bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting Insulin-Mediated β
2
-Adrenergic Receptor Activation Prevents Diabetes-Associated Cardiac Dysfunction
Authors: Wang Qingtong , Liu Yongming , Fu Qin , Xu Bing , Zhang Yuan , Kim Sungjin , Tan Ruensern , Barbagallo Federica , West Toni , Anderson Ethan , Wei Wei , Abel E. Dale , Xiang Yang K. 
Published: November 2016

Background:
Type 2 diabetes mellitus (DM) and obesity independently increase the risk of heart failure by incompletely understood mechanisms. We propose that hyperinsulinemia might promote adverse consequences in the hearts of subjects with type-2 DM and obesity.

Methods:

High-fat diet feeding was used to induce obesity and DM in wild-type mice or mice lacking β
2
-adrenergic receptor (β
2
AR) or β-arrestin2. Wild-type mice fed with high-fat diet were treated with a β-blocker carvedilol or a GRK2 (G-protein-coupled receptor kinase 2) inhibitor. We examined signaling and cardiac contractile function.

Results:

High-fat diet feeding selectively increases the expression of phosphodiesterase 4D (PDE4D) in mouse hearts, in concert with reduced protein kinase A phosphorylation of phospholamban, which contributes to systolic and diastolic dysfunction. The expression of PDE4D is also elevated in human hearts with DM. The induction of PDE4D expression is mediated by an insulin receptor, insulin receptor substrate, and GRK2 and β-arrestin2-dependent transactivation of a β
2
AR-extracellular regulated protein kinase signaling cascade. Thus, pharmacological inhibition of β
2
AR or GRK2, or genetic deletion of β
2
AR or β-arrestin2, all significantly attenuate insulin-induced phosphorylation of extracellular regulated protein kinase and PDE4D induction to prevent DM-related contractile dysfunction.

Conclusions:

These studies elucidate a novel mechanism by which hyperinsulinemia contributes to heart failure by increasing PDE4D expression and identify β
2
AR or GRK2 as plausible therapeutic targets for preventing or treating heart failure in subjects with type 2 DM.
Treatment With Tissue Plasminogen Activator in the Golden Hour and the Shape of the 4.5-Hour Time-Benefit Curve in the National United States Get With The Guidelines-Stroke Population
Authors: Kim Joon-Tae , Fonarow Gregg C. , Smith Eric E. , Reeves Mathew J. , Navalkele Digvijaya D. , Grotta James C. , Grau-Sepulveda Maria V. , Hernandez Adrian F. , Peterson Eric D. , Schwamm Lee H. , Saver Jeffrey L. 
Published: November 2016

Background:
Earlier tissue plasminogen activator treatment improves ischemic stroke outcome, but aspects of the time-benefit relationship still not well delineated are: (1) the degree of additional benefit accrued with treatment in the first 60 minutes after onset, and (2) the shape of the time-benefit curve through 4.5 hours.

Methods:
We analyzed patients who had acute ischemic stroke treated with intravenous tissue plasminogen activator within 4.5 hours of onset from the Get With The Guidelines-Stroke US national program. Onset-to-treatment time was analyzed as a continuous, potentially nonlinear variable and as a categorical variable comparing patients treated within 60 minutes of onset with later epochs.

Results:
Among 65 384 tissue plasminogen activator–treated patients, the median onset-to-treatment time was 141 minutes (interquartile range, 110–173) and 878 patients (1.3%) were treated within the first 60 minutes. Treatment within 60 minutes, compared with treatment within 61 to 270 minutes, was associated with increased odds of discharge to home (adjusted odds ratio, 1.25; 95% confidence interval, 1.07–1.45), independent ambulation at discharge (adjusted odds ratio, 1.22; 95% confidence interval, 1.03–1.45), and freedom from disability (modified Rankin Scale 0–1) at discharge (adjusted odds ratio, 1.72; 95% confidence interval, 1.21–2.46), without increased hemorrhagic complications or in-hospital mortality. The pace of decline in benefit of tissue plasminogen activator from onset-to-treatment times of 20 through 270 minutes was mildly nonlinear for discharge to home, with more rapid benefit loss in the first 170 minutes than later, and linear for independent ambulation and in-hospital mortality.

