bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absorption of Folic Acid and Ascorbic Acid from Nutrient Comparable Beverages
Authors: Carter Brett , Monsivais Pablo , Drewnowski Adam 
Published: November 2010

Abstract: One hundred percent fruit juices can help consumers increase the nutrient content of the diet since these beverages can be naturally rich in micronutrients. Micronutrient‐fortified low‐calorie beverages are an important alternative to those wishing to minimize their calorie intakes. However, little is known about the bioavailability of nutrients from fortified beverages relative to 100% fruit juices. The present study examined the bioavailability of ascorbic acid (AA) and folic acid (FA) in 100% orange juice (OJ) and a low‐calorie beverage fortified with these nutrients. In a within‐subjects, cross‐over design, 12 adult men consumed a 591 mL serving of OJ, a low‐calorie beverage fortified with AA and FA, and 1% low fat milk. Participants were aged 20 to 35 y, with body mass indexes between 20 and 30 kg/m2. Blood plasma concentrations of AA and serum concentrations of FA were assayed by serial blood draws, made at 30 min intervals for 4.5 h. Blood plasma concentration of AA was significantly greater after ingestion of the fortified beverage compared to after OJ ingestion. However, the bioavailability of AA did not significantly differ from that of OJ. Analyses of FA indicated no significant difference between fortified beverage and OJ. Consumption of both vitamin containing beverages led to higher concentrations of AA and FA than the milk control. This study showed that similar levels of AA and FA bioavailability can be attained through ingestion of 100% OJ and a fortified beverage.Practical Application: A nutrient fortified beverage and a 100% OJ delivered similar amounts of folic acid and AA. However, the fortified beverage contained far fewer calories than the juice. Fortification can provide an effective way to increase the nutrient‐to‐calorie ratio of the diet.
Brief Report: Burnout Among Early Career Clinical Investigators
Authors: Primack Brian A. , Dilmore Terri C. , Switzer Galen E. , Bryce Cindy L. , Seltzer Deborah L. , Li Jie , Landsittel Douglas P. , Kapoor Wishwa N. , Rubio Doris M. 
Published: November 2010

AbstractBurnout is a pervasive problem among clinicians. However, little is known about burnout among early career clinical investigators, who must balance clinical responsibilities with challenges related to research. We aimed to determine the prevalence of and demographic associations with burnout in a cohort of early career clinical investigators.A cross‐sectional questionnaire was administered to 179 trainees at the University of Pittsburgh Institute for Clinical Research Education in 2007–2008. We used chi‐square analyses and Fisher’s exact test to determine whether associations between demographic characteristics and burnout were significant. Of the participants, 29 (16%) reported feeling burned out. Burnout was more prevalent among those over 35 years of age relative to their younger counterparts (29% vs. 13%, p= 0.01) and among females relative to males (22% vs. 10%, p= 0.03). With regard to race and ethnicity, burnout was most common among underrepresented minorities (30%) followed by Caucasians (18%) and Asians (3%); these differences were significant (p= 0.02). Considering the early career status of these research trainees, rates of burnout were concerning. Certain demographic subgroups—including older trainees, females, and underrepresented minorities—had particularly high rates of burnout and may benefit from interventions that provide them with skills needed to sustain successful clinical research careers. Clin Trans Sci 2010; Volume 3: 186–188
Fibrin presence within aortic valves in patients with aortic stenosis: Association with in vivo thrombin generation and fibrin clot properties
Authors: Natorska Joanna , Marek Grzegorz , Hlawaty Marta , Sadowski Jerzy , Tracz Wieslawa , Undas Anetta 
Published: November 2010

