tbuckley/cabot-search huggingface dataset:
Abstract 18428: Implication of HDAC1/HDAC2 in Paracrine Protection of Mesenchymal Stem Cells Following Acute Myocardial Ischemia
Authors: Meijing Wang, Lina Wang, Mark Turrentine
Journal: Circulation (2013)

INTRODUCTION: We have previously indicated that inhibition of histone deacetylase1 (HDAC1) or HDAC2 promoted cardiomyogenic potential of mesenchymal stem cells (MSCs). But little is known regarding implication of HDAC1 or HDAC2 in MSC-induced paracrine protection. We and others have shown that MSCs mediate their beneficial effects primarily via paracrine action. In this study, therefore, we hypothesize that MSCs with specific inhibition of HDAC1 or HDAC2 not only possess increased cardiomyogenesis, but are able to acutely improve cardiac function following ischemia/reperfusion (I/R). METHODS: MSCs were isolated from bone marrow (femur/tibia) of C57BL mice, and transfected with siRNAs of scramble, HDAC1, or HDAC2. Conditioned medium (CM) was collected from these transfected MSCs. Cardiac I/R was performed in isolated mouse hearts via Langendorff. 1.5ml CM was infused immediately before ischemia. Heart tissue was studied for activation of STAT3 and caspase3. Data were analyzed with two-way ANOVA, p&lt;0.05=statistically significant. RESULTS: Decreased HDAC1 or HDAC2 expression was observed in HDAC1 or HDAC2 siRNA transfected MSCs (Figure A). Inhibition of HDAC1 or HDAC2 resulted in increased expression of cardiac α-MHC , troponin I, and troponin T. Infusion of CM from MSC transfected with HDAC1 siRNA or HDAC2 siRNA significantly improved myocardial function following acute I/R as did CM from the cells treated with scramble siRNA (Figure B). Increased activation of myocardial STAT3 (a pro-survival signaling) was noticed among CM-pretreated groups after I/R compared to media control, whereas active caspase3 was reduced in these groups (Figure C). Conclusion: Our results represented initial evidence, showing that specific inhibition of HDAC1 or HDAC2 not only increased cardiomyogenesis of MSCs, but retained their paracrine protection following acute I/R. This study provides new understanding for modification of MSCs to optimize their therapeutic efficacy.
THU0341 MICRORNA27A3P REGULATES WNT SIGNALLING BY TARGETING SFRP-1 IN SYSTEMIC SCLEROSIS
Authors: Steven O’Reilly
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune idiopathic connective tissue disease that results in fibrosis of the skin and lungs. Wnt signaling is a highly conserved signaling pathways that is involved in organogenesis and tissue homeostasis. In recent years it has emerged that aberrant Wnt signaling is key in SSc and animal models of the disease. The Wnt pathway comprises of secreted glycoproteins that bind to specific receptors that initiate the pathway and result in beta catenin stabilization. However, secreted antagonists are secreted to block and negatively regulate Wnt signaling. We and others have found reduced sFRP-1 in SSc, a key Wnt antagonist. Although lower in SSc skin and isolated fibroblast from patients the mechanism governing this is unknown. This work seeks to identify epigenetic mechanisms. <h3>Objectives</h3> Determine the epigenetic regulation of sFRP-1 in SSc. <h3>Methods</h3> Serum sFRP-1 was measured in healthy and diffuse SSc patients to ascertain the levels of sFRP-1. Mir27a was identified as a possible microRNA that targets sFRP1 using in silico modeling. miR27a was transfected into healthy dermal fibroblasts using transfection methods and sFRP-1 was measured. Collagen was also measured by western blotting after transfection. MiR27a was also measured in SSc dermal fibroblasts using specific Taqman probes and normalized to RNU44 miR. Cloning of the 3'UTR of sFRP1 into a luciferase reporter vector was performed and then transfected into HEK293 cells with miR27a mimics or with concentration matched scramble and after 24 hours luciferase was monitored. <h3>Results</h3> Significantly reduced expression of sFRP-1 was found in SSc serum compared to controls (n=10). SSc dermal fibroblasts had 3 fold higher levels of miR27a compared to healthy fibroblasts. Increased miR27a in healthy dermal fibroblasts resulted in significantly less sFRP-1 secreted into conditioned media and this was co-incident with an increase of collagen1 levels. Finally cloning of the 3'UTR binding site in a luciferase plasmid and overexpression of miR27a led to reduced levels of luciferase in HEK293 cells in vitro. <h3>Conclusion</h3> Reduced sFRP-1 in systemic sclerosis is mediated by miR27a and this leads to fibrosis via enhanced Wnt signaling. Targeting the epigenetic changes that mediate this may be a therapy in SSc. <h3>Disclosure of Interests</h3> None declared
Abstract 17260: Prognostic Impact of Wasting Syndrome in Patients Admitted for Acute Decompensated Heart Failure With Reduced or Preserved Left Ventricular Ejection Fraction
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Jun Nakamura, Makoto Abe, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Circulation (2017)

Backgrounds: Congestive heart failure is one of a number of disorders associated with the development of wasting syndrome. Previous studies have reported reduced mortality rates in heart failure pa...
