tbuckley/cabot-search huggingface dataset:
Impaired Synaptic Development, Maintenance, and Neuromuscular Transmission in LRP4-Related Myasthenia
Authors: Duygu Selcen, Bisei Ohkawara, Xin-Ming Shen, Kathleen McEvoy, Kinji Ohno, Andrew G. Engel
Journal: JAMA Neurology (2015)

<h3>Importance</h3> Congenital myasthenic syndromes (CMS) are heterogeneous disorders. Defining the phenotypic features, genetic basis, and pathomechanisms of a CMS is relevant to prognosis, genetic counseling, and therapy. <h3>Objectives</h3> To characterize clinical, structural, electrophysiologic, and genetic features of a CMS and to search for optimal therapy. <h3>Design, Settings, and Participants</h3> Two sisters with CMS affecting the limb-girdle muscles were investigated between 2012 and 2014 at an academic medical center by clinical observation, in vitro analysis of neuromuscular transmission, cytochemical and electron microscopy studies of the neuromuscular junction, exome sequencing, expression studies in HEK293 and COS7 cells, and for response to therapy, and they were compared with 15 historical control participants. <h3>Main Outcomes and Measures</h3> We identified the disease gene and mutation, confirmed pathogenicity of the mutation by expression studies, and instituted optimal pharmacotherapy. <h3>Results</h3> Quantitative analysis of single EP regions was done for all 15 control participants and microelectrode studies of neuromuscular transmission and α-bgt binding sites per EP was conducted for 13 control participants. Examination of the older sister’s intercostal muscle end plates (EPs) showed them to be abnormally small, with attenuated reactivities for the acetylcholine receptor and acetylcholinesterase. Most EPs had poorly differentiated or degenerate junctional folds, and some appeared denuded of nerve terminals. The amplitude of the EP potential (EPP), the miniature EPP, and the quantal content of the EPP were all markedly reduced. Exome sequencing identified a novel homozygous p.Glu1233Ala mutation in low-density lipoprotein receptor–related protein 4 (LRP4), a coreceptor for agrin to activate muscle-specific tyrosine kinase (MuSK), which is required for EP development and maintenance. Expression studies indicate that the mutation compromises the ability of LRP4 to bind to, phosphorylate, and activate MuSK. Treatment with albuterol sulfate improved the patients’ symptoms. A previously identified patient harboring 2 heterozygous mutations in LRP4 had structurally abnormal intercostal EPs but no identifiable defect of neuromuscular transmission at these EPs. <h3>Conclusions and Relevance</h3> We identified a second CMS kinship harboring mutations in<i>LRP4</i>, identified the mechanisms that impair neuromuscular transmission, and mitigated the disease by appropriate therapy.
100 years of hyposensitization: history of allergen-specific immunotherapy (ASIT)
Authors: J. Ring, J. Gutermuth
Journal: Allergy (2011)

To cite this article: Ring J, Gutermuth J. 100 years of hyposensitization: history of allergen-specific immunotherapy (ASIT). Allergy 2011; 66: 713–724. Hundred years ago, Leonhard Noon and John Freeman published their pioneering works on allergen-specific immunotherapy (ASIT) using grass pollen extracts. To honor their contribution to the development of ASIT as the only causal treatment of IgE-mediated allergies, we review the history of ASIT that started with the anecdotal descriptions of ASIT performed by the ancient king Mithridates (132–63 B.C.) and Jenner's development of a cowpox vaccine. Following Noon's and Freeman's first controlled human trials, ASIT was performed by a large number of modalities and with a myriad of pharmacologic preparations. These developments range from early aqueous pollen extracts and whole bee extracts to chemically modified allergens (allergoids) and various recombinant allergens. In addition to allergen-specific immunotherapy, non-specific immune response modifiers have been used in the past or are in the developmental stage. Also, currently many innovative experimental approaches of ASIT are studied in animal models and human in vitro systems and will hopefully further broaden the range of allergies that can be treated by ASIT, with enhanced efficacy and further reduced side-effects.
Abstract 102: Out-of-Hospital Cardiac Arrest Clinical Trial Control Groups: Time Capsules for Discovery of Secular Trends---Fraction of Patients with Good Neurological Outcomes, 1985 to Present
Authors: Katelin M Engerer, James V Coleman, Luca F Valle, Matt Roginski, Norman A Paradis
Journal: Circulation (2014)

