tbuckley/cabot-search huggingface dataset:
Effects of resistance training on arterial stiffness: a meta-analysis
Authors: Motohiko Miyachi
Journal: British Journal of Sports Medicine (2012)

Background Regular aerobic exercise prevents and reverses arterial stiffening, but the association between resistance training and arterial stiffness is unclear. Aim This study was performed to conduct a systematic review and meta-analysis of randomised controlled clinical trials (RCTs) assessing the associations between resistance training and changes in arterial stiffness. Methods MEDLINE and SPORTDiscus databases were searched from January 1980 through to April 2011. RCTs evaluating the ability of resistance training to increase arterial stiffness in comparison with a control group were included in the meta-analysis. Two independent reviewers extracted data and assessed the quality of the included studies. Data from 185 reports of eight RCTs (193 participants) were included. Pooled mean differences in arterial stiffness indices (carotid arterial β stiffness and pulse wave velocity (PWV)) between intervention and control groups were calculated using a random-effects model. Results The overall association of resistance training versus control with relative changes in carotid β index or PWV (eight studies; 193 participants) was 10.7% (95% CI 3.4% to 18.0%; I 2 , 89%; heterogeneity, p&lt;0.001). Five studies indicated that resistance training in young subjects (n=115) was significantly associated with an increase in stiffness index of 14.3% (95% CI 8.5% to 20.1%; I 2 , 71%; heterogeneity, p&lt;0.001) compared with controls. However, three studies showed that resistance training in middle-aged subjects (n=78) was not associated with changes in arterial stiffness. In addition, although high-intensity resistance training (n=87) was significantly associated with an increase in stiffness of 11.6%, moderate-intensity resistance training (n=106) showed no such association. Conclusion High-intensity resistance training is associated with increased arterial stiffness in young subjects with low baseline levels of arterial stiffness.
Intermittent Parasystole—Mechanism of Protection
Authors: HOWARD COHEN, RICHARD LANGENDORF, ALFRED PICK
Journal: Circulation (1973)

Analysis of ten cases of intermittent ventricular parasystole suggested temporary loss of protection of the parasystolic focus resulting in discharge and "resetting" of the parasystole by sinus or other supraventricular beats. Parasystolic centers appear to be protected from supraventricular and other ventricular ectopic impulses early in their cycle by their refractory periods, and late in the cycle by diastolic depolarization. Between these two areas of protection is a period of "susceptibility" during which supraventricular beats can discharge the parasystolic focus. This phenomenon accounted for fixed coupling of the first parasystolic beat of a series to a preceding sinus beat. Under certain conditions all parasystolic beats may have such fixed coupling, a new and previously unconsidered mechanism for parasystole with fixed coupling. In one case of intermittent ventricular parasystole, the parasystole was shown to originate in the posterior fascicle of the left bundle branch on the basis of the shape of the standard electrocardiogram and by His bundle recordings. These parasystolic impulses produced a compensatory pause regardless of whether their discharge was manifest or concealed, and thus imitated a second degree (Type II) atrioventricular (A-V) block. This represents the first description of completely blocked atrial impulses resulting from concealed parasystolic beats arising within the ventricular conduction system.
Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome
Authors: P. Michael Ho
Journal: JAMA (2009)

REATMENT WITH CLOPIDOGREL in addition to aspirin reduces recurrent cardiovascular events following hospitalization for acute coronary syndrome (ACS) for patients treated either medically or with percutaneous coronary intervention. [1]2][3] Proton pump inhibitor (PPI) medications are often prescribed prophylactically with initiation of clopidogrel, with the goal of reducing the risk of gastrointestinal tract bleeding while taking dual-antiplatelet therapy.Recent mechanistic studies, however, suggest that PPIs may reduce the inhibitory effect of clopidogrel on platelet aggregation. 4,5In addition, variations in platelet reactivity have been associated with adverse outcomes following stent implantation. 6,7These investigations open the question of whether the efficacy of clopidogrel is influenced by concomitant use of PPI medication.To date, there remains significant ongoing controversy regarding the clinical outcomes of patients taking clopidogrel and PPIs. 8The US Food and Drug Administration recently released an early communication about a safety review of the potential interaction between these 2 types of medications. 9However, there were insufficient data to make any recommendations, and the Food and Drug Administration highlighted the need for
Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment
Authors: Xochitl C Morgan, Timothy L Tickle, Harry Sokol, Dirk Gevers, Kathryn L Devaney, Doyle V Ward, Joshua A Reyes, Samir A Shah, Neal LeLeiko, Scott B Snapper, Athos Bousvaros, Joshua Korzenik, Bruce E Sands, Ramnik J Xavier, Curtis Huttenhower
Journal: Genome biology (2012)