Renal Denervation Update From the International Sympathetic Nervous System Summit
Authors: Márcio G. Kiuchi, Murray D. Esler, Gregory D. Fink, John W. Osborn, Christopher T. Banek, Michael Böhm, Kate M. Denton, Gerald F. DiBona, Thomas H. Everett, Guido Grassi, Richard E. Katholi, Mark M. Knuepfer, Ulla C. Kopp, David J. Lefer, Thomas E. Lohmeier, Clive N. May, Felix Mahfoud, Julian F.R. Paton, Roland E. Schmieder, Peter R. Pellegrino, Yehonatan Sharabi, Markus P. Schlaich
Journal: Journal of the American College of Cardiology (2019)
Absolute Risk Estimates of the Association Between Concussion and Suicide—Reply
Authors: Michael Fralick, Eric Sy, Todd Karsies
Journal: JAMA Neurology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
SP0198 CASE 1 DISCUSSANT: HOW TO DIFFERENTIATE ILD FROM OTHER CAUSES OF LUNG INVOLVEMENT IN RA
Authors: Ivan Castellvi
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The lung in Rheumatoid Arthritis (RA) can be affected by different manifestations and Interstitial Lung Disease (ILD) related to RA is one of the most devastating complications that we can find in the disease. The lung parenchyma involvement can be present with different patterns. As opposite with other forms of connective tissue diseases the usual interstitial pneumonia pattern (UIP) is more frequent than nonspecific interstitial pneumonia pattern (NSIP) in RA. Currently high-resolution computed tomography (<b>HRCT</b>) and pulmonary function test are the best tools to detect and to follow ILD in RA. Nevertheless, other lung involvements, infections and drug toxicity of nonbiological and biological disease-modifying antirheumatic drugs (DMARDs) can affect patients with rheumatoid arthritis and simulate ILD. To know which affectation are present in our patients with interstitial lung compromise is crucial to proceed against the problem. Patient characteristics, clinical presentation, radiological distribution or bronchoalveolar lavage would be helpful to discriminate ILD from other causes of lung involvement. An individual and multidisciplinary approach is very important to do the best management in these patients. <h3>Disclosure of Interests:</h3> None declared
AB0350 RHEUMATOID ARTHRITIS MANAGEMENT IN SOUTHEAST TURKEY, EXPERIENCE FROM RURAL AREA
Authors: Senem Tekeoglu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis is a chronic disease affecting more commonly women in all age groups. Access to healthcare, taking part in decision making and compliance with the treatment are very important in management. In Turkey, after completion of their fellowships, rheumatologist work for a limited time in state hospitals mandatorily (especially in under-developed cities of the country). Batman city lies in the southeast of Turkey with a population of 585.000 people; 7% of whom is illiterate. Due to ethnic and cultural reasons women suffer more commonly in obtaining and maintaining education and healthcare. <h3>Objectives</h3> To define the clinical characteristics, adherence to follow-up appointments and treatments ever received in patients with rheumatoid arthritis in Batman State Hospital. <h3>Methods</h3> Hospital records between July 15th 2017 and January 1st 2019 were viewed retrospectively. Only 1 rheumatologist works in the hospital. Appointments were scheduled between 1-3 months intervals, patients were defined as 'lost to follow-up' if there was no clinical appointment in last 3 months. Patients were categorized as recently or formerly diagnosed and according to receiving conventional synthetic disease modifying agents (DMARDs) (methotrexate, leflunomide, hydroxy-chloroquine, sulfasalazine) or biologic DMARDs (adalimumab, etanercept, infliximab, golimumab, certolizumab