bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding factors influencing vulnerable older people keeping warm and well in winter: a qualitative study using social marketing techniques
Authors: Tod Angela Mary , Lusambili Adelaide , Homer Catherine , Abbott Joanne , Cooke Joanne Mary , Stocks Amanda Jayne , McDaid Kathleen Anne 
Published: July 2012

ObjectivesTo understand the influences and decisions of vulnerable older people in relation to keeping warm in winter.DesignA qualitative study incorporating in-depth, semi-structured individual and group interviews, framework analysis and social marketing segmentation techniques.SettingRotherham, South Yorkshire, UK.Participants50 older people (>55) and 25 health and social care staff underwent individual interview. The older people also had household temperature measurements. 24 older people and 19 health and social care staff participated in one of the six group interviews.ResultsMultiple complex factors emerged to explain whether vulnerable older people were able to keep warm. These influences combined in various ways that meant older people were not able to or preferred not to access help or change home heating behaviour. Factors influencing behaviours and decisions relating to use of heating, spending money, accessing cheaper tariffs, accessing benefits or asking for help fell into three main categories. These were situational and contextual factors, attitudes and values, and barriers. Barriers included poor knowledge and awareness, technology, disjointed systems and the invisibility of fuel and fuel payment. Findings formed the basis of a social marketing segmentation model used to develop six pen portraits that illustrated how factors that conspire against older people being able to keep warm.ConclusionsThe findings illustrate how and why vulnerable older people may be at risk of a cold home. The pen portraits provide an accessible vehicle and reflective tool to raise the capacity of the NHS in responding to their needs in line with the Cold Weather Plan.
Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register
Authors: Ekström Nils , Schiöler Linus , Svensson Ann-Marie , Eeg-Olofsson Katarina , Miao Jonasson Junmei , Zethelius Björn , Cederholm Jan , Eliasson Björn , Gudbjörnsdottir Soffia 
Published: July 2012

ObjectiveTo evaluate the effectiveness and safety of metformin use in clinical practice in a large sample of pharmacologically treated patients with type 2 diabetes and different levels of renal function.DesignObservational study between July 2004 and December 2010, mean follow-up 3.9 years.SettingHospital outpatient clinics and primary care in Sweden.Participants51 675 men and women with type 2 diabetes, registered in the Swedish National Diabetes Register, and on continuous glucose-lowering treatment with oral hypoglycaemic agents (OHAs) or insulin.Main outcome measuresRisks of cardiovascular disease (CVD), all-cause mortality and acidosis/serious infection, associated with each treatment regimens, were analysed in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. Covariance adjustment and propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression.ResultsCompared with metformin in monotherapy, HRs for fatal/non-fatal CVD and all-cause mortality with all other OHAs combined (approximately 80% sulphonylureas) in monotherapy were 1.02 (95% CI 0.93 to 1.12) and 1.13 (1.01 to 1.27), while 1.18 (1.07 to 1.29) and 1.34 (1.19 to 1.50) with insulin in monotherapy, adjusting using propensity scores. Metformin, compared with any other treatment, showed reduced risks of acidosis/serious infection (adjusted HR 0.85, 95% CI 0.74 to 0.97) and all-cause mortality (HR 0.87, 95% CI 0.77 to 0.99), in patients with eGFR 45–60 ml/min/1.73 m2, and no increased risks of all-cause mortality, acidosis/serious infection or CVD were found in patients with eGFR 30–45 ml/min/1.73 m2.ConclusionsMetformin showed lower risk than insulin for CVD and all-cause mortality and slightly lower risk for all-cause mortality compared with other OHA, in these 51 675 patients followed for 4 years. Patients with renal impairment showed no increased risk of CVD, all-cause mortality or acidosis/serious infection. In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects.
Proximity to health services and child survival in low- and middle-income countries: a systematic review and meta-analysis
Authors: Okwaraji Yemisrach Behailu , Edmond Karen M 
Published: July 2012

