tbuckley/cabot-search huggingface dataset:
Distinct evolution of TLR-mediated dendritic cell cytokine secretion in patients with limited and diffuse cutaneous systemic sclerosis
Authors: L. van Bon, C. Popa, R. Huijbens, M. Vonk, M. York, R. Simms, R. Hesselstrand, D. M. Wuttge, R. Lafyatis, T. R. D. J. Radstake
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease and accumulating evidence suggests a role for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). <h3>Objective</h3> To map TLR-mediated cytokine responses of DCs from patients with SSc. <h3>Methods</h3> 45 patients with SSc were included. Patients were stratified as having diffuse cutaneous SSc (dSSc) or limited cutaneous SSc (lSSc) according to the extent of skin involvement, and further divided into those with late (&gt;3 years) or early disease (&lt;2 years). DCs were stimulated with ligands for TLR2, TLR3, TLR4, TLR7/8 or combinations. Plasma samples were collected from patients with SSc (n=167) and measured for interleukin 6 (IL-6), tumour necrosis factor α (TNFα), IL-12, IL-10 and interferon γ. <h3>Results</h3> Stimulation of DC subsets from patients with early lSSc and dSSc with ligands for TLR2, TLR3 or TLR4 resulted in higher secretion of IL-6 and TNFα compared with those having late disease or healthy controls. Remarkably, the production of IL-12 was lower upon stimulation with TLR ligands in most patients with SSc, whereas the secretion of IL-10 was very high in patients with the dSSc phenotype, particularly in those having early dSSc. The combination of various TLR ligands led to reduced cytokine secretion in all patients with SSc. Circulating levels of these cytokines further underscored the presence of differences between various SSc phenotypes. <h3>Discussion</h3> The altered TLR-mediated activation of DCs may be responsible for Th2 skewed T-cell activation in SSc that may be orchestrated by fibrogenic T-cell cytokines, such as IL-4 and IL-13. DC targeting could thus offer new avenues for therapeutic intervention.
Impact of Preoperative Moderate/Severe Mitral Regurgitation on 2-Year Outcome After Transcatheter and Surgical Aortic Valve Replacement
Authors: Marco Barbanti, John G. Webb, Rebecca T. Hahn, Ted Feldman, Robert H. Boone, Craig R. Smith, Susheel Kodali, Alan Zajarias, Christopher R. Thompson, Philip Green, Vasilis Babaliaros, Raj R. Makkar, Wilson Y. Szeto, Pamela S. Douglas, Tom McAndrew, Irene Hueter, D. Craig Miller, Martin B. Leon
Journal: Circulation (2013)

Background— The effect of preoperative mitral regurgitation (MR) on clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) is controversial. This study sought to examine the impact of moderate and severe MR on outcomes after TAVR and surgical aortic valve replacement (SAVR). Methods and Results— Data were drawn from the randomized Placement of Aortic Transcatheter Valve (PARTNER) Trial cohort A patients with severe, symptomatic aortic stenosis undergoing either TAVR (n=331) or SAVR (n=299). Both TAVR and SAVR patients were dichotomized according to the degree of preoperative MR (moderate/severe versus none/mild). At baseline, moderate or severe MR was reported in 65 TAVR patients (19.6%) and 63 SAVR patients (21.2%). At 30 days, among survivors who had isolated SAVR/TAVR, moderate/severe MR had improved in 25 SAVR patients (69.4%) and 30 TAVR patients (57.7%), was unchanged in 10 SAVR patients (27.8%) and 19 TAVR patients (36.5%), and worsened in 1 SAVR patient (2.8%) and 4 TAVR patients (5.8%; all P =NS). Mortality at 2 years was higher in SAVR patients with moderate or severe MR than in those with mild or less MR (49.8% versus 28.1%; adjusted hazard ratio, 1.73; 95% confidence interval, 1.01–2.96; P =0.04). In contrast, MR severity at baseline did not affect mortality in TAVR patients (37.0% versus 32.7%, moderate/severe versus none/mild; hazard ratio, 1.14; 95% confidence interval, 0.72–1.78; P =0.58; P for interaction=0.05). Conclusions— Both TAVR and SAVR were associated with a significant early improvement in MR in survivors. However, moderate or severe MR at baseline was associated with increased 2-year mortality after SAVR but not after TAVR. TAVR may be a reasonable option in selected patients with combined aortic and mitral valve disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00530894.
Plasmacytoid Dendritic Cells Protect Against Atherosclerosis by Tuning T-Cell Proliferation and Activity
Authors: Isabelle T.M.N. Daissormont, Anette Christ, Lieve Temmerman, Stefan Sampedro Millares, Tom Seijkens, Marco Manca, Mat Rousch, Marjorie Poggi, Louis Boon, Chris van der Loos, Mat Daemen, Esther Lutgens, Bente Halvorsen, Pal Aukrust, Edith Janssen, Erik A.L. Biessen
Journal: Circulation Research (2011)

