tbuckley/cabot-search huggingface dataset:
Drd3 Signaling in the Lateral Septum Mediates Early Life Stress-Induced Social Dysfunction
Authors: Sora Shin, Horia Pribiag, Varoth Lilascharoen, Daniel Knowland, Xiao-Yun Wang, Byung Kook Lim
Journal: Neuron (2017)

Highlights•Early social deprivation (ESD) causes downregulation of Drd3 signaling in the LS•Blunted LS Drd3 neuronal activity mediate ESD-induced social dysfunctions•Drd3 signaling has corresponding effects on neuronal activity in the LS•Activation of Drd3 signaling in the LS normalize social impairments of ESD miceSummaryEarly life stress (ELS) in the form of child abuse/neglect is associated with an increased risk of developing social dysfunction in adulthood. Little is known, however, about the neural substrates or the neuromodulatory signaling that govern ELS-induced social dysfunction. Here, we show that ELS-induced downregulation of dopamine receptor 3 (Drd3) signaling and its corresponding effects on neural activity in the lateral septum (LS) are both necessary and sufficient to cause social abnormalities in adulthood. Using in vivo Ca2+ imaging, we found that Drd3-expressing-LS (Drd3LS) neurons in animals exposed to ELS show blunted activity in response to social stimuli. In addition, optogenetic activation of Drd3LS neurons rescues ELS-induced social impairments. Furthermore, pharmacological treatment with a Drd3 agonist, which increases Drd3LS neuronal activity, normalizes the social dysfunctions of ELS mice. Thus, we identify Drd3 in the LS as a critical mediator and potential therapeutic target for the social abnormalities caused by ELS.
Nueva variante de la enfermedad de Creutzfeldt Jakob: ¿Qué hay de nuevo?
Authors: O N Gill
Journal: Eurosurveillance (2000)

Esta edicion de Eurosurveillance resulta especialmente oportuna tras el anuncio, emitido el 17 de julio de 2000, de que el incremento en la incidencia de la nueva variante de la enfermedad de Creutzfeldt Jakob (nvECJ) en el Reino Unido ha alcanzado significacion estadistica (1). En estos momentos se investiga una agrupacion de cinco casos, observada en una zona concreta, que incluye un caso probable (2). Desde la muerte del primer caso en 1995, se han detectado 76 casos confirmados y probables de nvECJ. La incidencia aumenta a un ritmo estimado del 20% al 30 % anual. Sin embargo, el Comite Asesor sobre Encefalopatia Espongiforme del Reino Unido (UK’s Spongiform Encephalopathy Advisory Committee) estima que aun es demasiado pronto para saber con certeza si esta tendencia al alza se mantendra, o para prever el tamano definitivo de la epidemia de nvECJ (1).
Atypical Cause of “Typical” Hypertensive Intracranial Bleeding
Authors: Sujan T. Reddy, David Rosenbaum, Sunil A. Sheth
Journal: JAMA Neurology (2017)

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
Abstract 12494: Optimal Timing for Echocardiographic Assessment of Left Ventricular Function During Reduced Left Ventricular Assist Device Support
Authors: Ayesha Salahuddin, Kana Fujikura, Emma J Birks, Chris Cunningham, Faouzi Kallel, Daniel M Spevack, Mario J Garcia
Journal: Circulation (2015)

Introduction: In some circumstances left ventricular assist devices (LVAD) can be used to bridge patients with advanced heart failure to myocardial recovery or “remission”. Evaluation of the underlying myocardial function in patients supported with an LVAD is often performed with the pump speed turned down to minimal support for 15 minutes, to simulate unassisted ventricular loading conditions. Longer duration of reduced support and performance of exercise may allow for a more realistic evaluation of myocardial function to assess for recovery. Methods: Nine turn-down exams from 4 patients were analyzed. Subjects were participants in a multi-center prospective non-randomized study of LV recovery with HeartMate II LVAD together with a standardized protocol of pharmacological therapy (REmission from STAGE D Heart Failure (RESTAGE-HF)). LVEF and speckle tracking parameters were measured during full support, at 15 minutes of reduced support (6000 rpm) and again after a 6-min walk test. Averaged radial and circumferential strain, and global circumferential strain were analyzed from papillary muscle level short-axis view using speckle-tracking. Results: LV systolic parameters for each of these patients are shown, (Table). Improvement in LV function was not evident at 15 minutes of reduced support, compared to full support but was evident after the 6-min walk test. Conclusions: After 15 minutes of LVAD turndown, LV systolic parameters did not differ from full support values. Improvement in LV function compared to full support became evident when the protocol was extended to include imaging after a longer period of turndown with the addition of a 6-min walk test.
Abstract 13039: Uric Acids and Risk of Development of Atrial Fibrillation
Authors: Nobue Yagihara, Hiroshi Watanabe, Toru Watanabe, Yoshifusa Aizawa, Tohru Minamino
Journal: Circulation (2015)