ObjectivesFew studies have systematically examined the effects of barriers such as distance to health facilities on child survival in low- and middle-income countries. Our primary objective was to estimate the effect of proximity to health facilities on child survival in low- and middle-income countries. The secondary objective was to compare effects in different age categories (perinatal (28 weeks of gestation to 1 week of age), neonatal (0–27 days), infant (0–11 months) and child (0–59 months) mortality).DesignA systematic review and meta-analysis was conducted of studies published from 1980 to 2012 that assessed the effect of proximity to health facilities on child survival in low- and middle-income countries. Synthesis was by random-effects meta-analysis, and variation between studies was investigated by meta-regression.SettingLow- and middle-income countries.Participants13 studies were included in the meta-analysis, 11 from low-income and two from middle-income countries and none were from remote areas.Primary outcome measuresThe primary outcome measures of interest were perinatal, neonatal, infant and child mortality.ResultsOverall, children who lived farthest from health facilities were more likely to die compared with those who lived closer (OR 1.32, 95% CI 1.19 to 1.47). This effect appeared stronger during the perinatal (OR 2.76, 95% CI 1.80 to 4.24) and neonatal (OR 1.98, 95% CI 1.43 to 2.72) periods compared with the infant (OR 1.18, 95% CI 1.0 to 1.38) and under-5 (OR 1.20, 95% CI 1.04 to 1.39) periods.ConclusionsProximity to health facilities appears to be an important determinant of under-5 mortality in low- and middle-income countries, especially in the perinatal and neonatal periods. Higher quality studies are needed, which examine the effect of access to health services on child survival, especially studies from remote areas and hard to reach populations.
Attitudes and expectations of gastroenterology outpatients about the importance of diet and possible relationship to their symptoms
Authors: Adesokan Akintayo , Neild Penny 
Published: July 2012

ObjectivesTo evaluate gastroenterology outpatients’ attitudes to the importance of diet and its relationship to their symptoms, as well as their expectations of dietary advice from health professionals.DesignProspective clinical audit.SettingGastroenterology outpatient department of St George's Healthcare NHS Trust.PatientsTwo hundred and twenty-five patients, aged between 18 and 70 years met the inclusion criteria.InterventionsNone.Main outcome measuresParticipants’ responses to a structured questionnaire.ResultsSixty-nine per cent of participants felt their diet played an important role in their condition. Factors significantly associated with a positive dietary attitude included younger age (40.6 years vs 46.0 years, p<0.01), regularity of dietary pattern (108 vs 35, p<0.01), number of symptoms (4.6 vs 2.5, p<0.01), severity of gastrointestinal symptoms (2.3 vs 1.5, p<0.01), history of weight loss (34% vs 20.3%, p<0.05) and history of dietary advice (71.1% vs 33.3%, p<0.01). Sixty-eight per cent (68%) of participants were interested in receiving dietary advice, though only 36% expected to receive it. No differences were found for any comparisons based on average body mass index.ConclusionThe majority of gastroenterology outpatients view diet as playing an important role in their condition, particularly those who have more severe symptoms and those who have received dietary advice. Although a large proportion of patients are interested in receiving dietary advice, few expect to receive it in clinics. Further research is required to explore the reasons why, and to assess the confidence of health professionals in providing nutritional advice.
Functional Effects of GRM1 Suppression in Human Melanoma Cells
Authors: Wangari-Talbot Janet , Wall Brian A. , Goydos James S. , Chen Suzie 
Published: July 2012

Abstract
Ectopic expression of a neuronal receptor, metabotropic glutamate receptor 1 (Grm1), in melanocytes has been implicated in melanoma development in mouse models. The human relevance of this receptor's involvement in melanoma pathogenesis was shown by detecting GRM1 expression in subsets of human melanomas, an observation lacking in benign nevi or normal melanocytes. Grm1-transformed mouse melanocytes and a conditional Grm1 transgenic mouse model confirmed a requirement for sustained expression of Grm1 for the maintenance of transformed phenotypes in vitro and tumorigenicity in vivo. Here, we investigate if continued GRM1 expression is also required in human melanoma cell lines by using two inducible, silencing RNA systems: the ecdysone/Ponasterone A and tetracycline on/off approaches to regulate GRM1 expression in the presence of each inducer. Various in vitro assays were conducted to assess the consequences of a reduction in GRM1 expression on cell proliferation, apoptosis, downstream targeted signaling pathways, and in vivo tumorigenesis. We showed that suppression of GRM1 expression in several human melanoma cell lines resulted in a reduction in the number of viable cells and a decrease in stimulated mitogen-activated protein kinase (MAPK) and PI3K/AKT and suppressed tumor progression in vivo. These results reinforce earlier observations where a reduction in cell growth in vitro and tumorigenesis in vivo were correlated with decreased GRM1 activities by pharmacologic inhibitors of the receptor, supporting the notion that GRM1 plays a role in the maintenance of transformed phenotypes in human melanoma cells in vitro and in vivo and could be a potential therapeutic target for the treatment of melanoma. Mol Cancer Res; 10(11); 1440–50. ©2012 AACR.
RBM38 Is a Direct Transcriptional Target of E2F1 that Limits E2F1-Induced Proliferation
Authors: Feldstein Orit , Ben-Hamo Rotem , Bashari Dana , Efroni Sol , Ginsberg Doron 
Published: July 2012

