tbuckley/cabot-search huggingface dataset:
MMP-2 Regulates Erk1/2 Phosphorylation and Aortic Dilatation in Marfan Syndrome
Authors: Wanfen Xiong, Trevor Meisinger, Rebecca Knispel, Jennifer M. Worth, B. Timothy Baxter
Journal: Circulation Research (2012)

Aneurysm and dissection of the ascending thoracic aorta are the main cardiovascular complications of Marfan syndrome (MFS) resulting in premature death. Studies using mouse models of MFS have shown that activation of transforming growth factor-beta (TGF-β) and the concomitant upregulation of matrix metalloproteinases (MMPs) contribute to aneurysm development. Our previous study showed that doxycycline delayed aneurysm rupture in a mouse model of MFS, Fbn1(mgR/mgR). Losartan has been shown to prevent aneurysms in another mouse model of MFS, Fbn1(C1039G/+), through inhibition of the Erk1/2 pathway. However, the role of MMP-2 in MFS and effect of losartan on the lifespan of MFS mice remain unknown.We investigated the role of MMP-2 in MFS and compared the effects of losartan and doxycycline on aortic dilatation and survival in Fbn1(mgR/mgR) mice.By life table analysis, we found that losartan and doxycycline improved the survival of Fbn1(mgR/mgR) mice. Gelatin zymography and Western blot data showed that only doxycycline inhibited MMP-2 expression, whereas both drugs decreased Erk1/2 phosphorylation. When combined, only one of nine mice died within the 30-week study; aortic histology and diameter were normalized and the effects on Smad2 phosphorylation was additive. To further explore the role of MMP-2 in MFS, we created MMP-2-deficient Fbn1(mgR/mgR) mice. MMP-2 deletion inhibited activation of TGF-β and phosphorylation of Erk1/2 and Smad2 and prolonged the lifespan of the mice.These studies demonstrated that inhibition of MMP-2 by doxycycline delayed the manifestations of MFS, in part, through its ability to decrease active TGF-β and the noncanonical signaling cascade downstream of TGF-β. This study further suggested that targeting TGF-β signaling at different points might be a more effective strategy for inhibiting disease progression.
A Novel Histologic Scoring System to Evaluate Mucosal Biopsies From Patients With Eosinophilic Esophagitis
Authors: Cheryl Protheroe, Samantha A. Woodruff, Giovanni de Petris, Vince Mukkada, Sergei I. Ochkur, Sailajah Janarthanan, John C. Lewis, Shabana Pasha, Tisha Lunsford, Lucinda Harris, Virender K. Sharma, Michael P. McGarry, Nancy A. Lee, Glenn T. Furuta, James J. Lee
Journal: Clinical Gastroenterology and Hepatology (2009)
Quality of life in low-grade glioma patients receiving temozolomide
Authors: Raymond Liu, Karla Solheim, Mei-Yin Polley, Kathleen R. Lamborn, Margaretta Page, Anne Fedoroff, Jane Rabbitt, Nicholas Butowski, Michael Prados, Susan M. Chang
Journal: Neuro-Oncology (2008)

The purpose of this study was to describe the quality of life (QOL) of low-grade glioma (LGG) patients at baseline prior to chemotherapy and through 12 cycles of temozolomide (TMZ) chemotherapy. Patients with histologically confirmed LGG with only prior surgery were given TMZ for 12 cycles. QOL assessments by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) were obtained at baseline prior to chemotherapy and at 2-month intervals while receiving TMZ. Patients with LGG at baseline prior to chemotherapy had higher reported social well-being scores (mean difference = 5.0; p < 0.01) but had lower reported emotional well-being scores (mean difference = 2.2; p < 0.01) compared to a normal population. Compared to patients with left hemisphere tumors, patients with right hemisphere tumors reported higher physical well-being scores (p = 0.01): 44% could not drive, 26% did not feel independent, and 26% were afraid of having a seizure. Difficulty with work was noted in 24%. Mean change scores at each chemotherapy cycle compared to baseline for all QOL subscales showed either no significant change or were significantly positive (p < 0.01). Patients with LGG on TMZ at baseline prior to chemotherapy reported QOL comparable to a normal population with the exception of social and emotional well-being, and those with right hemisphere tumors reported higher physical well-being scores compared to those with left hemisphere tumors. While remaining on therapy, LGG patients were able to maintain their QOL in all realms. LGG patients' QOL may be further improved by addressing their emotional well-being and their loss of independence in terms of driving or working.
Uninsured Children and Adolescents With Insured Parents
Authors: Jennifer E DeVoe, Carrie Tillotson, Lorraine S Wallace
Journal: JAMA (2008)