pegol, rituximab, tociluzimab, abatacept, tofacitinib). Most of the patients received low-dose steroids. <h3>Results</h3> Patient characteristics and treatments are displayed in the table. Follow-up duration for the patients who continued follow-ups was 8.9 months on average (max: 17 months). Average follow-up duration for patients who lost to follow-up was 2.8 months (min: 1 month, max:13 months). Seventy-one of 146 patients who lost to follow-up came to appointment only once. Route of administration was very important in biological treatment decisions, oral treatments and intravenous administration in hospital were favored over subcutaneous administration especially for elderly illiterate patients. <h3>Conclusion</h3> Even though management goal is directed at remission induction in the earliest stages of rheumatoid arthritis with molecular targeted therapies in most of the developed countries, in rural parts of the developing countries low rate of adherence to follow-up appointments and medications is still an important difficulty in management. Patients receiving biologic DMARDs have higher adherence to treatment. Awareness and education of patients in rheumatoid arthritis, as well as in all chronic diseases, is most important aspect of management. <h3>Disclosure of Interests</h3> None declared
AB0854 PERSPECTIVES OF WOMEN WITH EXPERIENCE OF A FRAGILITY FRACTURE IN EUROPE: ATTITUDES TOWARDS FUTURE FRACTURE RISK, OSTEOPOROSIS AND PHARMACOTHERAPY
Authors: Charles Chaine, Peter Ray, Jen Timoshanko
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Fragility fractures (FF) are common in women &gt;50 years (yrs), with 1 in 3 experiencing a fracture (Fx).<sup>1</sup> However, the cause of these Fx is poorly recognised and measures taken to prevent future Fx are often inadequate. Recent US patient (pt) survey data suggest that awareness of osteoporosis (OP) and its contribution to Fx risk, appreciation of the benefits of OP pharmacotherapy (Rx), and discussion about OP with healthcare professionals (HCPs) are limited.<sup>2</sup> <h3>Objectives</h3> This study gained insight into the attitudes and experiences of post-FF women in Europe regarding future Fx risk management. <h3>Methods</h3> Women ≥51 yrs from Germany (DE), Spain (ES), UK, France (FR) and Italy (IT) (EU5) with self-reported experience of a FF completed a 30–min online survey (AplusA; 13–20 Feb 2018). Data are reported for EU5 pts who had their first Fx at ≥50 yrs; pts whose first Fx was a hand/finger or ankle/foot/toe Fx were excluded. <h3>Results</h3> 199 women participated (DE: 38; ES: 36; UK: 41; FR: 34; IT:50). The most commonly experienced Fx was of the lower arm/wrist (43%). 43% reported &gt;1 Fx (any type). Most women discussed bone health with an HCP within 6 months (mo) (70%; 42% with a GP) and HCPs were their primary source of information on OP (85%). Around a third reported taking a DEXA test within 6 mo of their first FF (37%). Advice from HCPs to prevent Fx focused on calcium/vitamin D supplements (74%) and diet/exercise changes (54%); 46% were prescribed OP-Rx. After having a FF, around half worried about future Fx (51%) and 39% voiced concerns about their general health (Figure). A third of pts thought that OP had caused their Fx (33%), most were likely to attribute it to a fall (67%). Only 18% felt empowered to manage their bone health; 61% did not think OP-Rx reduces risk of Fx or were unsure. 97% had never joined a support group. <h3>Conclusion</h3> These results indicate that pts discuss future Fx risk with an HCP soon after having a FF and are concerned about future Fx. However, low levels of DEXA testing and OP-Rx, and poor awareness of the link between OP and Fx risk remain. Better education to empower women at risk of FF is critical. <h3>Reference</h3> [1] Hernlund E. Arch Osteoporos2013;8:136; 2. Boudreau D. J Am Geriatr Soc2017;65:1829–35. <h3>Acknowledgement</h3> The study was funded by UCB Pharma and Amgen, conducted by AplusA, medical writing by Arianna Psichas, Costello Medical, UK <h3>Disclosure of Interests</h3> Charles Chaine: None declared, Peter Ray: None declared, Jen Timoshanko Employee of: UCB Pharma
