tbuckley/cabot-search huggingface dataset:
Prenatally Fabricated Autologous Human Living Heart Valves Based on Amniotic Fluid–Derived Progenitor Cells as Single Cell Source
Authors: Dörthe Schmidt, Josef Achermann, Bernhard Odermatt, Christian Breymann, Anita Mol, Michele Genoni, Gregor Zund, Simon P. Hoerstrup
Journal: Circulation (2007)

Background— A novel concept providing prenatally tissue engineered human autologous heart valves based on routinely obtained fetal amniotic fluid progenitors as single cell source is introduced. Methods and Results— Fetal human amniotic progenitors were isolated from routinely sampled amniotic fluid and sorted using CD133 magnetic beads. After expansion and differentiation, cell phenotypes of CD133− and CD133+ cells were analyzed by immunohistochemistry and flowcytometry. After characterization, CD133− derived cells were seeded onto heart valve leaflet scaffolds (n=18) fabricated from rapidly biodegradable polymers, conditioned in a pulse duplicator system, and subsequently coated with CD133+ derived cells. After in vitro maturation, opening and closing behavior of leaflets was investigated. Neo-tissues were analyzed by histology, immunohistochemistry, and scanning electron microscopy (SEM). Extracellular matrix (ECM) elements and cell numbers were quantified biochemically. Mechanical properties were assessed by tensile testing. CD133− derived cells demonstrated characteristics of mesenchymal progenitors expressing CD44 and CD105. Differentiated CD133+ cells showed features of functional endothelial cells by eNOS and CD141 expression. Engineered heart valve leaflets demonstrated endothelialized tissue formation with production of ECM elements (GAG 80%, HYP 5%, cell number 100% of native values). SEM showed intact endothelial surfaces. Opening and closing behavior was sufficient under half of systemic conditions. Conclusions— The use of amniotic fluid as single cell source is a promising low-risk approach enabling the prenatal fabrication of heart valves ready to use at birth. These living replacements with the potential of growth, remodeling, and regeneration may realize the early repair of congenital malformations.
Natural History of Asymptomatic Mitral Valve Prolapse in the Community
Authors: Jean-François Avierinos, Bernard J. Gersh, L. Joseph Melton, Kent R. Bailey, Clarence Shub, Rick A. Nishimura, A. Jamil Tajik, Maurice Enriquez-Sarano
Journal: Circulation (2002)

Background— The outcome of mitral valve prolapse (MVP) is controversial, with marked discrepancies in reported complication rates. Methods and Results— We conducted a community study of all Olmsted County, Minn, residents first diagnosed with asymptomatic MVP between 1989 and 1998 (N=833). Diagnosis, motivated by auscultatory findings (n=557) or incidental (n=276), was always confirmed by echocardiography with the use of current criteria. End points analyzed during 4581 person-years of follow-up were mortality (n=96, 19±2% at 10 years), cardiovascular morbidity (n=171), and MVP-related events (n=109, 20±2% at 10 years). The most frequent primary risk factors for cardiovascular mortality were mitral regurgitation from moderate to severe ( P =0.002, n=131) and, less frequently, ejection fraction &lt;50% ( P =0.003, n=31). Secondary risk factors independently predictive of cardiovascular morbidity were slight mitral regurgitation, left atrium ≥40 mm, flail leaflet, atrial fibrillation, and age ≥50 years (all P &lt;0.01). Patients with only 0 or 1 secondary risk factor (n=430) had excellent outcome, with 10-year mortality of 5±2% ( P =0.17 versus expected), cardiovascular morbidity of 0.5%/y, and MVP-related events of 0.2%/y. Patients with ≥2 secondary risk factors (n=250) had mortality similar to expected ( P =0.20) but high cardiovascular morbidity (6.2%/y, P &lt;0.01) and notable MVP-related events (1.7%/y, P &lt;0.01). Patients with primary risk factors (n=153) showed excess 10-year mortality (45±9%, P =0.01 versus expected), high morbidity (18.5%/y, P &lt;0.01), and high MVP-related events (15%/y, P &lt;0.01). Conclusions— Natural history of asymptomatic MVP in the community is widely heterogeneous and may be severe. Clinical and echocardiographic characteristics allow separation of the majority of patients with excellent prognosis from subsets of patients displaying, during follow-up, high morbidity or even excess mortality as direct a consequence of MVP.
An Economic Evaluation of rt-PA Locking Solution in Dialysis Catheters
Authors: Braden J. Manns, Nairne Scott-Douglas, Marcello Tonelli, Pietro Ravani, Martine LeBlanc, Marc Dorval, Rachel Holden, Louise Moist, Charmaine Lok, Deborah Zimmerman, Flora Au, Brenda R. Hemmelgarn
Journal: Journal of the American Society of Nephrology (2014)

