bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative Stress–Mediated Thrombospondin-2 Upregulation Impairs Bone Marrow–Derived Angiogenic Cell Function in Diabetes Mellitus
Authors: Bae Ok-Nam , Wang Jie-Mei , Baek Seung-Hoon , Wang Qingde , Yuan Hong , Chen Alex F. 
Published: May 2013

Objective—
Circulating angiogenic cells play an essential role in angiogenesis but are dysfunctional in diabetes mellitus characterized by excessive oxidative stress. We hypothesize that oxidative stress–mediated upregulation of thrombospondin-2 (TSP-2), a potent antiangiogenic protein, contributes to diabetic bone marrow–derived angiogenic cell (BMAC) dysfunction.

Approach and Results—
BMACs were isolated from adult male type 2 diabetic db/db mice and control db/+ (C57BLKS/J) mice. In Matrigel tube formation assay, angiogenic function was impaired in diabetic BMACs, accompanied by increased oxidative stress and nicotinamide adenine dinucleotide phosphate oxidase activity. BMAC angiogenic function was restored by overexpression of dominant negative Rac1 or by overexpression of manganese superoxide dismutase. TSP-2 mRNA and protein were both significantly upregulated in diabetic BMACs, mediated by increased oxidative stress as shown by a decrease in TSP-2 level after overexpression of dominant negative Rac1 or manganese superoxide dismutase. Silencing TSP-2 by its small interfering RNA in diabetic BMACs improved BMAC function in tube formation, adhesion, and migration assays. Notably, the upregulation of TSP-2 was also found in BMACs from streptozotocin-induced type 1 diabetic mice, and normal BMACs with high glucose treatment. let-7f, a microRNA which has been related to endothelial angiogenic function, is found to play key role in TSP-2 increase, but let-7f did not directly interact with TSP-2 mRNA.

Conclusions—
The upregulation of TSP-2 mediated by increased oxidative stress contributes to angiogenesis dysfunction in diabetic BMACs.
Plasma Dimethylglycine and Risk of Incident Acute Myocardial Infarction in Patients With Stable Angina Pectoris
Authors: Tveitevåg Svingen Gard Frodahl , Ueland Per Magne , Pedersen Eva Kristine Ringdal , Schartum-Hansen Hall , Seifert Reinhard , Ebbing Marta , Løland Kjetil Halvorsen , Tell Grethe S. , Nygård Ottar 
Published: May 2013

Objective—
Dimethylglycine is linked to lipid metabolism, and increased plasma levels may be associated with adverse prognosis in patients with coronary artery disease. We evaluated the relationship between plasma dimethylglycine and risk of incident acute myocardial infarction in a large prospective cohort of patients with stable angina pectoris, of whom approximately two thirds were participants in a B-vitamin intervention trial. Model discrimination and reclassification when adding plasma dimethylglycine to established risk factors were obtained. We also explored temporal changes and the test–retest reliability of plasma dimethylglycine.

Approach and Results—

Four thousand one hundred fifty patients (72% men; median age 62 years) were included. Plasma dimethylglycine was associated with several traditional coronary artery disease risk factors. During a median follow-up of 4.6 years, 343 (8.3%) patients experienced an acute myocardial infarction. The hazard ratio (95% confidence interval) for acute myocardial infarction was 1.95 (1.42–2.68;
P
<0.001) when comparing plasma dimethylglycine quartile 4 to 1 in a Cox regression model adjusted for age, sex, and fasting status. Adjusting for traditional coronary artery disease risk factors only slightly modified the estimates, which were particularly strong among nonsmokers and among patients with serum triglyceride or apolipoprotein B100 levels ≤median (
P
for interaction=0.004, 0.004, and 0.03, respectively). Plasma dimethylglycine improved discrimination and reclassification and had high test–retest reliability.

Conclusions—
Plasma dimethylglycine is independently related to incident acute myocardial infarction and enhances risk prediction in patients with stable angina pectoris. Our results motivate further studies on the relationship between 1-carbon metabolism and atherothrombosis. A potential interplay with lipid and energy metabolism merits particular attention.
Efficacy and Safety of Rivaroxaban in Patients With Heart Failure and Nonvalvular Atrial Fibrillation
Authors: van Diepen Sean , Hellkamp Anne S. , Patel Manesh R. , Becker Richard C. , Breithardt Günter , Hacke Werner , Halperin Jonathan L. , Hankey Graeme J. , Nessel Christopher C. , Singer Daniel E. , Berkowitz Scott D. , Califf Robert M. , Fox Keith A.A. , Mahaffey Kenneth W. 
Published: May 2013

Background—
In Rivaroxaban Once daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), rivaroxaban was noninferior to warfarin for the prevention of stroke and systemic embolic events and significantly reduced intracranial bleeding in patients with nonvalvular atrial fibrillation. We explore the safety and efficacy of rivaroxaban in patients with heart failure (HF).

