bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational assessment of drug‐induced effects on the electrocardiogram: from ion channel to body surface potentials
Authors: Zemzemi Nejib , Bernabeu Miguel O , Saiz Javier , Cooper Jonathan , Pathmanathan Pras , Mirams Gary R , Pitt‐Francis Joe , Rodriguez Blanca 
Published: September 2012

Background and PurposeUnderstanding drug effects on the heart is key to safety pharmacology assessment and anti‐arrhythmic therapy development. Here our goal is to demonstrate the ability of computational models to simulate the effect of drug action on the electrical activity of the heart, at the level of the ion‐channel, cell, heart and ECG body surface potential.Experimental ApproachWe use the state‐of‐the‐art mathematical models governing the electrical activity of the heart. A drug model is introduced using an ion channel conductance block for the hERG and fast sodium channels, depending on the IC50 value and the drug dose. We simulate the ECG measurements at the body surface and compare biomarkers under different drug actions.Key ResultsIntroducing a 50% hERG‐channel current block results in 8% prolongation of the APD90 and 6% QT interval prolongation, hERG block does not affect the QRS interval. Introducing 50% fast sodium current block prolongs the QRS and the QT intervals by 12% and 5% respectively, and delays activation times, whereas APD90 is not affected.Conclusions and ImplicationsBoth potassium and sodium blocks prolong the QT interval, but the underlying mechanism is different: for potassium it is due to APD prolongation; while for sodium it is due to a reduction of electrical wave velocity. This study shows the applicability of in silico models for the investigation of drug effects on the heart, from the ion channel to the ECG‐based biomarkers.
Correlates of dementia attitudes in a sample of middle‐aged Australian adults
Authors: Phillipson Lyn , Magee Christopher A , Jones Sandra C , Skladzien Ellen 
Published: September 2012

AimsTo examine sociodemographic factors associated with attitudes regarding dementia.MethodA cross‐sectional, convenience sample of 616 adults aged 40–65 years completed an online survey examining sociodemographic factors and dementia attitudes. The associations between sociodemographic variables and dementia attitudes were examined using general linear modelling.ResultsFour attitudinal factors were identified. Three were associated with negative attitudes (Personal Avoidance, Fear of Labelling and Fear of Discrimination) and one with more positive attitudes (Person Centredness). Demographic factors (e.g. age, sex, education) were significantly associated with some attitudinal factors. For example, men (P = 0.001) and individuals with lower education levels (P = 0.03) had higher scores on the Personal Avoidance factor.ConclusionsThis study is the first to examine correlates of attitudes towards dementia in an Australian sample. Future research could improve understanding of distinct factors associated with dementia and lead to strategies to reduce stigmatised views of people with dementia in the community.
Chest radiographic appearances in adult inpatients admitted with swine flu infection: Local experience in Melbourne
Authors: Pirakalathanan Janu , Lau Kenneth K , Joosten Simon A 
Published: September 2012

AbstractIntroductionThe influenza A virus (H1N1) pandemic began in Mexico in March 2009. As of July 2009, there were 5298 reported cases in Australia including 10 deaths. The aim of this review is to demonstrate the local chest radiographic findings in adult inpatients with proven H1N1, to assess the radiological disease progression and resolution, and to evaluate whether the severity of chest X‐rays findings had a bearing on the length of admission and need for intensive care admission.MethodsEleven H1N1 patients (5 males and 6 females, mean age of 36), presenting with cough (64%), fever (55%) and shortness of breath (55%), were admitted to our hospital between 13 August and 1 November 2010. Details of radiographic features, risk factors, clinical course including length of stay, doubling time of consolidation and time for 50% resolution of consolidation were recorded and analysed.ResultsSeventy‐three per cent of our patients presented with bilateral mid and/or lower zone alveolar consolidation. One patient with underlying cystic fibrosis had only bilateral upper zone consolidation. No pleural effusion, lymphadenopathy or cardiomegaly was noted on any of the plain chest radiographs. The mean doubling time of consolidation was 1.5 days. The mean time for 50% resolution of consolidation after antiviral treatment was 10.5 days. The average length of stay in hospital was 22 days. Ninety‐one per cent of our patients required intensive‐care unit admission with 50% of those requiring intubation.ConclusionRapid progression of bilateral mid and lower zone air‐space opacities in relatively young unwell patients, with lack of pleural effusion, pericardial effusion or lymphadenopathy on plain radiographs, should raise the clinical suspicion of H1N1 infection. Patients requiring hospital admission usually show slow clinical and radiological improvement, and require prolonged hospital stays.
Investigation into Causes of Abnormal Cerebral MRI Findings Following PVAC Duty‐Cycled, Phased RF Ablation of Atrial Fibrillation
Authors: WIECZOREK MARCUS , LUKAT MICHAEL , HOELTGEN REINHARD , CONDIE CATHY , HILJE THOMAS , MISSLER ULRICH , HIRSCH JESSICA , SCHARF CHRISTOPH 
Published: September 2012

