tbuckley/cabot-search huggingface dataset:
European court calls for submissions on Scotland's plan for minimum alcohol pricing
Authors: R. Watson
Journal: BMJ (2014)

The Scottish government’s campaign to introduce a minimum price on a unit of alcohol is entering a new phase. The European Court of Justice has asked European Union governments, trade bodies, and other interested parties to present any submissions before the end of October. These will be taken into account before the judges deliver their ruling, possibly in the first half of next year.

The government wants to introduce the measure as part of its overall aim of reducing alcohol related harm. It accepts that minimum unit pricing is capable of affecting trade between EU countries and so goes against the general principle of …
Cognitive and psychosocial function post hematopoietic stem cell transplantation in children with hemophagocytic lymphohistiocytosis
Authors: Jessica Jackson, Penny Titman, Stephen Butler, Kathryn Bond, Anupama Rao, Paul Veys, Robert Chiesa, Alison Leiper, Lynne Riley, Kimberly Gilmour, Persis Amrolia, Kanchan Rao
Journal: Journal of Allergy and Clinical Immunology (2013)
Modernizing the Diagnostic and Decision-Making Pathway for Prostate Cancer
Authors: Thomas J. Polascik, Niccolo' M. Passoni, Arnauld Villers, Peter L. Choyke
Journal: Clinical Cancer Research (2014)

PSA has led to a drastic increase in the detection of prostate cancer, rendering this biomarker the gateway for the diagnostic pathway of prostatic neoplasms. However, the increase in incidence has not been mirrored by a similar reduction in mortality. Widespread PSA testing has facilitated the overdiagnosis and overtreatment of indolent disease. To reduce this phenomenon and avoid negative repercussions on the quality of life of men undergoing unnecessary therapies, the diagnostic pathway of prostate cancer needs to be improved. Multiparametric MRI (mp-MRI) can enhance the sensitivity and specificity of PSA, as well as the shortcomings of random biopsy sampling. This novel imaging technique has been proven to identify larger and more aggressive cancer foci, which should be targeted for treatment. New technological developments now allow for fusion of mp-MRI images with real-time ultrasound, opening the way to lesion-targeted biopsies. Furthermore, mp-MRI and targeted biopsies can also improve active surveillance protocols and permit more conservative focal therapy strategies. By implementing targeted biopsies, the diagnostic pathway will focus on clinically significant disease, consequently reducing overdiagnosis and overtreatment. Before this novel protocol becomes the new gold standard, mp-MRI acquisition and interpretation need to be standardized and targeted-biopsy strategies need to be further validated prior to abandoning random-sampling ones. Several multidisciplinary consortiums are already working on the standardization of prostate MRI, and there are ongoing prospective trials on targeted biopsies and MRI. Soon, imaging of prostatic lesions and selected biopsies will modify the diagnostic evaluation of prostate cancer, reducing overtreatment and therapy-derived complications that negatively affect quality of life.
Abstract 2271: Autophagy induction by low dose cisplatin: The role of p53 in autophagy
Authors: Sei-Hoon Yang, Kang Kyoo Lee, Sun Rock Moon
Journal: Cancer Research (2012)

Abstract Cisplatin has been mainly used for lung-cancer. However, cisplatin has many side effects, so the usage of cisplatin has a limitation. Recently, autophagy has become an important mechanism of cell death. The purpose of this study was to determine whether low dose cisplatin treated lung cancer cell induce autophagy and the autophagy inhibition resulted in apoptosis or necrosis. H460 cells were treated with 5 μM or 20 μM cisplatin for 12, 24, or 48 h. To detect the cisplatin-induced autophagy, we examined the autophagic vacuoles, and LC3 localization. To confirm the low-dose of cisplatin could induce autophagy, we detectd acidic vesicle using autophagy specific inhibitors(3-MA). To confirm the result of autophagy inhibition, we had done Annexin-V/PI and cell cycle assay. To find out the cisplatin mediated autophagic mechanisms, we examined the apoptotic regulator, p53. We used p53-/- null cancer cell line, H1299, to prove the role of p53 during autophagy. Low dose of cisplatin(5 μM) induced the autophagy after 24 h treatment in H460. Also low dose of cisplatin showed autophagic vacuoles and cytoplasmic LC3 formation in H460. The induction of autophagy by low dose cisplatin was inhibited by 3-MA, which was proven by reduced acidic vesicles. When the autohpagy inhibited, Annexin-V+/PI- and subG1 was an increased. The inhibition of autophagy resulted in decrease of LC3B-II band. Also cleaved caspase-3 and PARP were increased. Taken together, low dose cisplatin induced autophagy and the inhibition of autophagy resulted in the apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2271. doi:1538-7445.AM2012-2271
Switching statins: Cost of simvastatin is overestimated
Authors: John S Ashcroft
Journal: BMJ (2006)

