflammation by the liver, such are CRP, are associated with an increased risk of cardiovascular disease (CVD). We examined the IL-17A/TNF-α effect in the hepatic inflammatory response, compared to that of IL-6, on HepaRG hepatoma cell line and primary human hepatocytes (PHH). <h3>Materials and methods</h3> HepaRG cells and PHH were cultured with or without IL-6, IL-17A and/or TNF-α. mRNA expression of IL-8, MCP-1 and CCL-20 chemokines and CRP and IL-6 was analysed by qRT-PCR. IL-6 and IL-8 production was measured by ELISA and the aspartate aminotransferase (ASAT) secretion by an automated analyzer. Anti-IL-6 receptor antibody or MAPK inhibitors were added to determine the possible contribution of IL-6 and the signalling pathway mediated by the IL-17A/TNF combination. <h3>Results</h3> IL-17A and TNF-α induced in synergy hepatic IL-6 and IL-8 production (&gt;8 fold, p&lt;0.01). The expression of IL-6, IL-8, MCP-1, CCL-20 and CRP genes was also synergistically up-regulated (47-; 19-; 10-, 70- and 35-fold respectively, p&lt;0.01) by the IL-17A/TNF-α combination in HepaRG cells. IL-8 up-regulation leads to neutrophil recruitment, involved in the acute-phase of inflammation. Furthermore MCP-1 and CCL-20 up-regulation leads to T cell, monocyte and dendritic cell recruitment involved in the chronicity of inflammatory response. The addition of an anti-IL-6 receptor antibody with the IL-17A/TNF-α exposure highly reduced the CRP expression (92% of inhibition, p&lt;0.01) and the ASAT secretion (28% of inhibition, ASAT level similar to control) compared to the IL-17A/TNF-α-stimulated condition. By contrast, IL-8, MCP-1 and CCL-20 up-regulation after IL-17A/TNF-α-stimulation was not affected by IL-6 inhibition. The IL-17A/TNF-α synergistic effect was mediated through the ERK-MAPK-signalling pathway. <h3>Conclusions</h3> IL-17A and TNF-α, acting in synergy, mediate systemic inflammation, by inducing CRP and possibly increasing CVD risk, and liver damage in hepatocytes through the IL-6 pathway. Conversely, the IL-17A/TNF-α combination synergistically increases IL-8, MCP-1 and CCL-20 expression independently of IL-6, leading to the recruitment of immune cells for the initiation and the chronicity of the inflammatory response.
The Identification of Calcified Coronary Plaque Is Associated With Initiation and Continuation of Pharmacological and Lifestyle Preventive Therapies
Authors: Ankur Gupta, Emily Lau, Ravi Varshney, Edward A. Hulten, Michael Cheezum, Marcio S. Bittencourt, Michael J. Blaha, Nathan D. Wong, Roger S. Blumenthal, Matthew J. Budoff, Craig A. Umscheid, Khurram Nasir, Ron Blankstein
Journal: JACC. Cardiovascular imaging (2017)
<i>Pseudomonas aeruginosa</i>LasB protease impairs innate immunity in mice and humans by targeting a lung epithelial cystic fibrosis transmembrane regulator–IL-6–antimicrobial–repair pathway
Authors: Vinciane Saint-Criq, Bérengère Villeret, Fabien Bastaert, Saadé Kheir, Aurélie Hatton, Aurélie Cazes, Zhou Xing, Isabelle Sermet-Gaudelus, Ignacio Garcia-Verdugo, Aleksander Edelman, Jean-Michel Sallenave
Journal: Thorax (2017)

Background Pseudomonas aeruginosa lung infections are a huge problem in ventilator-associated pneumonia, cystic fibrosis (CF) and in chronic obstructive pulmonary disease (COPD) exacerbations. This bacterium secretes virulence factors that may subvert host innate immunity. Objective We evaluated the effect of P. aeruginosa elastase LasB, an important virulence factor secreted by the type II secretion system, on ion transport, innate immune responses and epithelial repair, both in vitro and in vivo. Methods Wild-type (WT) or cystic fibrosis transmembrane conductance regulator (CFTR)-mutated epithelial cells (cell lines and primary cells from patients) were treated with WT or ΔLasB pseudomonas aeruginosa O1 (PAO1) secretomes. The effect of LasB and PAO1 infection