Unlike conventional dendritic cells, plasmacytoid DCs (PDC) are poor in antigen presentation and critical for type I interferon response. Though proposed to be present in human atherosclerotic lesions, their role in atherosclerosis remains elusive.To investigate the role of PDC in atherosclerosis.We show that PDC are scarcely present in human atherosclerotic lesions and almost absent in mouse plaques. Surprisingly, PDC depletion by 120G8 mAb administration was seen to promote plaque T-cell accumulation and exacerbate lesion development and progression in LDLr⁻/⁻ mice. PDC depletion was accompanied by increased CD4⁺ T-cell proliferation, interferon-γ expression by splenic T cells, and plasma interferon-γ levels. Lymphoid tissue PDC from atherosclerotic mice showed increased indoleamine 2,3-dioxygenase (IDO) expression and IDO blockage abrogated the PDC suppressive effect on T-cell proliferation.Our data reveal a protective role for PDC in atherosclerosis, possibly by dampening T-cell proliferation and activity in peripheral lymphoid tissue, rendering PDC an interesting target for future therapeutic interventions.
Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia
Authors: Kenneth L. Subotnik, Laurie R. Casaus, Joseph Ventura, John S. Luo, Gerhard S. Hellemann, Denise Gretchen-Doorly, Stephen Marder, Keith H. Nuechterlein
Journal: JAMA Psychiatry (2015)

Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia.To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia.A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014.A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training.Psychotic relapse and control of breakthrough psychotic symptoms.Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (β = -0.30; t68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (χ21 = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t80 = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (χ21 =11.1; P = .003) and control of breakthrough psychotic symptoms (β = 0.2; t79 = 2.1; P = .04).The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness.clinicaltrials.gov Identifier: NCT00333177.
Effect of anticipation during unknown or unexpected exercise duration on rating of perceived exertion, affect, and physiological function
Authors: D A Baden, T L McLean, R Tucker, T D Noakes, A St Clair Gibson
Journal: British Journal of Sports Medicine (2005)

To determine the effect of unknown exercise duration and an unexpected increase in exercise duration on rating of perceived exertion (RPE), affect, and running economy during treadmill running.Sixteen well trained male and female runners completed three bouts of treadmill running at 75% of their peak treadmill running speed. In the first trial, they were told to run for 20 minutes and were stopped at 20 minutes (20 MIN). In another trial, they were told to run for 10 minutes, but at 10 minutes were told to run for a further 10 minutes (10 MIN). In the final trial, they were not told for how long they would be running but were stopped after 20 minutes (unknown, UN). During each of the running bouts, RPE, oxygen consumption (ml/kg/min), heart rate (beats/min), stride frequency (min(-1)), affect scores (arbitrary units), and attentional focus (percentage associative thought scores) were recorded.RPE increased significantly between 10 and 11 minutes in the 10 MIN compared with the 20 MIN and UN trials (p<0.05). The affect score decreased significantly between 10 and 11 minutes in the 10 MIN compared with the 20 MIN trial (p<0.05). Running economy, as measured by oxygen consumption, was significantly lower in the UN compared with the 20 MIN trial from 10 to 19 minutes (p<0.05).The change in RPE between 10 and 11 minutes in the 10 MIN trial suggests that RPE is not purely a measure of physical exertion, as treadmill speed was maintained at a constant pace both before and after the unexpected increase in exercise duration. The associated changes in affect score at similar times in the 10 MIN trial supports the hypothesis that RPE has an affective component.
The need for an NHS Staff College
Authors: Aidan Halligan
Journal: Journal of the Royal Society of Medicine (2010)

‘A recognized but extremely rare complication results in an avoidable patient fatality. A structured debrief surfaces inadequate team safety training. Of the seven consultants in the specialty, five recognize the need for standardizing technique and implementing team training. Two of the consultants do not, and claim that the complication is just one of those things.’ (Author’s experiences of anonymized NHS situations)
Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes.
Authors: S Teno, Y Uto, H Nagashima, Y Endoh, Y Iwamoto, Y Omori, T Takizawa
Journal: Diabetes Care (2000)