SummaryA role of coagulation in the pathogenesis of aortic stenosis (AS) is unknown. The aim of this study was to investigate the fibrin (Fn) presence and its determinants in calcified stenotic aortic valve leaflets. Twenty-one patients with dominant AS and 17 well-matched patients with dominant aortic insufficiency (AI) undergoing aortic valve replacement were studied. Immunofluorescence analysis was performed on decalcified leaflets using antibodies against human Fn and tissue factor (TF). Fn-positive (41.4%) and TF-positive (25.3%) areas were increased in AS valves compared with AI valves (7.9% and 5.9%, respectively, both p<0.001). Patients with AS had elevated plasma D-dimer (236.4 ± 28 ng/ml, p=0.002) and prothrombin fragment 1+2 (F1.2) (261.7 ± 27.1 pM, p=0.005) compared to AI subjects (142.8 ± 10 ng/ml and 131.2 ± 1.3 pM, respectively). In AS patients Fn-positive areas correlated with TF-positive areas (r=0.68, p=0.0005), D-dimer (r=0.45, p=0.018), F1.2 (r=0.64, p=0.002), the time required for plasma fibrin clot formation (r=0.44, p=0.015) and maximum absorbance of fibrin clots (r=-0.38, p<0.0001), but not with clot permeability or lysis time. Thickness of Fn layer within AS valves was associated with maximum transvalvular gradient (r =0.41, p=0.048). Patients with maximal gradient above 75 mmHg (n=11) showed significant associations between Fn-positive area and both maximal (r =0.63) and mean (r =0.67) transvalvular gradients. Large fibrin amounts, mostly co-localised with TF, are present within the valve leaflets of patients with advanced AS. In vivothrombin generation and fibrin clot formation are associated with the extent of Fn presence within leaflets, which might contribute to the AS progression.
Deletion of the High-Density Lipoprotein Receptor Scavenger Receptor BI in Mice Modulates Thrombosis Susceptibility and Indirectly Affects Platelet Function by Elevation of Plasma Free Cholesterol
Authors: Korporaal Suzanne J.A. , Meurs Illiana , Hauer Arnaud D. , Hildebrand Reeni B. , Hoekstra Menno , Cate Hugo Ten , Praticò Domenico , Akkerman Jan-Willem N. , Van Berkel Theo J.C. , Kuiper Johan , Van Eck Miranda 
Published: November 2010

Objective—
Scavenger receptor BI (SR-BI) is a cell surface receptor that promotes the selective uptake of cholesteryl esters from high-density lipoprotein (HDL) by the liver. In mice, SR-BI deficiency results in increased plasma HDL cholesterol levels and enhanced susceptibility to atherosclerosis. The aim of this study was to investigate the role of SR-BI deficiency on platelet function.

Methods and Results—

SR-BI-deficient mice were thrombocytopenic, and their platelets were abnormally large, probably because of an increased cholesterol content. The FeCl
3
acute injury model to study arterial thrombosis susceptibility showed that SR-BI wild-type mice developed total arterial occlusion after 24±2 minutes. In SR-BI-deficient mice, however, the time to occlusion was reduced to 13±1 minutes (
P
=0.02). Correspondingly, in SR-BI-deficient mice, platelets circulated in an activated state and showed increased adherence to immobilized fibrinogen. In contrast, platelet-specific disruption of SR-BI by bone marrow transplantation in wild-type mice did not alter plasma cholesterol levels or affect platelet count, size, cholesterol content, or reactivity, suggesting that changes in plasma cholesterol levels were responsible for the altered responsiveness of platelets in SR-BI-deficient mice.

Conclusion—
The function of SR-BI in HDL cholesterol homeostasis and prevention of atherosclerosis is indirectly also essential for maintaining normal platelet function and prevention of thrombosis.
Pin1 Prolyl Isomerase Regulates Endothelial Nitric Oxide Synthase
Authors: Ruan Ling , Torres Christina M. , Qian Jin , Chen Feng , Mintz James D. , Stepp David W. , Fulton David , Venema Richard C. 
Published: November 2010

Objective—
The Pin1 prolyl isomerase acts in concert with proline-directed protein kinases to regulate function of protein substrates through isomerization of peptide bonds that link phosphoserine or phosphothreonine to proline. We sought to determine whether Pin1 interacts with endothelial nitric oxide synthase (eNOS) in endothelial cells in a manner that depends on proline-directed phosphorylation of the eNOS enzyme and whether this interaction influences basal or agonist-stimulated eNOS activity.

Methods and Results—
Inhibitors of the extracellular-regulated kinase (ERK) 1/2 MAP kinases inhibit proline-directed phosphorylation of eNOS at serine 116 (Ser116) in bovine aortic endothelial cells (BAECs). Moreover, eNOS and Pin1 can be coimmunoprecipitated from BAECs only when Ser116 is phosphorylated. In addition, phosphomimetic Ser116Asp eNOS, but not wild-type eNOS, can be coimmunoprecipitated with Pin1 coexpressed in COS-7 cells. Inhibition of Pin1 in BAECs by juglone or by dominant negative Pin1 increases basal and agonist-stimulated NO release from the cells, whereas overexpression of wild-type Pin1 in BAECs suppresses basal and agonist-stimulated NO production. Overexpression of wild-type Pin1 in intact aortae also reduces agonist-induced relaxation of aortic rings.