Abstract
The E2F family of transcription factors plays a pivotal role in the regulation of cell proliferation in higher eukaryotes and is a critical downstream target of the tumor suppressor pRB. The pRB/E2F pathway is defective in most human tumors, resulting in deregulated E2F activity that induces uncontrolled cell proliferation, a hallmark of tumor cells.
The RNA-binding protein RBM38, also named RNPC1, induces cell-cycle arrest in G1, at least in part, via binding to and stabilizing the mRNA of the cyclin-dependent kinase inhibitor p21. RBM38 levels are altered in human cancer. Generally, RBM38 is overexpressed in various tumors; however, RBM38 mRNA levels are reduced in some breast tumors due to increased methylation of its promoter region.
We show here that expression of RBM38 is regulated by E2F1. Specifically, RBM38 mRNA and protein levels are elevated upon activation of either exogenous E2F1 or endogenous E2Fs. Moreover, endogenous E2F1 binds the human RBM38 promoter and E2F1 knockdown reduces RBM38 levels. Our data raise the possibility that E2F1 together with E2F1-regulated RBM38 constitute a negative feedback loop that modulates E2F1 activity. In support of this, inhibition of RBM38 expression increases E2F1-mediated cell-cycle progression. Moreover, in human ovarian cancer, high correlation between expression of E2F1 and RBM38 is associated with increased survival.
Overall, our data identify RBM38 as novel transcriptional target of E2F1 that restricts E2F1-induced proliferation. Furthermore, this negative feedback loop seems to restrict tumor aggressiveness, thereby promoting survival of patients with cancer. Mol Cancer Res; 10(9); 1169–77. ©2012 AACR.
Intima-Media Thickness of Brachial Artery, Vascular Function, and Cardiovascular Risk Factors
Authors: Iwamoto Yumiko , Maruhashi Tatsuya , Fujii Yuichi , Idei Naomi , Fujimura Noritaka , Mikami Shinsuke , Kajikawa Masato , Matsumoto Takeshi , Kihara Yasuki , Chayama Kazuaki , Noma Kensuke , Nakashima Ayumu , Higashi Yukihito 
Published: July 2012

Objective—
Cardiovascular diseases are associated with impaired flow-mediated vasodilation (FMD) and increase in carotid intima-media thickness (IMT). Both FMD and IMT are independent predictors for cardiovascular outcomes. When measuring FMD and nitroglycerine-induced vasodilation in the brachial artery, IMT can also be simultaneously assessed in the same brachial artery. The purpose of this study was to determine the relationships between IMT of the brachial artery, vascular function, and cardiovascular risk factors.

Methods and Results—

We measured brachial IMT, FMD, and nitroglycerine-induced vasodilation by ultrasound in 388 subjects who underwent health examination (mean age, 45±22 years; age range, 19–86), including patients with cardiovascular diseases. Univariate regression analysis revealed that brachial IMT significantly correlated with age (
r
=0.71;
P
<0.001), body mass index (
r
=0.27;
P
<0.001), systolic blood pressure (
r
=0.40;
P
<0.001), diastolic blood pressure (
r
=0.31;
P
<0.001), heart rate (
r
=0.15;
P
=0.002), glucose level (
r
=0.18;
P
=0.01), and smoking pack-years (
r
=0.42;
P
<0.001), as well as Framingham risk score, a cumulative cardiovascular risk index for heart attack (
r
=0.49;
P
<0.001). FMD and nitroglycerine-induced vasodilation were inversely associated with brachial IMT (
r
=−0.39,
P
<0.001;
r
=−0.32,
P
<0.001, respectively). In addition, there was a significant relationship between brachial IMT and carotid IMT (
r
=0.58;
P
<0.001). Multivariate analysis revealed that age, sex, hypertension, and brachial artery diameter were independent predictors of brachial IMT.