Serum triglyceride levels are important in the development of atherosclerosis. Although triglyceride levels are generally increased in the postprandial periods, the association between postprandial triglyceride (pTG) levels and atherosclerosis has not been investigated in diabetic patients. To investigate the role of pTG levels in atherosclerosis, we examined the correlation between pTG levels and carotid intimal-medial thickness (IMT).Carotid IMT was measured by ultrasonography in 61 patients with type 2 diabetes. Plasma glucose (PG), insulin, total cholesterol, triglycerides, and HDL cholesterol levels were measured after overnight fasting and 4 h after a meal.Carotid IMT of the patients with fasting hypertriglyceridemia was greater than that of the patients with normal fasting triglyceride (fTG) levels (0.85+/-0.12 vs. 0.76+/-0.14 mm; P = 0.02). The carotid IMT was increased in the patients with pTG levels >2.27 mmol/l. The normo-normo (NN) and normo-hyper (NH) groups consisted of patients with normal fTG levels but with pTG levels <2.27 and >2.27 mmol/l, respectively. Patients with both hypertriglyceridemia and pTG levels >2.27 mmol/l formed the hyper-hyper (HH) group. Carotid IMT was significantly increased in the NH (0.86+/-0.13 mm) and HH (0.85+/-0.12 mm) groups compared with the NN group (0.73+/-0.13 mm; P<0.01). Although postprandial PG, pTG, and fasting LDL cholesterol levels were all independently correlated with carotid IMT, pTG levels had the strongest statistical influence (P = 0.002).Postprandial hypertriglyceridemia despite normal fTG levels may be an independent risk factor for early atherosclerosis in type 2 diabetes.
Local iontophoretic administration of cytotoxic therapies to solid tumors
Authors: James D. Byrne, Mohammad N. R. Jajja, Adrian T. O’Neill, Lissett R. Bickford, Amanda W. Keeler, Nabeel Hyder, Kyle Wagner, Allison Deal, Ryan E. Little, Richard A. Moffitt, Colleen Stack, Meredith Nelson, Christopher R. Brooks, William Lee, J. Chris Luft, Mary E. Napier, David Darr, Carey K. Anders, Richard Stack, Joel E. Tepper, Andrew Z. Wang, William C. Zamboni, Jen Jen Yeh, Joseph M. DeSimone
Journal: Science Translational Medicine (2015)

Local administration of cytotoxic drugs using iontophoresis results in drug accumulation and therapeutic efficacy in mouse models of pancreatic and breast cancer and favorable PK in a large animal model.
Bronchial responsiveness in active steelworkers
Authors: JL Corhay, T Bury, R Louis, JP Delavignette, JM Kayembe, G Weber, A Albert, MF Radermecker
Journal: European Respiratory Journal (1998)

Coke-oven workers are exposed to dust and irritant gases. Therefore they are at risk of developing lung diseases including chronic bronchitis. Nonspecific bronchial hyperresponsiveness (BHR) has been advocated as a potential risk factor predisposing to the development of chronic bronchitis. In a previous study, we showed that prevalence of BHR was higher in retired coke-oven workers than in retired blast furnace workers. The present study was carried out to determine the prevalence of BHR in active steelworkers. Thus, 137 coke-oven workers and 150 blast furnace workers underwent clinical examination, a standardized questionnaire for the study of respiratory symptoms, pulmonary function testing and methacholine aerosol challenge. The study demonstrates a higher prevalence and degree of BHR [provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) &lt; or = 8 mg x mL(-1)] in coke-oven workers than in blast furnace workers (31.4 versus 6.7%; p&lt;0.001). Moreover, the frequency of respiratory symptoms and basal bronchial obstruction were greater among coke-oven workers with BHR in nonresponders. The basal maximum expiratory flow from 25-75% of forced vital capacity and the respiratory symptoms were correlated with bronchial responsiveness. The lack of correlation observed between BHR and the intensity of smoking or years spent in coke-oven environment may be explained by the high proportion of smokers, the worker turnover in the steel plant, and the "healthy worker effect". In conclusion, the higher prevalence and degree of bronchial hyperresponsiveness in coke-oven workers suggests that coke-oven pollutants are more intense irritants than those that escape from blast furnaces.
Late developing mammary tumors and hyperplasia induced by a low-oncogenic variant of mouse mammary tumor virus (MMTV) express genes identical to those induced by canonical MMTV
Authors: Robert D Bruno, Sonia M Rosenfield, Gilbert H Smith
Journal: Molecular Cancer (2013)

The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3.These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant.
THE PASSAGE OF NEUTRALIZING SUBSTANCES FROM THE BLOOD INTO THE CEREBROSPINAL FLUID IN POLIOMYELITIS
Authors: Simon Flexner, Harold L. Amoss
Journal: The Journal of Experimental Medicine (1917)