Conclusions:
Thrombolysis started within the first 60 minutes after onset is associated with best outcomes for patients with acute ischemic stroke, and benefit declined more rapidly early after onset for the ability to be discharged home. These findings support intensive efforts to organize stroke systems of care to improve the timeliness of thrombolytic therapy in acute ischemic stroke.
Impact of Smoking on Circulating Cardiac Troponin I Concentrations and Cardiovascular Events in the General Population
Authors: Lyngbakken Magnus Nakrem , Skranes Julia Brox , de Lemos James A. , Nygård Ståle , Dalen Håvard , Hveem Kristian , Røsjø Helge , Omland Torbjørn 
Published: November 2016

Background:
Both tobacco smoking and circulating cardiac troponin I (cTnI) levels are associated with the risk of acute myocardial infarction, heart failure, and cardiovascular death. However, whether cTnI levels differ according to smoking status and whether smoking modifies the prognostic relationship between cTnI and outcomes remain unclear.

Methods:
Using data from a large, population-based cohort, we assessed the association between smoking and cTnI and the impact of smoking on the associations between cTnI levels and the incidence of acute myocardial infarction, heart failure, and cardiovascular death. cTnI was measured with a high-sensitivity assay in 3824 never smokers, 2341 former smokers, and 2550 current smokers participating in the prospective observational HUNT Study (Nord-Trøndelag Health Study). All subjects were free from known prior cardiovascular disease and diabetes mellitus at baseline.

Results:

The age of the participants ranged from 19 to 94 years; 55.5% were women. Current smokers exhibited significantly lower levels of cTnI (median, 2.9 ng/L; interquartile range, 2.0–4.1 ng/L) than never smokers (3.2 ng/L; interquartile range, 2.2–4.7 ng/L;
P
<0.001) and former smokers (3.4 ng/L; interquartile range, 2.3–5.0 ng/L;
P
<0.001). This association remained significant after adjustment for potential confounders (B=−0.098; 95% confidence interval, −0.129 to −0.068). We observed an association between increasing concentrations of cTnI and clinical end points in the total study cohort (adjusted hazard ratio per log unit increase in cTnI, 1.41; 95% confidence interval, 1.29–1.54). This association was attenuated for current smokers (hazard ratio, 1.17; 95% confidence interval, 0.98–1.40) and was significantly weaker than in never/former smokers (
P
for interaction=0.003). Prognostic accuracy, as assessed by C statistics, was significantly lower in current smokers than in never smokers (
P
<0.001). In addition, cTnI provided no incremental prognostic information to the Framingham Cardiovascular Disease risk score in current smokers (
P
=0.08).

Conclusions:
Current smoking is associated with lower concentrations of cTnI, suggesting that substances in tobacco smoke may affect cardiomyocyte injury. The association between cTnI levels and cardiovascular end points is stronger in never/former smokers than in current smokers, compatible with the theory that the detrimental cardiovascular impact of current smoking is mediated via mechanisms other than subclinical myocardial injury.
Female Mice With an XY Sex Chromosome Complement Develop Severe Angiotensin II–Induced Abdominal Aortic Aneurysms
Authors: Alsiraj Yasir , Thatcher Sean E. , Charnigo Richard , Chen Kuey , Blalock Eric , Daugherty Alan , Cassis Lisa A. 
Published: November 2016

Background:
Abdominal aortic aneurysms (AAAs) are a deadly pathology with strong sexual dimorphism. Similar to humans, female mice exhibit far lower incidences of angiotensin II–induced AAAs than males. In addition to sex hormones, the X and Y sex chromosomes, and their unique complements of genes, may contribute to sexually dimorphic AAA pathology. Here, we defined the effect of female (XX) versus male (XY) sex chromosome complement on angiotensin II–induced AAA formation and rupture in phenotypically female mice.

Methods:

Female low-density lipoprotein receptor (
Ldlr
) deficient mice with an XX or XY sex chromosome complement were infused with angiotensin II for 28 days to induce AAAs. Abdominal aortic lumen diameters were quantified by ultrasound, whereas AAA diameters were quantified at study end point. DNA microarrays were performed on abdominal aortas. To mimic males, female mice were administered a single dose of testosterone as neonates or as adults before angiotensin II infusions.