Contraction and convergence: myth and realityEditor-The review of climate change issues in the BMJ of 10 June was comprehensive.On grounds of morality, the principle of contraction and convergence is unassailable. 1 In the real world, it is a pipe dream.It would work only by being enforcible, which implies an international policing authority with real teeth.Can we seriously believe that the United States, China, or Russia would submit to such an authority?Sadly there is no mileage in morality when affluent lifestyles are threatened.It is right to plead for changes in individual behaviour, but only the de-carbonising of energy at source will make a predictable and sustained impact on carbon dioxide emissions.The only long term route to this goal will be through the adoption of renewable energy technologies on two levels.Firstly, small scale to micro-generation systems are rapidly approaching market viability.Within five to 10 years, millions of homes could become cost effective mini-power stations linked to a local mini-grid under the umbrella of distributed generation.The Energy Saving Trust estimates that this sector could meet 40% of UK electricity demand. 2 Secondly, base load electricity could be provided by gigawatt scale technologies mostly drawing energy from wind, rivers, and seas.Tidal stream, tidal estuary, tidal impoundment, wave power, and offshore wind could more than match the output of today's nuclear power. 3 In the short term, "balancing power" to compensate for intermittency would be provided by combined cycle gas power plants.In the longer term, surplus electricity, which is an intrinsic problem with renewables, will be directed to producing hydrogen for grid connected gigawatt scale fuel cells in a symbiotic coupling with high energy density renewables installations.All this will, of course, depend on massive government investment, but so would nuclear energy.On the demand side, buildings are the biggest carbon culprits.The only effective answer, embracing both new and existing buildings, is the concept of the carbon budget, enforcible by law.This could also be adapted for transport.These have complex implications, perhaps for another time.
Oxygen Uptake of the Nonworking Left Ventricle
Authors: W. P. MCKEEVER, D. E. GREGG, P. C. CANNEY
Journal: Circulation Research (1958)

Comparisons have been made in the open chest dog of the oxygen usage of the left ventricle whose external work has been reduced to zero by 4 different procedures. The average oxygen usage of the left myocardium/100 Gm./min. is about 2.0 cc. in complete arrest with vagal stimulation or with intracoronary potassium injection; 3.8 cc. in fibrillation; and 3.4 cc. in the empty but beating heart. The oxygen value in the arrested heart approximates 27 per cent of that in the control state and the uptake during vagal stoppage varies directly with the control metabolic level. In the fibrillating ventricle the higher values are related to the intensity of fibrillatory movements, and in the empty beating heart to the control metabolic rate and to the frequency of the heart beat. The experiments with vagal arrest also permit estimation of the oxygen debt of the myocardium.
Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites
Authors: Gregory L Lyford, Kanato Yamagata, Walter E Kaufmann, Carol A Barnes, Laura K Sanders, Neal G Copeland, Debra J Gilbert, Nancy A Jenkins, Anthony A Lanahan, Paul F Worley
Journal: Neuron (1995)

Neuronal activity is an essential stimulus for induction of plasticity and normal development of the CNS. We have used differential cloning techniques to identify a novel immediate-early gene (IEG) cDNA that is rapidly induced in neurons by activity in models of adult and developmental plasticity. Both the mRNA and the encoded protein are enriched in neuronal dendrites. Analysis of the deduced amino acid sequence indicates a region of homology with alpha-spectrin, and the full-length protein, prepared by in vitro transcription/translation, coprecipitates with F-actin. Confocal microscopy of the native protein in hippocampal neurons demonstrates that the IEG-encoded protein is enriched in the subplasmalemmal cortex of the cell body and dendrites and thus colocalizes with the actin cytoskeletal matrix. Accordingly, we have termed the gene and encoded protein Arc (activity-regulated cytoskeleton-associated protein). Our observations suggest that Arc may play a role in activity-dependent plasticity of dendrites.
Serial Assessment of the Cardiovascular System in Normal Pregnancy
Authors: Athena Poppas, Sanjeev G. Shroff, Claudia E. Korcarz, Judith U. Hibbard, David S. Berger, Marshall D. Lindheimer, Roberto M. Lang
Journal: Circulation (1997)