Methods and Results—

A total of 9033 (63.7%) patients had HF. The primary efficacy analysis was rates of stroke or systemic embolism (per 100 patient-years) by intention to treat. The safety outcomes were major or nonmajor clinically relevant bleeding and hemorrhagic stroke during treatment. Patients with HF were younger (72 versus 74 years), more likely to have persistent atrial fibrillation (83.0% versus 77.6%), and had higher mean CHADS
2
scores (3.7 versus 3.1). The efficacy of rivaroxaban compared with warfarin was similar in patients with HF (1.90 versus 2.09) and without HF (2.10 versus 2.54;
P
-interaction=0.62). The risk of major or nonmajor clinically relevant bleeding with rivaroxaban was similar to warfarin in patients with HF (14.22 versus 14.02) and without HF (16.12 versus 15.35;
P
-interaction=0.99). A reduction in hemorrhagic stroke was observed with rivaroxaban in patients with HF as in the overall trial (adjusted hazard ratio, 0.38; 95% confidence interval, 0.19–0.76;
P
-interaction=0.067). Among patients with HF, the efficacy of rivaroxaban was similar, irrespective of ejection fraction <40 or ≥40% (
P
-interaction=0.38), New York Heart Association class I-II versus III-IV (
P
-interaction=0.68), HF preserved or reduced ejection fraction (
P
-interaction=0.35), or CHADS
2
score 2 versus ≥3 (
P
-interaction=0.48).

Conclusions—
Treatment-related outcomes were similar in patients with and without HF and across HF subgroups. These findings support the use of rivaroxaban as an alternative to warfarin in patients with atrial fibrillation and HF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00403767.
Electrocardiographic Predictors of Coronary Heart Disease and Sudden Cardiac Deaths in Men and Women Free From Cardiovascular Disease in the Atherosclerosis Risk in Communities Study
Authors: Rautaharju Pentti M. , Zhang Zhu‐Ming , Warren James , Gregg Richard E. , Haisty Wesley K. , Kucharska‐Newton Anna M. , Rosamond Wayne D. , Soliman Elsayed Z. 
Published: May 2013

Background

We evaluated predictors of coronary heart disease (
CHD
) death and sudden cardiac death (
SCD
) in the Atherosclerosis Risk in Communities (
ARIC
) study.

Methods and Results

The study population included 13 621 men and women 45 to 65 years of age free from manifest cardiovascular disease at entry. Hazard ratios from
C
ox regression with 95% confidence intervals were computed for 18 dichotomized repolarization‐related
ECG
variables. The average follow‐up was 14 years. Independent predictors of
CHD
death in men were TaVR‐ and rate‐adjusted
QT
end (
QT
ea
), with a 2‐fold increased risk for both, and spatial angles between mean
QRS
and T vectors and between Tpeak (T
p
) and normal R reference vectors [θ(R
m
|T
m
) and θ(T
p
|T
ref
), respectively], with a >1.5‐fold increased risk for both. In women, independent predictors of the risk of
CHD
death were θ(R
m
|T
m
), with a 2‐fold increased risk for θ(R
m
|T
m
), and θ(T
p
|T
ref
), with a 1.7‐fold increased risk. Independent predictors of
SCD
in men were θ(T
p
|T
ref
) and
QT
ea
, with a 2‐fold increased risk, and θ(T
init
|T
term
), with a 1.6‐fold increased risk. In women, θ(T
init
|T
term
) was an independent predictor of
SCD
, with a >3‐fold increased risk, and θ(R
m
|T
m
) and
TV
1 were >2‐fold for both.

Conclusions

θ(R
m
|T
m
) and θ(T
p
|T
ref
), reflecting different aspects of ventricular repolarization, were independent predictors of
CHD
death and
SCD
, and Ta
VR
and
TV
1 were also independent predictors. The risk levels for independent predictors for both
CHD
death and
SCD
were stronger in women than in men, and
QT
ea
was a significant predictor in men but not in women.
Smoking and Hemorrhagic Stroke Mortality in a Prospective Cohort Study of Older Chinese
Authors: Xu Lin , Schooling Catherine Mary , Chan Wai Man , Lee Siu Yin , Leung Gabriel M. , Lam Tai Hing 
Published: May 2013

Background and Purpose—
Hemorrhagic stroke is more common in non-Western settings and does not always share risk factors with other cardiovascular diseases. The association of smoking with hemorrhagic stroke subtypes has not been established. We examined the association of cigarette smoking with hemorrhagic stroke, by subtype (intracerebral hemorrhage and subarachnoid hemorrhage), in a large cohort of older Chinese from Hong Kong.

