tbuckley/cabot-search huggingface dataset:
Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection
Authors: Marieke Pingen, Steven R. Bryden, Emilie Pondeville, Esther Schnettler, Alain Kohl, Andres Merits, John K. Fazakerley, Gerard J. Graham, Clive S. McKimmie
Journal: Immunity (2016)

Highlights•Mosquito bites enhance virus replication and dissemination and increase host mortality•Neutrophil-driven inflammation retains virus in skin to drive macrophage recruitment•Recruited and resident myeloid cells become infected and replicate virus•Blocking leukocyte recruitment to bite site inhibits viral infectionSummaryAedes aegypti mosquitoes are responsible for transmitting many medically important viruses such as those that cause Zika and dengue. The inoculation of viruses into mosquito bite sites is an important and common stage of all mosquito-borne virus infections. We show, using Semliki Forest virus and Bunyamwera virus, that these viruses use this inflammatory niche to aid their replication and dissemination in vivo. Mosquito bites were characterized by an edema that retained virus at the inoculation site and an inflammatory influx of neutrophils that coordinated a localized innate immune program that inadvertently facilitated virus infection by encouraging the entry and infection of virus-permissive myeloid cells. Neutrophil depletion and therapeutic blockade of inflammasome activity suppressed inflammation and abrogated the ability of the bite to promote infection. This study identifies facets of mosquito bite inflammation that are important determinants of the subsequent systemic course and clinical outcome of virus infection.Graphical abstract
Bacteremia due to carbapenem-resistant Enterobacteriaceae in neutropenic patients with hematologic malignancies
Authors: Michael J. Satlin, Nina Cohen, Kevin C. Ma, Zivile Gedrimaite, Rosemary Soave, Gülce Askin, Liang Chen, Barry N. Kreiswirth, Thomas J. Walsh, Susan K. Seo
Journal: Journal of Infection (2016)
Government should think again about prioritising seven day NHS services, King’s Fund says
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The government needs to reconsider its commitment to delivering seven day NHS services and to review key waiting time targets if the priority for the NHS is to reduce its deficit, the King’s Fund think tank has said.

The NHS ended the 2015-16 financial year with an unprecedented deficit of £1.85bn (€2.2bn; $2.4bn), a figure three times that of the previous year, despite stringent financial controls and short term measures implemented by the government and NHS bodies to reduce costs.

A briefing document from the King’s Fund, called Deficits in the NHS , said that the deficit did not result from mismanagement in specific organisations but illustrated a …
Truncated netrin-1 contributes to pathological vascular permeability in diabetic retinopathy
Authors: Khalil Miloudi, François Binet, Ariel Wilson, Agustin Cerani, Malika Oubaha, Catherine Menard, Sullivan Henriques, Gaelle Mawambo, Agnieszka Dejda, Phuong Trang Nguyen, Flavio A. Rezende, Steve Bourgault, Timothy E. Kennedy, Przemyslaw Sapieha
Journal: Journal of Clinical Investigation (2016)

Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness in the working-age population. Impaired blood-retinal barrier function leads to macular edema that is closely associated with the deterioration of central vision. We previously demonstrated that the neuronal guidance cue netrin-1 activates a program of reparative angiogenesis in microglia within the ischemic retina. Here, we provide evidence in both vitreous humor of diabetic patients and in retina of a murine model of diabetes that netrin-1 is metabolized into a bioactive fragment corresponding to domains VI and V of the full-length molecule. In contrast to the protective effects of full-length netrin-1 on retinal microvasculature, the VI-V fragment promoted vascular permeability through the uncoordinated 5B (UNC5B) receptor. The collagenase matrix metalloprotease 9 (MMP-9), which is increased in patients with diabetic macular edema, was capable of cleaving netrin-1 into the VI-V fragment. Thus, MMP-9 may release netrin-1 fragments from the extracellular matrix and facilitate diffusion. Nonspecific inhibition of collagenases or selective inhibition of MMP-9 decreased pathological vascular permeability in a murine model of diabetic retinal edema. This study reveals that netrin-1 degradation products are capable of modulating vascular permeability, suggesting that these fragments are of potential therapeutic interest for the treatment of DR.
Plasma Fetuin-a concentration, genetic variation in the AHSG gene and risk of colorectal cancer
Authors: K Nimptsch, K Aleksandrova, H Boeing, J Janke, Lee Y-A., M Jenab, B Bueno-De-Mesquita, K K Tsilidis, E W Vainio, Jansen Ehjm., T J Key, A Trichopoulou, K Overvad, E Riboli, T Pischon, Canc Epi.
Journal: Cancer Research (2014)
Identification of a rabid dog in France illegally introduced from Morocco
Authors: Collective French multidisciplinary investigation team
Journal: Eurosurveillance (2008)