ORE THAN 9 MILLION children in the UnitedStates have no health insurance coverage. 1 , 21][12][13][14] Discontinuities in children's health insurance coverage, even for only a few months, are associated with significant unmet health care needs. 15,16tates seeking to maximize rates of continuous coverage for eligible children and adolescents have sought federal waivers to expand Medicaid coverage to low-income parents.8][19][20][21][22] Conversely, when state Medicaid programs have scaled back parental benefits for low-income families, their children's coverage has been adversely affected. 16he association between coverage for parents and their children has been widely reported. 20,23,24In a recent Oregon study, children eligible for public insurance who had uninsured parents were 14 times more likely to be uninsured than those with insured parents. 16When entire families have access to health insurance, children and adolescents not only benefit from more consistent insurance coverage but also have improved access to a regular source of care and higher rates of preventive services. 7,19,22,25,26If entire
Nuclear Cyclin D1/CDK4 Kinase Regulates CUL4 Expression and Triggers Neoplastic Growth via Activation of the PRMT5 Methyltransferase
Authors: Priya Aggarwal, Laura Pontano Vaites, Jong Kyong Kim, Hestia Mellert, Buddha Gurung, Hiroshi Nakagawa, Meenhard Herlyn, Xianxin Hua, Anil K. Rustgi, Steven B. McMahon, J. Alan Diehl
Journal: Cancer Cell (2010)
Salvianolic acid B protects human endothelial cells from oxidative stress damage: a possible protective role of glucose-regulated protein 78 induction
Authors: H.-L. Wu, Y.-H. Li, Y.-H. Lin, R. Wang, Y.-B. Li, L. Tie, Q.-L. Song, D.-A. Guo, H.-M. Yu, X.-J. Li
Journal: Cardiovascular Research (2008)

AimsThe purposes of the present study were to both evaluate the protective effects of Salvianolic acid B (Sal B) and to determine the possible molecular mechanisms by which Sal B protects endothelial cells from damage caused by oxidative stress.
The effect of forced exercise on knee joints in Dio2<sup>−/−</sup> mice: type II iodothyronine deiodinase-deficient mice are less prone to develop OA-like cartilage damage upon excessive mechanical stress
Authors: Nils Bomer, Frederique M F Cornelis, Yolande FM Ramos, Wouter den Hollander, Lies Storms, Ruud van der Breggen, Nico Lakenberg, P Eline Slagboom, Ingrid Meulenbelt, Rik JL Lories
Journal: Annals of the Rheumatic Diseases (2014)

To further explore deiodinase iodothyronine type 2 (DIO2) as a therapeutic target in osteoarthritis (OA) by studying the effects of forced mechanical loading on in vivo joint cartilage tissue homeostasis and the modulating effect herein of Dio2 deficiency.Wild-type and C57BL/6-Dio2(-/-) -mice were subjected to a forced running regime for 1 h per day for 3 weeks. Severity of OA was assessed by histological scoring for cartilage damage and synovitis. Genome-wide gene expression was determined in knee cartilage by microarray analysis (Illumina MouseWG-6 v2). STRING-db analyses were applied to determine enrichment for specific pathways and to visualise protein-protein interactions.In total, 158 probes representing 147 unique genes showed significantly differential expression with a fold-change ≥1.5 upon forced exercise. Among these are genes known for their association with OA (eg, Mef2c, Egfr, Ctgf, Prg4 and Ctnnb1), supporting the use of forced running as an OA model in mice. Dio2-deficient mice showed significantly less cartilage damage and signs of synovitis. Gene expression response upon exercise between wild-type and knockout mice was significantly different for 29 genes.Mice subjected to a running regime have significant increased cartilage damage and synovitis scores. Lack of Dio2 protected against cartilage damage in this model and was reflected in a specific gene expression profile, and either mark a favourable effect in the Dio2 knockout (eg, Gnas) or an unfavourable effect in wild-type cartilage homeostasis (eg, Hmbg2 and Calr). These data further support DIO2 activity as a therapeutic target in OA.
Medical management of hamstring muscle injury: strained evidence for platelet rich plasma
Authors: Bruce Hamilton
Journal: British Journal of Sports Medicine (2014)