Background: Uric acid is a final product of xanthine oxidase pathway and is positively correlated with levels of oxidative stress and inflammation, both of which are the important pathogenesis of atrial fibrillation. We aimed to study the impact of serum uric acid level on risk of development of atrial fibrillation in the general population. Methods: This prospective observational cohort study was based upon an annual health check-up program including a detailed medical history, physical examination, blood and urine examination, chest x-ray, and a 12-lead electrocardiogram. We included 23,436 individuals (8,611 males; age, 61±12 years) without atrial fibrillation at baseline who were followed for more than one year. Results: During a follow up of 6.5±1.9 years, atrial fibrillation developed in 426 individuals (incidence, 2.78 per 1000 person-years; 95% confidence interval [CI], 2.52 to 3.05 per 1000 person-years). Incidence of atrial fibrillation increased with an increasing quartile of serum uric acid levels (Table). In multivariate analysis, elevated serum level of uric acid was independently associated with increased risk of development of atrial fibrillation (hazard ratio [HR], 1.127 per 1.0 mg/dL increase; 95% CI, 1.041-1.219 per 1.0 mg/dL increase). Hyperuricemia defined as serum uric acid more than 7.0 mg/dL was associated with risk of atrial fibrillation (hazard ratio [HR], 1.592; 95% CI, 1.127 - 2.249). The impact of hyperuricemia on risk of atrial fibrillation was higher in women than men. Conclusion: Hyperuricemia was a potentially modifiable risk factor for atrial fibrillation. Our study indicates the possibility that interventions to decrease uric acid may reduce the population of atrial fibrillation.
International Union of Basic and Clinical Pharmacology CIII: Chemerin Receptors CMKLR1 (Chemerin<sub>1</sub>) and GPR1 (Chemerin<sub>2</sub>) Nomenclature, Pharmacology, and Function
Authors: Amanda J. Kennedy, Anthony P. Davenport
Journal: Pharmacological Reviews (2017)

Chemerin, a chemoattractant protein and adipokine, has been identified as the endogenous ligand for a G protein–coupled receptor encoded by the gene <i>CMKLR1</i> (also known as ChemR23), and as a consequence the receptor protein was renamed the chemerin receptor in 2013. Since then, chemerin has been identified as the endogenous ligand for a second G protein–coupled receptor, encoded by the gene <i>GPR1</i>. Therefore, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification recommends that the official name of the receptor protein for chemokine-like receptor 1 (CMKLR1) is chemerin receptor 1, and G protein–coupled receptor 1 is chemerin receptor 2 to follow the convention of naming the receptor protein after the endogenous ligand. Chemerin receptor 1 and chemerin receptor 2 can be abbreviated to Chemerin<sub>1</sub> and Chemerin<sub>2</sub>, respectively. Chemerin requires C-terminal processing for activity, and human chemerin21–157 is reported to be the most active form, with peptide fragments derived from the C terminus biologically active at both receptors. Small-molecule antagonist, CCX832, selectively blocks CMKLR1, and resolvin E1 activation of CMKLR1 is discussed. Activation of both receptors by chemerin is via coupling to G<sub>i/o</sub>, causing inhibition of adenylyl cyclase and increased Ca<sup>2+</sup> flux. Receptors and ligand are widely expressed in humans, rats, and mice, and both receptors share ∼80% identity across these species. <i>CMKLR1</i> knockout mice highlight the role of this receptor in inflammation and obesity, and similarly, <i>GPR1</i> knockout mice exhibit glucose intolerance. In addition, the chemerin receptors have been implicated in cardiovascular disease, cancer, steroidogenesis, human immunodeficiency virus replication, and neurogenerative disease.
Substitution Rates Predicted by Stability-Constrained Models of Protein Evolution Are Not Consistent with Empirical Data
Authors: María José Jimenez, Miguel Arenas, Ugo Bastolla
Journal: Molecular Biology and Evolution (2017)