Temporal changes in systemic arterial compliance and wave propagation properties (pulsatile arterial load) and their role in ventricular-systemic arterial coupling during gestation have not been explored. Noninvasive methods combined with recently developed mathematical modeling techniques were used to characterize vascular and left ventricular (LV) mechanical adaptations during normal gestation.Fourteen healthy women were studied at each trimester of pregnancy and again postpartum. Experimental measurements included instantaneous aortic pressure (subclavian pulse tracings) and flow (aortic Doppler velocities) and echocardiographic imaging of the LV. A small increase in LV muscle mass and end-diastolic chamber dimension occurred by late gestation, with no significant alterations in myocardial contractility. Cardiac output increased and the steady component of arterial load (total vascular resistance) decreased during pregnancy. Several changes in pulsatile arterial load were noted: Global arterial compliance increased (approximately 30%) during the first trimester and remained elevated thereafter. The magnitude of peripheral wave reflections at the aorta was reduced. The mathematical model-based analysis revealed that peripheral wave reflections at the aorta were delayed and that both conduit and peripheral vessels contributed to the increased arterial compliance. Finally, coordinated changes in the pulsatile arterial load and LV properties were responsible for maintaining the efficiency of LV-to-arterial system energy transfer.The rapid time course of compliance changes and the involvement of both conduit and peripheral vessels are consistent with reduced vascular tone as being the main underlying mechanism. The pulsatile arterial load alterations during normal pregnancy are adaptive in that they help to accommodate the increased intravascular volume while maintaining the efficiency of ventricular-arterial coupling and diastolic perfusion pressure.
Prognostic Value of Baseline and Changes in Circulating Soluble ST2 Levels and the Effects of Nesiritide in Acute Decompensated Heart Failure
Authors: W.H. Wilson Tang, Yuping Wu, Justin L. Grodin, Amy P. Hsu, Adrian F. Hernandez, Javed Butler, Marco Metra, Adriaan A. Voors, G. Michael Felker, Richard W. Troughton, Roger M. Mills, John J. McMurray, Paul W. Armstrong, Christopher M. O'Connor, Randall C. Starling
Journal: JACC Heart Failure (2015)
Abstract 1825: The inhibitory effect of long non-coding RNA MALAT1 on Smads signaling pathway.
Authors: Jinqiang Zhang, Chang Han, Tong Wu
Journal: Cancer Research (2013)