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status.Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways.This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis.
A Novel Fluorescence Method for the Rapid Detection of Functional β1-Adrenergic Receptor Autoantibodies in Heart Failure
Authors: Viacheslav O. Nikolaev, Valérie Boivin, Stefan Störk, Christiane E. Angermann, Georg Ertl, Martin J. Lohse, Roland Jahns
Journal: Journal of the American College of Cardiology (2007)
Correlation of in vitro culture pattern and Q‐banded karyotype in acute nonlymphocytic leukemia
Authors: Carol M. Richman, Janet D. Rowley
Journal: American Journal of Hematology (1983)

Abstract Both cytogenetic abnormalities and in vitro growth patterns of leukemic cells have prognostic significance in acute nonlymphocytic leukemia (ANLL). The present study was undertaken to analyze the interrelationship between these two factors and response to therapy. Blast cells from 43 patients with de novo ANLL, four patients with secondary ANLL, and two patients with ANLL following a preleukemic phase were studied using both in vitro culture in methylcellulose and quinacrine chromosome banding techniques. In 19 patients with de novo ANLL, minimal growth in culture (≤ 5 colonies without prominence of small clusters) was noted (Pattern I). Blast cells from the remaining 24 patients formed numerous abnormal clusters and colonies in a continuum distribution (Pattern II). Sixty‐three percent of Pattern I patients had completely normal karyotypes (NN). Only 29% of Pattern II patients were NN. No Pattern I patient had only abnormal karyotypes (AA), while 25% of Pattern II patients were AA (p&lt;0.05). All six patients with secondary leukemia or leukemia following a preleukemic phase demonstrated both Pattern II growth and cytogenetic abnormalities. Fifty‐six percent of Pattern I patients with de novo ANLL responded to chemotherapy, 35% of Pattern II patients responded, and 0% of patients with secondary or post‐preleukemic ANLL responded. The correlation between the presence of cytogenetic abnormalities in leukemic cells and a pattern of excessive, abnormal growth in vitro coupled with the trend toward poor prognosis in these patients suggests that cytogenetically abnormal cells may have a proliferative advantage both in vitro and in vivo.
Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia
Authors: Li Li, Timo L.M. ten Hagen, Michiel Bolkestein, Astrid Gasselhuber, Jeremy Yatvin, Gerard C. van Rhoon, Alexander M.M. Eggermont, Dieter Haemmerich, Gerben A. Koning
Journal: Journal of Controlled Release (2013)
Likelihood-Based Inferences under Isolation by Distance: Two-Dimensional Habitats and Confidence Intervals
Authors: François Rousset, Raphaël Leblois
Journal: Molecular Biology and Evolution (2011)

Likelihood-based methods of inference of population parameters from genetic data in structured populations have been implemented but still little tested in large networks of populations. In this work, a previous software implementation of inference in linear habitats is extended to two-dimensional habitats, and the coverage properties of confidence intervals are analyzed in both cases. Both standard likelihood and an efficient approximation are considered. The effects of misspecification of mutation model and dispersal distribution, and of spatial binning of samples, are considered. In the absence of model misspecification, the estimators have low bias, low mean square error, and the coverage properties of confidence intervals are consistent with theoretical expectations. Inferences of dispersal parameters and of the mutation rate are sensitive to misspecification or to approximations inherent to the coalescent algorithms used. In particular, coalescent approximations are not appropriate to infer the shape of the dispersal distribution. However, inferences of the neighborhood parameter (or of the product of population density and mean square dispersal rate) are generally robust with respect to complicating factors, such as misspecification of the mutation process and of the shape of the dispersal distribution, and with respect to spatial binning of samples. Likelihood inferences appear feasible in moderately sized networks of populations (up to 400 populations in this work), and they are more efficient than previous moment-based spatial regression method in realistic conditions.
Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis
Authors: Rachel Mackley
Journal: Thorax (2012)

Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasisThis randomised, double-blind placebo control trial from New Zealand looked at the use of azithromycin in non-cystic fibrosis bronchiectasis and aimed to assess its effect on exacerbation frequency, lung function and health-related quality of life.The trial enrolled 141 participants and randomly assigned them to receive either azithromycin 500 mg three times a week for 6 months, or placebo, with a follow up period of 1 year.Groups were well matched in terms of baseline characteristics.The co-primary endpoints were rate of exacerbations, change in forced expiratory volume in 1 s (FEV1) and change in total score on a St Georges Respiratory questionnaire (SGRQ).The azithromycin group experienced a statistically significant decrease in the rate of exacerbations requiring antibiotic therapy over the treatment period (relative risk reduction 62%); this reduction was sustained over the 6 month period after cessation of treatment (relative risk reduction of 42% over 1 year).Time to first exacerbation requiring antibiotics was also significantly longer in the azithromycin arm.There was no significant change in FEV1 or SGRQ score.Azithromycin is increasingly used in clinical practice in non-cystic fibrosis bronchiectasis and this study shows some promising results supporting its use.However, the dose of azithromycin used differs from that commonly used in UK practice.As the authors acknowledge, there was also no routine microbial resistance testing performed and macrolide resistance may ultimately impact on azithromycin's usefulness in the long-term.Further research is needed before azithromycin could be confidently considered a routine therapy advocated for use in non-cystic fibrosis bronchiectasis.
Pharmacogenomic Strategies Provide a Rational Approach to the Treatment of Cisplatin-Resistant Patients With Advanced Cancer
Authors: David S. Hsu, Bala S. Balakumaran, Chaitanya R. Acharya, Vanja Vlahovic, Kelli S. Walters, Katherine Garman, Carey Anders, Richard F. Riedel, Johnathan Lancaster, David Harpole, Holly K. Dressman, Joseph R. Nevins, Phillip G. Febbo, Anil Potti
Journal: Journal of Clinical Oncology (2007)

Standard treatment for advanced non-small-cell lung cancer (NSCLC) includes the use of a platinum-based chemotherapy regimen. However, response rates are highly variable. Newer agents, such as pemetrexed, have shown significant activity as second-line therapy and are currently being evaluated in the front-line setting. We utilized a genomic strategy to develop signatures predictive of chemotherapeutic response to both cisplatin and pemetrexed to provide a rational approach to effective individualized medicine.Using in vitro drug sensitivity data, coupled with microarray data, we developed gene expression signatures predicting sensitivity to cisplatin and pemetrexed. Signatures were validated with response data from 32 independent ovarian and lung cancer cell lines as well as 59 samples from patients previously treated with cisplatin.Genomic-derived signatures of cisplatin and pemetrexed sensitivity were shown to accurately predict sensitivity in vitro and, in the case of cisplatin, to predict treatment response in patients treated with cisplatin. The accuracy of the cisplatin predictor, based on available clinical data, was 83.1% (sensitivity, 100%; specificity 57%; positive predictive value, 78%; negative predictive value, 100%). Interestingly, an inverse correlation was seen between in vitro cisplatin and pemetrexed sensitivity, and importantly, between the likelihood of cisplatin and pemetrexed response in patients.The use of genomic predictors of response to cisplatin and pemetrexed can be incorporated into strategies to optimize therapy for advanced solid tumors.
Late‐Breaking Abstracts
Authors: H.E. Vonkeman, M.G. Moghadam, M.A.F.J. van de Laar, P.M. ten Klooster, T. Jansen, P. van Riel
Journal: Arthritis & Rheumatology (2014)