was also assessed in vivo in murine models. Results We showed that LasB was the most abundant protein in WT PAO1 secretomes and that it decreased epithelial CFTR expression and activity. In airway epithelial cell lines and primary bronchial epithelial cells, LasB degraded the immune mediators interleukin (IL)-6 and trappin-2, an important epithelial-derived antimicrobial molecule. We further showed that an IL-6/STAT3 signalling pathway was downregulated by LasB, resulting in inhibition of epithelial cell repair. In mice, intranasally instillated LasB induced significant weight loss, inflammation, injury and death. By contrast, we showed that overexpression of IL-6 and trappin-2 protected mice against WT-PAO1-induced death, by upregulating IL-17/IL-22 antimicrobial and repair pathways. Conclusions Our data demonstrate that PAO1 LasB is a major P. aeruginosa secreted factor that modulates ion transport, immune response and tissue repair. Targeting this virulence factor or upregulating protective factors such as IL-6 or antimicrobial molecules such as trappin-2 could be beneficial in P. aeruginosa- infected individuals.
Cell-Type-Specific Translation Profiling Reveals a Novel Strategy for Treating Fragile X Syndrome
Authors: Sophie R. Thomson, Sang S. Seo, Stephanie A. Barnes, Susana R. Louros, Melania Muscas, Owen Dando, Caoimhe Kirby, David J.A. Wyllie, Giles E. Hardingham, Peter C. Kind, Emily K. Osterweil
Journal: Neuron (2017)

Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu1/5) is a core pathophysiology of fragile X syndrome (FX); however, the differentially translating mRNAs that contribute to altered neural function are not known. We used translating ribosome affinity purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1-/y) hippocampus, which exhibit exaggerated mGlu1/5-induced long-term synaptic depression (LTD). In these neurons, we find that the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis of M4 downstream of mGlu5 activation is mimicked and occluded. Surprisingly, enhancement rather than inhibition of M4 activity normalizes core phenotypes in the Fmr1-/y, including excessive protein synthesis, exaggerated mGluR-LTD, and audiogenic seizures. These results suggest that not all excessively translated mRNAs in the Fmr1-/y brain are detrimental, and some may be candidates for enhancement to correct pathological changes in the FX brain.
大うつ病の治療におけるオメガ‐3多価不飽和脂肪酸エイコサペンタエン酸とドコサヘキサエン酸の役割とアルツハイマー病:単独または相乗的に作用する【Powered by NICT】
Authors: Song Cai, Shieh Chu-Hsin, Wu Yi-Shyuan, Kalueff Allan, Gaikwad Siddharth, Su Kuan-Pin
Journal: Progress in Lipid Research (2016)
PTH-124 Centrally mediated disorders, abdominal allodynia and neuropathic pain: the first cohort-specific evaluation of rome iv criteria
Authors: E Kilgallon, DH Vasant, PL Shields, S Hamdy, S Lal, PA Paine
Journal: Gut (2017)

Introduction  Centrally mediated disorders (chronic abdominal pain syndrome (CAPS) and narcotic bowel syndrome (NBS)) have been redefined by Rome IV 1 . We aimed to compare Rome IV and neuropathic pain (NP) 2  criteria performance in a disease specific cohort of chronic continuous or nearly continuous abdominal pain (CCAP).  Method  Patients with unexplained CCAP in a tertiary neurogastroenterology clinic (2009–2016) were initially assessed for ‘clinical’ diagnoses of NP or NBS based on history and presence of cutaneous abdominal allodynia. Other primary functional diagnoses and anterior cutaneous nerve entrapment were excluded. Two independent investigators retrospectively reviewed case notes for Rome IV centrally mediated disorders and NP criteria.  