Protein structures strongly influence molecular evolution. In particular, the evolutionary rate of a protein site depends on the number of its native contacts. Stability-constrained models of protein evolution consider this influence of protein structure on evolution by predicting the effect of mutations on the stability of the native state, but they currently neglect how mutations affect the protein structure. These models predict that buried protein sites with more native contacts are more constrained by natural selection and less variable, as observed. Nevertheless, previous work did not consider the stability against compact misfolded conformations, although it is known that the negative design that destabilizes these misfolded conformations influences protein evolution significantly. Here, we show that stability-constrained models that consider misfolding predict that site-specific sequence entropy and substitution rate peak at amphiphilic sites with an intermediate number of contacts, as these sites are less constrained than exposed sites with few contacts whose hydrophobicity must be limited. This result holds both for a mean-field model with independent sites and for a pairwise model that takes as a reference the wild-type sequence, but it contrasts with the observations that indicate that the entropy and the substitution rate decrease monotonically with the number of contacts. Our work suggests that stability-constrained models overestimate the tolerance of amphiphilic sites against mutations, either because of the limits of the free energy function or, more importantly in our opinion, because they do not consider how mutations perturb the native protein structure.
ANP32A dysregulation contributes to abnormal megakaryopoiesis in acute megakaryoblastic leukemia
Authors: Xueqin Sun, Bin Lu, Cuijuan Han, Wanlin Qiu, Qi Jin, Dengju Li, Qiubai Li, Qiong Yang, Qiang Wen, Puneet Opal, Ameet R. Kini, John D. Crispino, Zan Huang
Journal: Blood Cancer Journal (2017)
Re-emerging and newly recognized sexually transmitted infections: Can prior experiences shed light on future identification and control?
Authors: Kyle Bernstein, Virginia B. Bowen, Caron R. Kim, Michel J. Counotte, Robert D. Kirkcaldy, Edna Kara, Gail Bolan, Nicola Low, Nathalie Broutet
Journal: PLoS Medicine (2017)

Determining sexual contact as a mode of pathogen transmission and quantifying the risk of sexual transmission pose epidemiologic challenges.• Prior experiences with nontraditional sexually transmitted infections present valuable epidemiologic lessons, including comparisons of disease rates by sex, molecular analyses among sexually linked clusters, and methods to control for other potential modes of transmission.• Applying lessons learned from prior infections might be critical for rapid and effective detection, prevention, and control of other reemerging and newly recognized sexually transmitted infections.The spectrum of pathogens that have a sexually transmitted component is broad.Globally, there are more than 30 recognized sexually transmitted infections (STIs), including those transmitted primarily by sexual contact and those that are sexually transmissible but whose primary mode of transmission is by food, vector, or droplet [1].This latter group of nontraditional STIs poses unique methodologic and epidemiologic challenges for public health practitioners and researchers, who need to anticipate, identify, and contain the next new STI outbreak.In this paper, we explore these challenges using examples of nontraditional STIs, including 2 (shigellosis and Neisseria meningitidis) that have recently reemerged as sexually transmissible and 2 (Zika and Ebola) that are newly recognized as being sexually transmissible (Table 1). Shigella: Raised male-to-female ratios in routine surveillance dataShigellosis is a diarrheal illness caused by several species of the bacterium Shigella.Shigella is transmitted by direct or indirect contact with human feces, often via contaminated food, water, or fomites [13].Prior to the 1970s, Shigella incidence was highest among children <5
The PHQ-2 in Dermatology—Standardized Screening for Depression and Suicidal Ideation
Authors: Katherine McDonald, Amanda Shelley, Mohammad Jafferany
Journal: JAMA Dermatology (2017)

This Viewpoint examines the role of the Patient Health Questionnaire-2 in dermatology concerning secondary psychiatric disorders that involve emotional disturbances and manifest in response to the psychologic stress caused by dermatologic conditions.
CSM should rethink its approach for such announcements
Authors: S. Stewart-Brown, C. Pyper
Journal: BMJ (1996)

EDITOR,—Klim McPherson estimates that in making its announcement when it did rather than waiting until all the relevant studies of third generation oral contraceptives had been published, the Committee on Safety of Medicines saved one life and prevented 80 cases of venous thrombo-embolism.1 Our concern is not with the timing of the announcement in relation to the publication of peer reviewed papers or with the committee members' appraisal of the research evidence but with the manner in which the committee communicated the information …
SETD2-mediated crosstalk between H3K36me3 and H3K79me2 in MLL-rearranged leukemia
Authors: J Bu, A Chen, X Yan, F He, Y Dong, Y Zhou, J He, D Zhan, P Lin, Y Hayashi, Y Sun, Y Zhang, Z Xiao, H L Grimes, Q F Wang, G Huang
Journal: Leukemia (2017)
AngioCRIME in Acute Myeloid Leukemia (AML)
Authors: Elizabeth Macintyre
Journal: HemaSphere (2017)