Methods—
Multivariable Cox regression analysis was used to assess the adjusted associations of smoking at baseline with death from hemorrhagic stroke and its subtypes, using a population-based prospective cohort of 66 820 Chinese aged >65 years enrolled from July 1998 to December 2001 at all the 18 Elderly Health Centers of the Hong Kong Government Department of Health and followed until May 31, 2012.

Results—
After follow-up for an average of 10.9 years (SD=3.1), 648 deaths from hemorrhagic stroke had occurred, of which 530 (82%) were intracerebral hemorrhage. Current smoking was associated with a higher risk of hemorrhagic stroke (hazard ratio, 2.19; 95% confidence interval, 1.49–3.22), intracerebral hemorrhage (1.94; 1.25–3.01), and subarachnoid hemorrhage (3.58; 1.62–7.94), adjusted for age, sex, education, public assistance, housing type, monthly expenditure, alcohol use, and exercise. Further adjustment for hypertension and body mass index slightly changed the estimates.

Conclusions—
Smoking is strongly associated with hemorrhagic stroke mortality, particularly for subarachnoid hemorrhage.
Davies on Easy Knowledge
Authors: McBride Mark 
Published: May 2013

Stewart Cohen considers a case where his son wants a red table for his room. Cohen and his son go to the furniture store. Cohen’s son is concerned that the table his father is considering purchasing, which appears red, may in fact be white with red lights shining on it. Cohen responds with the following reasoning:

(WARRANT FOR 1) The table looks red.

(EK)

(1)
The table is red.

(2)
If the table is red, then it is not white with red lights shining on it.

(3)
The table is not white with red lights shining on it.

If one reasons thus, say one’s engaged in (EK)-reasoning. Cohen finds such a response unsatisfactory. It is not a way of coming to know (3)—it is too easy. And structurally similar reasoning delivers (knowledge of) the falsity of sceptical hypotheses concerning the external world, testimony, other minds etc. So the unsatisfactoriness threatens to generalise. I consider Martin Davies’s attempt to diagnose this unsatisfactoriness and find it incomplete. I then attempt to remedy the incompleteness in Davies’s attempt.
How Does the Boundary Layer Contribute to Eyewall Replacement Cycles in Axisymmetric Tropical Cyclones?
Authors: Kepert Jeffrey D. 
Published: May 2013

Abstract
Three diagnostic models of the axisymmetric tropical cyclone boundary layer, with different levels of approximation, are applied to the problem of tropical cyclones with concentric eyewalls. The outer eyewall is shown to have an inherently stronger frictional updraft than the inner because it is in an environment of lower vorticity. Similarly, a relatively weak local enhancement of the radial vorticity gradient outside the primary radius of maximum winds can produce a significant frictional updraft, even if there is no outer wind maximum. Based on these results, it is proposed that the boundary layer contributes to the formation of outer eyewalls through a positive feedback among the local enhancement of the radial vorticity gradient, the frictional updraft, and convection. The friction-induced secondary circulation associated with the inner eyewall is shown to weaken as the outer wind maximum strengthens and/or contracts, so boundary layer processes will contribute, along with the heating-induced secondary circulation, to the weakening of the inner eyewall during an eyewall replacement cycle. An integral mass constraint on the friction-induced secondary circulation is derived and used to examine the oft-stated proposition that “the outer eyewall uses up the inflowing energy-rich boundary layer air.” Using the integral constraint, the author argues that formation of a secondary eyewall will tend to increase the total friction-induced secondary circulation and that, if the moat between the two eyewalls has a local vorticity minimum, then sufficient subsidence may occur there to maintain the primary eyewall's updraft. It is noted, however, that the enthalpy of the updraft is important as well as its mass.
Is there an increase in the incidence of uterine carcinosarcoma in north-east Scotland? A 19 years population-based cohort study
Authors: Gurumurthy M , Lahiri R , Scott N , Miller I , Cruickshank ME , Parkin DE 
Published: May 2013

