bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Thrombin Formation and Altered Fibrin Clot Properties Induced by Polyunsaturated Omega-3 Fatty Acids on Top of Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention (OMEGA-PCI Clot)
Authors: Gajos Grzegorz , Zalewski Jaroslaw , Rostoff Pawel , Nessler Jadwiga , Piwowarska Wiesława , Undas Anetta 
Published: May 2011

Objective—
The goal of this study was to investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) are able to alter plasma fibrin clot properties and reduce thrombin formation in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI).

Methods and Results—

In an investigator-initiated, prospective, double-blind, placebo-controlled, randomized study, patients undergoing PCI who received standard pharmacotherapy were assigned to the treatment with 1 g/day n-3 PUFA (n=30) or placebo (n=24) for 1 month. Plasma fibrin clot permeability (
K
s
); lysis time (
t
50%
); prothrombin fragment 1.2; and peak thrombin generation from automated thrombogram, 8-isoprostaglandin F
2α
(8-iso-PGF
2α
, an oxidative stress marker), and C-reactive protein were determined at baseline, 3 to 5 days after randomization, and 30 days after randomization. At baseline, both treatment groups did not differ significantly. A 1-month treatment with n-3 PUFA compared with placebo was associated with 15.3% higher
K
s
, indicating larger pores in the fibrin network (
P
=0.0005); 14.3% shorter
t
50%
, indicating increased susceptibility to fibrinolysis (
P
<0.0001); 33.8% lower prothrombin fragment 1.2 (
P
=0.0013); 13.4% lower peak thrombin generation (
P
=0.04); and 13.1% lower 8-iso-PGF
2α
(
P
=0.009). Treatment with n-3 PUFA had no effect on fibrinogen and C-reactive protein. After 1 month of treatment, fibrinogen (
r
=−0.53,
P
<0.0001), treatment assignment (
r
=0.29,
P
=0.006) and 8-iso-PGF
2α
(
r
=−0.27,
P
=0.015) were independently associated with clot permeability (
P
<0.0001,
R
2
=0.66).

Conclusion—
Adding n-3 PUFA to standard therapy in stable patients undergoing PCI significantly decreases thrombin formation and oxidative stress and favorably alters fibrin clot properties. These findings indicate novel antithrombotic effects induced by n-3 PUFA in humans.
Cerebrospinal Fluid 20-HETE Is Associated With Delayed Cerebral Ischemia and Poor Outcomes After Aneurysmal Subarachnoid Hemorrhage
Authors: Crago Elizabeth A. , Thampatty Bhavani P. , Sherwood Paula R. , Kuo Chie-Wen J. , Bender Catherine , Balzer Jeffrey , Horowitz Michael , Poloyac Samuel M. 
Published: May 2011

Background and Purpose—
Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (aSAH); it is manifested by changes in cerebral blood flow accompanied by neurological decline, and it results in long-term functional and neuropsychological impairment. Preclinical evidence has demonstrated that the arachidonic acid metabolite, 20-hydroxyeicosatetraenoic acid (20-HETE), affects cerebral microvascular tone and cerebral blood flow after aSAH. The purpose of this study was to determine whether cerebrospinal fluid 20-HETE levels were associated with DCI and long-term neuropsychological outcomes in aSAH patients.

Methods—
Cerebrospinal fluid samples were collected twice daily through 14 days after hemorrhage on 108 acute, adult, aSAH patients. Samples were analyzed for 20-HETE via HPLC MSQ single quadrupole mass spectrometry. DCI was defined as the presence of impaired cerebral blood flow (angiographic vasospasm, elevated transcranial Dopplers, abnormal computed tomography or magnetic resonance perfusion scans) accompanied by neurological deterioration. Outcomes, including death and neuropsychological testing, were completed at 3 months after hemorrhage.

Results—

Detectable 20-HETE levels were observed in 31% of patient samples and were associated with severity of hemorrhage (Hunt & Hess [HH],
P
=0.04; Fisher,
P
=0.05). Detection of 20-HETE was not associated with angiographic vasospasm (
P
=0.34); however, detectable 20-HETE was significantly associated with DCI (
P
=0.016). Our data also suggest that detectable 20-HETE was associated with decreased performance in 5 neuropsychological domains.