Conclusion—
Our results demonstrate a novel form of eNOS regulation in endothelial cells and blood vessels through Ser116 phosphorylation–dependent interaction of eNOS with Pin1.
p190 RhoGTPase-Activating Protein Links the β1 Integrin/Caveolin-1 Mechanosignaling Complex to RhoA and Actin Remodeling
Authors: Yang Baohua , Radel Chris , Hughes Dalton , Kelemen Sheri , Rizzo Victor 
Published: November 2010

Objective—
To determine whether the β1 integrin/caveolin-1 signaling complex plays a role in shear stress regulation of RhoA activity .

Methods and Results—

Hemodynamic shear stress influences the phenotype of the endothelium. Integrins and RhoA are essential components in the process that allows endothelial cells to adapt to flow. However, the signaling mechanisms that relay from integrins to RhoA are not well defined. Bovine aortic endothelial cells were subjected to laminar shear stress (10 dyne/cm
2
) for up to 6 hours. β1 integrin blockade inhibited Src family kinases and p190RhoGAP tyrosine phosphorylation observed after the immediate onset of shear stress. Depletion of caveolin-1 blocked the decline in p190RhoGAP tyrosine phosphorylation observed at later points by sustaining Src family kinase activity. The manipulation of β1 integrin and caveolin-1 also altered shear regulation of RhoA activity. More importantly, cells depleted of p190RhoGAP showed faulty temporal regulation of RhoA activity. Each of these treatments attenuated actin reorganization induced by flow. Similarly, stress fibers failed to form in endothelial cells exposed to enhanced blood flow in caveolin-1 knockout mice.

Conclusion—
Our studies demonstrate that p190RhoGAP links integrins and caveolin-1/caveolae to RhoA in a mechanotransduction cascade that participates in endothelial adaptation to flow.
Taking Armed Groups Seriously: Ways to Improve their Compliance with International Humanitarian Law
Authors: Sassòli Marco 
Published: November 2010

AbstractMost contemporary armed conflicts are not of an international character. International Humanitarian Law (IHL) applicable to these conflicts is equally binding on non-State armed groups as it is on States. The legal mechanisms for its implementation are, however, still mainly geared toward States. The author considers that the perspective of such groups and the difficulties for them in applying IHL should be taken into account in order to make the law more realistic and more often respected. It is submitted that the law is currently often developed and interpreted without taking into account the realities of armed groups. This contribution explores how armed groups could be involved in the development, interpretation and operationalization of the law. It argues that armed groups should be allowed to accept IHL formally, to create – amongst other things – a certain sense of ownership. Their respect of the law should also be rewarded. Possible methods to encourage, monitor and control respect of IHL by armed groups are described. The author suggests in particular that armed groups should be allowed and encouraged to report on their implementation of IHL to an existing or newly created institution. Finally, in case of violations, this contribution proposes ways to apply criminal, civil and international responsibility, including sanctions, to non-State armed groups.
Direct Participation in Hostilities – A Discussion of the ICRC Interpretive Guidance
Authors: Boothby William 
Published: November 2010

AbstractThe ICRC's published 'Interpretive Guidance on the Notion of Direct Participation' by civilians in hostilities contributes usefully to the debate but is flawed. It creates an imbalance between members of the armed forces on the one hand, who are targetable at all times, and members of organised armed groups who do not have a continuous combat function, and civilians who persistently participate in hostilities on the other, who are said to be protected during intervals between specific acts of hostility. This imbalance is exacerbated by assertions that there is a presumption at law that civilians are not directly participating, that to be DPH there must be a single causal step linking the civilian's activity with the hostilities, that voluntary human shields may not be direct participants and that periods of preparation for, deployment towards and return from acts of direct participation, during which a civilian is liable to lawful attack, must be interpreted restrictively. This article takes aspects of the interpretive guidance in turn, analysing them to determine their legal and practical acceptability. It concludes that states must consider the guidance with some caution before determining their own position on this vexed issue.
Second-Look Arthroscopic Findings After Repairs of Posterior Root Tears of the Medial Meniscus
Authors: Seo Hee-Soo , Lee Su-Chan , Jung Kwang-Am 
Published: November 2010