Introduction: Over time there have been changes in consensus therapy for out of hospital cardiac arrest (OOHCA), including changes in BLS-ACLS, and recently targeted temperature management. There has been only limited success, however, in determining the effect of specific interventions on neurological outcome using randomized clinical trials (RCT’s) and registries. Hypothesis: The control groups in OOHCA RCT’s can be utilized to identify the presence or absence of potential trends in neurological outcome related to secular changes in care. Methods: Comprehensive online search for RCT’s in OOHCA with n &gt; 50 in control group, and reporting neurological outcome, 1960 to present. Extraction of demographic and outcome variables. Analysis, fraction of resuscitated patients with good neurological outcome (GNO), defined as CPC 1 or 2 as a function of year. Results: n=32 usable RCTS were identified, all since 1985. No significant trends in the fraction of patients with GNO were identified (Figure). There was relatively large variability. Outcomes in the epoch since the promulgation of hypothermia have not changed overall. However, since about 2012 there have been a handful of RCT’s with relatively high fraction of patients with GNO compared to historical norms. Limitations: Retrospective methodology and background regional differences limits significance and applicability, hypothesis generating only. Conclusion: Between 1985 and the present, there were no trends in GNO rates in the control groups of RCTs, possibly indicating lack of efficacy or toxicity with respect to therapies experiencing changing patterns of utilization, or an offsetting change in substrate.
Review: Interstitial Lung Disease Associated With Systemic Sclerosis and Idiopathic Pulmonary Fibrosis: How Similar and Distinct?
Authors: Erica L. Herzog, Aditi Mathur, Andrew M. Tager, Carol Feghali‐Bostwick, Frank Schneider, John Varga
Journal: Arthritis & Rheumatology (2014)

Fibrosis of the lung, a common complication of systemic sclerosis (SSc) and the hallmark of idiopathic pulmonary fibrosis (IPF), is associated with substantial mortality and has no approved therapy. Despite some degree of overlap in their clinical features and pathogenesis, SSc-associated interstitial lung disease (ILD) and IPF have differences, with significant implications for diagnosis, evaluation, and management. To shed light on these issues, this review compares and contrasts salient features of these 2 entities, focusing on clinical manifestations, lung imaging, and pathology, along with current concepts of pathogenesis, including animal models, translational studies, genetic factors, and predictive biomarkers. We conclude by posing questions that might unveil new areas of investigation and inform novel and targeted approaches to therapy.
Abstract P416: Low Vitamin D does not correlate with Cardiometabolic Risk in African Immigrants
Authors: Anne E Sumner, Caroline K Thoreson, Michelle Y O'Connor, Madia Ricks, Stephanie T Chung
Journal: Circulation (2014)

Controversy exists as to whether low vitamin D levels contribute to the development of cardiometabolic disease. As African descent populations have a high prevalence of low vitamin D levels and cardiometabolic disease, clarification is important. However, current cross-sectional studies linking low vitamin D concentrations to cardiometabolic disease not only provide conflicting results, data specifically on people of African descent is very limited. Therefore, we evaluated the association between vitamin D levels, measured as 25(OH)D, and cardiometabolic risk factors in 78 African immigrants (77% male, age 35±y (mean±SD) age range 22-63y). Participants had oral glucose tolerance tests, insulin sensitivity index (S I ) determined with the minimal model and abdominal computerized tomographic scans to measure visceral adipose tissue (VAT). Cardiometabolic risk factors were related to 25(OH)D levels by Pearson correlations and one-way ANOVA across quartiles of 25(OH)D. Mean 25(OH)D levels were 22±7, range 10-36 ng/mL. BMI was 27.9±4.4 kg/m2 and 74% of Africans were either overweight or obese. Nine percent had newly identified diabetes and 33% had pre-diabetes. Mean arterial BP was 88±10 mmHg and 44% of Africans had either pre-hypertension or hypertension. Cardiometabolic variables did not change across quartiles of 25(OH)D (Table). In addition, there were no significant correlations between 25(OH)D and the cardiometabolic variables listed in the Table (all r&lt;0.2, all P &gt;0.1). As cardiometabolic risk factors do not become more severe as 25(OH)D levels decline, vitamin D may not modulate cardiometabolic risk in people of African descent.
Bioethics: An Introduction to the History, Methods, and Practice
Authors: Nancy Ann Silbergeld Jecker, Albert R. Jonsen, Robert A. Pearlman
Journal: Annals of Internal Medicine (1997)