Results:

Female
Ldlr
–/–
deficient mice with an XX and XY sex chromosome complement had similar sex organ weights and low serum testosterone concentrations. Abdominal aortas from female XY mice selectively expressed Y chromosome genes, whereas genes known to escape X inactivation were higher in XX females. The majority of aortic gene differences in XY versus XX females fell within inflammatory pathways. AAA incidences doubled and aneurysms ruptured in XY females. AAAs from XY females exhibited inflammation, and plasma interleukin-1β concentrations were increased in XY females. Moreover, aortas from XY females had augmented matrix metalloproteinase activity and increased oxidative stress. Last, testosterone exposure applied chronically, or as a single bolus at postnatal day 1, markedly worsened AAA outcomes in XY in comparison with XX adult females.

Conclusions:
An XY sex chromosome complement in phenotypic females profoundly influenced aortic gene expression profiles and promoted AAA severity. When XY females were exposed to testosterone, aneurysm rupture rates were striking. Mechanisms for augmented AAA severity in XY females include increased inflammation, augmented matrix metalloproteineases, and oxidative stress. Our results demonstrate that genes on the sex chromosomes regulate aortic vascular biology and contribute to sexual dimorphism of AAAs. Sex chromosome genes may serve as novel targets for sex-specific AAA therapeutics.
Relationship of Platelet Reactivity With Bleeding Outcomes During Long‐Term Treatment With Dual Antiplatelet Therapy for Medically Managed Patients With Non‐ST‐Segment Elevation Acute Coronary Syndromes
Authors: Cornel Jan H. , Ohman E. Magnus , Neely Benjamin , Jakubowski Joseph A. , Bhatt Deepak L. , White Harvey D. , Ardissino Diego , Fox Keith A.A. , Prabhakaran Dorairaj , Armstrong Paul W. , Erlinge David , Tantry Udaya S. , Gurbel Paul A. , Roe Matthew T. 
Published: November 2016

Background
The relationship between “on‐treatment” low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention.

Methods and Results

We analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes
(TRILOGY ACS
) trial who had serial platelet reactivity measurements (P2Y
12
reaction units;
PRU
s) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady‐state
PRU
values could distinguish high versus low bleeding risk using 2‐level composites: Global Use of Strategies to Open Occluded Coronary Arteries (
GUSTO
) severe/life‐threatening or moderate bleeding unrelated to coronary artery bypass grafting (
CABG
) and non‐
CABG
Thrombolysis In Myocardial Infarction (
TIMI
) major or minor bleeding. Exploratory analyses used 3‐level composites that incorporated mild and minimal
GUSTO
and
TIMI
events. Continuous measures of
PRU
s (per 10‐unit decrease) were not independently associated with the 2‐level
GUSTO
(adjusted hazard ratio [
HR
], 1.01; 95%
CI
, 0.96–1.06) or
TIMI
composites (1.02; 0.98–1.07). Furthermore, no
PRU
cut point could significantly distinguish bleeding risk using the 2‐level composites. However, the
PRU
cut point of 75 differentiated bleeding risk with the 3‐level composites of
GUSTO
(26.5% vs 12.6%; adjusted
HR
, 2.28; 95%
CI
, 1.77–2.94;
P
<0.001) and
TIMI
bleeding events (25.9% vs 12.2%; adjusted
HR
, 2.30; 95%
CI
, 1.78–2.97;
P
<0.001).

Conclusions

Among medically managed non‐
ST
‐segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy,
PRU
values were not significantly associated with the long‐term risk of major bleeding events, suggesting that low on‐treatment platelet reactivity does not independently predict serious bleeding risk.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00699998.
Length of Residence in the United States is Associated With a Higher Prevalence of Cardiometabolic Risk Factors in Immigrants: A Contemporary Analysis of the National Health Interview Survey
Authors: Commodore‐Mensah Yvonne , Ukonu Nwakaego , Obisesan Olawunmi , Aboagye Jonathan Kumi , Agyemang Charles , Reilly Carolyn M. , Dunbar Sandra B. , Okosun Ike S. 
Published: November 2016

Background

Cardiometabolic risk (
CMR
) factors including hypertension, overweight/obesity, diabetes mellitus, and hyperlipidemia are high among United States ethnic minorities, and the immigrant population continues to burgeon.