Asymptomatic Cerebral Lesions with Phased RF. Introduction: Left atrial catheter ablation of the pulmonary veins (PVs) is an established option for patients with atrial fibrillation (AF). Asymptomatic cerebral emboli (ACE) detected by diffusion weighted MRI (DW‐MRI) following AF ablation has been reported at varying rates. This variability may be linked to procedural variables and demographic risk factors. Animal studies with the multielectrode pulmonary vein ablation catheter (PVAC) have identified potential sources of emboli, including air introduced during PVAC introduction, inadequate anticoagulation, and high current densities when the distal (E1) and proximal (E10) electrodes are in contact. We sought to evaluate the incidence, size, and number of DW‐MRI findings with procedural modifications that potentially reduce the embolic load.Methods: Thirty‐seven AF patients (59 ± 10 years, 73% male, all with paroxysmal AF, left atrial [LA] diameter 44 ± 7 mm, left ventricular ejection fraction 57 ± 7%) underwent MRI sequences preceding ablation, within 24 hours postablation, and at 4–6 weeks. During the procedure all patients were on uninterrupted phenprocoumon, an attempted activated clotting time (ACT) level >300 seconds, had the PVAC introduced under saline, and antral ablation was started with a 2:1 bipolar/unipolar mode. Files from the ablation unit (GENius v14.4) were retrospectively analyzed to determine the relationship between E1 and E10 in close proximity and DW‐MRI findings.Results: Post procedure, 10/37 patients (27%) were positive for new DWI cerebral lesions. Nine of 10 patients had a single lesion, and 1/10 patient had 2 lesions. Average lesion size was 3.1 ± 3.9 mm (2–14 mm). One of 10 (10%) had lesions at MRI follow‐up. No neurological symptoms were observed. Eighteen of 37 (49%) of procedures had evidence of E1/E10 interaction. In the subgroup of patients with and without E1 and E10 in close proximity, the DW‐MRI rate was 8/18 (44%) and 2/19 (11%), respectively (P = 0.029).Conclusions: The source of positive DW‐MRI findings in LA ablation involves several factors. Controlling anticoagulation and careful sheath management helps to reduce the number and size of DW‐MRI lesions. With the PVAC catheter, an ablation with the E1 and E10 in close proximity increases the risk of a DW‐MRI finding. In the future, electrodes E1 and E10 should be kept apart to help reduce the incidence of acute ACE. (J Cardiovasc Electrophysiol, Vol. 24, pp. 121‐128, February 2013)
Investigation of L‐type Ca2+ current in the aganglionic bowel segment in Hirschsprung’s disease
Authors: Large R. J. , Bradley E. , Webb T. , O’Donnell A. M. , Puri P. , Hollywood M. A. , Thornbury K. D. , McHale N. G. , Sergeant G. P. 
Published: September 2012