In a recent randomized trial, weekly recombinant tissue plasminogen activator (rt-PA), 1 mg per lumen, once per week, and twice-weekly heparin as a locking solution (rt-PA/heparin) resulted in lower risks of hemodialysis catheter malfunction and catheter-related bacteremia compared with thrice-weekly heparin (heparin alone). We collected detailed costs within this trial to determine how choice of locking solution would affect overall health care costs, including the cost of locking solutions and all other relevant medical costs over the course of the 6-month trial. Nonparametric bootstrap estimates were used to derive 95% confidence intervals (CIs) and mean cost differences between the treatment groups. The cost of the locking solution was higher in patients receiving rt-PA/heparin, but this was partially offset by lower costs for managing complications. Overall, the difference in unadjusted mean cost for managing patients with rt-PA/heparin versus heparin alone was Can$323 (95% CI, −$935 to $1581; P=0.62). When the costs were extrapolated over a 1-year time horizon using decision analysis, assuming ongoing rt-PA effectiveness, the overall costs of the strategies were similar. This finding was sensitive to plausible variation in the frequency and cost of managing patients with catheter-related bacteremia, and whether the benefit of rt-PA on catheter-related bacteremia was maintained in the long term. In summary, we noted no significant difference in the mean overall cost of an rt-PA/heparin strategy as a locking solution for catheters compared with thrice-weekly heparin. Cost savings due to a lower risk of hospitalization for catheter-related bacteremia partially offset the increased cost of rt-PA.
GIS-Based Estimation of Exposure to Particulate Matter and NO <sub>2</sub> in an Urban Area: Stochastic versus Dispersion Modeling
Authors: Josef Cyrys, Matthias Hochadel, Ulrike Gehring, Gerard Hoek, Volker Diegmann, Bert Brunekreef, Joachim Heinrich
Journal: Environmental Health Perspectives (2005)

Stochastic modeling was used to predict nitrogen dioxide and fine particles [particles collected with an upper 50% cut point of 2.5 microm aerodynamic diameter (PM2.5)] levels at 1,669 addresses of the participants of two ongoing birth cohort studies conducted in Munich, Germany. Alternatively, the Gaussian multisource dispersion model IMMIS(net/em) was used to estimate the annual mean values for NO2 and total suspended particles (TSP) for the 40 measurement sites and for all study subjects. The aim of this study was to compare the measured NO2 and PM2.5 levels with the levels predicted by the two modeling approaches (for the 40 measurement sites) and to compare the results of the stochastic and dispersion modeling for all study infants (1,669 sites). NO2 and PM2.5 concentrations obtained by the stochastic models were in the same range as the measured concentrations, whereas the NO2 and TSP levels estimated by dispersion modeling were higher than the measured values. However, the correlation between stochastic- and dispersion-modeled concentrations was strong for both pollutants: At the 40 measurement sites, for NO2, r = 0.83, and for PM, r = 0.79; at the 1,669 cohort sites, for NO2, r = 0.83 and for PM, r = 0.79. Both models yield similar results regarding exposure estimate of the study cohort to traffic-related air pollution, when classified into tertiles; that is, 70% of the study subjects were classified into the same category. In conclusion, despite different assumptions and procedures used for the stochastic and dispersion modeling, both models yield similar results regarding exposure estimation of the study cohort to traffic-related air pollutants.
Chemokines and the Homing of Dendritic Cells to the T Cell Areas of Lymphoid Organs
Authors: Jason G. Cyster
Journal: The Journal of Experimental Medicine (1999)