Conclusions—
These results provide the first clinical evidence that cerebrospinal fluid 20-HETE concentrations are associated with DCI and poor outcomes, and this provides impetus for future studies to elucidate the clinical utility of inhibiting 20-HETE formation as a novel therapeutic intervention in patients with aSAH.
Outcomes After Carotid Artery Stenting and Endarterectomy in the Medicare Population
Authors: Wang Fen Wei , Esterbrooks Dennis , Kuo Yong-Fang , Mooss Aryan , Mohiuddin Syed M. , Uretsky Barry F. 
Published: May 2011

Background and Purpose—
Carotid artery stenting (CAS) is an alternative to carotid endarterectomy (CEA) for stroke prevention. The value of this therapy relative to CEA remains uncertain.

Methods—
In 10 958 Medicare patients aged 66 years or older between 2004 and 2006, we analyzed in-hospital, 1-year stroke, myocardial infarction, and death rate outcomes and the effects of potential confounding variables.

Results—

CAS patients (87% were asymptomatic) had a higher baseline risk profile, including having a higher percentage of coronary and peripheral arterial disease, heart failure, and renal failure. In-hospital stroke rate (1.9% CAS versus 1.4% CEA;
P
=0.14) and mortality (CAS 0.9% versus 0.6% CEA;
P
=0.20) were similar. By 1 year, CAS patients had similar stroke rates (5.3% CAS versus 4.1% CEA;
P
=0.12) but higher all-cause mortality rates (9.9% CAS versus 6.1% CEA;
P
<0.001). Using Cox multivariable models, there was a similar stroke risk (hazard ratio, 1.28; 95% CI, 0.90–1.79) but CAS patients had a significantly higher mortality (HR, 1.32; 95% CI, 1.02–1.71). Sensitivity analyses suggested that unmeasured confounders could be responsible for the mortality difference. In multivariable analysis, stroke risk was highest in the patients symptomatic at the time of revascularization.

Conclusions—
CAS patients had a similar stroke risk but an increased mortality rate at 1 year compared with CEA patients, possibly related to the higher baseline risk profile in the CAS patient group.
Identifying Children at Risk for Type 2 Diabetes in Underserved Communities
Authors: Vivian Eva M. , Carrel Aaron L. , Becker Tara 
Published: May 2011

Purpose The purpose of this study was to identify and assess health behaviors among ethnic minority children at high risk for type 2 diabetes. Methods Diabetes screenings were conducted at community centers, churches, and local neighborhood health fairs in Madison, Wisconsin. During these events, diabetes risk assessment surveys were given to parents of children between the ages of 10 to 19 years. Parents who identified their children as having 2 or more risk factors for type 2 diabetes were invited to have their child screened for type 2 diabetes. Results A total of 86 children between the ages of 10 to 19 years (mean age = 13; 58% male) were screened for diabetes. Fifty-one percent of the children were overweight or obese with 38% having >3 risk factors for type 2 diabetes. While there was no significant difference in the nutritional habits reported between normal, overweight, or obese children, fewer overweight and obese children reported exercising at least 30 minutes 5 to 7 days a week compared to children with a normal weight (P = .033). Conclusion Prevention of diabetes is a powerful public health intervention. Targeted diabetes screening in disadvantaged, underserved communities is an effective way to identify families with children at risk for type 2 diabetes. In addition, information obtained from these screenings can assist researchers and clinicians in designing accessible and affordable health promotion interventions that are culturally relevant to the youth and families within the community.
fMRI evidence that precision ophthalmic tints reduce cortical hyperactivation in migraine
Authors: Huang Jie , Zong Xiaopeng , Wilkins Arnold , Jenkins Brian , Bozoki Andrea , Cao Yue 
Published: May 2011

Background: Certain patterns can induce perceptual illusions/distortions and visual discomfort in most people, headaches in patients with migraine, and seizures in patients with photosensitive epilepsy. Visual stimuli are common triggers for migraine attacks, possibly because of a hyperexcitability of the visual cortex shown in patients with migraine. Precision ophthalmic tints (POTs) are claimed to reduce perceptual distortions and visual discomfort and to prevent migraine headaches in some patients. We report an fMRI visual cortical activation study designed to investigate neurological mechanisms for the beneficial effects of POTs in migraine. Methods: Eleven migraineurs and 11 age- and sex-matched non-headache controls participated in the study using non-stressful and stressful striped patterns viewed through gray, POT, and control coloured lenses. Results: For all lenses, controls and migraineurs did not differ in their response to the non-stressful patterns. When the migraineurs wore gray lenses or control coloured lenses, the stressful pattern resulted in activation that was greater than in the controls. There was also an absence of the characteristic low-pass spatial frequency (SF) tuning in extrastriate visual areas. When POTs were worn, however, both cortical activation and SF tuning were normalized. Both when observing the stressful pattern and under more typical viewing conditions, the POTs reduced visual discomfort more than either of the other two lenses. Conclusion: The normalization of cortical activation and SF tuning in the migraineurs by POTs suggests a neurological basis for the therapeutic effect of these lenses in reducing visual cortical hyperactivation in migraine.
Pain Perception in Knees With Circumscribed Cartilage Lesions Is Associated With Intra-articular IGF-1 Expression
Authors: Schmal Hagen , Niemeyer Philipp , Südkamp Norbert P. , Gerlach Ulrike , Dovi-Akue David , Mehlhorn Alexander T. 
Published: May 2011