Background: A posterior root tear of the medial meniscus disrupts hoop tension and causes extrusion of the meniscus, which results in progressive cartilage degeneration. Purpose: To identify the structural integrity of healing after arthroscopic repair of a posterior root tear of the medial meniscus by second-look arthroscopy and to determine the clinical relevance of the findings. Study Design: Case series; Level of evidence, 4. Methods: From December 2006 to August 2008, 21 consecutive patients underwent arthroscopic pullout suture repair for a posterior root tear of the medial meniscus. Eleven were available for second-look arthroscopy evaluation (mean, 13.4 months; range, 10 to 22 months). The healing status of the repaired meniscus was classified as complete healing, lax healing, scar tissue healing, and failed healing. Chondral lesions were reviewed using arthroscopic photographs, and clinical evaluation was based on the Lysholm knee scores and the Hospital for Special Surgery scores. Results: There was no case with complete healing. Five knees had lax healing (symptomatic in 2 and asymptomatic in 3); 4, scar tissue healing (asymptomatic in all 4); and 2, failed healing (symptomatic in 1 and asymptomatic in 1). Progression of the chondral lesion was found in 1 case. Mean Lysholm scores improved from 56.1 preoperatively (range, 41 to 71) to 83.0 at follow-up (range, 69 to 91; P = .003); mean Hospital for Special Surgery score also significantly increased, from 64.1 (range, 50 to 76) to 87.4 (range, 77 to 95; P = .003). Conclusion: Complete healing was not observed in this retrospective case series of posterior horn meniscus repairs performed by 2 surgeons using a single technique. Further research is needed to clarify why all patients showed clinical improvement despite findings of incomplete or failed healing on second-look arthroscopy. Treatment modalities for managing posterior root tears of the medial meniscus require further investigation to determine their efficacy.
A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia
Authors: Fehniger Todd A. , Uy Geoffrey L. , Trinkaus Kathryn , Nelson Alissa D. , Demland Jeffery , Abboud Camille N. , Cashen Amanda F. , Stockerl-Goldstein Keith E. , Westervelt Peter , DiPersio John F. , Vij Ravi 
Published: November 2010

Abstract
Older patients with acute myeloid leukemia (AML) have limited treatment options and a poor prognosis, thereby warranting novel therapeutic strategies. We evaluated the efficacy of lenalidomide as front-line therapy for older AML patients. In this phase 2 study, patients 60 years of age or older with untreated AML received high-dose (HD) lenalidomide at 50 mg daily for up to 2 28-day cycles. If patients achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) or did not progress after 2 cycles of HD lenalidomide, they received low-dose lenalidomide (10 mg daily) until disease progression, an unacceptable adverse event, or completion of 12 cycles. Thirty-three AML patients (median age, 71 years) were enrolled with intermediate (55%), unfavorable (39%), or unknown (6%) cytogenetic risk. Overall CR/CRi rate was 30%, and 53% in patients completing HD lenalidomide. The CR/CRi rate was significantly higher in patients presenting with a low (< 1000/μL) circulating blast count (50%, P = .01). The median time to CR/CRi was 30 days, and duration of CR/CRi was 10 months (range, 1- ≥ 17 months). The most common grades ≥ 3 toxicities were thrombocytopenia, anemia, infection, and neutropenia. HD lenalidomide has evidence of clinical activity as initial therapy for older AML patients, and further study of lenalidomide in AML and MDS is warranted. This study is registered at www.clinicaltrials.gov as #NCT00546897.
Thermodynamically consistent Bayesian analysis of closed biochemical reaction systems
Authors: Jenkinson Garrett , Zhong Xiaogang , Goutsias John 
Published: November 2010