AbstractBackground  Studies on animal models of Hirschsprung’s disease (HD) suggest that L‐type Ca2+ channels are down‐regulated in the aganglionic bowel segment, however, this has yet to be confirmed in HD patients. The objective of this study was to test the hypothesis that L‐type Ca2+ current density is decreased in smooth muscle cells (SMC) obtained from the aganglionic bowel segment of patients with HD in comparison with those from the ganglionic segment.Methods  Smooth muscle cells were freshly isolated from colon samples obtained from HD patients undergoing pull‐through surgery. L‐type Ca2+ currents were recorded using the perforated patch configuration of the whole cell voltage clamp technique and the expression levels of CACNA1C transcripts (which encode L‐type Ca2+ channels) in the ganglionic and aganglionic bowel segments were compared using real‐time quantitative PCR.Key Results  All SMC displayed robust currents that had activation/inactivation kinetics typical of L‐type Ca2+ current, were inhibited by nifedipine and enhanced by the L‐type Ca2+ channel agonists FPL 64176 and Bay K 8644. Moreover, FPL 64176 activated currents were also inhibited by nifedipine. However, there was no significant difference in L‐type Ca2+ current density, CACNA1C subunit expression or sensitivity to the pharmacological agents noted above, between SMC isolated from the ganglionic and aganglionic regions of the HD colon.Conclusions & Inferences  In contrast to studies on genetic animal models of HD, L‐type Ca2+ currents are not down‐regulated in the aganglionic bowel segment of HD patients and are therefore unlikely to account for the impaired colonic peristalsis observed in these patients.
Contribution of Selected Gene Mutations to Resistance in Clinical Isolates of Vancomycin-Intermediate Staphylococcus aureus
Authors: Hafer Cory , Lin Ying , Kornblum John , Lowy Franklin D. , Uhlemann Anne-Catrin 
Published: September 2012

ABSTRACT

Infections with vancomycin-intermediate
Staphylococcus aureus
(VISA) have been associated with vancomycin treatment failures and poor clinical outcomes. Routine identification of clinical isolates with increased vancomycin MICs remains challenging, and no molecular marker exists to aid in diagnosis of VISA strains. We tested vancomycin susceptibilities by using microscan, Etest, and population analyses in a collection of putative VISA, methicillin-resistant
S. aureus
, and methicillin-sensitive
S. aureus
(VSSA) infectious isolates from community- or hospital-associated
S. aureus
infections (
n
= 77) and identified 22 VISA and 9 heterogeneous VISA (hVISA) isolates. Sequencing of VISA candidate loci
vraS
,
vraR
,
yvqF
,
graR
,
graS
,
walR
,
walK
, and
rpoB
revealed a high diversity of nonsynonymous single-nucleotide polymorphisms (SNPs). For
vraS
,
vraR
,
yvqF
,
walK
, and
rpoB
, SNPs were more frequently present in VISA and hVISA than in VSSA isolates, whereas mutations in
graR
,
graS
, and
walR
were exclusively detected in VISA isolates. For each of the individual loci, SNPs were only detected in about half of the VISA isolates. All but one VISA isolate had at least one SNP in any of the genes sequenced, and isolates with an MIC of 6 or 8 μg/ml harbored at least 2 SNPs. Overall, increasing vancomycin MICs were paralleled by a higher proportion of isolates with SNPs. Depending on the clonal background, SNPs appeared to preferentially accumulate in
vraS
and
vraR
for sequence type 8 (ST8) and in
walK
and
walR
for ST5 isolates. Taken together, by comparing VISA, hVISA, and VSSA controls, we observed preferential clustering of SNPs in VISA candidate genes, with an unexpectedly high diversity across these loci. Our results support a polygenetic etiology of VISA.
Structural and Functional Properties of Staphylococcal Superantigen-Like Protein 4
Authors: Hermans Stefan J. , Baker Heather M. , Sequeira Richard P. , Langley Ries J. , Baker Edward N. , Fraser John D. 
Published: September 2012

ABSTRACT

Staphylococcus aureus
is a prevalent and significant human pathogen. Among the repertoire of virulence factors produced by this bacterium are the 14 staphylococcal superantigen-like (SSL) proteins. SSL protein 4 (SSL4) is one member of this family and contains a highly conserved carbohydrate binding site also found in SSL2, SSL3, SSL5, SSL6, and SSL11. Recombinant SSL4
t
, comprising amino acids 109 to 309 of Newman strain SSL4 (SSL4-Newman), has been shown to bind and be internalized by human granulocytes and macrophages in a sialic-acid (Sia)-dependent manner. SSL4
t
can compete with itself for cell binding, indicating that binding is target specific. A 2.5-Å-resolution crystal structure of SSL4
t
complexed with sialyl Lewis X (sLe
x
) [sLe
x
-Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc] revealed a similar binding site to SSL5 and SSL11. These data, along with data on SSL4
t
binding to a glycan array and biosensor analysis of sLe
x
and sialyllactosamine (sLacNac) binding are compared with those for SSL11. Although these proteins show great similarity in their carbohydrate binding sites, with a root mean square (RMS) difference between main chain atom positions of only 0.34 Å, these proteins differ in detail in their affinity for sLe
x
and sLacNac, as well as their glycan preference. Together with cell binding data, this shows how
S. aureus
produces multiple related proteins that target myeloid cells through specific sialyllactosamine-containing glycoproteins.
A Synthetic Matrix with Independently Tunable Biochemistry and Mechanical Properties to Study Epithelial Morphogenesis and EMT in a Lung Adenocarcinoma Model
Authors: Gill Bartley J. , Gibbons Don L. , Roudsari Laila C. , Saik Jennifer E. , Rizvi Zain H. , Roybal Jonathon D. , Kurie Jonathan M. , West Jennifer L. 
Published: September 2012