Conclusion—
These findings suggest that brachial IMT may be a marker of the grade of atherosclerosis and may be used as a marker of vascular function, providing additive information for stratifying subjects with cardiovascular risk factors.
Thrombomodulin Protects Endothelial Cells From a Calcineurin Inhibitor–Induced Cytotoxicity by Upregulation of Extracellular Signal–Regulated Kinase/Myeloid Leukemia Cell-1 Signaling
Authors: Ikezoe Takayuki , Yang Jing , Nishioka Chie , Honda Goichi , Furihata Mutsuo , Yokoyama Akihito 
Published: July 2012

Objective—
We have recently reported that recombinant human soluble thrombomodulin (rTM) counteracted capillary leakage associated with engraftment, as well as sinusoidal obstructive syndrome after hematopoietic stem cell transplantation. These observations prompted us to explore whether rTM possessed cytoprotective effects on endothelial cells.

Methods and Results—
Exposure of human umbilical vein endothelial cells to rTM induced expression of antiapoptotic protein myeloid leukemia cell-1 through the activation of extracellular signal–regulated kinase in these cells. Additional studies found that exposure of human umbilical vein endothelial cells to cyclosporine A and FK506, an immunosuppressant used for the individuals receiving hematopoietic stem cell transplantation, induced apoptosis, which was attenuated when human umbilical vein endothelial cells were exposed to these agents in the presence of rTM. Further studies using deletion mutants of thrombomodulin (TM) identified that the epidermal growth factor domain of TM possessed cytoprotective effects. A single nucleotide substitution at codon 376 or 424 of TM, which impairs the ability of TM to produce activated protein C or bind to thrombin, respectively, did not hamper the cytoprotective effects of TM, which suggested that cytoprotective effects of rTM were distinctive from those of activated protein C.

Conclusion—
TM may be useful for prevention, as well as treatment of endothelial cell damage after hematopoietic stem cell transplantation.
Mineralocorticoid Receptor Antagonists and Cardiovascular Mortality in Patients With Atrial Fibrillation and Left Ventricular Dysfunction
Authors: O’Meara Eileen , Khairy Paul , Blanchet Malorie Chabot , de Denus Simon , Pedersen Ole D. , Levesque Sylvie , Talajic Mario , Ducharme Anique , White Michel , Racine Normand , Rouleau Jean-Lucien , Tardif Jean-Claude , Roy Denis ,   and for the AF-CHF investigators
Published: July 2012

Background—
Patients with heart failure (HF) and atrial fibrillation (AF) may differ from the larger HF population with respect to comorbidities, including renal impairment and overall prognosis. Associated cardiorenal interactions may mitigate the effects of pharmacological agents. Our primary objective was to assess the impact of mineralocorticoid receptor antagonists on cardiovascular mortality in patients with AF and HF enrolled in the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial.

Methods and Results—

All 1376 patients randomized in the AF-CHF trial were included. The median baseline creatinine was 105.2 (Q1 88.4, Q3 125.0) μmol/L, and the median estimated glomerular filtration rate was 62.3 (Q1 49.0, Q3 77.2) mL/min per 1.73 m
2
. The renal function was moderately or severely impaired (ie, estimated glomerular filtration rate <60 mL/min per 1.73 m
2
) in 46.5% of patients. In multivariable analyses, increased creatinine was associated with worsening HF but not mortality. Mineralocorticoid receptor antagonists were prescribed in 44.8% and were independently associated with a 1.4-fold increase in total mortality (hazard ratio, 1.4; 95% CI [1.1–1.8];
P
=0.005) and a 1.4-fold increase in cardiovascular mortality (hazard ratio, 1.4; 95% CI [1.1–1.9];
P
=0.009). This was driven by an increased incidence of sudden cardiac death (hazard ratio, 2.0; 95% CI [1.3, 3.0];
P
=0.001).

Conclusions—
Renal dysfunction was highly prevalent in patients with AF and HF. Mineralocorticoid receptor antagonists were independently associated with an increased incidence of cardiovascular deaths, predominantly of presumed arrhythmic cause. Although these provocative findings merit prospective validation, they underscore the importance of careful monitoring of renal function and electrolytes in patients with AF and HF receiving mineralocorticoid receptor antagonists.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00597077.
Hemodynamic, Hormonal, and Renal Effects of (Pro)Renin Receptor Blockade in Experimental Heart Failure
Authors: Rademaker Miriam T. , Yandle Tim G. , Ellmers Leigh J. , Charles Christopher J. , Nicholls M. Gary , Richards A. Mark 
Published: July 2012

Background—
The (pro)renin receptor (P)RR is implicated in blood pressure regulation and the pathophysiology of heart failure (HF). The effects of (P)RR blockade in HF have not been previously investigated.