On 26 February 2008, the National Reference Centre for Rabies at the Institut Pasteur in Paris, France, confirmed the diagnosis of rabies in a domestic dog living in Grandpuits, Seine-et-Marne district, a suburb of Paris. The dog was a nine-month-old mixed-breed female, named Cracotte (pictures available at http://www.invs.sante.fr/display/?doc=surveillance/rage/actu.htm). It developed its first symptoms on 15 February, had bitten its owner and one neighbour and had been euthanized on 19 February. The viral strain was identified by the National Reference Centre for Rabies as a strain belonging to Lyssavirus genotype 1, Africa 1 lineage, originating from Morocco. According to its owner, Cracotte had never been outside France. France has been declared officially rabies-free since 2001. An investigation was undertaken to identify the source of infection and modes of transmission for Cracotte in order to identify potentially exposed individuals and animals and to carry out an assessment of the risk of rabies virus transmission in France.
A phase I study to determine the comparative bioavailability of two different oral formulations of the PARP inhibitor, olaparib (AZD2281), in patients with advanced solid tumors.
Authors: L. R. Molife, M. D. Forster, M. Krebs, T. Pwint, M. R. Middleton, S. B. Kaye, P. McCormack, H. Swaisland, J. Carmichael, M. Ranson
Journal: Journal of Clinical Oncology (2010)

2599 Background: Olaparib (AZD2281; KU-0059436) is an oral PARP inhibitor with single-agent activity and minimal toxicity in BRCA1- and BRCA2-mutation carriers. The current formulation is a 50 mg capsule. To achieve the recommended dose of 400 mg bid, 16 large (size 0) capsules are required which may compromise patient convenience and compliance. In preclinical models, a tablet formulation designed to deliver the therapeutic dose of olaparib in fewer dose units showed at least a 2-fold improvement in bioavailability and reduced pharmacokinetic (PK) variability compared with the capsule formulation. Methods: In this randomized, two-period, crossover study, patients with advanced solid tumors received a single dose of 50, 100, or 400 mg po capsule formulation followed after 6–14 days by a single dose of 25, 50, or 250 mg tablet formulation. Single-dose PK, dose linearity, and comparative bioavailability of the two formulations were assessed. Nonlinear mixed effects modeling (NONMEM) of tablet PK data, followed by multiple-dose simulation, was undertaken to predict the tablet dose needed to give matching exposure to the 400 mg bid capsule dose. Results: Twenty-four patients were included in this PK evaluation; median age was 57.5 years and 10 patients were male. Comparative bioavailability data are shown in the Table. Olaparib exposure did not increase linearly with dose following the capsule formulation but did increase linearly across the tablet dose range. A 200 mg bid tablet dose was predicted to give matching exposure to the 400 mg bid capsule dose. The individual patient steady-state Cmax and AUC0-12 values obtained following 200 mg bid tablet dosing fell within the range of values from previous studies with the 400 mg bid capsule dose. Conclusions: An equivalent tablet formulation dose of olaparib to the 400 mg bid capsule formulation (16 capsules) was established as 200 mg bid (4 tablets). Parameter Dose 25 mg tablet vs. 50 mg capsule 50 mg tablet vs. 100 mg capsule 250 mg tablet vs. 400 mg capsule Cmax ratio (95% CI) 1.29 (0.92–1.81) 1.53 (1.17–2.00) 2.49 (1.93–3.20) AUC ratio (95% CI) 1.03 (0.83–1.27) 0.99 (0.71–1.38) 1.74 (1.27–2.38) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca AstraZeneca
Notes from the Field: Meningococcal Disease in an International Traveler on Eculizumab Therapy — United States, 2015
Authors: Allen O. Applegate, Vanessa C. Fong, Kara Tardivel, Susan A. Lippold, Sheilah Zarate
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On June 2, 2015, CDC was notified that a male airline passenger, aged 41 years, with a fever of 105.4°F, headache, nausea, photophobia, diarrhea, and vomiting, which began approximately 3 hours after departure, was arriving to San Francisco, California, on a flight from Frankfurt, Germany. His symptoms reportedly started with neck stiffness 1 day earlier. Upon arrival, the patient was immediately transported to a local hospital, where he was in septic shock, which was followed by multisystem organ failure. Cerebrospinal fluid, obtained approximately 12 hours after initiation of treatment, was Gram stain- and culture-negative. Blood cultures, which were drawn before antibiotic treatment, were positive for Neisseria meningitides of indeterminate serogroup. A review of the patient's medical records revealed a history of paroxysmal nocturnal hemoglobinuria and current biweekly eculizumab (Soliris) therapy.
Cardiovascular News
Authors: Paul W. Armstrong, James T. Willerson, Dan M. Roden
Journal: Circulation (1998)