Table.Characteristics of RA patients at baseline, 6 months post-bariatric surgery, 12 months post-bariatric surgery, and most recent follow-up visit (n ϭ 53).Baseline, prior to bariatric surgery (Reference) 6 months post-bariatric surgery 12 months post-bariatric surgery Most recent follow-up Anthropometrics and laboratory values, mean (SD) 1 Body mass index, kg/m 2 47.8 (7.7) 35.7 (6.9)** 32.6 (7.0)** 34.6 (8.0)** Weight, lbs 282.7 (53.2) 211.1 (44.0)** 193.4 (44.2)** 205.4 (52.9)**Change in weight, lbs N/A Ϫ71.6 (30.0)Ϫ90.4 (38.2) Ϫ78.1 (50.7) % Excess weight loss N/A 56 (21) 70 (24) 57 (47) C-reactive protein, mg/L 26.1 (42.0) 10.1 (13.1)* 5.9 (8.2)* 4.1 (5.4)** ESR, mm/hr 45.7 (26.2) 35.4 (20.9)* 26.1 (20.9)* 18.0 (12.6)** White blood cell count, K/L 8.7 (2.5) 7.5 (1.9)* 7.4 (2.0)** 7.0 (1.9)** Platelets, K/L 317 (99) 306 (80) 289 (85) 281 (79)* RA disease activity and medication use, N (%) 1 RA disease activity Remission 14 (26) 38 (72)** 36 (68)** 39 (74)** Low 9 (17) 12 (23)** 9 (17)** 12 (23)** Moderate 27 (51) 2 (4)** 3 (6)** 1 (2)** High 3 (6) 1 (2)** 0 (0)** 0 (0)** RA-related medications On any DMARD 49 (93) 41 (77)* 31 (59)** 33 (62)** On any bDMARD 2 27 (51) 23 (43)** 19 (36)** 25 (47)** On any nbDMARD 3 37 (70) 29 (55)* 23 (43)* 22 (42)* Number of DMARDs 0 4 (8) 12 (23)* 17 (32)* 19 (36)* 1 32 (60) 27 (51)* 16 (30)* 17 (32)* 2 13 (25) 12 (23)* 12 (23)* 12 (23)* 3 4 (8) 2 (4)* 3 (6)* 4 (8)* On NSAID 4 24 (45) 8 (15)* 8 (15)* 8 (15)* On glucocorticoid 9 (17) 7 (13)* 5 (9)* 3 (6)* On any DMARD, NSAID, or glucocorticoid 52 (98) 44 (83) 35 (66) 35 (66) Remission and on no DMARD, NSAID, or glucocorticoid 1 (2) 8 (15) 12 (23) 15 (28) Columns may not add up to 100% due to missing values or rounding.*PϽ0.05 compared to baseline.**PϽ0.0001compared to baseline. 1 Changes in anthropometrics, laboratory values, RA disease activity, and medication usage are compared to baseline. 2Biologic DMARDs used were etanercept, adalimumab, infliximab, golimumab, abatacept, rituximab, and tocilizumab. 3Non-biologic DMARDs used were methotrexate, hydroxychloroquine, sulfasalazine, azathioprine, and mycophenolate mofetil. 4Non-steroidal anti-inflammatory drugs used were ibuprofren, naproxen, celecoxib,
Carotid and Cerebral Arteriosclerosis in the Rat
Authors: BERNARD C. WEXLER, CHARLES W. TRUE, Nancy Beamer, Dilman Conatser
Journal: Circulation Research (1963)

Male and female breeder rats spontaneously develop arteriosclerosis. This occurs first in the aorta and coronary arteries and subsequently in the carotid and intracranial arteries. The carotid arteries show mesenchymal cell proliferation in the media followed by subintimal swelling and mucoid deposition, elastosis, cartilaginous metaplasia and eventual bone formation. Lipid deposition occurs infrequently, and then only in advanced lesions in the media. Severe lesions are much more frequent in the female breeder and the tendency towards cartilaginous metaplasia and bone formation is peculiar to the carotid arteries. The cerebral arteries show little arteriosclerotic involvement except for aneurysm-like outpouchings of the internal elastic membrane associated with mucopolysaccha-ride accumulation about the sites of elastic tissue disruption. Despite severe fulminating arteriosclerosis in the carotid arteries, the cerebral arteries and the brain tissue itself show little or no significant evidence of degenerative change. These results are interpreted to mean that the cerebral arteries of the breeder rat follow a different physiological and morphological pattern of response than the rest of the arterial system.
Interferon-Alfa as a Comparative Treatment for Clinical Trials of New Therapies Against Advanced Renal Cell Carcinoma
Authors: Robert J. Motzer, Jennifer Bacik, Barbara A. Murphy, Paul Russo, Madhu Mazumdar
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To define outcome data and prognostic criteria for patients with metastatic renal cell carcinoma (RCC) treated with interferon-alfa as initial systemic therapy. The data can be applied to design and interpretation of clinical trials of new agents and treatment programs against this refractory malignancy. PATIENTS AND METHODS: Four hundred sixty-three patients with advanced RCC administered interferon-α as first-line systemic therapy on six prospective clinical trials were the subjects of this retrospective analysis. Three risk categories for predicting survival were identified on the basis of five pretreatment clinical features by a stratified Cox proportional hazards model. RESULTS: The median overall survival time was 13 months. The median time to progression was 4.7 months. Five variables were used as risk factors for short survival: low Karnofsky performance status, high lactate dehydrogenase, low serum hemoglobin, high corrected serum calcium, and time from initial RCC diagnosis to start of interferon-α therapy of less than one year. Each patient was assigned to one of three risk groups: those with zero risk factors (favorable risk), those with one or two (intermediate risk), and those with three or more (poor risk). The median time to death of patients deemed favorable risk was 30 months. Median survival time in the intermediate-risk group was 14 months. In contrast, the poor-risk group had a median survival time of 5 months. CONCLUSION: Progression-free and overall survival with interferon-α treatment can be compared with new therapies in phase II and III clinical investigations. The prognostic model is suitable for risk stratification of phase III trials using interferon-α as the comparative treatment arm.
Opiate Pharmacology and Relief of Pain
Authors: Gavril W. Pasternak
Journal: Journal of Clinical Oncology (2014)