Methods and Results

Hypothesizing that acculturation (length of residence) would be associated with a higher prevalence of
CMR
factors, the authors analyzed data on 54, 984 US immigrants in the 2010–2014 National Health Interview Surveys. The main predictor was length of residence. The outcomes were hypertension, overweight/obesity, diabetes mellitus, and hyperlipidemia. The authors used multivariable logistic regression to examine the association between length of US residence and these
CMR
factors.

The mean (
SE
) age of the patients was 43 (0.12) years and half were women. Participants residing in the United States for ≥10 years were more likely to have health insurance than those with <10 years of residence (70% versus 54%,
P
<0.001). After adjusting for region of birth, poverty income ratio, age, and sex, immigrants residing in the United States for ≥10 years were more likely to be overweight/obese (odds ratio [
OR
], 1.19; 95%
CI
, 1.10–1.29), diabetic (
OR
, 1.43; 95%
CI
, 1.17–1.73), and hypertensive (
OR
, 1.18; 95%
CI
, 1.05–1.32) than those residing in the United States for <10 years.

Conclusions

In an ethnically diverse sample of US immigrants, acculturation was associated with
CMR
factors. Culturally tailored public health strategies should be developed in US immigrant populations to reduce
CMR
.
Woodstock Scholarship
Authors: Gatten Jeffrey N. 
Published: November 2016

Since August 1969, the Woodstock Music and Art Fair looms large when recounting the history and impact of the baby boom generation and the societal upheavals of the Sixties. Scholars study the sociological, political, musical, and artistic impact of the event and use it as a cultural touchstone when exploring alternative perspectives or seeking clarity. This interdisciplinary annotated bibliography records the details of over 400 English-language resources on the Festival, including books, chapters, articles, websites, transcriptions and videos. Divided into six main subsections―Culture & Society, History, Biography, Music, Film, Arts & Literature―for ease of consultation Woodstock Scholarship sheds light on all facets of a key happening in our collective history.
Throughout the 1960s, popular music became increasingly reflective and suggestive of the rising political and social consciousness of the youth culture. Examples can be seen in the development of the protest song genre within the folk music boom of the early Sixties and the marriage of lifestyle to music first reflected by The Beatles with fashion, followed by psychedelic music with the emerging drug culture. Woodstock was where these themes coalesced, thus becoming the defining and last great moment of the 1960s. However, Woodstock also represented an abundant amount of experiences and ideas and moments. Thus, when exploring the complicated accounts and numerous facets of America during the turbulent Sixties one discovers scholarship on the key subjects, such as the Vietnam War or the Civil Rights Movement, often considering and debating the importance, relevance, and epic nature of Woodstock. Multiple narratives emerge: a radical engagement of the hippie movement, an overt commercial exploitation of youth culture, a political statement. Woodstock scholarship does not stand alone as field of study, but it is at the cross-road of a number of disciplines―music history, cultural studies, sociology, arts and literature, media studies, politics and economics.
Providing full bibliographical details and concise, informative annotation for each entry, Woodstock Scholarship is an essential tool for students, scholars, teachers, and librarians in all these areas, as well as for anyone seeking a deeper understanding of both the Woodstock Music and Art Fair phenomenon and of the confluence of music, commerce and politics.
The social representations of suicide in France: An inter-regional study in Alsace and Brittany
Authors: Kopp-Bigault Céline , Walter Michel , Thevenot Anne 
Published: November 2016

Background: Suicide is a major worldwide public health issue. Various studies showed that individual attitudes toward suicide change in a region with high suicide rate. Attitudes are one of the components of a global and complex system: social representations (SRs). Aims: In France, the Brittany region has an abnormally high death rate due to suicides. Our research focuses on the SRs of suicide in this region. The hypothesis underlying this project is that suicide SRs are different between an area with a high suicide rate and a region less affected by suicide. Method: A comparative study between the Brittany and Alsace regions, with the latter showing a statistically much lower suicide rate. The persons polled responded to a three-word free-association task around the question ‘For you, suicide is …?’ An analysis of word frequency and evocation rank was then carried out. Results: In confirmation of our hypothesis, SRs were different between Brittany and the control region. Conclusion: The study’s results open new avenues of research, specific to Brittany, in terms of the collective or individual effects of suicides, in terms of psycho-pathological conditions – essentially on depression, and in terms of training, on the stereotypes associated with suicide.
Schizophrenia: Impact of psychopathology, faith healers and psycho-education on adherence to medications
Authors: Abdel Aziz Karim , Elamin Mohammed H , El-Saadouni Nisrin M , El-Gabry Dina Aly , Barakat Mahmoud , Alhayyas Fatima , Moselhy Hamdy F 
Published: November 2016