Results  Of 104 referrals (mean age 40 years, 86% female) with CCAP, 92/104 (88%) were initially diagnosed with NP and 12/104, 12% with NBS. NBS compared to NP had greater unresolved or worsened pain despite escalating narcotic doses (p=0.0002), “soar and crash” (p=0.03) and progressive pain (p  Retrospective analysis revealed only 51/104 (49%) met Rome IV criteria of a centrally mediated disorder. In particular, only 42/92 initially diagnosed with NP met CAPS criteria and only 9/12 diagnosed NBS patients met NBS criteria. The main reason (47/50, 94%) for not meeting Rome IV CAPS criteria in non-NBS patients was frequent CCAP exacerbation by ‘physiological events’ (post-prandially (n=37), on defecation (n=8), preceding defecation (n=5) and menstruation (n=2) with some overlap).  By contrast, most patients retrospectively satisfied several NP criteria including 101/104, 97% reporting ‘spontaneous’ pain and 103/104, 99% ‘difficult to manage’. Cutaneous abdominal allodynia was present in 83/104, 80%. NP criteria for ‘shooting pain’ (p=0.04) and cutaneous allodynia (p=0.0002) were associated with opiate use. Pain relieved by applying topical heat and erythema ab igne were associated with opiate non-use (p=0.03).  Conclusion  This first evaluation of Rome IV CAPS and NBS criteria in a disease-specific cohort suggests considerable overlap with NP. Rome IV had low sensitivity compared with NP, due to frequent exacerbation of CCAP by physiological events. This may reflect visceral allodynia and should not preclude a centrally mediated diagnosis. Cutaneous abdominal allodynia is associated with opiate use and may be a marker for opioid-induced hyperalgesia in pre-existing NP.  References  . Keefer, et al. Gastro2016.  . Searle, et al. Br J Anaes2012.  Disclosure of Interest  None Declared
Traitement du reflux gastro-oesophagien par injection d’Enteryx™ dans le cardia: Etude clinique multicentrique française
Authors: R Laugier, D Sautereau, JC Letard, A Lesidaner, F Mion, B Napoléon, T Barrioz, G Gay, JM Canard, JF Rey, M Charbit, T Ponchon
Journal: Endoscopy (2004)

Introduction: Plusieurs traitements endoscopiques du reflux gastro-oesophagien (RGO) ont été disponibles en France ces derniers mois. L’injection intra-cardiale de poly-vinyl-alcool (Enteryx™) a montré son efficacité dans une étude internationale. La SFED a initié une étude clinique multicentrique pour évaluer l’efficacité et les risques d’un tel traitement. Patients et Méthodes: Soixante-trois patients ayant un RGO traité par IPP depuis plus de 3 mois et une pH-métrie montrant un temps de reflux acide > 5% ont été inclus dans cette étude prospective comprenant un suivi de 3 ans. Enteryx™ était injecté, en ambulatoire, dans le muscle cardial sous contrôle scopique et visuel grâce à une aiguille endoscopique. Les symptômes liés au reflux ont été évalués par un score de brûlures et de régurgitations ésophagiennes (type Velanovich) et de qualité de vie (SFQ 12), pendant leur traitement par IPP, sans traitement, puis à 1 et 6 mois, 2 et 3 ans post-procédure. Résultats: Soixante-deux patients ont été traités (dont 7 à 2 reprises) avec 6,7 (± 1,3) mL d’Enteryx injectés en 4,2 (± 1,2) endroits au cours d’examens ayant duré 32,2 (± 12,3) min. 42% des patients ont présenté pendant 1 à 7 jours des douleurs épigastriques, bien soulagées par des antalgiques légers (à comparer avec un pourcentage de 90% de douleurs rapportées dans les études précédentes). Une dysphagie transitoire a été notée dans 39% des cas. A 6 mois, 68,2% des patients étaient sevrés de leur IPP, partiellement ou complètement (54,4%). Les scores moyens de pyrosis avaient significativement diminués de 21,3 ± 9,1 à 6,5 ± 7,1 à 6 mois, ceux de régurgitations de 11,0 ± 5,2 à 2,1 ± 3,6. Conclusion: Les résultats préliminaires de cette étude thérapeutique du RGO par injection d’Enteryx démontrent une excellente sécurité d’emploi et une efficacité marquée par le fait que 68,2% des patients ont pu diminuer significativement leur consommation d’IPP à 6 mois. Ces résultats sont en accord avec les données des autres études internationales.