Abstract Long non-coding RNA (lncRNA) is arbitrarily defined as RNA longer than 200 bases that does not encode mRNA, rRNA or tRNA. LncRNAs are involved in almost every aspect of cellular and molecular biology. In most cases, lncRNAs assemble with proteins as RNA-protein complexes to execute their functions. We hypothesize some important molecular in critical signaling pathway, such as Smad2 and Smad3 in TGF-β/Activin pathway, might have their lncRAN partner/partners to fine regulate their function. Based on the hypothesis, we carried on little scale screen and finally identified lncRAN MALAT1 can exclusively bind to pSmad2 and pSmad3 in hepatocellular carcinoma cell lines Hep3B, SK-Hep1 and cholangiocarcinoma cell line CCLP1 by methods of RNA Immunoprecipitation (RIP). After quantifying by qRT-PCR, we found that MALAT1 enriched by anti-pSmad2/3 antbodies is &amp;gt;15 times more than that by IgG control. Co-localization of MALAT1 and pSmad2 and 3 in nuclear speckles of Hep3B cells were also proved by methods of combining FISH and immunofluorescence staining. Further bioinformatics analysis and immunoprecipitation reveal that pSmad2/3 binding to MALAT1 through SET domain containing 2 (SETD2) indirectly. Accordingly, if SETD2 was knockdown by siRNA, the binding between pSmad2/3 with MALAT1 was proved decreasing dramatically by methods of RIP. We also found that MALAT1 knockdown by shRNA or antisense oligonucleotide will increase the Smad2/3 signaling activity significantly, which was proved by Smad2/3 luciferase reporter constructs, DNA pull-down using synthesized oligonucleotide containing consensus sequence of Smads binding elements (SBE) and enhanced inhibition effect of TGF-β on the proliferation of Hep3B and CCLP1 cells. Next, Protein Phosphatase 1A (PPMA1), which act as a Smad phosphatase to terminate pSmad2/3 activity, was proved to bind to MALAT1 and MALAT1 knockdown decreased the binding of pSmad2/3 to PPM1A. Therefore, MALAT1 (together with SETD2) might act as scaffold to facility the interaction between pSmad2/3 and PPM1A, which lead to the dephosphorylation of pSmad2/3. This kinetically decrease of pSmad2/3 dephosphorylation might be the reason of increased Smads signaling activity in MALAT1 knockdown cells. This work was supported by National Institutes of Health grants CA102325, CA106280, CA134568, DK077776 (to T.W.) and CA137729 (to C.H.) Citation Format: Jinqiang Zhang, Chang Han, Tong Wu. The inhibitory effect of long non-coding RNA MALAT1 on Smads signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1825. doi:10.1158/1538-7445.AM2013-1825
Even Slightly Elevated Plasma Uric Acid Levels Could be a Predictor of Cardiovascular Death in Chronic Heart Failure
Authors: Yasar Akay, Guliz Kozdag, Ender Emre, Tayfun Sahin, Gokhan Ertas, Teoman Kilic, Goksel Kahraman, Ulas Bildirici, Metin Cetin, Umut Celikyurt, Kurtulus Karauzum, Ertan Ural, Dilek Ural
Journal: Journal of the American College of Cardiology (2013)
Epidemiology of Tension-Type Headache
Authors: Brian S. Schwartz
Journal: JAMA (1998)

Context.—Tension-type headache is a highly prevalent condition. Because few population-based studies have been performed, little is known about its epidemiology.Objectives.—To estimate the 1-year period prevalence of episodic tension-type headache (ETTH) and chronic tension-type headache (CTTH) in a population-based study; to describe differences in 1-year period prevalence by sex, age, education, and race; and to describe attack frequency and headache pain intensity.Design.—Telephone survey conducted 1993 to 1994.Setting.—Baltimore County, Maryland.Participants.—A total of 13345 subjects from the community.Main Outcome Measures.—Percentage of respondents with diagnoses of headache using International Headache Society criteria. Workdays lost and reduced effectiveness at work, home, and school because of headache, based on self-report.Results.—The overall prevalence of ETTH in the past year was 38.3%. Women had a higher 1-year ETTH prevalence than men in all age, race, and education groups, with an overall prevalence ratio of 1.16. Prevalence peaked in the 30- to 39-year-old age group in both men (42.3%) and women (46.9%). Whites had a higher 1-year prevalence than African Americans in men (40.1% vs. 22.8%) and women (46.8% vs 30.9%). Prevalence increased with increasing educational levels in both sexes, reaching a peak in subjects with graduate school educations of 48.5% for men and 48.9% for women. The 1-year period prevalence of CTTH was 2.2%; prevalence was higher in women and declined with increasing education. Of subjects with ETTH, 8.3% reported lost workdays because of their headaches, while 43.6% reported decreased effectiveness at work, home, or school. Subjects with CTTH reported more lost workdays (mean of 27.4 days vs 8.9 days for those reporting lost workdays) and reduced-effectiveness days (mean of 20.4 vs 5.0 days for those reporting reduced effectiveness) compared with subjects with ETTH.Conclusions.—Episodic tension-type headache is a highly prevalent condition with a significant functional impact at work, home, and school. Chronic tension-type headache is much less prevalent than ETTH; despite its greater individual impact, CTTH has a smaller societal impact than ETTH.
Hilde, the Teacher
Authors: Stuart Yudofsky
Journal: JAMA (1987)

Dr Hilde Bruch died recently at the age of 80. Pediatrician, psychiatrist, and psychoanalyst, Dr Bruch was a pioneer in the field of eating disorders and is considered a major contributor to the conceptualization of anorexia nervosa. During the 18 years that it was my privilege to know Hilde Bruch I never presumed to understand her. This was not the way she would have it. She would discuss her ideas, her work, and, eventually, even her physical problems; but never, with me, would she discuss her personal life. With Dr Bruch, one always knew one's place. On the other hand, she knew nearly everything about me.<b>1968.—</b>I was a third-year student at Baylor College of Medicine in Houston, which I had attended, as did many of my classmates, with the hope of becoming a heart surgeon. My first rotation was in surgery at the Heart Palace, Houston's Methodist Hospital.
A 20 year old man with a high pressure steam burn
Authors: Robert Charles, Robert Jackson, James Dodman
Journal: BMJ (2014)