Abstract
Better understanding of the biophysical and biochemical cues of the tumor extracellular matrix environment that influence metastasis may have important implications for new cancer therapeutics. Initial exploration into this question has used naturally derived protein matrices that suffer from variability, poor control over matrix biochemistry, and inability to modify the matrix biochemistry and mechanics. Here, we report the use of a synthetic polymer-based scaffold composed primarily of poly(ethylene glycol), or PEG, modified with bioactive peptides to study murine models of lung adenocarcinoma. In this study, we focus on matrix-derived influences on epithelial morphogenesis of a metastatic cell line (344SQ) that harbors mutations in Kras and p53 (trp53) and is prone to a microRNA-200 (miR-200)–dependent epithelial–mesenchymal transition (EMT) and metastasis. The modified PEG hydrogels feature biospecific cell adhesion and cell-mediated proteolytic degradation with independently adjustable matrix stiffness. 344SQ encapsulated in bioactive peptide-modified, matrix metalloproteinase–degradable PEG hydrogels formed lumenized epithelial spheres comparable to that seen with three-dimensional culture in Matrigel. Altering both matrix stiffness and the concentration of cell-adhesive ligand significantly influenced epithelial morphogenesis as manifest by differences in the extent of lumenization, in patterns of intrasphere apoptosis and proliferation, and in expression of epithelial polarity markers. Regardless of matrix composition, exposure to TGF-β induced a loss of epithelial morphologic features, shift in expression of EMT marker genes, and decrease in mir-200 levels consistent with EMT. Our findings help illuminate matrix-derived cues that influence epithelial morphogenesis and highlight the potential utility that this synthetic matrix-mimetic tool has for cancer biology. Cancer Res; 72(22); 6013–23. ©2012 AACR.
Hospital Variation in Readmission After Coronary Artery Bypass Surgery in California
Authors: Li Zhongmin , Amstrong Ehrin J. , Parker Joseph P. , Danielsen Beate , Romano Patrick S. 
Published: September 2012

Background—
Readmissions are common after coronary artery bypass grafting (CABG) surgery and account for a significant percentage of hospital healthcare costs. Readmission rates also vary widely between hospitals, but the reasons for this variation have not been studied previously.

Methods and Results—

We linked 2009 California CABG clinical registry data to hospital discharge data for 2009 and 2010 to identify 30-day readmissions for all patients undergoing isolated CABG surgery. Both standard and hierarchical logistic models were developed to predict readmission risk and explore sources of hospital readmission variation. Among 11 823 patients discharged alive after isolated CABG in 2009, 1565 (13.2%) patients were readmitted within 30 days of surgery. Heart failure and postoperative infections were the most frequent reasons for readmission (15.3% and 12.9%, respectively). Multiple patient risk factors, including age, sex, and lower zip code-level median household income, were significant predictors of readmission (all adjusted odds ratios >1.0;
P
<0.05). The readmission rates among the 119 hospitals performing CABG varied from 0% to 26.9%. Compared with hospitals in lower quartiles for readmission, hospitals in higher quartiles had a significantly higher readmission rates due to circulatory diseases, infections, complications for surgical and medical care and digestive diseases (all
P
<0.05). In a hierarchical model, including several hospital characteristics, hospital-level variables did not predict readmission risk (all
P
>0.05, with an intraclass correlation of 0.004 for hospitals).

Conclusions—
California hospitals performing CABG surgery vary widely in 30-day readmission rates. Patient demographic and clinical risk factors, rather than measured hospital characteristics, accounted for most of the observed hospital-level variation in CABG readmissions.
How Are Household Economic Circumstances Affected After a Stroke? The Psychosocial Outcomes In StrokE (POISE) Study
Authors: Essue Beverley M. , Hackett Maree L. , Li Qiang , Glozier Nick , Lindley Richard , Jan Stephen 
Published: September 2012

Background and Purpose—
Stroke is associated with severe economic consequences. This is the first study to investigate in younger survivors the household economic burden of stroke.