AMLs have stubbornly resisted attempts to improve overall outcome using chemotherapy, epitherapy and immunotherapy approaches, including stem cell transplantation. Passaro et al use intravital 2-photon microscopy to demonstrate that this may reflect too much concentration on the leukemic population and not enough on the angiocrine factors (growth factors, trophogens and chemokines) produced by bone marrow vascular endothelial cells hosting the leukemic blasts. They show that the latter induce vascular abnormalities, including leakiness and hypoxia, mediated by increased reactive oxygen and nitric oxide (NO) production, which is resistant to chemotherapy in patient-derived xenografts. NO inhibition reduced vascular permeability and improved both normal stem cell function and leukemic blast response to chemotherapy, thus raising promise for use of NO inhibitors against the angiocrine culprits in acute myeloid leukemogenesis.FigureLinks to: Passaro D et al. Cancer Cell 32, 324-341, September 11, 2017, PMID 28870739; https://www.ncbi.nlm.nih.gov/m/pubmed/28870739/ And the accompanying commentary, Itkin T and Rafii S, Cancer Cell 32, 276–278; https://www.ncbi.nlm.nih.gov/pubmed/28898691
Transcriptional and functional profiling defines human small intestinal macrophage subsets
Authors: Anna Bujko, Nader Atlasy, Ole J.B. Landsverk, Lisa Richter, Sheraz Yaqub, Rune Horneland, Ole Øyen, Einar Martin Aandahl, Lars Aabakken, Hendrik G. Stunnenberg, Espen S. Bækkevold, Frode L. Jahnsen
Journal: The Journal of Experimental Medicine (2017)

Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos.
Rescue plan for Achilles: Therapeutics steering the fate and functions of stem cells in tendon wound healing
Authors: Magdalena Schneider, Peter Angele, Tero A.H. Järvinen, Denitsa Docheva
Journal: Advanced Drug Delivery Reviews (2017)

Due to the increasing age of our society and a rise in engagement of young people in extreme and/or competitive sports, both tendinopathies and tendon ruptures present a clinical and financial challenge. Tendon has limited natural healing capacity and often responds poorly to treatments, hence it requires prolonged rehabilitation in most cases. Till today, none of the therapeutic options has provided successful long-term solutions, meaning that repaired tendons do not recover their complete strength and functionality. Our understanding of tendon biology and healing increases only slowly and the development of new treatment options is insufficient. In this review, following discussion on tendon structure, healing and the clinical relevance of tendon injury, we aim to elucidate the role of stem cells in tendon healing and discuss new possibilities to enhance stem cell treatment of injured tendon. To date, studies mainly apply stem cells, often in combination with scaffolds or growth factors, to surgically created tendon defects. Deeper understanding of how stem cells and vasculature in the healing tendon react to growth factors, common drugs used to treat injured tendons and promising cellular boosters could help to develop new and more efficient ways to manage tendon injuries.
Caregiver report of child’s asthma control predicts future acute visits in a mouse-sensitized population, independent of guideline-based measures of asthma control
Authors: Suzanne L. Rossi, Torie L. Grant, Wanda Phipatanakul, Matthew Perzanowski, Susan L. Balcer-Whaley, Jean Curtin-Brosnan, Michelle Newman, Amparito Cunningham, Mary Beth Bollinger, Elizabeth C. Matsui
Journal: Journal of Allergy and Clinical Immunology (2018)
A Delphi developed syllabus for the medical specialty of sport and exercise medicine
Authors: David Humphries, Rod Jaques, Hendrik Paulus Dijkstra
Journal: British Journal of Sports Medicine (2017)

Training in the medical specialty of sport and exercise medicine is now available in many, but not all countries. Lack of resources may be a barrier to the development of this important specialty field and the International Syllabus in Sport and Exercise Medicine Group was convened to reduce one potential barrier, the need to develop a syllabus. The group is composed of 17 sport and exercise medicine specialists residing in 12 countries (Australia, Canada, India, Ireland, Malaysia, the Netherlands, Qatar, South Africa, Sweden, Switzerland, the UK and USA). This paper presents the first phase of this project covering the domains and general learning areas of a specialist training syllabus in sport and exercise medicine.
President Trump’s Mental Health — Is It Morally Permissible for Psychiatrists to Comment?
Authors: Claire Pouncey
Journal: New England Journal of Medicine (2018)

Interview with Dr. Claire Pouncey on the controversy surrounding psychiatrists' comments on President Trump's mental health. (14:49)Download In The Dangerous Case of Donald Trump, psychiatrist Bandy Lee and other mental health professionals, believing they have a duty to warn the public, reject the idea that psychiatrists should never offer diagnostic opinions about persons they haven't personally examined.