A 75 kg (165 lb), previously fit and well 20 year old man sustained a high pressure steam burn (~42 bar) while working in an oil refinery. He was attended to at the scene by the air ambulance service. On assessment, his airway appeared clear; he had a respiratory rate of 25 breaths/min, with oxygen saturations of 90% on ambient air. He was tachycardic at a rate of 135 beats/min. His blood pressure could not be taken initially because of the extent of his burns; however, clinical examination showed that he had reduced peripheral perfusion. He was fully conscious, with a Glasgow coma score of 15/15.

The burns affected about 60% of his body surface area. This included full thickness burns to his chest and circumferential burns to his arms. Partial thickness burns affected his head, neck, back, and thighs.

Initial resuscitation was undertaken by the air ambulance team. He was sedated, his airway was secured by intubating the trachea, and he was mechanically ventilated. Intravenous access was difficult, so fluid resuscitation was started through an intraosseous needle. He was airlifted to the regional burns centre for urgent assessment by the burns intensive care and plastic surgical teams.



### 1. What are the common causes of major burn injuries in adults and how often do they occur?

#### Short answer

Scalds (including steam), flame burns, and contact burns are the three main causes of major burn injuries in adults. The annual incidence …
491 Estrogen upregulates nitric oxide production via estrogen receptor alpha of hepatic sinusoidal endothelial cells in cirrhosis
Authors: M SAKAMOTO, T NAKAMURA, T TORIMURA, R SAKATA, O HASHIMOTO, T UENO, M SATA
Journal: Hepatology (2003)

Complications such as ascites during the pathogenesis of hepatic fibrosis and cirrhosis may lead to several abnormalities in mineral metabolism. In the present investigation, we have monitored serum and liver concentrations of calcium, magnesium, sodium and potassium during experimentally induced hepatic fibrosis in rats.The liver injury was induced by intraperitoneal injections of dimethylnitrosamine (DMN; N-nitrosodimethylamine, NDMA) in doses 1 mg/100 g body weight on 3 consecutive days of each week over a period of 21 days. Calcium, magnesium, sodium and potassium were measured by atomic absorption spectrophotometry in the serum and liver on days 7, 14 and 21 after the start of DMN administration.Negative correlations were observed between liver function tests and serum mineral levels, except with albumin. Calcium, magnesium, potassium and sodium concentrations in the serum were decreased after the induction of liver injury. The liver calcium content was increased after DMN treatment. No change occurred in liver sodium content. However, magnesium and potassium content was significantly reduced in the hepatic tissue.The results suggest that DMN-induced hepatic fibrosis plays certain role in the alteration of essential elements. The low levels of albumin and the related ascites may be one of the major causes of the imbalance of mineral metabolism in hepatic fibrosis and further aggravation of the disease.
Therapeutic value of eptifibatide at community hospitals transferring patients to tertiary referral centers early after admission for acute coronary syndromes
Authors: Adam B Greenbaum, Robert A Harrington, Michael P Hudson, Cynthia M MacAulay, Robert G Wilcox, Maarten L Simoons, Lisa G Berdan, Alan Guerci, Dennis V Cokkinos, Michael M Kitt, A.Michael Lincoff, Eric J Topol, Robert M Califf, E.Magnus Ohman
Journal: Journal of the American College of Cardiology (2001)
New agency should take over GPs' role of certifying long term illness, review concludes
Authors: I. Torjesen
Journal: BMJ (2011)

GPs in England should be stripped of much of their responsibility for deciding whether people with long term illness are fit and able to work, recommends a review commissioned by the government.

The Independent Review of Sickness Absence says that the current system pushes people away from work and provides little support for them to return. It recommends that a new government funded Independent Assessment Service should be responsible for signing off people for long term sick leave rather than their own GP.

People could be referred to the service by their employer or GP after they have been off work for four weeks, and health professionals would assess their physical or mental function and advise on how they could be helped to return to work.

The …