Abstract 20926: Sex-Specific Cardioprotective Effects of Annexin A1 Peptide Mimetic Involve the Sirtuin 3 Signaling Pathway
Authors: Zhiquan Zhang, Qing Ma, Alina Nicoara, Quintin Quinones, Matthew Hirschey, Mihai V Podgoreanu
Journal: Circulation (2016)

Introduction: We reported cardioprotective efficacy of a novel Annexin-A1 peptide mimetic (Ac10-12, ANXA1sp) in multiple experimental models of cold myocardial ischemia-reperfusion (IR), across spe...
AB0182 RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B LIGAND (RANKL)/RANK AND OSTEOPROTEGERIN (OPG) PATHWAY ACTIVATION IN SJöGREN’S SYNDROME
Authors: Charalampos Skarlis, Eleni Palli, Adrianos Nezos, Clio Mavragani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Primary Sjogren's syndrome (SS) is an autoimmune exocrinopathy characterized by chronic salivary and lacrimal glands dysfunction. Recent studies suggest that activation of the receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK and osteoprotegerin (OPG) pathway is implicated in the development of autoimmunity. <h3>Objectives:</h3> The aim of this study is to investigate the contribution of RANK/RANKL/OPG pathway in primary SS pathogenesis. <h3>Methods:</h3> Sixty-six primary SS patients fulfilling the American/European criteria and 13 subjects with oral and/or ocular dryness without satisfying the aforementioned criteria (sicca controls, SC) and 11 healthy controls (HC) have been enrolled. RANKL and OPG serum levels were determined by ELISA in 29 SS patients and 11 HC. Total RNA was extracted from minor salivary glands biopsies (MSG) from 43 SS patients and 13 SC and RANKL mRNA expression was assessed by qRT-PCR. Protein expression of RANKL was determined by Western Blot and immunohistochemistry (IHC) in total protein extract and paraffin embedded tissue respectively, derived from MSG biopsies of 6 primary SS patients and 5 SC. Statistical analysis was performed with SPSS 24.0 package. <h3>Results:</h3> Increased serum levels (pg/ml) of RANKL (mean±SD=4.197±897.6vs mean±SD=144.8±290.2, p=0.013) and OPG (mean±SD=173.4±57.52, mean±SD=48.42±21.89, p=0.015) were detected in SS patients compared to HC. Higher RANKL at both mRNA and protein level by IHC were detected, in MSG derived from primary SS patients compared to SC. RANKL protein expression was significantly increased in MSG biopsies from primary SS patients compared to SC by Western Blot (mean±SD=2.468±1.896 vs mean±SD=0.5138±0.823, p=0.0335). <h3>Conclusion:</h3> Increased serum levels, mRNA and protein expression of RANKL in association with increased OPG titers in SS patients compared to controls, suggests that the activation of RANK/RANKL/OPG pathway contributes to SS pathogenesis. <h3>References</h3> [1] Skopouli, F. N. &amp; Moutsopoulos, H. M. Autoimmune epitheliitis: Sjögren's syndrome. Clin. Exp. Rheumatol. 12Suppl 11, S9-11 (1994). [2] Assmann, G. et al. Genetic variations in genes encoding RANK, RANKL, and OPG in rheumatoid arthritis: a case-control study. J. Rheumatol. 37, 900–904 (2010). <h3>Acknowledgement:</h3> Research Grant from the Greek Rheumatology Society and Professional Association of Rheumatologists <h3>Disclosure of Interests:</h3> None declared
Neoadjuvant chemotherapy (NACT) with DCF regimen in stage III, squamous cell cancer: Esophagus followed by oesophagectomy—Indian experience.