Bioethics: An Introduction To The History, Methods, And Practice Is One Of The Only Texts To Cover The History, Methodology, And Practice Of Bioethics. The Text Is Broken Into Three Sections. The First Addresses The History Of Bioethics, Explaining Its Emergence As Discipline And Discourse. The Second Looks Carefully At Ethical Reasoning And The Justification Of Moral Beliefs, And The Final Section Asks Students To Turn A Critical Eye To The Topics Of Bioethics, Including Ethical Issues That Arise At The Beginning And End Of Life. Bioethics Is Ideal For Both Graduate Students And Professional Students In Law, Medicine, Nursing Or Other Health-Related Fields Who Will Face Bioethical Issues In Future Careers.
Defining the Eye-of-the-Tiger Sign
Authors: Kapil D. Sethi, Shyamal H. Mehta, John C. Morgan
Journal: JAMA Neurology (2015)

To the Editor We read with interest the article titled "Hemidystonia With One Eye-of-the-Tiger Sign" by Pandey et al.1 The authors published an interesting image depicting a unilateral eye-of-the-tiger sign in a young patient with hemidystonia.
Sports Medicine for the Primary Care Physician.
Authors: Richard B. Birrer, Francis G. O'Connor
Journal: Annals of Internal Medicine (1988)

GENERAL SPORTS MEDICINE The Role of the Physician in Sports The History of Sports Medicine: A Full Circle, R.D. Smith and R. Levandowski, M.D. The Team Physician, D. Garfinkel, M.D. and R. Birrer, M.D. The Preparticipation Health Inventory, J.T. Marron, M.D. and J.B. Tucker, M.D. Legal Aspects of Sports Medicine, E.A. Bianco, M.D.,J.D. and E.J. Walker, M.Ed, J.D. Ethical Considerations in Sports Medicine, W.B. Howe, M.D. Principles of Healthy Exercise Exercise Physiology, K.D. Steele, Ph.D. Training and Conditioning, M. DeBevec, M.D. Performance Variables in Sports, J.L. Tanji, M.D. Psychological Aspects of Sports, M.A. Howe, Ph.D. and B.C. Ogilvie, Ph.D. Environmental Factors, J.T. Marron, M.D. and J.B. Tucker, M.D. Nutrition in Sports, R.L. Pearson, M.D., P.M. Hartmann, and E.H. Bell Drugs and Sports, B.H. Wholley, Pharm. D. and R.B. Birrer, M.D. Medical Probelms in Athletes, M.B. Mellion, M.D., M.A. Sitorius, M.D. and J. Butcher, M.D. Protective Equipment in H igh-Risk Sports, J.L. Lord, M.D. Writing a Prescription for Exercise, R.B. Birrer, M.D. Profiles of Athletes The Competitive Athlete, H.Parris, M.D. The Weekend Athlete, E.J. Swenson, Jr., M.D. The Female Athlete, J.W. Cassels, Jr., M.D. and D.J. Magelssen, M.D., M.A. The Child Athlete, S.S. Harris, M.D., The Older Athlete, T. Epperly, M.D., LTC, MC, USA The Athlete with Chronic Illness, W.B. Howe, M.D. The Disabled Athlete, R.B. Birrer, M.D. The Runner, S.M. Tanner, M.D. The Swimmer, R.E. Sallis, M.D. The Thrower, R.E. Sallis, M.D. The Outdoor Athlete, J.D. Butcher, M.D. CLINICAL SPORTS MEDICINE PRACTICE Sports Injuries: A General Guide The Epidemiology of Sports Injuries, R.B. Birrer, M.D. General Types of Injuries, J.E. Hocutt, M.D. Sports Medicine Emergencies, E.J. Swenson, Jr., M.D. The On-Field Management of Injuries: Should an Injured Athlete Return to Play?, E.J. Swenson, Jr., M.D. Guidelines for the Treatment and Rehabilitation of Sports Injuries, R. B.Birrer, M.D. Physical Therapy in the Treatment of Sports Injuries, R.M. Poole, MEd, PT, AT, C Casting of Sports Injuries, R.M. Poole, MEd, PT, AT, C The Use of Orthoses for Athletes, R.M. Poole, MEd, PT, AT, C, R. Gaines, ATC, and K.K. Jepson, PT Taping Procedures for Athletic Competition, R.M. Poole, MEd, PT, AT, C and R. Gaines, ATC The Head Head Injuries, T. Robinson, D.O., M. Greenberg, M.D. and R.B. Birrer, M.D. Eye Injuries, T. Robinson, D.O., and R.B. Birrer, M.D. Ear Injuries, T. Robinson, D.O., and R.B. Birrer, M.D. Nasal Injuries, T. Robinson, D.O., and M. Greenberg, M.D. Injuries to Facial Bones and Teeth, T. Robinson, D.O., and R.B. Birrer, M.D. The Trunk Chest Injuries, R.B. Birrer, M.D. Abdominal Injuries, R.B. Birrer, M.D. Spinal Injuries, J.M. Henderson, D.O., K.M. Bialak, M.D. and R.B. Birrer, M.D. The Upper Extremity Shoulder Injuries, B.C. Halpern, M.D.
Psychological support of skin cancer patients
Authors: E.M.J. Peters
Journal: British Journal of Dermatology (2012)

