tbuckley/cabot-search huggingface dataset:
IL-4 subverts mycobacterial containment in<i>Mycobacterium tuberculosis</i>-infected human macrophages
Authors: Anil Pooran, Malika Davids, Andrew Nel, Aubrey Shoko, Jonathan Blackburn, Keertan Dheda
Journal: European Respiratory Journal (2019)

Protective immunity against Mycobacterium tuberculosis is poorly understood. The role of interleukin (IL)-4, the archetypal T-helper type 2 (Th2) cytokine, in the immunopathogenesis of human tuberculosis remains unclear.Blood and/or bronchoalveolar lavage fluid (BAL) were obtained from participants with pulmonary tuberculosis (TB) (n=23) and presumed latent TB infection (LTBI) (n=22). Messenger RNA expression levels of interferon (IFN)-γ, IL-4 and its splice variant IL-4δ2 were determined by real-time PCR. The effect of human recombinant (hr)IL-4 on mycobacterial survival/containment (CFU·mL-1) was evaluated in M. tuberculosis-infected macrophages co-cultured with mycobacterial antigen-primed effector T-cells. Regulatory T-cell (Treg) and Th1 cytokine levels were evaluated using flow cytometry.In blood, but not BAL, IL-4 mRNA levels (p=0.02) and the IL-4/IFN-γ ratio (p=0.01) was higher in TB versus LTBI. hrIL-4 reduced mycobacterial containment in infected macrophages (p<0.008) in a dose-dependent manner and was associated with an increase in Tregs (p<0.001), but decreased CD4+Th1 cytokine levels (CD4+IFN-γ+ p<0.001; CD4+TNFα+ p=0.01). Blocking IL-4 significantly neutralised mycobacterial containment (p=0.03), CD4+IFNγ+ levels (p=0.03) and Treg expression (p=0.03).IL-4 can subvert mycobacterial containment in human macrophages, probably via perturbations in Treg and Th1-linked pathways. These data may have implications for the design of effective TB vaccines and host-directed therapies.
ENDOSCOPIC BILIARY LARGE BALLOON DILATION LITHOTRIPSY (“BALLOON LITHOTRIPSY”) FOR DIFFICULT BILE DUCT STONES REMOVAL
Authors: J Pereira Lima, G Pereira Lima, I Contin, ID Arciniegas, C Saul, CE Oliveira dos Santos
Journal: Endoscopy (2019)

Endoscopic removal of multiple, large or impacted stones, in which a lithotriptor basket cannot be deployed or is unable to grasp the stone(s), is challenging, and inevitably leads to repeat procedures such as stent insertion and extra or intracorporal lithotripsy. The aim of this study is to evaluate the safety and efficacy of “endoscopic billiary dilation balloon lithotripsy” (EBBD, a novel technique) for difficult stones, which were not amenable to basket or balloon retrieval after papillotomy and papillary large balloon dilation.
Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation
Authors: Daniela Egli-Spichtig, Pedro Henrique Imenez Silva, Bob Glaudemans, Nicole Gehring, Carla Bettoni, Martin Y.H. Zhang, Eva M. Pastor-Arroyo, Désirée Schönenberger, Michal Rajski, David Hoogewijs, Felix Knauf, Benjamin Misselwitz, Isabelle Frey-Wagner, Gerhard Rogler, Daniel Ackermann, Belen Ponte, Menno Pruijm, Alexander Leichtle, Georg-Martin Fiedler, Murielle Bochud, Virginia Ballotta, Sandra Hofmann, Farzana Perwad, Michael Föller, Florian Lang, Roland H. Wenger, Ian Frew, Carsten A. Wagner
Journal: Kidney International (2019)
RELMα-expressing macrophages protect against fatal lung damage and reduce parasite burden during helminth infection
Authors: Branislav Krljanac, Christoph Schubart, Ronald Naumann, Stefan Wirtz, Stephan Culemann, Gerhard Krönke, David Voehringer
Journal: Science Immunology (2019)

RetnlaCre fate mapping mice reveal differentiation, tissue localization, and in vivo functions of RELMα + macrophages.
Immunometabolic function of cholesterol in cardiovascular disease and beyond
Authors: Laurent Yvan-Charvet, Fabrizia Bonacina, Rodolphe Renè Guinamard, Giuseppe Danilo Norata
Journal: Cardiovascular Research (2019)