Muscle strain injuries remain one of the most common injuries in sport, with a significant morbidity for elite and non-elite athletes.1 The past 25 years has seen a significant increase in our understanding of the epidemiology and pathophysiology of this injury. While prevention of muscle injuries remains the Holy Grail and is appropriately attracting significant research activity, we are yet to observe a sustained reduction in the incidence of muscle injuries in elite sport.1 Furthermore, despite the high prevalence of muscle injuries, there remains limited research into the best management of muscle strain injuries2; research has typically been limited to low-level studies3 and considered analogous to ‘snake-oil’. Since the 1990s, solutions of concentrated platelets derived from the manipulation of autologous blood, in the form of platelet rich plasma (PRP), have been used to enhance healing of a range of medical conditions.4 PRP is alleged to facilitate muscle healing through the optimised provision of …
European Union Standards for Tuberculosis Care
Authors: G.B. Migliori, J.P. Zellweger, I. Abubakar, E. Ibraim, J.A. Caminero, G. De Vries, L. D'Ambrosio, R. Centis, G. Sotgiu, O. Menegale, K. Kliiman, T. Aksamit, D.M. Cirillo, M. Danilovits, M. Dara, K. Dheda, A.T. Dinh-Xuan, H. Kluge, C. Lange, V. Leimane, R. Loddenkemper, L.P. Nicod, M.C. Raviglione, A. Spanevello, V.Ø. Thomsen, M. Villar, M. Wanlin, J.A. Wedzicha, A. Zumla, F. Blasi, E. Huitric, A. Sandgren, D. Manissero
Journal: European Respiratory Journal (2012)

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB). The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting. A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed. These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.
Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial
Authors: Andreas Engert, Heinz Haverkamp, Carsten Kobe, Jana Markova, Christoph Renner, Antony Ho, Josée Zijlstra, Zdenek Král, Michael Fuchs, Michael Hallek, Lothar Kanz, Hartmut Döhner, Bernd Dörken, Nicole Engel, Max Topp, Susanne Klutmann, Holger Amthauer, Andreas Bockisch, Regine Kluge, Clemens Kratochwil, Otmar Schober, Richard Greil, Reinhard Andreesen, Michael Kneba, Michael Pfreundschuh, Harald Stein, Hans Theodor Eich, Rolf-Peter Müller, Markus Dietlein, Peter Borchmann, Volker Diehl
Journal: The Lancet (2012)
MECHANISMS OF ENDOTOXIN TOLERANCE
Authors: Sheldon E. Greisman, Edward J. Young, William E. Woodward
Journal: The Journal of Experimental Medicine (1966)