Background: Circumscribed cartilage defects are considered as prearthritic lesions and lead to differential intra-articular cytokine expression. Mechanisms of associated pain development and influence of smoking behavior are not yet fully understood in humans. Purpose: This study aimed to reveal relations between synovial cytokine levels in knees with circumscribed cartilage defects and pain sensation. Study Design: Descriptive laboratory study. Methods: In a clinical trial, knee lavage fluids of 42 patients with circumscribed cartilage lesions treated by either microfracturing (n = 19) or by autologous chondrocyte implantation (n = 23) and fluids of 5 healthy control individuals were prospectively collected. Preoperative knee pain was evaluated according to frequency and strength; subjective knee function was assessed using a visual analog scale and the International Knee Documentation Committee (IKDC) score. Synovial concentrations of aggrecan, insulin-like growth factor (IGF)-I, basic fibroblast growth factor (bFGF), interleukin (IL)-1β, bone morphogenetic protein (BMP)-2, and BMP-7 were determined by enzyme-linked immunosorbent assay. Results: Pain strength showed a highly significant association with intra-articular IGF-1 levels (ρ = .48, P < .01), but no correlation with synovial concentrations of aggrecan, bFGF, IL-1β, BMP-2, and BMP-7. Although pain strength and frequency demonstrated a statistically significant relationship, no substantial association between pain frequency and any of the examined cytokine levels was found. Intra-articular IGF-1 concentrations significantly correlated with the area of cartilage damage (ρ = .35, P < .02); the other investigated cytokines failed to show this association. Neither of the determined intra-articular mediators demonstrated statistically significant correlations with subjective knee function or IKDC score. Only intra-articular concentrations of IGF-1 and BMP-2 statistically significantly correlated with age; total protein content was negatively associated with body mass index ( P < .05). In smokers, synovial expression of total protein content, IGF-1, and bFGF was significantly diminished compared to nonsmokers ( P < .05). Conclusion: Insulin-like growth factor–I is present in knees with circumscribed cartilage lesions in a size-dependent manner. IGF-1 levels correlated with indicators of pain perception; smoking negatively influenced synovial cytokine expression related to cartilage metabolism, but pain perception was not altered.
Community walking can be assessed using a 10-metre timed walk test
Authors: Kempen JCE , de Groot V , Knol DL , Polman CH , Lankhorst GJ , Beckerman H 
Published: May 2011

Background: A decline in mobility is a common feature of multiple sclerosis (MS). Community walking scales are used to categorize patients in their ability to move independently. The first purpose of this study was to determine which specific gait speed corresponded with the categories of the Modified Functional Walking Categories (MFWC). The second purpose was to determine the Minimally Important Change (MIC) in absolute gait speed using the MFWC and Expanded Disability Status Scale (EDSS) as external criteria. Method: MS patients were measured six times in 6 years. Gait velocity was measured with the 10-metre timed walk test (10-m TWT), the severity of MS was determined with the EDSS, and community walking was assessed with the MFWC. For each category of the MFWC, Receiver Operating Characteristic (ROC) curves were used to find the best possible cut-off point on the 10-m TWT. The MIC in absolute gait speed was determined using a change of one category on the MFWC or one point on the EDSS. Results: A strong relationship was found between gait speed and the MFWC; all areas under the ROC curves (AUCs) were between 0.74 and 0.86. The MIC in absolute gait speed could not be determined, because the AUCs were below the threshold of 0.70 and changes in gait speed were small. Conclusions: Gait speed is related to community walking, but an MIC in absolute gait speed could not be determined using a minimally important change on the MFWC or the EDSS as external criteria.
Impact of rituximab on relapse rate and disability in neuromyelitis optica
Authors: Bedi Gurdesh S , Brown Andrew D , Delgado Sylvia R , Usmani Nida , Lam Byron L , Sheremata William A 
Published: May 2011