Background and aims The incidence of uterine carcinosarcoma and factors associated with its survival are little known and this study helps to address this question for women residing in north-east Scotland. Methods and results Data were collected from women diagnosed with carcinosarcoma of the uterus residing in north-east of Scotland from 1991 to 2009. Kaplan–Meier plots and Cox regression analysis were used for analysis. A total of 43 women were analysed during this period. The median survival was 25 months. The estimated five-year survival for stage I/II disease was 52.5% (95% CI: 30.5–74.5%). The 2-year survival rate for stage III/IV disease was 46% (95% CI: 16–75%). There was an increase in the incidence during this period. Improved survival was seen in early-stage disease (FIGO stages I and II) and in the absence of lymphovascular space invasion (LVSI; p = 0.015). A total of 26% of the women had a history of tamoxifen usage with no effect seen on survival. Multivariate analysis showed that when treatment modality and LVSI were adjusted for FIGO staging, there was no statistical significance in the survival outcomes. Conclusion The incidence of uterine carcinosarcomas is increasing parallel with endometrial carcinomas with no significant effect of tamoxifen on survival.
Symptoms do not predict colorectal cancer in an FOB screened population
Authors: Saldanha JD , Moug SJ , Linton K , Diament RH 
Published: May 2013

Background and aims: The Scottish Bowel Screening Programme aims to detect cancer in asymptomatic individuals. We aimed to measure the prevalence of lower gastrointestinal symptoms in faecal occult blood (FOB) screen-positive patients, to correlate the symptoms with neoplasia and to compare the predictive value of FOB screening with urgent symptomatic referrals in Ayrshire and Arran. Methods: Data were collected prospectively on FOB screen-positive patients undergoing colonoscopy. Patients completed a symptom questionnaire. Positive predictive values (PPVs) for detecting neoplasia were calculated and a chi-square test was performed to determine any influence of symptoms in diagnosing neoplasia. Symptomatic patients undergoing colonoscopy via a general practice fast-track system were compared. Results: A total of 378 FOB screen-positive patients were included. In all, 198 (52%) had colorectal symptoms. Overall, 32 were diagnosed with colorectal cancer and 93 had polyps . FOB positivity and symptoms gave a PPV of 34% for neoplasia. FOB positivity without symptoms gave a PPV of 32% for neoplasia. Urgent referral of symptomatic patients had a lower PPV of 21% for neoplasia ( p < 0.001). Conclusion: Half the FOB screen-positive patients had bowel symptoms. Symptoms in these patients had no correlation with an increased rate of neoplasia. The PPV for neoplasia is superior in symptomatic and asymptomatic screen-positive patients when compared to conventional urgent symptom-based referral.
A young healthy male with syncope and complete heart block
Authors: Chauhan V , Chauhan N , Chauhan CGS , Vaid M 
Published: May 2013

Introduction It is rare to see heart block as the first-and-only presentation of Lyme disease, the reported incidence being just 1% in untreated patients. Case presentation We report a patient who presented with syncope secondary to a fluctuating heart block. He had no previous manifestations of Lyme disease. Lyme carditis was suspected after the other usual etiologies of heart block were ruled out. Later, serologies came positive and patient’s heart block resolved on ceftriaxone therapy. Conclusion In at-risk individuals, clinicians should rule out this readily-treatable cause of heart block before proceeding with permanent pacemaker implantation due to enormous clinical and cost implications involved. Missing the diagnosis also exposes the patient to the risk of developing the late complications of Lyme disease. Diagnosis of isolated Lyme carditis is a challenge because the clinician does not have the diagnostic-clues that can usually be gleaned from the more common stigmata of Lyme disease.
The Rate of Subsequent Surgery and Predictors After Anterior Cruciate Ligament Reconstruction
Authors: Hettrich Carolyn M. , Dunn Warren R. , Reinke Emily K. ,   MOON Group, Spindler Kurt P. , Parker Richard D. , Andrish Jack T. , Kaeding Christopher C. , Amendola Annunziato , Wright Rick W. , Marx Robert G. , McCarty Eric C. 
Published: May 2013