A quarter of a century ago, it was proposed that veiled cells in the lymph were antigen-bearing Langerhans' cells (LCs) en route to the LN T cell area (([1][1]), ([2][2])). Extensive investigations have since established that LCs are immature dendritic cells (DCs) and that insults to the skin—
Cancer Burden in the HIV-Infected Population in the United States
Authors: Meredith S. Shiels, Ruth M. Pfeiffer, Mitchell H. Gail, H. Irene Hall, Jianmin Li, Anil K. Chaturvedi, Kishor Bhatia, Thomas S. Uldrick, Robert Yarchoan, James J. Goedert, Eric A. Engels
Journal: JNCI Journal of the National Cancer Institute (2011)

Effective antiretroviral therapy has reduced the risk of AIDS and dramatically prolonged the survival of HIV-infected people in the United States. Consequently, an increasing number of HIV-infected people are at risk of non-AIDS-defining cancers that typically occur at older ages. We estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States.Incidence rates for individual cancer types were obtained from the HIV/AIDS Cancer Match Study by linking 15 HIV and cancer registries in the United States. Estimated counts of the US HIV-infected and AIDS populations were obtained from Centers for Disease Control and Prevention surveillance data. We obtained estimated counts of AIDS-defining (ie, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers in the US AIDS population during 1991-2005 by multiplying cancer incidence rates and AIDS population counts, stratified by year, age, sex, race and ethnicity, transmission category, and AIDS-relative time. We tested trends in counts and standardized incidence rates using linear regression models. We multiplied overall cancer rates and HIV-only (HIV infected, without AIDS) population counts, available from 34 US states during 2004-2007, to estimate cancers in the HIV-only population. All statistical tests were two-sided.The US AIDS population expanded fourfold from 1991 to 2005 (96,179 to 413,080) largely because of an increase in the number of people aged 40 years or older. During 1991-2005, an estimated 79 656 cancers occurred in the AIDS population. From 1991-1995 to 2001-2005, the estimated number of AIDS-defining cancers decreased by greater than threefold (34,587 to 10,325 cancers; P(trend) < .001), whereas non-AIDS-defining cancers increased by approximately threefold (3193 to 10,059 cancers; P(trend) < .001). From 1991-1995 to 2001-2005, estimated counts increased for anal (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004-2007, including 454 lung, 166 breast, and 154 anal cancers.Over a 15-year period (1991-2005), increases in non-AIDS-defining cancers were mainly driven by growth and aging of the AIDS population. This growing burden requires targeted cancer prevention and treatment strategies.
THE CORNEAL REFLEX THE MOST RELIABLE GUIDE IN ANAESTHESIA
Authors: H. B. Gardner
Journal: BMJ (1905)

2. In Class A the average number of days is greater than in Class B, or, in other words, those in which the date of delivery is after the estimated date are nearer the latter than those in Class A.I argue, tben, from these facts that, in Naegeli's method, the number of days added on is too great, and that by adding fewer days a still nearer approximation to the date of delivery might be got, and this conclusion comes into line with the average length of gestation arrived at from the authorities quoted above, which is less than that given by Naegeli.If two days less be added the result corresponds both to the average length of pregnancy which I have quoted, and with the average (practically) in Class A.Where available-which, unfortunately, is seldom-Lowenhardt's method will be found to be more accurate than Naegeli's, and the two will be found to correspond almost exactly.provided two days fewer are added to the latter.In fifty other cases which I calculated by L6wenhardt's method, the date of delivery was in all within i.6 days of the estimated date.Lowenhardt's method consists in counting the number of: days between the last menstrual period and the one pre- celing that and multiplying by ten.The date can then be got by tables.
QVA149 demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary disease
Authors: J. A. van Noord, R. Buhl, C. LaForce, C. Martin, F. Jones, M. Dolker, T. Overend
Journal: Thorax (2010)