Background: Neuromyelitis optica (NMO) is a severe demyelinating disease often leading to serious disability. Accumulating evidence now implicates humoral mechanisms in its pathogenesis. In the absence of an approved therapy, anti-inflammatory/immunosuppressant drugs have been used empirically for more than three decades. Recent evidence for a role of antibody to aquaporin-4 in the pathogenesis of NMO has led to the use of rituximab, a monoclonal antibody targeting the CD20 epitope on the entire B cell lineage. Objectives: To evaluate the impact of rituximab on the relapse rate and disability in NMO. Methods: This is an IRB approved retrospective longitudinal study of NMO patients treated with rituximab. Results: We identified 53 patients with NMO, 23 of whom had been treated with rituximab. These patients (2 males, 21 females) had a mean age of 37.1 ± 14.6 years at the time of diagnosis. Eight of the 23 treated with rituximab were treatment naïve. All 23 were scheduled to receive infusions every six or 12 months after treatment initiation with a minimum follow-up of six months (median 32.5 months, range 7–63 months). Median relapse rate declined significantly from 1.87 relapses/patient per year to 0.0 relapses/patient per year. Kurtzke Expanded Disability Status Scale (EDSS) scores stabilized or improved in all patients. Use of rituximab is associated with a significant reduction in relapses and disability in patents with NMO.
Regulation of TMPRSS6 by BMP6 and iron in human cells and mice
Authors: Meynard Delphine , Vaja Valentina , Sun Chia Chi , Corradini Elena , Chen Shanzhuo , López-Otín Carlos , Grgurevic Lovorka , Hong Charles C. , Stirnberg Marit , Gütschow Michael , Vukicevic Slobodan , Babitt Jodie L. , Lin Herbert Y. 
Published: May 2011

Abstract
Mutations in transmembrane protease, serine 6 (TMPRSS6), encoding matriptase-2, are responsible for the familial anemia disorder iron-refractory iron deficiency anemia (IRIDA). Patients with IRIDA have inappropriately elevated levels of the iron regulatory hormone hepcidin, suggesting that TMPRSS6 is involved in negatively regulating hepcidin expression. Hepcidin is positively regulated by iron via the bone morphogenetic protein (BMP)-SMAD signaling pathway. In this study, we investigated whether BMP6 and iron also regulate TMPRSS6 expression. Here we demonstrate that, in vitro, treatment with BMP6 stimulates TMPRSS6 expression at the mRNA and protein levels and leads to an increase in matriptase-2 activity. Moreover, we identify that inhibitor of DNA binding 1 is the key element of the BMP-SMAD pathway to regulate TMPRSS6 expression in response to BMP6 treatment. Finally, we show that, in mice, Tmprss6 mRNA expression is stimulated by chronic iron treatment or BMP6 injection and is blocked by injection of neutralizing antibody against BMP6. Our results indicate that BMP6 and iron not only induce hepcidin expression but also induce TMPRSS6, a negative regulator of hepcidin expression. Modulation of TMPRSS6 expression could serve as a negative feedback inhibitor to avoid excessive hepcidin increases by iron to help maintain tight homeostatic balance of systemic iron levels.
Computed tomography measurements of parapneumonic effusion indicative of thoracentesis
Authors: Moffett B.K. , Panchabhai T.S. , Anaya E. , Nakamatsu R. , Arnold F.W. , Peyrani P. , Wiemken T. , Guardiola J. , Ramirez J.A. 
Published: May 2011

Patients with parapneumonic effusions (PPE) measuring <1 cm by lateral decubitus radiograph (LDR) or <5 cm by lateral erect radiograph (LER) do not require thoracentesis. No such data exist for chest computed tomography (CCT). The objective of this study was to identify a PPE measurement by CCT that indicates the need for thoracentesis.A secondary data analysis of two pneumonia databases was conducted to identify patients with PPE. Measurements of PPE using LDR, LER and CCT were correlated by linear regression analysis. The clinical outcome of community-acquired pneumonia patients managed with the newly defined CCT measurement was evaluated.PPE was identified in 419 out of 1,460 patients with possible pneumonia. PPE measurements of 1 cm and 5 cm by LDR and LER, respectively, correlated with a measurement of 2.5 cm by CCT. Out of 95 patients with CCT measurements <2.5 cm, 31 poor clinical outcomes were reported: outcome was PPE related (n=1); outcome was PPE unrelated (n=26); and outcome was not evaluable (n=4). The single case of poor outcome also measured <1 cm by LDR.This study indicates that patients with community-acquired pneumonia and a PPE measuring <2.5 cm by CCT can be managed without the need for thoracentesis.
Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years
Authors: Yao T-C. , Lee W-I. , Ou L-S. , Chen L-C. , Yeh K-W. , Huang J-L. 
Published: May 2011