ポリイミドをベースにした神経内刺激電極の長期有用性とバイオインテグレーション【Powered by NICT】
Authors: S Wurth, M Capogrosso, S Raspopovic, J Gandar, G Federici, N Kinany, A Cutrone, A Piersigilli, N Pavlova, R Guiet, G Taverni, J Rigosa, P Shkorbatova, X Navarro, Q Barraud, G Courtine, S Micera
Journal: Biomaterials (2017)
The new ACR / EULAR Definition of Remission in Rheumatoid Arthritis: Is the Patient Global Assessment Criterion too strict?
Authors: M. Vermeer, H.H. Kuper, Arie E. van der Bijl, H. Baan, M. Posthumus, H. Brus, P.L. van Riel, Mart A F J van de Laar
Journal: Annals of the Rheumatic Diseases (2012)
Maintenance Therapy After Stem-Cell Transplantation for Multiple Myeloma with Bortezomib/Thalidomide Vs. Thalidomide Vs. alfa2b-Interferon: Final Results of a Phase III Pethema/GEM Randomized Trial
Authors: Laura Rosiñnol, Albert Oriol, Ana Isabel Teruel, Dolores Hernández, Javier Lopez-Jimenez, Javier De La Rubia, Miquel Granell, Juan Besalduch, Luis Palomera, Yolanda González, Maria Asunción Etxebeste, Joaquín Díaz-Mediavilla, Miguel Teodoro Hernández, Felipe de Arriba, Adrian Alegre, María Teresa Cibeira, Maria Victoria Mateos, Joaquin Martinez, Juan José Lahuerta, Jesús F San Miguel, Joan Bladé
Journal: Blood (2012)
The Selective Anti Leukemic Effect of BL-8040, a Peptidic CXCR4 Antagonist, Is Mediated By Induction of Leukemic Blast Mobilization, Differentiation and Apoptosis: Results of Correlative Studies from a Ph2a Trial in Acute Myeloid Leukemia
Authors: Gautam Borthakur, Martin S. Tallman, Yishai Ofran, James M. Foran, Geoffrey L Uy, John F DiPersio, Arnon Nagler, Jacob M. Rowe, Margaret M. Showel, Jessica Altman, Ahmed Al-Rawi, Rui-Yu Wang, Amnon Peled, Michal Abraham, Yaron Pereg, Abi Vainstein, Galia Oberkovitz, Tzipi Lustig, Arnon Aharon, Carlos E. Bueso-Ramos, Jorge E. Cortes, Michael Andreeff
Journal: Blood (2016)
Rendement diagnostique de la coloscopie par indication: l’étude multicentrique européenne EPAGE
Authors: JJ Gonvers, V Wietlisbach, B Burnand, JP Vader, F Froehlich
Journal: Endoscopy (2004)

Introduction: Le rendement diagnostique est considéré comme un des paramètres les plus importants d’une procédure diagnostique. La plupart des données concernant le rendement diagnostique de la coloscopie proviennent d’études effectuées dans un seul centre ou un seul pays. Une grande étude européenne multicentrique a ainsi été conduite pour examiner les facteurs déterminants du rendement diagnostique de la coloscopie. Patients et Méthodes: Vingt et un centres (20 européens, 1 canadien) ont participé à cette étude prospective observationnelle. 6004 patients consécutifs référés pour coloscopie (hommes: 48,7%; âge moyen 57,6 ± 15,9 ans) ont été inclus dans l’étude. Les données suivantes ont été évaluées pour chaque patient: données démographiques, indication à la coloscopie, diagnostics endoscopique et histologique. Résultats: L’indication la plus fréquente à la coloscopie était l’hématochésie (17%), suivie des douleurs abdominales non compliquées (13%), du screening pour cancer colo rectal chez des patients asymptomatiques (12%), de la surveillance après polypectomie (11%), des diarrhées non compliquées chez les patients HIV négatifs (8%), de l’anémie ferriprive (7%), de l’évaluation d’une maladie inflammatoire intestinale (7%), de la surveillance après résection d’un cancer colo rectal (7%), de la présence de sang occulte dans les selles (2%). Le rendement diagnostique par indication pour le cancer (C) et les polypes adénomateux (PA) était le suivant: hématochésie C 7,3%; PA 12,3%; anémie ferriprive (hommes et femmes ménopausées) C 11,4%; PA 8,3%; surveillance après polypectomie C 1,5%; PA 28,6%; surveillance après résection de cancer colo rectal C 3,3%; PA 19,1%; screening pour cancer colo rectal chez des patients asymptomatiques C 1%; PA 12%; sang occulte dans les selles C 3,1%; PA 21,1%; douleurs abdominales non compliquées C 3,5%; PA 13%; diarrhées non compliquées C 1,4%; PA 10,2%. Conclusion: Le diagnostic précoce du cancer colo rectal et la résection de polypes adénomateux représentent des buts importants de la coloscopie. En ce qui concerne la détection du cancer colo rectal, l’hématochésie, l’anémie ferriprive, la présence de sang occulte dans les selles ont un rendement diagnostique élevé. Par contre, les symptômes coliques non accompagnés de perte de sang macroscopique ou occulte ont un rendement plus faible. Les indications jouent un rôle moins important dans la détection des polypes adénomateux. Cela est dû à la prévalence élevée de polypes adénomateux asymptomatiques dans la population.
適応高分子足場からの調整可能な用量BMP-2の表面送達は体積骨再生を誘導する【Powered by NICT】
Authors: Bouyer Michael, Guillot Raphael, Lavaud Jonathan, Plettinx Cedric, Olivier Cecile, Curry Veronique, Boutonnat Jean, Coll Jean-Luc, Peyrin Francoise, Josserand Veronique, Bettega Georges, Picart Catherine
Journal: Biomaterials (2016)
An incidental finding on computed tomography scan
Authors: Anan Shtaya, Bassam Dabbous
Journal: BMJ (2017)

A 10 year old girl was referred for a computed tomography (CT) scan of the head after having had intermittent headaches for two months following a head injury (fig 1⇓). On examination, she had bilateral papilloedema. The main finding on the CT scan was a left subacute subdural haematoma. What else is shown in the …
敗血症性ショックに対する治療戦略としてのp22phoxとルビコン相互作用のペプチド阻害【Powered by NICT】
Authors: Kim Ye-Ram, Koh Hyun-Jung, Kim Jae-Sung, Yun Jin-Seung, Jang Kiseok, Lee Joo-Youn, U Jung Jae, Yang Chul-Su
Journal: Biomaterials (2016)
THE EFFECT OF ANKLE TAPING ON SHOCK ABSORPTION CHARACTERISTICS OF LOWER EXTREMITY
Authors: Joon-Haeng Cho, Hyung-pil Jun, Young Hee Lee, Sae Yong Lee
Journal: British Journal of Sports Medicine (2017)

Background Ankle taping has been widely used to prevent recurrent ankle sprain during dynamic tasks. However, it may alter joint stiffness result in an adverse effect on a shock absorption to the entire lower extremity kinetic chain during landing due to a restricted ankle joint. Objective To investigate changes in lower extremity biomechanics with and without taping during drop landing (DL). Design Case control study. Setting Laboratory. Patients (or Participants) A total of active 53 male college students with no history of lower extremity surgery or injury were participated. Interventions Each participant performed eight drop landings (four before and four after ankle taping). Eight infrared-optical cameras system (Vicon Motion Systems Ltd. Oxford, UK) and force-plates (Bertec Corporation. Columbus, OH) were used to collect all kinematics and kinetics during DL. Main Outcome Measurements Sagittal plane joint kinematics and kinetics were extracted between initial contact and maximum knee flexion angle. Cohen's D effect size ( d ) and 95% confidence interval (CI) were calculated to analyze size of difference. Results Sagittal plane total excursion of the ankle was statistically decreased ( d =1.01, CI :0.61∼1.42) but knee and hip were not changed after taping. Joint stiffness showed no significant changes at the ankle ( d =−0.25, CI :−0.63∼0.13), knee ( d =−0.11, CI :−0.49∼0.27), and hip ( d =−0.12, 95% CI :−0.51∼0.26) after taping There were significant decrease in both eccentric work ( d =−0.78, 95% CI :−1.18∼-0.39) and contribution to total work ( d =0.58, C I :0.19∼0.97) at ankle while no changes observed in the knee and the hip. Conclusions Even though ankle taping reduces ankle joint total excursion during DL and may impact on ankle stiffness, it does not alter proximal joint kinematics and stiffness. Reduced both eccentric work and%work at the ankle joint indicates possible changes in shock absorption mechanism during landing. Therefore, the clinicians may consider the importance of proximal joint movement strategy to attenuate shock during landing.
Repeated administration of dapirolizumab pegol in a randomised phase I study is well tolerated and accompanied by improvements in several composite measures of systemic lupus erythematosus disease activity and changes in whole blood transcriptomic profiles
Authors: Chris Chamberlain, Peter J Colman, Ann M Ranger, Linda C Burkly, Geoffrey I Johnston, Christian Otoul, Christian Stach, Miren Zamacona, Thomas Dörner, Murray Urowitz, Falk Hiepe
Journal: Annals of the Rheumatic Diseases (2017)

Objectives Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with diffuse immune cell dysfunction. CD40–CD40 ligand (CD40L) interaction activates B cells, antigen-presenting cells and platelets. CD40L blockade might provide an innovative treatment for systemic autoimmune disorders. We investigated the safety and clinical activity of dapirolizumab pegol, a polyethylene glycol conjugated anti-CD40L Fab' fragment, in patients with SLE. Methods This 32-week randomised, double-blind, multicentre study ( NCT01764594 ) evaluated repeated intravenous administration of dapirolizumab pegol in patients with SLE who were positive for/had history of antidouble stranded DNA/antinuclear antibodies and were on stable doses of immunomodulatory therapies (if applicable). Sixteen patients were randomised to 30 mg/kg dapirolizumab pegol followed by 15 mg/kg every 2 weeks for 10 weeks; eight patients received a matched placebo regimen. Randomisation was stratified by evidence of antiphospholipid antibodies. Patients were followed for 18 weeks after the final dose. Results No serious treatment-emergent adverse events, thromboembolic events or deaths occurred. Adverse events were mild or moderate, transient and resolved without intervention. One patient withdrew due to infection. Efficacy assessments were conducted only in patients with high disease activity at baseline. Five of 11 (46%) dapirolizumab pegol-treated patients achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment response (vs 1/7; 14% placebo) and 5/12 (42%) evaluable for SLE Responder Index-4 responded by week 12 (vs 1/7; 14% placebo). Mechanism-related gene expression changes were observed in blood RNA samples. Conclusions Dapirolizumab pegol could be an effective biological treatment for SLE. Further studies are required to address efficacy and safety. Trial registration number NCT01764594.