Cardiovascular medicine is undergoing extraordinary and rapid transformation.Circulation intends to keep its readership at the forefront of advances in our knowledge.Hence, in this issue, we introduce a section entitled "Clinical Cardiology: New Frontiers."Approximately once per month, we will engage topics of a clinically relevant nature to integrate new discoveries and knowledge into the armamentarium of the clinical practitioner.We intend that these articles will be helpful in influencing the thinking and clinical practice of physicians.Our primary goal is to provide useful information and practical advice on the management of contemporary clinical problems.Eligible topics will be drawn from a wide range of areas, including pathophysiology, diagnostic methods, epidemiology, natural history, and therapy.Because we aim to provide mechanistic insights and evaluate areas of controversy and uncertainty, we will generally invite two key opinion leaders to write articles in this section.Readers will note, however, that they will be from different institutions so as to achieve both diversity and balance.We welcome feedback on this new initiative.
222P FOLFIRINOX for advanced pancreato-biliary adenocarcinoma, a multi-centre retrospective analysis: The South Australian Experience
Authors: M. Klevansky, A.R.A. Mislang, V. Kwatra, C.L. Griffiths, A.H.-C. Hsieh, H. Takhar, S. Ullah, C.S. Karapetis, G. Kichenadasse, T.J. Price, T. Healey, N. Singhal, A. Roy
Journal: Annals of Oncology (2015)
Abstract 325: Dissociation of Oxidative Stress from High Fatty Acid-Induced Cardiac Myocyte Death
Authors: Nicolas Gutierrez Cortes, Huiliang Zhang, Shangcheng Xu, Guohua Gong, Wang Wang
Journal: Circulation Research (2014)

Metabolic syndrome, featured by obesity and diabetes, is an independent risk factor for cardiovascular disease. The high availability of free fatty acids characteristic of obesity has been proposed to increase fatty acid oxidation, impair mitochondrial function, stimulate reactive oxygen species (ROS) production and eventually lead to oxidative stress, which then would cause myocyte damage and heart dysfunction. However, the role of oxidative stress as the initial cause of obesity-induced heart failure is controversial. We evaluated the time-dependent effect of fatty acids in vitro in adult rat cardiac myocytes (treated with palmitate and oleate, the major saturated and unsaturated fatty acids in the plasma, respectively), and in vivo in mice fed a high-fat diet (fat calories = 60%). Palmitate and oleate dose-dependently stimulated mitochondrial respiration and superoxide flash activity, a respiration-coupled bursting ROS production event in single mitochondria. The flash frequency increased 2-fold (0.1 mM, the physiological level in plasma) and 3-fold (0.3 mM, the plasma level found in obese subjects) after only 2 hr incubation and up to 24 hr, increase that could be blocked by the CPT1 inhibitor etomoxir (100uM). Surprisingly, there was no obvious mitochondrial oxidative stress, although the high level of fatty acids caused mPTP opening and cell death at 48 hr. Further, aconitase activity was normal and NAD/NADH ratio was decreased, indicating a more reduced status rather than oxidative stress. Intriguingly, mitochondrial membrane potential was slightly lowered after only 2 hr of treatment. Finally, the high-fat diet-fed mice developed heart dysfunction after 12 weeks of treatment, but oxidative stress only appeared after 18 weeks. In the light of these results, we hypothesize that high fatty acid supply induced multiple adaptive and mal-adaptive responses in cardiac myocytes. The increased mitochondrial respiration and bursting ROS production is offset by a mild uncoupling and increased reducing equivalents. Therefore, oxidative stress is unlikely an initial cause of myocyte death and heart dysfunction in obesity, but rather a consequence of mitochondrial dysfunction, although the exact cause of this dysfunction remains to be elucidated.
Review of Reviews
Authors: E L Way
Journal: The Annual Review of Pharmacology and Toxicology (1981)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Antiretrovirals for HIV Treatment and Prevention
Authors: Kenneth H. Mayer, Douglas S. Krakower
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Congenital heart disease units will close in Manchester, Leicester, and the Royal Brompton
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Several heart specialist services are due to be closed across England under new proposals, and care will focus instead on centres of excellence that meet tough new standards.