This study was undertaken to establish reference values of exhaled nitric oxide fraction (FeNO) and its determinants in healthy Asian children.693 healthy Asian children aged 5–18 yrs were assessed using a single-breath onlineFeNOmeasurement (exhaled flow 50 mL·s−1), questionnaires, anthropometric measurements, spirometry and total and specific immunoglobulin (Ig) E.Geometric meanFeNOand the upper 95% CI were 13.7 ppb and 49.7 ppb, respectively, for healthy children, and 11.2 ppb and 30.2 ppb, respectively, for those without allergic sensitisation.FeNOwas positively associated with age, allergic sensitisation, total IgE, ambient nitric oxide, measurement in the afternoon, and drinking water within 1 h before testing, and was negatively associated with weight. In healthy children without allergic sensitisation, age was the single best explanatory variable. TheFeNOpredicted values were 1–2 ppb higher in Asian than in Caucasian children in earlier studies, while the upper 95% CI were 9–10 ppb higher.In conclusion, the upper limits of normalFeNOin Asian children depend on age, from 21 ppb in young children to 39 ppb in adolescents. Ethnicity, age, allergic sensitisation, total IgE, ambient nitric oxide, time of testing, drinking water and weight are important determinants.
Self-reported sleep apnoea and mortality in patients from the Swedish Obese Subjects study
Authors: Marshall N.S. , Delling L. , Grunstein R.R. , Peltonen M. , Sjöström C.D. , Karason K. , Carlsson L.M.S. , Hedner J. , Stenlöf K. , Sjöström L. 
Published: May 2011

Sleep apnoea is associated with increased mortality in sleep clinic and community population groups. It is unclear whether a clinical report of sleep apnoea results in additional mortality risk in patients with severe obesity.The Swedish Obese Subjects (SOS) study is a nonrandomised controlled trial of bariatric surgeryversusconventional treatment for the treatment of severe obesity and its complications (mean±sdbody mass index 41±5 kg·m−2). The presence or absence of sleep apnoea (witnessed pauses in breathing) was determined by self-reporting at baseline in 3,953 patients who were observed for 54,236 person-yrs (mean 13.5 maximum 21.0 yrs).Sleep apnoea was reported by 934 (23.6%) patients at baseline and was a significant univariate predictor of mortality (hazard ratio (95% CI) 1.74 (1.40–2.18)). In a range of multivariate models of mortality risk, controlling for ≤16 other potential confounders and established mortality risk factors, sleep apnoea remained a significant prognostic factor (fully adjusted model 1.29 (1.01–1.65)).Self-reported sleep apnoea is an independent prognostic marker of all-cause mortality in obese patients.
Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD
Authors: Pauwels N.S. , Bracke K.R. , Dupont L.L. , Van Pottelberge G.R. , Provoost S. , Vanden Berghe T. , Vandenabeele P. , Lambrecht B.N. , Joos G.F. , Brusselle G.G. 
Published: May 2011

Cigarette smoke (CS), the primary risk factor of chronic obstructive pulmonary disease (COPD), leads to pulmonary inflammation through interleukin-1 receptor (IL-1R)I signalling, as determined using COPD mouse models. It is unclear whether interleukin (IL)-1α or IL-1β, activated by the Nlrp3/caspase-1 axis, is the predominant ligand for IL-1RI in CS-induced responses.We exposed wild-type mice (treated with anti-IL-1α or anti-IL-1β antibodies), and IL-1RI knockout (KO), Nlrp3 KO and caspase-1 KO mice to CS for 3 days or 4 weeks and evaluated pulmonary inflammation. Additionally, we measured the levels of IL-1α and IL-1β mRNA (in total lung tissue by RT-PCR) and protein (in induced sputum by ELISA) of never-smokers, smokers without COPD and patients with COPD.In CS-exposed mice, pulmonary inflammation was dependent on IL-1RI and could be significantly attenuated by neutralising IL-1α or IL-1β. Interestingly, CS-induced inflammation occurred independently of IL-1β activation by the Nlrp3/caspase-1 axis. In human subjects, IL-1α and IL-1β were significantly increased in total lung tissue and induced sputum of patients with COPD, respectively, compared with never-smokers.These results suggest that not only IL-1β but also IL-1α should be considered as an important mediator in CS-induced inflammation and COPD.