Abstract Inflammation represents the driving feature of many diseases, including atherosclerosis, cancer, autoimmunity and infections. It is now established that metabolic processes shape a proper immune response and within this context the alteration in cellular cholesterol homeostasis has emerged as a culprit of many metabolic abnormalities observed in chronic inflammatory diseases. Cholesterol accumulation supports the inflammatory response of myeloid cells (i.e. augmentation of toll-like receptor signalling, inflammasome activation, and production of monocytes and neutrophils) which is beneficial in the response to infections, but worsens diseases associated with chronic metabolic inflammation including atherosclerosis. In addition to the innate immune system, cells of adaptive immunity, upon activation, have also been shown to undergo a reprogramming of cellular cholesterol metabolism, which results in the amplification of inflammatory responses. Aim of this review is to discuss (i) the molecular mechanisms linking cellular cholesterol metabolism to specific immune functions; (ii) how cellular cholesterol accumulation sustains chronic inflammatory diseases such as atherosclerosis; (iii) the immunometabolic profile of patients with defects of genes affecting cholesterol metabolism including familial hypercholesterolaemia, cholesteryl ester storage disease, Niemann–Pick type C, and immunoglobulin D syndrome/mevalonate kinase deficiency. Available data indicate that cholesterol immunometabolism plays a key role in directing immune cells function and set the stage for investigating the repurposing of existing ‘metabolic’ drugs to modulate the immune response.
TOLERANCE AND EFFICACY OF A NOVEL LOW-VOLUME PEG + ASCORBATE (NER1006) PREPARATION IN THE ELDERLY: A REAL-LIFE SINGLE CENTER STUDY
Authors: A Oliveira, M Mascarenhas-Saraiva
Journal: Endoscopy (2019)

A low-volume preparation with Polyethylene Glycol (PEG) and Ascorbate (PEG-Asc) – NER1006 was recently launched, however, its efficacy and tolerance in the elderly population remain unclear. We evaluated efficacy, tolerance, and acceptability of the NER1006 (1L) preparation, in comparison to the standard PEG-Asc 2L preparation, in elderly patients.
Multifunctional iron-based Metal−Organic framework as biodegradable nanozyme for microwave enhancing dynamic therapy
Authors: Xiaoyan Ma, Xiangling Ren, Xudong Guo, Changhui Fu, Qiong Wu, Longfei Tan, Hongbo Li, Wei Zhang, Xudong Chen, Hongshan Zhong, Xianwei Meng
Journal: Biomaterials (2019)
Abstract 67: Peroral Administration Of Extract Of Candida Albicans Induce Kawasaki Disease-like Vasculitis In Mice
Authors: Toshiaki Oharaseki, Yuki Yokouchi, Yasunori Enomoto, Hitomi Yamada, Noriko Miura, Naohito Ohno, Kei Takahashi
Journal: Circulation (2015)

Background: The cause of Kawasaki disease (KD) has been still unknown though the intestinal flora was reported as one of the candidate etiology of KD. Candida is known as one of the intestinal flora. Intraperitoneal injection of Candida albicans water-soluble fractions (CAWS) that compose of polysaccharide of cell wall of the yeast can induce systemic vasculitis in mice. It is evaluated as animal model of Kawasaki disease vasculitis because this experimental vasculitis is similar to those observed in KD patients. However it is uncertain whether or not oral administration of CAWS can induce vasculitis in mice. Aim: The present study aimed to elucidate whether or not oral administration of CAWS can induce vasculitis. Materials and methods: Mice, DBA/2, male, 4 weeks of age were used. CAWS suspended in PBS was administered perorally to mice for 28 consecutive days. As a priming agent, 20 micrograms of LPS was injected to mice intraperitoneally before administration of CAWS. Experimental groups are as follows. Group-I : Peroral administration of 800 micrograms of CAWS with LPS, Group-II: Peroral administration of 800 micrograms of CAWS without LPS, Group-III : Peroral administration of 250 micrograms of CAWS with LPS. Mice injected CAWS intraperitoneally (conventional procedure) were used as control group. Vasculitis was evaluated by routine histological techniques. This study conformed with regulations of position of the American Heart Association on research animal use and Toho University’s Animal Ethics Committee. Result: The incidence of vasculitis in each group were as follows : Group-I : 1/6, Group-II:0/6, Group-III:1/6, Control : 3/3. Dense infiltration of neutrophils and macrophages was observed in coronary artery and/or aortic root. Severity of inflammatory cell infiltration and extent of the lesion in Group-I and Group-III were milder and smaller than those of control. Conclusion: Present study revealed that peroral administration of CAWS could induce vasculitis in mice though the incidence of vasculitis was lower than that of control. This model is considered to be useful to clarify the relation between intestinal immunity and vasculitis. We should clarify the mechanism that oral administration of CAWS induced vasculitis.
Abstract 15303: Left Ventricular Hypertrabeculation Has Clinical Impact in Idiopathic Dilated Cardiomyopathy: Comparison to Left Ventricular Non-Compaction
Authors: Takayuki Kawamura, Yoshitaka Iwanaga, Yuki Miyaji, Masakazu Yasuda, Takashi Nakamura, Shunichi Miyazaki
Journal: Circulation (2017)