Methods and Results—

Eight sheep received on 2 separate days a vehicle control and incremental intravenous boluses of a (P)RR antagonist, ovine handle region peptide (HRP) (1, 5, and 25 mg at 90-minute intervals), both before (normal) and after induction of HF by rapid left ventricular pacing. In normal sheep, HRP reduced heart rate (
P
<0.001) and hematocrit (
P
=0.019) compared with time-matched control data, without significantly affecting any other hemodynamic, hormonal, or renal variables. In sheep with HF, HRP treatment induced progressive falls in mean arterial pressure (
P
<0.001) in association with decreases in left atrial pressure (
P
<0.001), peripheral resistance (
P
=0.014), and hematocrit (
P
<0.001). Cardiac contractility tended to decline (
P
=0.096), whereas cardiac output was unaltered. HRP administration produced a dose-dependent decrease in plasma renin activity (
P
=0.004), with similar trends observed for plasma angiotensin II and aldosterone (
P
=0.093 and
P
=0.088, respectively). Circulating natriuretic peptides, endothelin-1, and catecholamine levels were unchanged. HRP also induced a reduction in plasma sodium concentrations relative to control (
P
=0.024), a natriuresis (
P
=0.046), and a tendency for creatinine excretion and clearance to improve.

Conclusions—
(P)RR antagonism in experimental HF resulted in cardiovascular and renal benefits in association with inhibition of the renin-angiotensin-aldosterone system. These findings suggest that (P)RR contributes to pressure/volume regulation in HF and identifies the receptor as a potential therapeutic target in this disease.
Evaluation of Aortic Valve Stenosis Using Cardiovascular Magnetic Resonance
Authors: Defrance Carine , Bollache Emilie , Kachenoura Nadjia , Perdrix Ludivine , Hrynchyshyn Nataliya , Bruguière Eric , Redheuil Alban , Diebold Benoit , Mousseaux Elie 
Published: July 2012

Background—
Accurate quantification of aortic valve stenosis (AVS) is needed for relevant management decisions. However, transthoracic Doppler echocardiography (TTE) remains inconclusive in a significant number of patients. Previous studies demonstrated the usefulness of phase-contrast cardiovascular magnetic resonance (PC-CMR) in noninvasive AVS evaluation. We hypothesized that semiautomated analysis of aortic hemodynamics from PC-CMR might provide reproducible and accurate evaluation of aortic valve area (AVA), aortic velocities, and gradients in agreement with TTE.

Methods and Results—

We studied 53 AVS patients (AVA
TTE
=0.87±0.44 cm
2
) and 21 controls (AVA
TTE
=2.96±0.59 cm
2
) who had TTE and PC-CMR of aortic valve and left ventricular outflow tract on the same day. PC-CMR data analysis included left ventricular outflow tract and aortic valve segmentation, and extraction of velocities, gradients, and flow rates. Three AVA measures were performed: AVA
CMR1
based on Hakki formula, AVA
CMR2
based on continuity equation, AVA
CMR3
simplified continuity equation=left ventricular outflow tract peak flow rate/aortic peak velocity. Our analysis was reproducible, as reflected by low interoperator variability (<4.56±4.40%). Comparison of PC-CMR and TTE aortic peak velocities and mean gradients resulted in good agreement (
r
=0.92 with mean bias=−29±62 cm/s and
r
=0.86 with mean bias=−12±15 mm Hg, respectively). Although good agreement was found between TTE and continuity equation–based CMR-AVA (
r
>0.94 and mean bias=−0.01±0.38 cm
2
for AVA
CMR2
, −0.09±0.28 cm
2
for AVA
CMR3
), AVA
CMR1
values were lower than AVA
TTE
especially for higher AVA (mean bias=−0.45±0.52 cm
2
). Besides, ability of PC-CMR to detect severe AVS, defined by TTE, provided the best results for continuity equation–based methods (accuracy >94%).

Conclusions—
Our PC-CMR semiautomated AVS evaluation provided reproducible measurements that accurately detected severe AVS and were in good agreement with TTE.