The diagnosis of skin cancer imposes a great stress on our patients. Ultraviolet (UV) radiation‐induced skin cancers are on the rise and frequently occur in younger patients and unexposed sites despite improved protective behaviour. Environmental factors and lifestyle habits have changed greatly in the last century and in addition to UV radiation exposure, psychosocial stressors and physical inactivity may play a role in the rising tumour incidence. With environmental stressors such as UV radiation they share the capacity to change the stress reaction. So far research into the interaction between stress, cancer and psychosocial intervention has generated some interesting results with respect to improvement of quality of life and the function of the hypothalamic–pituitary–adrenal axis, the sympathetic axis and natural killer cells. These results hint at a suppressive effect of chronic stress on cellular immunity and the importance of a sufficient length and intensity of any psychosocial intervention for it to be effective. Nevertheless, the evidence remains inconclusive and does not take into account the findings of current psychoneuroimmunological research. This research has demonstrated the importance of a third stress axis along which neurotrophins and neuropeptides are effective. Along this axis, regulatory mechanisms may contribute to suppress tumoricidal immune responses. This may be instrumental in the establishment of an immune response that promotes tumour progression and holds important implications for integrated therapeutic strategies. However, research into the psychoneuroimmunological benefits of psychosocial intervention is largely missing, and future interdisciplinary research is warranted for understanding and further promoting improved quality of life and psychological as well as physical well‐being after psychosocial intervention.
390. eNOS Gene Transfected Endothelial Cells Inhibit Smooth Muscle Cell Proliferation and Platelet Aggregation In Vitro
Authors: Guanhua Xue, Jiwei Zhang, Hao Zhang, baigen Zhang, Minli Sun
Journal: Molecular Therapy (2004)

Objective: To test the function of endothelial cells transfected eNOS gene.Methods: To test the function of eNOS-overexpressing endothelial cells inhibiting smooth muscle cell proliferation and platelet aggregation in vitro by colorimetry, MTT and 3H-TdR permeate, respectively.Results: The platelet aggregation is significiently decreasing between the groups of EC and eNOS at the different time (P<0.05), is 42.20 and 32.60 seperately at the time of 120h. The SMC proliferation is significiently decreasing between the groups of EC and eNOS at the different time (P<0.05). It is 0.28 and 0.22 by MTT test, 4691.83 and 3995.00 by 3H-TdR permeate, separately, at the time of 120h.Conclution: eNOS-overexpressing endothelial cells inhibited significantly smooth muscle cells proliferation and platelet aggregation in vitro; which showed powerful effection 48 hours post transfection and lasted up to 120 hours at the least; and were holden back by L-NAME.
Dr. Afshar's Grid
Authors: Bennett W. Clark
Journal: Annals of Internal Medicine (2015)