Introduction: Hypertrabeculation has been associated with adverse cardiovascular events in patients with left ventricular (LV) non-compaction (LVNC). However, the clinical significance remains unce...
Understanding the Long-term Effects of Bariatric Surgery
Authors: Margaret E. Smith, Amir A. Ghaferi
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Alpelisib for <i>PIK3CA</i>-Mutated, Hormone Receptor–Positive Advanced Breast Cancer
Authors: Fabrice André, Eva Ciruelos, Gabor Rubovszky, Mario Campone, Sibylle Loibl, Hope S. Rugo, Hiroji Iwata, Pierfranco Conte, Ingrid A. Mayer, Bella Kaufman, Toshinari Yamashita, Yen-Shen Lu, Kenichi Inoue, Masato Takahashi, Zsuzsanna Pápai, Anne-Sophie Longin, David Mills, Celine Wilke, Samit Hirawat, Dejan Juric
Journal: New England Journal of Medicine (2019)

PIK3CA mutations occur in approximately 40% of patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. The PI3Kα-specific inhibitor alpelisib has shown antitumor activity in early studies.
Nanophotosensitizer-engineered Salmonella bacteria with hypoxia targeting and photothermal-assisted mutual bioaccumulation for solid tumor therapy
Authors: Fuming Chen, Zhongsheng Zang, Ze Chen, Liao Cui, Zhiguang Chang, Aiqing Ma, Ting Yin, Ruijing Liang, Yutong Han, Zhihao Wu, Mingbin Zheng, Chenli Liu, Lintao Cai
Journal: Biomaterials (2019)
Lipidoid-siRNA Nanoparticle-Mediated IL-1β Gene Silencing for Systemic Arthritis Therapy in a Mouse Model
Authors: Ping Song, Chuanxu Yang, Jesper Skovhus Thomsen, Frederik Dagnæs-Hansen, Maria Jakobsen, Annemarie Brüel, Bent Deleuran, Jørgen Kjems
Journal: Molecular Therapy (2019)

Interleukin-1 beta (IL-1β) plays a central role in the induction of rheumatoid arthritis (RA). In the present study, we demonstrated that lipidoid-polymer hybrid nanoparticle (FS14-NP) can efficiently deliver siRNA against IL-1β (siIL-1β) to macrophages and effectively suppress the pathogenesis of experimental arthritis induced by collagen antibody (CAIA mice). FS14-NP/siIL-1β achieved approximately 70% and 90% gene-silencing efficiency in the RAW 264.7 cell line and intraperitoneal macrophages, respectively. Intravenous administration of FS14-NP/siRNA led to rapid accumulation of siRNA in macrophages within the arthritic joints. Furthermore, FS14-NP/siIL-1β treatment lowered the expression of pro-inflammatory cytokines in arthritic joints and dramatically attenuated ankle swelling, bone erosion, and cartilage destruction. These results demonstrate that FS14-NP/siIL-1β may represent an effective therapy for systemic arthritis and other inflammatory disorders. Interleukin-1 beta (IL-1β) plays a central role in the induction of rheumatoid arthritis (RA). In the present study, we demonstrated that lipidoid-polymer hybrid nanoparticle (FS14-NP) can efficiently deliver siRNA against IL-1β (siIL-1β) to macrophages and effectively suppress the pathogenesis of experimental arthritis induced by collagen antibody (CAIA mice). FS14-NP/siIL-1β achieved approximately 70% and 90% gene-silencing efficiency in the RAW 264.7 cell line and intraperitoneal macrophages, respectively. Intravenous administration of FS14-NP/siRNA led to rapid accumulation of siRNA in macrophages within the arthritic joints. Furthermore, FS14-NP/siIL-1β treatment lowered the expression of pro-inflammatory cytokines in arthritic joints and dramatically attenuated ankle swelling, bone erosion, and cartilage destruction. These results demonstrate that FS14-NP/siIL-1β may represent an effective therapy for systemic arthritis and other inflammatory disorders.
NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY FINDINGS IN 101 CONSECUTIVE UNDIFFERENTIATED PANCREATIC CYSTS: DOES ROUTINE USE OF CYTOPATHOLOGY CHANGE MANAGEMENT?
Authors: M Keegan, B Pujol, R Gincul, C Lefort, B Napoleon
Journal: Endoscopy (2019)