Authors: S. P. Somashekhar, Amit Rauthan, Shabber Zaveri, Poonam Patil, Soumya Holla
Journal: Journal of Clinical Oncology (2012)

e14710 Background: Despite improved surgical techniques and peri-operative care in cancer of the esophagus, the 5 yr OS is 10%. Additional therapy could improve prognosis. At least 10 RCTs comparing NACT to surgery alone have demonstrated a significant increase in median survival of 17 months in the former, compared to 13 months in the latter. We aimed at studying impact of NACT in Indian patients and its impact on surgery and outcome. Methods: The study – Prospective non-randomised study. Between 2007-12, 20 patients were included to analyze the benefit of NACT with DCF (docetaxel 75mg/m 2 day 1, cisplatin 75mg/m 2 day 1, 5-FU 750mg/m 2 per day 1-4) regimen, in stage III Ca. Esophagus, assessed by EUS and PET-CT scan , pre-chemo and post-chemo, in biopsy proven Squamous cell Carcinoma Oesophagus. Prophylactic growth factors were used in all cycles. Results: Post NACT, Partial response of 58.8%, and a complete pathological response of 17.6% were observed with response rage of 76.4%. NACT x 3 cycles used. 4 pt.s had mucositis, but none had grade 3 toxicity, neutropenia in 4 pt.s and febrile neutropenia in only one pt., vomiting and fatige in 5 pt.s . Surgery post NACT was, very easy and there was no significant morbidity, or surgical complication nor any mortality observed due to NACT. On follow-up, two patients died due to systemic recurrence and progression disease progression. Two patients had regional and one patient had , non-regional lymph node disease recurrence. In remaining 16 patients, till to date there is no recurrences and are disease free. All but 2 patients are alive to date. Conclusions: The response rate to NACT (TPF-Regimen) is 76.4%, with maximum benefit in the complete responders. NACT has no adverse impact on the surgical outcome. Surgery is done with acceptable morbidity and very low mortality. Surgical resection post NACT was easy. Impact of this regimen on DFS and OS, have to be ascertained over time.
The Demographic and Adaptive History of the African Green Monkey
Authors: Susanne P. Pfeifer
Journal: Molecular Biology and Evolution (2017)

Relatively little is known about the evolutionary history of the African green monkey (genus Chlorocebus) due to the lack of sampled polymorphism data from wild populations. Yet, this characterization of genetic diversity is not only critical for a better understanding of their own history, but also for human biomedical research given that they are one of the most widely used primate models. Here, I analyze the demographic and selective history of the African green monkey, utilizing one of the most comprehensive catalogs of wild genetic diversity to date, consisting of 1,795,643 autosomal single nucleotide polymorphisms in 25 individuals, representing all five major populations: C. a. aethiops, C. a. cynosurus, C. a. pygerythrus, C. a. sabaeus, and C. a tantalus. Assuming a mutation rate of 5.9 × 10-9 per base pair per generation and a generation time of 8.5 years, divergence time estimates range from 523 to 621 kya for the basal split of C. a. aethiops from the other four populations. Importantly, the resulting tree characterizing the relationship and split-times between these populations differs significantly from that presented in the original genome paper, owing to their neglect of within-population variation when calculating between population-divergence. In addition, I find that the demographic history of all five populations is well explained by a model of population fragmentation and isolation, rather than novel colonization events. Finally, utilizing these demographic models as a null, I investigate the selective history of the populations, identifying candidate regions potentially related to adaptation in response to pathogen exposure.