The mechanisms underlying the pyrogenic refractory state which develops rapidly during a continuous intravenous infusion of bacterial endotoxin have been further explored. The findings demonstrate that: (a) rabbits rendered refractory to a continuous intravenous infusion of E. coli endotoxin at a standard rate (18 x 10(-4) microg/min) become highly refractory to a single intravenous test bolus of endotoxin, but remain fully responsive to preformed endogenous pyrogen and to substances known to release endogenous pyrogen, i.e. influenza virus, old tuberculin in specifically sensitized rabbits, and staphylococcal enterotoxin; (b) administration of fresh whole blood from normal donors containing an average of 1.6 - 10(8) granulocytes fails to restore febrile responsiveness to the continuing E. coli endotoxin infusion; (c) refractory phase plasma and liver homogenates exhibit no enhanced capacity to inactivate E. coli endotoxin pyrogenicity; (d) splenectomized animals readily develop the pyrogenic refractory state during E. coli endotoxin infusions and exhibit diminished, rather than the increased inflammatory responses to intradermal endotoxin seen in sham-operated controls; (e) continuous intravenous infusions of gelatin-stabilized, heat-killed pneumococci produce sustained fevers; and (f) continuous intravenous infusions of old tuberculin into specifically sensitized animals rapidly elicit a pyrogenic refractory state. The present observations, considered together with those of other investigators, support the hypothesis that pyrogenic unresponsiveness to endotoxin involves two distinct immunologic mechanisms. In terms of this hypothesis, the rapid reduction in febrile responsiveness to endotoxin is mediated by desensitization at the cellular level. With small doses of endotoxin, such as those employed in the present studies, this desensitization is primarily specific; with larger doses, nonspecific mechanisms are superimposed. So long as the subsequent doses of endotoxin are closely spaced or continuously infused, optimal conditions are provided for cellular desensitization and pyrogenic unresponsiveness to a given quantity of endotoxin can be induced rapidly and maintained without the requirement for antibody. However, as the interval between endotoxin challenge is lengthened, cellular desensitization wanes and tolerance becomes increasingly dependent upon those antibodies directed against the common toxophore groupings responsible for endotoxin pyrogenicity which assist the reticuloendothelial system in the clearance and destruction of this molecule.
Percutaneous transhepatic assistance for duodenoscopic sphincterotomy.
Authors: P J Shorvon, P B Cotton, R R Mason, J H Siegel, A R Hatfield
Journal: Gut (1985)

Duodenoscopic sphincterotomy is an established method for dealing with common bile duct stones and papillary stenosis. Occasionally even an experienced operator is unable to carry out a sphincterotomy, for instance in the presence of large peri-papillary diverticula or Billroth II gastrectomy. Most of these patients will be offered surgery--a few will refuse or be unfit for operation. One further therapeutic option is a combined approach involving a radiologist and endoscopist, in which percutaneous transhepatic insertion of a guide wire through the papilla, with or without balloon dilatation, is used to facilitate insertion of the sphincterotome by the endoscopist. This has been done successfully in 10 of 11 patients attempted, without significant complication.
Effects of Glucose and Parathyroid Hormone on the Renal Handling of Myoinositol by Isolated Perfused Dog Kidneys
Authors: B. A. Molitoris, K. A. Hruska, N. Fishman, W. H. Daughaday
Journal: Journal of Clinical Investigation (1979)

The effects of glucose and parathyroid hormone (PTH) on the transport and metabolism of myoinositol (MI) and [2-(3)H]MI were studied in isolated perfused dog kidneys. Studies during perfusion of kidneys with normal and elevated glucose concentrations demonstrated that under normal conditions the isolated kidney reabsorbed 94.7+/-0.2% of the filtered MI, and the renal production of (3)H-metabolities of MI was 117.9+/-6% of the filtered MI load. This indicated that entry of MI into tubular cells by reabsorption was not the sole pathway for entry into the pool of MI within the kidney undergoing catabolism. High glucose perfusate decreased MI reabsorption to 68.6+/-4.7% and thus decreased delivery of [2-(3)H]MI into the catabolic pool from the reabsorptive pathway. In the high glucose experiments, the rate of [2-(3)H]MI catabolism exceeded [2-(3)H]MI reabsorption by the same fraction as in normal glucose experiments, which indicates that high glucose did not affect nonreabsorptive access of MI to the catabolic site. In contrast to the effects of glucose, PTH administration resulted in an increase in perfusate MI concentration and a decrease in the perfusate [2-(3)H]MI specific activity. Concomitantly, urinary MI and [2-(3)H]MI concentrations were increased, again with a decrease in [2-(3)H]MI specific activity. These results indicate that PTH caused a release of MI into the urine (not the same as decreased MI reabsorption, which would not affect urinary [(3)H]MI specific activity) and into the perfusate of the isolated kidneys. These effects on MI release were about coincidental with the increase in urinary cyclic 3',5'-AMP after PTH and preceded the peak phosphaturic effect of PTH. There was no detectable effect of PTH on MI synthesis from glucose as a source of the MI released into the urine and perfusate. However, PTH temporarily halted accumulation of tritiated MI catabolites. There was no effect of inactivated PTH on urinary cyclic 3',5'-AMP or on MI transport, which indicates that the PTH effect on MI handling was a specific hormonal effect. These studies clarify the renal metabolism of MI, and they demonstrate heretofore unknown effects of PTH on the renal handling and metabolism of MI. The effects of PTH on renal MI metabolism have important implications in renal carbohydrate metabolism and phospholipid turnover.
Occupational exposures and the risk of COPD: dusty trades revisited
Authors: P D Blanc, C Iribarren, L Trupin, G Earnest, P P Katz, J Balmes, S Sidney, M D Eisner
Journal: Thorax (2008)