Pancreatic cysts are common and cyst fluid cytology lacks sensitivity. We aimed to describe needle-based confocal laser endomicroscopy findings (nCLE) and measure the yield of cytopathology after successful nCLE.
Cathepsin K–deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression
Authors: Sutada Lotinun, Yoshihito Ishihara, Kenichi Nagano, Riku Kiviranta, Vincent T. Carpentier, Lynn Neff, Virginia Parkman, Noriko Ide, Dorothy Hu, Pamela Dann, Daniel Brooks, Mary L. Bouxsein, John Wysolmerski, Francesca Gori, Roland Baron
Journal: Journal of Clinical Investigation (2019)

Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic bone resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which osteocytes contribute to bone loss remain elusive. Osteocytes express genes required in osteoclasts for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression. We show that Ctsk deletion in osteocytes prevented the increase in osteocyte lacunar area seen during lactation, as well as the effects of lactation to increase osteoclast numbers and decrease trabecular bone volume, cortical thickness and mechanical properties. In addition, Ctsk deletion in osteocytes increased bone Parathyroid Hormone related Peptide (PTHrP), prevented the decrease in serum Parathyroid Hormone (PTH) induced by lactation, but amplified the increase in serum 1,25(OH)2D. The net result of these changes is to maintain serum and milk calcium levels in the normal range, ensuring normal offspring skeletal development. Our studies confirm the fundamental role of osteocytic perilacunar remodeling in physiological states of lactation and provides genetic evidence that osteocyte-derived Ctsk contributes not only to osteocyte perilacunar remodeling, but also to the regulation of PTH, PTHrP, 1,25-Dyhydroxyvitamin D (1,25(OH)2D), osteoclastogenesis and bone loss in response to the high calcium demand associated with lactation.
Association between fat mass through adolescence and arterial stiffness: a population-based study from The Avon Longitudinal Study of Parents and Children
Authors: Frida Dangardt, Marietta Charakida, Georgios Georgiopoulos, Scott T Chiesa, Alicja Rapala, Kaitlin H Wade, Alun D Hughes, Nicholas J Timpson, Konstantinos Pateras, Nick Finer, Naveed Sattar, George Davey Smith, Debbie A Lawlor, John E Deanfield
Journal: The Lancet Child & Adolescent Health (2019)

The link between adiposity, metabolic abnormalities, and arterial disease progression in children and adolescents remains poorly defined. We aimed to assess whether persistent high adiposity levels are associated with increased arterial stiffness in adolescence and any mediation effects by common metabolic risk factors.
Correction: Assay to rapidly screen for immunoglobulin light chain glycosylation: a potential path to earlier AL diagnosis for a subset of patients
Authors: Sanjay Kumar, David Murray, Surendra Dasari, Paolo Milani, David Barnidge, Benjamin Madden, Taxiarchis Kourelis, Bonnie Arendt, Giampaolo Merlini, Marina Ramirez-Alvarado, Angela Dispenzieri
Journal: Leukemia (2019)
Targeting VLA4 integrin and CXCR2 mobilizes serially repopulating hematopoietic stem cells
Authors: Darja Karpova, Michael P. Rettig, Julie Ritchey, Daniel Cancilla, Stephanie Christ, Leah Gehrs, Ezhilarasi Chendamarai, Moses O. Evbuomwan, Matthew Holt, Jingzhu Zhang, Grazia Abou-Ezzi, Hamza Celik, Eliza Wiercinska, Wei Yang, Feng Gao, Linda G. Eissenberg, Richard F. Heier, Stacy D. Arnett, Marvin J. Meyers, Michael J. Prinsen, David W. Griggs, Andreas Trumpp, Peter G. Ruminski, Dwight M. Morrow, Halvard B. Bonig, Daniel C. Link, John F. DiPersio
Journal: Journal of Clinical Investigation (2019)