Units that currently provide congenital heart surgery at the Central Manchester, Leicester, and Royal Brompton hospitals are set to close. The proposed changes, announced by NHS England on 8 July, are said to be necessary to ensure consistently high quality services across England for patients with congenital heart disease. The condition affects as many as 9 in 1000 babies born in the United Kingdom, with differing types of disease and levels of severity.

Services and surgery in this area of care are clustered in a small number of specialist centres across England, …
Approaching measles and rubella elimination in the European Region – need to sustain the gains
Authors: R Martin, S Deshevoi, N Buddha, D Jankovic
Journal: Eurosurveillance (2009)

Preview this article: Approaching measles and rubella elimination in the European Region – need to sustain the gains, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/14/50/art19449-en-1.gif
Case 35-1977
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Simmons Lessell, Max L. Goodman
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 76-year-old woman was admitted to the hospital because of visual loss.She was well until 30 years previously, when she experienced the sudden onset of intermittent diplopia. Spectacles with prisms were prescribed, with improvement. Five years later she began to have right frontal headaches, which were often present on awakening and were relieved by aspirin. Twenty years before admission the diplopia became more prominent. She came to this hospital, where examination revealed partial paralysis of the left oculomotor nerve and questionable paralysis of the right oculomotor nerve. A neostigmine test was positive. There was no history . . .
Surveillance data on paediatric HIV infection and AIDS in Greece
Authors: G Nikolopoulos, V Konte, A Masgala, E Eleni, A Tsantes, D Paraskeva
Journal: Eurosurveillance (2004)

In Greece, HIV/AIDS surveillance is conducted by the Hellenic Centre for Infectious Diseases Control. The AIDS case reporting system was implemented in 1984, followed by notification of HIV infections in 1998. This article presents surveillance and trend analysis of paediatric HIV infection and AIDS, including cases identified prior to 1998. The number of HIV infected children in Greece is relatively low, raising to a cumulative total of 69 cases by June 2003, 44 (64%) of whom are thought to have been infected through mother-to-child transmission. Thirty three paediatric AIDS cases have been reported since the onset of epidemic, with Pneumonocystis carinii pneumonia being the most frequent opportunistic infection. A significant number of children in Greece were diagnosed after the age of 1 year. This could be attributed to the fact that many HIV-infected women are not identified during pregnancy, despite that fact that voluntary testing is available. It could also be attributed to the fact that data includes HIV infections collected retrospectively after 1998, and that foreign HIV-infected children may arrive in Greece at a later age. Furthermore, new paediatric HIV positive cases that were reported during the first half-year period of 2003 were foreign children born in eastern Europe and sub-Saharan Africa. Efforts should be made to identify women in these populations in time for proper intervention. HIV infection in children remains a huge problem worldwide, and it is very important to focus on reducing the risk of mother-to-child transmission.
Taxanes in the Adjuvant Treatment of Breast Cancer
Authors: Donna Trauth, Lori J. Goldstein
Journal: Journal of the National Comprehensive Cancer Network (2003)