<h3>Background</h3> This randomised, double-blind, placebo controlled, four-period crossover study assessed the efficacy and safety of once-daily QVA149, a dual bronchodilator consisting of the long-acting β<sub>2</sub>-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237), in patients with moderate to severe chronic obstructive pulmonary disease (COPD). <h3>Methods</h3> Patients (N=154) were randomly assigned to receive QVA149 (indacaterol/NVA237) 300/50 μg, indacaterol 300 μg, indacaterol 600 μg, or placebo, once daily for 7 days with a 7-day washout period between each treatment. The primary endpoint was trough forced expiratory volume in 1 s (FEV<sub>1</sub>) (mean of 23 h 15 min and 23 h 45 min post-dose values) on day 7. Other endpoints included trough FEV<sub>1</sub> on day 1, individual time point FEV<sub>1</sub> and monitoring and recording of all adverse events. <h3>Results</h3> A total of 135 (87.7%) patients completed the study (all randomly assigned patients: mean age 61.7 years, 61.4% male, post-bronchodilator FEV<sub>1</sub> 52.2% predicted, FEV<sub>1</sub>/forced vital capacity 47.6%). The estimated treatment difference (95% CI) for trough FEV<sub>1</sub> on day 7 between QVA149 and placebo was 226 ml (192 to 260; p&lt;0.001). The estimated treatment difference between QVA149 and indacaterol 300 and 600 μg was 123 ml (89 to 157; p&lt;0.001) and 117 ml (83 to 150; p&lt;0.001), respectively. The improvements in mean trough FEV<sub>1</sub> exceeded the predefined minimal clinically important differences of 100–140 ml for QVA149 versus placebo and indacaterol. Similar results were observed on day 1. All treatments were well tolerated. <h3>Conclusions</h3> QVA149 demonstrated rapid and sustained bronchodilation with significant improvements compared with indacaterol monotherapy and placebo in patients with COPD. <h3>Clinical trial registration</h3> NCT00570778.
Impaired Long-Chain Fatty Acid Utilization by Cardiac Myocytes Isolated From Mice Lacking the Heart-Type Fatty Acid Binding Protein Gene
Authors: Frank G. Schaap, Bert Binas, Heike Danneberg, Ger J. van der Vusse, Jan F. C. Glatz
Journal: Circulation Research (1999)

Heart-type fatty acid binding protein (H-FABP), abundantly expressed in cardiac myocytes, has been postulated to facilitate the cardiac uptake of long-chain fatty acids (LCFAs) and to promote their intracellular trafficking to sites of metabolic conversion. Mice with a disrupted H-FABP gene were recently shown to have elevated plasma LCFA levels, decreased cardiac deposition of a LCFA analogue, and increased cardiac deoxyglucose uptake, which qualitatively establishes a requirement for H-FABP in cardiac LCFA utilization. To study the underlying defect, we developed a method to isolate intact, electrically stimulatable cardiac myocytes from adult mice and then studied substrate utilization under defined conditions in quiescent and in contracting cells from wild-type and H-FABP(-/-) mice. Our results demonstrate that in resting and in contracting myocytes from H-FABP(-/-) mice, both uptake and oxidation of palmitate are markedly reduced (between -45% and -65%), whereas cellular octanoate uptake, and the capacities of heart homogenates for palmitate oxidation and for octanoate oxidation, and the cardiac levels of mRNAs encoding sarcolemmal FA transporters remain unaltered. In contrast, in resting H-FABP(-/-) cardiac myocytes, glucose oxidation is increased (+80%) to a level that would require electrical stimulation in wild-type cells. These findings provide a physiological demonstration of a crucial role of H-FABP in uptake and oxidation of LCFAs in cardiac muscle cells and indicate that in H-FABP(-/-) mice the diminished contribution of LCFAs to cardiac energy production is, at least in part, compensated for by an increase in glucose oxidation.
Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla.
Authors: D Marples, S Christensen, E I Christensen, P D Ottosen, S Nielsen
Journal: Journal of Clinical Investigation (1995)

Lithium, a widely used treatment for bipolar affective disorders, often causes nephrogenic diabetes insipidus. The effect of chronic lithium therapy on the expression of the vasopressin-regulated water channel Aquaporin-2 (AQP2) in rat kidney was examined. Membranes were prepared from inner medulla of one kidney from each rat, while the contralateral one was fixed for immunofluorescence and immunoelectronmicroscopy. Immunoblotting revealed that lithium treatment reduced AQP2 expression dramatically, to 31 +/- 8% after 10 d and to 4 +/- 1% after 25 d, coincident with development of severe polyuria. Immunofluorescence and immunogold quantitation confirmed the lithium-induced decrease in AQP2 expression (from 11.2 +/- 1.0 to 1.1 +/- 0.2 particles/microns 2). The downregulation was only partly reversed by return to lithium-free diet for 1 wk (40 +/- 8% of control). Furthermore, immunoblotting and immunogold quantitation revealed that 2 d of thirsting or 7 d of dDAVP treatment, in the continued presence of lithium, increased AQP2 expression by six- and threefold, respectively, coincident with increased urinary osmolality. Thirsting increased AQP2 immunolabeling mainly of vesicles, whereas dDAVP caused accumulation of AQP2 predominantly in the subapical region and plasma membrane. Thus, lithium causes marked downregulation of AQP2 expression, only partially reversed by cessation of therapy, thirsting or dDAVP treatment, consistent with clinical observations of slow recovery from lithium-induced urinary concentrating defects.
A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women
Authors: Ulrike Blume-Peytavi, Kathrin Hillmann, Ekkehart Dietz, Douglas Canfield, Natalie Garcia Bartels
Journal: Journal of the American Academy of Dermatology (2011)
Poorest socioeconomic groups still have highest rates of cancer
Authors: M. Limb
Journal: BMJ (2014)