The contribution of occupational exposures to chronic obstructive pulmonary disease (COPD) and, in particular, their potential interaction with cigarette smoking remains underappreciated.Data from the FLOW study of 1202 subjects with COPD (of which 742 had disease classified as stage II or above by Global Obstructive Lung Disease (GOLD) criteria) and 302 referent subjects matched by age, sex and race recruited from a large managed care organisation were analysed. Occupational exposures were assessed using two methods: self-reported exposure to vapours, gas, dust or fumes on the longest held job (VGDF) and a job exposure matrix (JEM) for probability of exposure based on occupation. Multivariate analysis was used to control for age, sex, race and smoking history. The odds ratio (OR) and adjusted population attributable fraction (PAF) associated with occupational exposure were calculated.VGDF exposure was associated with an increased risk of COPD (OR 2.11; 95% CI 1.59 to 2.82) and a PAF of 31% (95% CI 22% to 39%). The risk associated with high probability of workplace exposure by JEM was similar (OR 2.27; 95% CI 1.46 to 3.52), although the PAF was lower (13%; 95% CI 8% to 18%). These estimates were not substantively different when the analysis was limited to COPD GOLD stage II or above. Joint exposure to both smoking and occupational factors markedly increased the risk of COPD (OR 14.1; 95% CI 9.33 to 21.2).Workplace exposures are strongly associated with an increased risk of COPD. On a population level, prevention of both smoking and occupational exposure, and especially both together, is needed to prevent the global burden of disease.
Cost-effectiveness of Dalteparin vs Unfractionated Heparin for the Prevention of Venous Thromboembolism in Critically Ill Patients
Authors: Robert A. Fowler, Nicole Mittmann, William Geerts, Diane Heels-Ansdell, Michael K. Gould, Gordon Guyatt, Murray Krahn, Simon Finfer, Ruxandra Pinto, Brian Chan, Orges Ormanidhi, Yaseen Arabi, Ismael Qushmaq, Marcelo G. Rocha, Peter Dodek, Lauralyn McIntyre, Richard Hall, Niall D. Ferguson, Sangeeta Mehta, John C. Marshall, Christopher James Doig, John Muscedere, Michael J Jacka, James R. Klinger, Nicholas Vlahakis, Neil Orford, Ian Seppelt, Yoanna K. Skrobik, Sachin Sud, John F. Cade, Jamie Cooper, Deborah Cook
Journal: JAMA (2014)

Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin.To evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients.Prospective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients.Costs, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges.Hospital costs per patient were $39,508 (interquartile range [IQR], $24,676 to $71,431) for 1862 patients who received LMWH compared with $40,805 (IQR, $24,393 to $76,139) for 1862 patients who received UFH (incremental cost, -$1297 [IQR, -$4398 to $1404]; P = .41). In 78% of simulations, a strategy using LMWH was most effective and least costly. In sensitivity analyses, a strategy using LMWH remained least costly unless the drug acquisition cost of dalteparin increased from $8 to $179 per dose and was consistent among higher- and lower-spending health care systems. There was no threshold at which lowering the acquisition cost of UFH favored prophylaxis with UFH.From a health care payer perspective, the use of the LMWH dalteparin for VTE prophylaxis among critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH. These findings were driven by lower rates of pulmonary embolus and heparin-induced thrombocytopenia and corresponding lower overall use of resources with LMWH.