Methods—
A multicenter, 3-year prospective cohort study was conducted of younger (18–65 years) survivors in Australia. Pre- and poststroke patterns of income and hardship were evaluated and multivariable logistic regression identified the predictors of economic hardship after stroke.

Results—
Four hundred fourteen participants were followed up over 12 months after stroke. The variables that independently predicted economic hardship after stroke were: female (OR, 2.94; 95% CI, 1.52–5.70), hazardous alcohol consumption (OR, 2.28; 95% CI, 1.00–5.20), manual occupation (OR, 1.88; 95% CI, 1.07–3.30), lack of health insurance (OR, 2.01; 95% CI, 1.12–3.60), and prior hardship (OR, 3.93; 95% CI, 2.12–7.29), whereas concessional status (OR, 0.50; 95% CI, 0.26–0.95) and more social contacts per week (OR, 0.99; 95% CI, 0.98–1.00) reduced hardship likelihood.

Conclusions—
Higher prestroke income did not buffer hardship after stroke nor did clinical, health service, or disability factors. Policies to reduce inequalities after stroke would be best aimed at socioeconomic targets.
Changing choices: disabled and chronically ill people’s experiences of reconsidering choices
Authors: Baxter Kate 
Published: September 2012

Objectives: To increase understanding of disabled and chronically ill people’s experiences of revisiting choices by considering events that prompted people to reconsider choices; what factors motivated them to act upon these events and what factors affected their experiences of revisiting choices. Methods: A sub-sample of 20 disabled and chronically ill people who took part in a qualitative, longitudinal study exploring choice-making in the context of changing circumstances. Each person was interviewed three times. Analysis focussed on choices that people had been prompted to revisit. Results: Most choices were about health or social care and were revisited within a year due to: changes in health or social circumstances; poorer than expected outcomes; and external interventions. People were motivated to make changes by a desire to maintain independence and control, but perceived short-term costs of decision-making could act as a deterrent. Experiences of revisiting choices were affected by help from other people and emotional strength. Discussion: Making and revisiting choices is complex; people need support to engage with the continual cycle of choice-making. People who instigate revisions of their own accord may be particularly vulnerable to lack of support.
High molecular mass proteomics analyses of left ventricle from rats subjected to differential swimming training
Authors: Rocha Luiz A O , Petriz Bernardo A , Borges David H , Oliveira Ricardo J , de Andrade Rosangela V , Domont Gilberto B , Pereira Rinaldo W , Franco Octávio L 
Published: September 2012

Abstract

Background
Regular exercises are commonly described as an important factor in health improvement, being directly related to contractile force development in cardiac cells.
In order to evaluate the links between swimming exercise intensity and cardiac adaptation by using high molecular mass proteomics, isogenic Wistar rats were divided into four groups: one control (CG) and three training groups (TG’s), with low, moderate and high intensity of exercises.
In order to evaluate the links between swimming exercise intensity and cardiac adaptation by using high molecular mass proteomics, isogenic Wistar rats were divided into four groups: one control (CG) and three training groups (TG’s), with low, moderate and high intensity of exercises.

Results
Findings here reported demonstrated clear morphologic alterations, significant cellular injury and increased energy supplies at high exercise intensities. α-MyHC, as well proteins associated with mitochondrial oxidative metabolism were shown to be improved. α-MyHC expression increase 1.2 fold in high intensity training group when compared with control group. α-MyHC was also evaluated by real-time PCR showing a clear expression correlation with protein synthesis data increase in 8.48 fold in high intensity training group. Other myofibrillar protein, troponin , appear only in high intensity group, corroborating the cellular injury data. High molecular masses proteins such as MRS2 and NADH dehydrogenase, involved in metabolic pathways also demonstrate increase expression, respectily 1.5 and 1.3 fold, in response to high intensity exercise.

Conclusions
High intensity exercise demonstrated an increase expression in some high molecular masses myofibrilar proteins, α-MyHC and troponin. Furthermore this intensity also lead a significant increase of other high molecular masses proteins such as MRS2 and NADH dehydrogenase in comparison to low and moderate intensities. However, high intensity exercise also represented a significant degree of cellular injury, when compared with the individuals submitted to low and moderate intensities.