New cancer figures for England are a stark reminder of the “magnitude” of socioeconomic inequalities, researchers have said. An analysis showed that the poorer people were, the more likely they were to get and to die from cancer, and it said that the gap in the number of cases between the most and least deprived groups had barely narrowed over the past 15 years.

A report by Public Health England’s National Cancer Intelligence Network and Cancer Research UK, published on Thursday 29 May,1 showed that around 19 200 “excess” cancer deaths a year were linked to lower levels of income in 2007-11. “Excess” refers here to the number of deaths that could have been prevented each year if all socioeconomic groups had had the rates of …
Gonococcal Invasion of Epithelial Cells Driven by P.IA, a Bacterial Ion Channel with GTP Binding Properties
Authors: Jos P.M. van Putten, Thomas D. Duensing, John Carlson
Journal: The Journal of Experimental Medicine (1998)

The neisserial porin P.I is a GTP binding protein that forms a voltage-gated channel that translocates into mammalian cell membranes and modulates host cell signaling events. Here, we report that P.I confers invasion of the bacterial pathogen Neisseria gonorrhoeae into Chang epithelial cells and that this event is controlled by GTP, as well as other phosphorus-containing compounds. Bacterial invasion was observed only for strains carrying the P.IA subtype of porin, which is typically associated with the development of disseminated neisserial disease, and did not require opacity outer membrane proteins, previously recognized as gonococcal invasins. Allelic replacement studies showed that bacterial invasiveness cotransferred with the P.IA (por1A) gene. Mutation of the P.I-associated protein Rmp did not alter the invasive properties. Cross-linking of labeled GTP to the porin revealed more efficient GTP binding to the P.IA than P.IB porin subtype. GTP binding was inhibited by an excess of unlabeled GTP, ATP, and GDP, as well as inorganic phosphate, but not by UTP or beta-glycerophosphate, fully in line with the respective invasion-inhibitory activities observed for these compounds. The P.IA-mediated cellular invasion may explain the more invasive behavior of P.IA strains in the natural infection and may broaden the basis for the development of a P.I-based gonococcal vaccine.
Impact of traffic-related air pollution on pulmonary oxidative stress
Authors: Marco Mantero, Stefano Aliberti, Paola Faverio, Luca Geroli, Luca Novelli, Rossella Alinovi, Silvana Pinelli, Alberto Pesci
Journal: European Respiratory Journal (2011)

Exposure to traffic-related air pollutants is known to increase morbidity and mortality. The aim of the study was to evaluate the impact of air pollution on pulmonary oxidative stress of police officers.  An observational prospective study on traffic police officers and controls was performed since August 2009 to March 2010 in Monza, Italy. Active smokers and asthmatics were excluded from the study. 8-isoprostane (8-iso) values were evaluated on exhaled breath condensate during both summer and winter visits. 8-iso values and pulmonary function test (PFTs) were correlated to air pollutant values detected by fixed measurements stations during one-month period before the visits. “TOSCA project”, supported by Cariplo Foundation.  A total of 17 officers (9 males; 41±1.4 yrs, mean±SE) and 12 controls (5 males; 34±2.4 yrs) were enrolled in the study. 8-iso values in officers were 5.30±0.83 and 12.43±0.98 pg/mL (mean±SE), respectively, in summer and winter period (p  Air pollution, especially long-term exposure, seems to impact pulmonary oxidative stress regardless occupational risks.