Opioids remain the mainstay of severe pain management in patients with cancer. The hallmark of pain management is individualization of therapy. Although almost all clinically used drugs act through mu opioid receptors, they display subtle but important differences pharmacologically. Furthermore, not all patients respond equally well to all drugs. Evidence suggests that these variable responses among patients have a biologic basis and are likely to involve both biased agonism and the many mu opioid receptor subtypes that have been cloned.
REEPing the benefits of an animal model of hereditary spastic paraplegia
Authors: Ariel Y. Deutch, Peter Hedera, Roger J. Colbran
Journal: Journal of Clinical Investigation (2013)

The hereditary spastic paraplegias (HSPs) are characterized by spasticity of the leg muscles due to axonal degeneration of corticospinal neurons. Beetz et al. report that the core motor phenotype and axonal pathology of HSPs are recapitulated in mice lacking the HSP-associated gene Reep1. REEP1 is shown to regulate ER structure in motor cortex neurons. The Reep1 knockout mouse should be a very useful model in which to study the mechanisms of progressive axon loss in HSPs and other disorders.
Analysis of Expired Air for Oxidation Products
Authors: Paolo Paredi, Sergei A. Kharitonov, Peter J. Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Section:ChooseTop of pageAbstract <<COMEASUREMENTASTHMACOPDCFVOLATILE HYDROCARBONSASTHMACOPDCFNOMEASUREMENTCLINICAL STUDIESEXHALED BREATH CONDENSATEDISCUSSIONFUTURE WORKNEW MARKERSReferencesCITING ARTICLES
Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis
Authors: Soraya Taleb, Mélissa Romain, Bhama Ramkhelawon, Catherine Uyttenhove, Gerard Pasterkamp, Olivier Herbin, Bruno Esposito, Nicolas Perez, Hideo Yasukawa, Jacques Van Snick, Akihiko Yoshimura, Alain Tedgui, Ziad Mallat
Journal: The Journal of Experimental Medicine (2009)

Atherosclerosis is an inflammatory vascular disease responsible for the first cause of mortality worldwide. Recent studies have clearly highlighted the critical role of the immunoinflammatory balance in the modulation of disease development and progression. However, the immunoregulatory pathways that control atherosclerosis remain largely unknown. We show that loss of suppressor of cytokine signaling (SOCS) 3 in T cells increases both interleukin (IL)-17 and IL-10 production, induces an antiinflammatory macrophage phenotype, and leads to unexpected IL-17–dependent reduction in lesion development and vascular inflammation. In vivo administration of IL-17 reduces endothelial vascular cell adhesion molecule–1 expression and vascular T cell infiltration, and significantly limits atherosclerotic lesion development. In contrast, overexpression of SOCS3 in T cells reduces IL-17 and accelerates atherosclerosis. We also show that in human lesions, increased levels of signal transducer and activator of transcription (STAT) 3 phosphorylation and IL-17 are associated with a stable plaque phenotype. These results identify novel SOCS3-controlled IL-17 regulatory pathways in atherosclerosis and may have important implications for the understanding of the increased susceptibility to vascular inflammation in patients with dominant-negative STAT3 mutations and defective Th17 cell differentiation.