On Being a Doctor2 June 2015Dr. Afshar's GridBennett W. Clark, MDBennett W. Clark, MDFrom Johns Hopkins University School of Medicine, Baltimore, Maryland.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-2719 Audio Reading - “Dr. Afshar's Grid” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Dr. Afshar's Grid," by B.W. Clark. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It was the morning after my first overnight call as an intern. I was nervous and reeked of sweat. Dr. Kia Afshar, youthful and rested, with buzzcut hair, leaned on a folding shelf outside a hospital room. Inside was the patient I had admitted for hypotension and decompensated heart failure. A ring of white coats—interns, residents, medical students—formed around Dr. Afshar. He took my H&P and turned it over to use as scratch paper. The white coats leaned in for a closer look.Dr. Afshar drew four vertical lines. He hatched them with horizontal lines. He labeled the columns: Mechanism ... Author, Article, and Disclosure InformationAffiliations: From Johns Hopkins University School of Medicine, Baltimore, Maryland.Corresponding Author: Bennett W. Clark, MD, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Dr. Afshar's Grid” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Dr. Afshar's Grid," by B.W. Clark. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byToward a Renascence of Physical Diagnosis in the Intensive Care Unit 2 June 2015Volume 162, Issue 11Page: 799-800KeywordsCathetersComputersDatabasesHyponatremiaInformation technologyShockSystemic vascular resistanceThrombosisUrineVasopressin ePublished: 2 June 2015 Issue Published: 2 June 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Long-term efficacy of rescue therapy with infliximab in steroid-refractory acute attack of ulcerative colitis
Authors: Mats Sjöberg, S. Almer, R. Befrits, C. Benoni, M. Carlson, A. Eriksson, I. Friis Liby, Jonas Halfvarson, E. Hertervig, P. Karlén, A. Lapidus, A. Magnusson, G. Midhagen, Curt Tysk
Journal: Gut (2011)

Long-term efficacy of rescue therapy with infliximab in steroid-refractory acute attack of ulcerative colitis
Is the NHS getting better or worse?: Better to be vaguely right than precisely wrong
Authors: D. Kernick
Journal: BMJ (2004)

EDITOR—In his editorial Smith asks whether the NHS is getting better or worse.1 By falling into the reductionist trap of assuming that the healthcare system can be understood by dissecting it into its component parts, he succeeds in being precisely wrong rather than vaguely right.

Underpinning his argument is a belief that the transfer processes that relate inputs to outputs …
Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells
Authors: Jung-Hyun Park, Stanley Adoro, Terry Guinter, Batu Erman, Amala S Alag, Marta Catalfamo, Motoko Y Kimura, Yongzhi Cui, Philip J Lucas, Ronald E Gress, Masato Kubo, Lothar Hennighausen, Lionel Feigenbaum, Alfred Singer
Journal: Nature Immunology (2010)
For and against: Why journals should not publish articles funded by the tobacco industry For Against
Authors: J. King
Journal: BMJ (2000)

That the tobacco industry is allowed a platform through scientific journals is a controversial issue. The Cancer Research Campaign already withholds research grants from academic departments closely linked with the tobacco industry; here it argues that respected journals should not publish articles funded by the industry. Such a notion is challenged by two editors, who prefer a policy of transparency and disclosure rather than prohibition.

# For {#article-title-2}

The arguments for scientists refusing to accept funding from the tobacco industry and, by extension, journals refusing to accept publications arising from such funding, fall into three main categories (box 1).

### Box 1: Arguments for refusing funding from the tobacco industry

#### Harm to health

The scale, range, and extent of the harm caused by tobacco far outweigh the effects of any other known product, legal or illegal

#### Distortion of scientific findings

Directly and indirectly the tobacco industry has systematically sought to undermine and misrepresent sound research on a massive scale, while itself funding studies and scientists of questionable credibility

#### Other disreputable activities

The tobacco industry's own documents show a uniquely discredited and disgraced sector that has sought to conceal evidence, recruit minors, and dupe the public and governments alike for many decades RETURN TO TEXT

The health risks associated with tobacco use have been detailed in many reports and were the basis of the justification for the Cancer Research Campaign's code of practice, which prohibits research groups in receipt of money from the tobacco industry from applying to it for funds (box 2).1–7

The tobacco industry has a long track record of seeking to cast doubt on good research, as shown in its own documents, now available on the internet owing to litigation cases in the United States. One tactic is to commission studies aimed at discrediting accepted findings: examples include studies that cast doubt on epidemiological findings, especially in relation to passive smoking, or which purport to identify other risk factors for …