The cerebrospinal fluid taken very early and quite late in the course of acute poliomyelitis exhibits no neutralizing action on filtered poliomyelitic virus. The blood serum on the 6th day of the disease already contains the neutralizing principles. The injection of sterile horse serum into the cerebrospinal meninges in monkeys increases their permeability, so that they permit the immunity neutralizing principles passively injected into the blood to pass into the cerebrospinal fluid. The passage in passively immunized monkeys takes place during a relatively brief space of time and apparently only while the inflammatory reaction produced by the horse serum is at its height. It is established for monkeys and rendered probable for man that the intraspinal injection of immune serum in poliomyelitis is curative. In monkeys normal serum exerts no such action, and at present nothing can be stated definitely regarding the therapeutic effect of normal serum in man except that probably any benefits which may arise from its employment would be attributable not to the action of the serum as such, but to the escape of circulating immunity principles in the blood made possible by the aseptic inflammation set up by it in the meninges. As the immunity principles appear in the blood only after several days, and the reported favorable effects of the immune serum treatment relate to the first days of illness, the employment of normal serum is thus not indicated, while that of an immune serum is.
P<scp>HYTOSTEROLS IN</scp>H<scp>UMAN</scp>N<scp>UTRITION</scp>
Authors: Richard E. Ostlund
Journal: Annual Review of Nutrition (2002)

▪ Abstract Phytosterols are cholesterol-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. They are absorbed only in trace amounts but inhibit the absorption of intestinal cholesterol including recirculating endogenous biliary cholesterol, a key step in cholesterol elimination. Natural dietary intake varies from about 167–437 mg/day. Attempts to measure biological effects in feeding studies have been impeded by limited solubility in both water and fat. Esterification of phytosterols with long-chain fatty acids increases fat solubility by 10-fold and allows delivery of several grams daily in fatty foods such as margarine. A dose of 2 g/day as the ester reduces low density lipoprotein cholesterol by 10%, and little difference is observed between Δ 5 -sterols and 5α-reduced sterols (stanols). Phytosterols can also be dispersed in water after emulsification with lecithin and reduce cholesterol absorption when added to nonfat foods. In contrast to these supplementation studies, much less is known about the effect of low phytosterol levels in the natural diet. However, reduction of cholesterol absorption can be measured at a dose of only 150 mg during otherwise sterol-free test meals, suggesting that natural food phytosterols may be clinically important. Current literature suggests that phytosterols are safe when added to the diet, and measured absorption and plasma levels are very small. Increasing the aggregate amount of phytosterols consumed in a variety of foods may be an important way of reducing population cholesterol levels and preventing coronary heart disease.
Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance
Authors: Chunmei Yang, Kenneth J. Coker, Jason K. Kim, Silvia Mora, Debbie C. Thurmond, Ann C. Davis, Baoli Yang, Roger A. Williamson, Gerald I. Shulman, Jeffrey E. Pessin
Journal: Journal of Clinical Investigation (2001)

To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4–knockout mice. Homozygotic disruption of the syntaxin 4 gene results in early embryonic lethality, whereas heterozygous knockout mice, Syn4+/–, had normal viability with no significant impairment in growth, development, or reproduction. However, the Syn4+/– mice manifested impaired glucose tolerance with a 50% reduction in whole-body glucose uptake. This defect was attributed to a 50% reduction in skeletal muscle glucose transport determined by 2-deoxyglucose uptake during hyperinsulinemic-euglycemic clamp procedures. In parallel, insulin-stimulated GLUT4 translocation in skeletal muscle was also significantly reduced in these mice. In contrast, Syn4+/– mice displayed normal insulin-stimulated glucose uptake and metabolism in adipose tissue and liver. Together, these data demonstrate that syntaxin 4 plays a critical physiological role in insulin-stimulated glucose uptake in skeletal muscle. Furthermore, reduction in syntaxin 4 protein levels in this tissue can account for the impairment in whole-body insulin-stimulated glucose metabolism in this animal model.
Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: A survey of the German Testicular Cancer Study Group
Authors: K.-P. Dieckmann, S. Wilken, V. Loy, C. Matthies, K. Kleinschmidt, J. Bedke, A. Martinschek, R. Souchon, U. Pichlmeier, S. Kliesch
Journal: Annals of Oncology (2013)
The World Trade Center attack: Increased frequency of defibrillator shocks for ventricular arrhythmias in patients living remotely from New York City
Authors: Omer L. Shedd, Samuel F. Sears, Jane L. Harvill, Aysha Arshad, Jamie B. Conti, Jonathan S. Steinberg, Anne B. Curtis
Journal: Journal of the American College of Cardiology (2004)