AbstractBackgroundEstimating the rate constants of a biochemical reaction system with known stoichiometry from noisy time series measurements of molecular concentrations is an important step for building predictive models of cellular function. Inference techniques currently available in the literature may produce rate constant values that defy necessary constraints imposed by the fundamental laws of thermodynamics. As a result, these techniques may lead to biochemical reaction systems whose concentration dynamics could not possibly occur in nature. Therefore, development of a thermodynamically consistent approach for estimating the rate constants of a biochemical reaction system is highly desirable.ResultsWe introduce a Bayesian analysis approach for computing thermodynamically consistent estimates of the rate constants of a closed biochemical reaction system with known stoichiometry given experimental data. Our method employs an appropriately designed prior probability density function that effectively integrates fundamental biophysical and thermodynamic knowledge into the inference problem. Moreover, it takes into account experimental strategies for collecting informative observations of molecular concentrations through perturbations. The proposed method employs a maximization-expectation-maximization algorithm that provides thermodynamically feasible estimates of the rate constant values and computes appropriate measures of estimation accuracy. We demonstrate various aspects of the proposed method on synthetic data obtained by simulating a subset of a well-known model of the EGF/ERK signaling pathway, and examine its robustness under conditions that violate key assumptions. Software, coded in MATLAB®, which implements all Bayesian analysis techniques discussed in this paper, is available free of charge athttp://www.cis.jhu.edu/~goutsias/CSS%20lab/software.html.ConclusionsOur approach provides an attractive statistical methodology for estimating thermodynamically feasible values for the rate constants of a biochemical reaction system from noisy time series observations of molecular concentrations obtained through perturbations. The proposed technique is theoretically sound and computationally feasible, but restricted to quantitative data obtained from closed biochemical reaction systems. This necessitates development of similar techniques for estimating the rate constants of open biochemical reaction systems, which are more realistic models of cellular function.
Cost analysis of centralized viral load testing for antiretroviral therapy monitoring in Nicaragua, a low‐HIV prevalence, low‐resource setting
Authors: Gerlach Jay , Sequeira Magda , Alvarado Vivian , Cerpas Christian , Balmaseda Angel , Gonzalez Alcides , de los Santos Tala , Levin Carol E , Amador Juan Jose , Domingo Gonzalo J 
Published: November 2010

BackgroundHIV viral load testing as a component of antiretroviral therapy monitoring is costly. Understanding the full costs and the major sources of inefficiency associated with viral load testing is critical for optimizing the systems and technologies that support the testing process. The objective of our study was to estimate the costs associated with viral load testing performed for antiretroviral therapy monitoring to both patients and the public healthcare system in a low‐HIV prevalence, low‐resource country.MethodsA detailed cost analysis was performed to understand the costs involved in each step of performing a viral load test in Nicaragua, from initial specimen collection to communication of the test results to each patient's healthcare provider. Data were compiled and cross referenced from multiple information sources: laboratory records, regional surveillance centre records, and scheduled interviews with the key healthcare providers responsible for HIV patient care in five regions of the country.ResultsThe total average cost of performing a viral load test in Nicaragua varied by region, ranging from US$99.01 to US$124.58, the majority of which was at the laboratory level: $88.73 to $97.15 per specimen, depending on batch size. The average cost to clinics at which specimens were collected ranged from $3.31 to $20.92, depending on the region. The average cost per patient for transportation, food, lodging and lost income ranged from $3.70 to $14.93.ConclusionsThe quantitative viral load test remains the single most expensive component of the process. For the patient, the distance of his or her residence from the specimen collection site is a large determinant of cost. Importantly, the efficiency of results reporting has a large impact on the cost per result delivered to the clinician and utility of the result for patient monitoring. Detailed cost analysis can identify opportunities for removing barriers to effective antiretroviral therapy monitoring programmes in limited‐resource countries with low HIV prevalence.
Shunt flow of arteriovenous fistulas from plantar artery
Authors: Yoshida Y , Fujita M 
Published: November 2010

Objective The purpose of this study was to visualize the shunt flow of arteriovenous fistulas (AVFs) passing towards the top side of the foot from the plantar artery. Methods Colour-flow duplex Doppler ultrasonography was performed in 112 patients who consulted an outpatient clinic with varicose veins and/or symptoms such as foot oedema, dullness, cramp and coldness. Thirteen age-and sex-matched healthy subjects served as controls. Results AVFs were detected in 86 of 112 patients (77%). They were also detected in 10 (77%) of 13 healthy subjects. The shunt flow pattern consisted of two phases of flow corresponding to systole and diastole, and the diastolic fraction of time–velocity integral was larger, although the peak flow velocity in systole was higher than that in diastole. Conclusion Colour-flow duplex Doppler ultrasonography is useful for non-invasive visualization of the shunt flow of AVFs connecting the plantar artery with the venous arch of the top side of the foot.