Background: Many patients suffering from psychosis are nonadherent to their medications. Nonadherence can range from treatment refusal to irregular use or partial change in daily medication doses. Aim: To investigate whether symptom dimensions, post-discharge care plans and being involved with faith healer affect the adherence to treatment in patients with schizophrenia. Method: A total of 121 patients with schizophrenia were examined 6 weeks post-discharge from the inpatient unit and assessed for full, partial or nonadherence to medication. Results: There was a significant association between family involvement and partial adherence and between community team involvement post-discharge and full adherence to medications. Psycho-education was a predictor for adherence to medications, persecutory delusions and lack of insight predicted partial adherence, while being involved with faith healers predicted nonadherence. Conclusion: Adherence to medications and socio-demographic variables are independent. This study demonstrated that nonadherence or partial adherence to medications is associated with lack of insight and persecutory delusions. Psycho-education could improve the adherence to medication compliances.
Paradoxical territorial management: the case of peri-urban agricultural areas
Authors: Hernandez Solange 
Published: November 2016

The purpose of this research is to understand the paradoxical practices of territorial management and to look into ways of supporting the local actors of peri-urban agriculture. To do so, we conducted a case study into the policy implemented for the past 25 years by the urban community of the Pays d’Aubagne et de l’Etoile (Bouches-du-Rhône). Drawing on quantitative analyses of qualitative data, we demonstrate the relevance of these management practices in action. We go on to propose managerial tools that can be applied in the framework of public action in peri-urban agriculture. Points for practitioners The practical uses of the article are: first, to identify and understand the paradoxes, a recurring source of tension and deadlock in territorial public administration; and, second, to contribute concrete avenues of reflection and solutions to the territorial managers faced with these situations, especially in the management of peri-urban agricultural areas.
Utility of the NECPAL CCOMS-ICO© tool and the Surprise Question as screening tools for early palliative care and to predict mortality in patients with advanced chronic conditions: A cohort study
Authors: Gómez-Batiste Xavier , Martínez-Muñoz Marisa , Blay Carles , Amblàs Jordi , Vila Laura , Costa Xavier , Espaulella Joan , Villanueva Alicia , Oller Ramon , Martori Joan Carles , Constante Carles 
Published: November 2016

Background: The Surprise Question (SQ) identifies patients with palliative care needs. The NECPAL CCOMS-ICO© (NECPAL) tool combines the Surprise Question with additional clinical parameters for a more comprehensive assessment. The capacity of these screening tools to predict mortality is still unknown. Aim: To explore the predictive validity of the NECPAL and SQ to determine 12- to 24-month mortality. Design: Longitudinal, prospective and observational cohort study. Setting/participants: Three primary care centres, one general hospital, one intermediate care centre, and four nursing homes. Population cohort with advanced chronic conditions and limited life prognosis. Patients were classified according to SQ and NECPAL criteria and followed for 24 months. Results: Data available to assess 1059 of 1064 recruited patients (99.6%) at 12 and 24 months: 837 patients were SQ+ and 780 were NECPAL+. Mortality rates at 24 months were as follows: 44.6% (SQ+) versus 15.8% (SQ−) and 45.8% (NECPAL+) versus 18.3% (NECPAL−) ( p = 0.000). SQ+ and NECPAL+ identification was significantly correlated with 24-month mortality risk (hazard ratios: 2.719 and 2.398, respectively). Both tools were highly sensitive (91.4, CI: 88.7–94.1 and 87.5, CI: 84.3–90.7) with high negative predictive values (84.2, CI: 79.4–89.0 and 81.7, CI: 77.2–86.2), with low specificity and positive predictive value. The prognostic accuracy of SQ and NECPAL was 52.9% and 55.2%, respectively. The predictive validity was slightly better for NECPAL. Conclusion: SQ and NECPAL are valuable screening instruments to identify patients with limited life prognosis who may require palliative care. More research is needed to increase its prognostic utility in combination with other parameters.