Adjuvant chemotherapy clearly demonstrates a reduction in mortality in breast cancer. However, the added benefit from the addition of taxanes remains uncertain. Paclitaxel and its cousin docetaxel have proven activity in the treatment of metastatic breast cancer. Toxicity has been tolerable when taxanes are used as single agents or in combination with anthracyclines. Several clinical trials are currently underway evaluating the role of taxanes in the adjuvant setting. Preliminary results from large phase III studies are promising; however, mature data are required before conclusions can be drawn. This article reviews the trials currently underway, evaluating the efficacy, dosage, scheduling, and regimens of taxanes in the adjuvant treatment of breast cancer.
Profiling of 149 Salivary Duct Carcinomas, Carcinoma Ex Pleomorphic Adenomas, and Adenocarcinomas, Not Otherwise Specified Reveals Actionable Genomic Alterations
Authors: Kai Wang, Jeffery S. Russell, Jessica D. McDermott, Julia A. Elvin, Depinder Khaira, Adrienne Johnson, Timothy A. Jennings, Siraj M. Ali, Molly Murray, Carrie Marshall, Dwight S. Oldham, Donna Washburn, Stuart J. Wong, Juliann Chmielecki, Roman Yelensky, Doron Lipson, Vincent A. Miller, Philip J. Stephens, Hilary S. Serracino, Jeffrey S. Ross, Daniel W. Bowles
Journal: Clinical Cancer Research (2016)

We sought to identify genomic alterations (GA) in salivary gland adenocarcinomas, not otherwise specified (NOS), salivary duct carcinomas (SDC), carcinoma ex pleomorphic adenoma (ca ex PA), and salivary carcinoma, NOS.DNA was extracted from 149 tumors. Comprehensive genomic profiling (CGP) was performed on hybridization-captured adaptor ligation-based libraries of 182 or 315 cancer-related genes plus introns from 14 or 28 genes frequently rearranged for cancer and evaluated for all classes of GAs.A total of 590 GAs were found in 157 unique genes (mean 3.9/tumor). GAs in the PI3K/AKT/mTOR pathway were more common in SDC (53.6%) than other histologies (P = 0.019) Cyclin-dependent kinase GAs varied among all histotypes: adenocarcinoma, NOS (34.6%); SDC (12.2%); ca ex PA (16.7%); carcinoma, NOS (31.2%; P = 0.043). RAS GAs were observed: adenocarcinoma, NOS (17.3%); SDC (26.8%); ca ex PA (4.2%); and carcinoma, NOS (9.4%; P = 0.054). ERBB2 GAs, including amplifications and mutations, were common: adenocarcinoma, NOS (13.5%); SDC (26.8%); ca ex PA (29.2%); carcinoma, NOS (18.8; P = 0.249). Other notable GAs include TP53 in >45% of each histotype; NOTCH1: adenocarcinoma, NOS (7.7%), ca ex PA (8.3%), carcinoma, NOS (21.6%); NF1: adenocarcinoma, NOS (9.6%), SDC (17.1%), carcinoma, NOS (18.8%). RET fusions were identified in one adenocarcinoma, NOS (CCDC6-RET) and two SDCs (NCOA4-RET). Clinical responses were observed in patients treated with anti-HER2 and anti-RET-targeted therapies.CGP of salivary adenocarcinoma, NOS, SDCs, ca ex PA, and carcinoma, NOS revealed diverse GAs that may lead to novel treatment options. Clin Cancer Res; 22(24); 6061-8. ©2016 AACR.
Studies on Human Cancer Using Sponge-Matrix Tissue Culture. III. The Invasive Properties of a Carcinoma (Strain He La) as Influenced by Temperature Variations, by Conditioned Media, and in Contact with Rapidly Growing Chick Embryonic Tissue
Authors: J LEIGHTON, I KLINE, M BELKIN, Z TETENBAUM
Journal: JNCI Journal of the National Cancer Institute (1956)
Frequency of Allogeneic Stem Cell Transplant(SCT) in Patients Presenting with Newly-Diagnosed AML or AML at Time of First Salvage Therapy.
Authors: Ravinder Sandhu, Stephen Petersdorf, Brenda M. Sandmaier, Paul O'Donnell, Pamela S. Becker, H. Joachim Deeg, Frederick R Appelbaum, Elihu H. Estey
Journal: Blood (2009)