Background: Subsequent surgeries have a profound effect on patient satisfaction and outcome after primary anterior cruciate ligament reconstruction (ACLR). There have been no prospective studies to date describing the rate and predictors (surgical and patient variables) of all subsequent knee surgeries at short-term and midterm follow-up along with analyses of surgical and patient variables that are associated with subsequent surgeries. Purpose: To report the rate and predictors of all subsequent surgeries at short-term and midterm follow-up along with associated patient variables. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 980 patients (540 male) were prospectively enrolled in a Multicenter Orthopaedic Outcomes Network (MOON) cohort from January 2002 to December 2003. The 2- and 6-year follow-up information for subsequent procedures was obtained. Operative reports were obtained, and all procedures were categorized. Results: One hundred eighty-five patients underwent a subsequent surgery on the ipsilateral leg (18.9%) and 100 on the contralateral knee (10.2%) at 6-year follow-up. On the ipsilateral knee, there was a 7.7% rate of ACL revisions, a 13.3% rate of cartilage procedures, a 5.4% rate of arthrofibrosis procedures, and a 2.4% rate of procedures related to hardware. For the contralateral knee, there was a 6.4% rate of primary ACL ruptures. Younger age at the index surgery and the use of allografts were predictors (risk factors) for subsequent surgery. Revision ACLR, female sex, body mass index, and surgical exposure were not significant predictors. Conclusion: At 6-year follow-up, 18.9% of patients who had undergone ACLR underwent subsequent surgeries on the ipsilateral knee. The rates between an ipsilateral ACLR graft versus a contralateral normal ACL tear were similar (7.7% vs 6.4%, respectively). Younger age and the use of allografts were risk factors for subsequent surgery.
Association of Symptoms and Cytokines in Prostate Cancer Patients Receiving Radiation Treatment
Authors: Dirksen Shannon Ruff , Kirschner Kenneth Ferris , Belyea Michael J. 
Published: May 2013

Introduction: Men with prostate cancer undergoing radiation treatment frequently report fatigue, insomnia, depression, anxiety and urinary, bowel, sexual, and hormonal symptoms. Plasma concentrations of cytokines may be related to these symptoms, but few studies have examined these relationships. The study purpose was to explore the association between prostate cancer symptoms and cytokine levels at pretreatment and posttreatment. Method: In this longitudinal, correlational study, 29 men with nonmetastatic prostate cancer completed symptom questionnaires at preradiation and postradiation treatment. Blood drawn at these same time points was used to determine levels of tumor necrosis factor-alpha (TNF-α) and interleukins-1β, 6, 10, and 4 (IL-1β, IL-6, IL-10, and IL-4). Results: Men reported symptom severity at pretreatment and posttreatment as low to moderate. There were significant differences from pretreatment to posttreatment in fatigue, insomnia, urinary irritative and incontinence, bowel, sexual, and hormonal problems. There were no significant differences in TNF-α, IL-6, IL-10, or IL-4. At pretreatment, TNF-α was associated with depression, anxiety, urinary irritative, and bowel problems, and IL-4 was related to urinary irritative symptoms. At posttreatment, IL-4 was associated with urinary irritative symptoms. Findings suggest that, in men with prostate cancer, there is no strong association between symptom reporting and cytokine levels. Ongoing research focused on neuroendocrine and genetic markers and their associations with symptoms is promising and may result in the provision of better markers for quantifying the symptom experience in patients with cancer.
Use of aliskiren in Latin America in a real-world setting: Aliskiren in Latin America Study (ALAS)
Authors: Volman Sergio , Benitez Fernando Nicolas , Cedenio Harold , Giorgi Mariano , Jaramillo Nicolas , Molina Nelys , Zilberman Judith 
Published: May 2013

Background: Hypertension (HTN) is one of the major risk factors for cardiovascular disease in Western countries, and disease control is of major relevance in order to reduce cardiovascular morbidity and mortality. Different approaches have shown efficacy, and one of the proven therapies for HTN control is the blockade of the renin–angiotensin–aldosterone system, which may be accomplished by means of various drugs with different modes of action. Aliskiren is a novel direct renin inhibitor that reduces both angiotensin I and II blood levels. Different randomized clinical trials (phase II and III) have shown its safety and efficacy either alone or in combination with hydrochlorothiazide. However, although aliskiren has been on the market for some years, reports on the post-marketing experience with aliskiren in the real-world setting are lacking. Methods: The Aliskiren in Latin America Study (ALAS) was designed with the aim of describing the effectiveness of aliskiren at reducing blood pressure (BP) values by prospectively assessing BP control in outpatient clinics in different countries in Latin America. A total of 435 sites in 5 Latin American countries (Mexico, Ecuador, Colombia, Argentina, and Venezuela) enrolled 4588 patients who had just been initiated on aliskiren (either alone or in combination with hydrochlorothiazide) based on their treating physicians’ discretion, and they were followed for a 6-month period. Prior antihypertensive drugs could be continued if their doses were not modified along the study. Results: At the end of the follow-up period, a statistically significant reduction in BP values was observed, with a mean systolic BP reduction of 29.2 mmHg and a mean diastolic BP reduction of 13.78 mmHg from baseline at the 6-month visit. Conclusion: The BP reduction levels and the low adverse event rate demonstrate the adequate efficacy and safety profile of aliskiren (alone or with hydrochlorothiazide).