Mobilized peripheral blood has become the primary source of hematopoietic stem and progenitor cells (HSPCs) for stem cell transplantation, with a 5-day course of granulocyte colony-stimulating factor (G-CSF) as the most common regimen used for HSPC mobilization. The CXCR4 inhibitor plerixafor is a more rapid mobilizer, yet not potent enough when used as a single agent, thus emphasizing the need for faster acting agents with more predictable mobilization responses and fewer side effects. We sought to improve hematopoietic stem cell transplantation by developing a new mobilization strategy in mice through combined targeting of the chemokine receptor CXCR2 and the very late antigen 4 (VLA4) integrin. Rapid and synergistic mobilization of HSPCs along with an enhanced recruitment of true HSCs was achieved when a CXCR2 agonist was coadministered in conjunction with a VLA4 inhibitor. Mechanistic studies revealed involvement of CXCR2 expressed on BM stroma in addition to stimulation of the receptor on granulocytes in the regulation of HSPC localization and egress. Given the rapid kinetics and potency of HSPC mobilization achieved by the VLA4 inhibitor and CXCR2 agonist combination in mice compared with currently approved HSPC mobilization methods, the combination represents an exciting potential strategy for clinical development in the future.
Effect of strikes by health workers on mortality between 2010 and 2016 in Kilifi, Kenya: a population-based cohort analysis
Authors: Gerald Ong'ayo, Michael Ooko, Ruth Wang'ondu, Christian Bottomley, Amek Nyaguara, Benjamin K Tsofa, Thomas N Williams, Philip Bejon, J Anthony G Scott, Anthony O Etyang
Journal: The Lancet Global Health (2019)

Health workers' strikes are a global occurrence. Kenya has had several strikes by health workers in recent years but their effect on mortality is unknown. We assessed the effect on mortality of six strikes by health workers that occurred from 2010 to 2016 in Kilifi, Kenya. Using daily mortality data obtained from the Kilifi Health and Demographic Surveillance System, we fitted a negative binomial regression model to estimate the change in mortality during strike periods and in the 2 weeks immediately after strikes. We did subgroup analyses by age, cause of death, and strike week. Between Jan 1, 2010, and Nov 30, 2016, we recorded 1 829 929 person-years of observation, 6396 deaths, and 128 strike days (median duration of strikes, 18·5 days [range 9-42]). In the primary analysis, no change in all-cause mortality was noted during strike periods (adjusted rate ratio [RR] 0·93, 95% CI 0·81-1·08; p=0·34). Weak evidence was recorded of variation in mortality rates by age group, with an apparent decrease among infants aged 1-11 months (adjusted RR 0·58, 95% CI 0·33-1·03; p=0·064) and an increase among children aged 12-59 months (1·75, 1·11-2·76; p=0·016). No change was noted in mortality rates in post-strike periods and for any category of cause of death. The brief strikes by health workers during the period 2010-16 were not associated with obvious changes in overall mortality in Kilifi. The combined effects of private (and some public) health care during strike periods, a high proportion of out-of-hospital deaths, and a low number of events might have led us to underestimate the effect. Wellcome Trust and MRC Tropical Epidemiology Group.
A Student Reflection on Doctoring With Confidence
Authors: Richard L. Kravitz
Journal: Annals of Internal Medicine (2019)

Letters21 May 2019A Student Reflection on Doctoring With ConfidenceRichard L. Kravitz, MDRichard L. Kravitz, MDUniversity of California, Davis, Sacramento, California (R.L.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0119 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Treadway's commentary (1) raises 2 fascinating and important questions: Are we encouraging overconfidence, and does gender matter? The answer to the first question is probably yes (with a caveat), but the answer to the second question is less clear than the author implies. Treadway cites an article by Blanch and colleagues (2) that states that the mean difference in confidence between men and women is approximately one third of an SD, implying a substantial overlap between the sexes. Overconfidence (and underconfidence) can be a problem for both men and women. To return to the caveat, there may ...References1. Treadway N. A student reflection on doctoring with confidence: mind the gap. Ann Intern Med. 2018;169:564-5. [PMID: 30208402]. doi:10.7326/M18-0865 LinkGoogle Scholar2. Blanch DC, Hall JA, Roter DL, Frankel RM. Medical student gender and issues of confidence. Patient Educ Couns. 2008;72:374-81. [PMID: 18656322] doi:10.1016/j.pec.2008.05.021 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of California, Davis, Sacramento, California (R.L.K.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0119. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Student Reflection on Doctoring With Confidence: Mind the Gap Nicole Treadway A Student Reflection on Doctoring With Confidence John E. Coda A Student Reflection on Doctoring With Confidence Juan N. Lessing and Mary E. Lacy A Student Reflection on Doctoring With Confidence Nicole Treadway Metrics 21 May 2019Volume 170, Issue 10Page: 738KeywordsConflicts of interestDisclosureSexual identity ePublished: 21 May 2019 Issue Published: 21 May 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...