bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation
Authors: Baczko Istvan , Liknes David , Yang Wei , Hamming Kevin C , Searle Gavin , Jaeger Kristian , Husti Zoltan , Juhasz Viktor , Klausz Gergely , Pap Robert , Saghy Laszlo , Varro Andras , Dolinsky Vernon , Wang Shaohua , Rauniyar Vivek , Hall Dennis , Dyck Jason RB , Light Peter E
Published: October 2013

Background and Purpose

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk for stroke, heart failure and cardiovascular‐related mortality. Candidate targets for anti‐AF drugs include a potassium channel Kv1.5, and the ionic currents IKACh and late INa, along with increased oxidative stress and activation of NFAT‐mediated gene transcription. As pharmacological management of AF is currently suboptimal, we have designed and characterized a multifunctional small molecule, compound 1 (C1), to target these ion channels and pathways.

Experimental Approach

We made whole‐cell patch‐clamp recordings of recombinant ion channels, human atrial IKur, rat atrial IKACh, cellular recordings of contractility and calcium transient measurements in tsA201 cells, human atrial samples and rat myocytes. We also used a model of inducible AF in dogs.

Key Results

C1 inhibited human peak and late Kv1.5 currents, frequency‐dependently, with IC50 of 0.36 and 0.11 μmol·L−1 respectively. C1 inhibited IKACh (IC50 of 1.9 μmol·L−1) and the Nav1.5 sodium channel current (IC50s of 3 and 1 μmol·L−1 for peak and late components respectively). C1 (1 μmol·L−1) significantly delayed contractile and calcium dysfunction in rat ventricular myocytes treated with 3 nmol·L−1 sea anemone toxin (ATX‐II). C1 weakly inhibited the hERG channel and maintained antioxidant and NFAT‐inhibitory properties comparable to the parent molecule, resveratrol. In a model of inducible AF in conscious dogs, C1 (1 mg·kg−1) reduced the average and total AF duration.

Conclusion and Implications

C1 behaved as a promising multifunctional small molecule targeting a number of key pathways involved in AF.
Parsing the players: 2‐arachidonoylglycerol synthesis and degradation in the CNS
Authors: Murataeva N , Straiker A , Mackie K
Published: October 2013

The endogenous cannabinoid signalling system, composed of endogenous cannabinoids, cannabinoid receptors and the enzymes that synthesize and degrade the endogenous cannabinoids, is much more complex than initially conceptualized. 2‐Arachidonoylglycerol (2‐AG) is the most abundant endocannabinoid and plays a major role in CNS development and synaptic plasticity. Over the past decade, many key players in 2‐AG synthesis and degradation have been identified and characterized. Most 2‐AG is synthesized from membrane phospholipids via sequential activation of a phospholipase Cβ and a diacylglycerol lipase, although other pathways may contribute in specialized settings. 2‐AG breakdown is more complicated with at least eight different enzymes participating. These enzymes can either degrade 2‐AG into its components, arachidonic acid and glycerol, or transform 2‐AG into highly bioactive signal molecules. The implications of the precise temporal and spatial control of the expression and function of these pleiotropic metabolizing enzymes have only recently come to be appreciated. In this review, we will focus on the primary organization of the synthetic and degradative pathways of 2‐AG and then discuss more recent findings and their implications, with an eye towards the biological and therapeutic implications of manipulating 2‐AG synthesis and metabolism.

Linked Articles

This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐6
Transient receptor potential (TRP) channels: a clinical perspective
Authors: Kaneko Yosuke , Szallasi Arpad
Published: October 2013

Transient receptor potential (TRP) channels are important mediators of sensory signals with marked effects on cellular functions and signalling pathways. Indeed, mutations in genes encoding TRP channels are the cause of several inherited diseases in humans (the so‐called ‘TRP channelopathies’) that affect the cardiovascular, renal, skeletal and nervous systems. TRP channels are also promising targets for drug discovery. The initial focus of research was on TRP channels that are expressed on nociceptive neurons. Indeed, a number of potent, small‐molecule TRPV1, TRPV3 and TRPA1 antagonists have already entered clinical trials as novel analgesic agents. There has been a recent upsurge in the amount of work that expands TRP channel drug discovery efforts into new disease areas such as asthma, cancer, anxiety, cardiac hypertrophy, as well as obesity and metabolic disorders. A better understanding of TRP channel functions in health and disease should lead to the discovery of first‐in‐class drugs for these intractable diseases. With this review, we hope to capture the current state of this rapidly expanding and changing field.

Linked Articles

This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐10
Podoplanin is expressed at the invasive front of esophageal squamous cell carcinomas and is involved in collective cell invasion
Authors: Nakashima Yuichiro , Yoshinaga Keiji , Kitao Hiroyuki , Ando Koji , Kimura Yasue , Saeki Hiroshi , Oki Eiji , Morita Masaru , Kakeji Yoshihiro , Hirahashi Minako , Oda Yoshinao , Maehara Yoshihiko
Published: October 2013

The expression of podoplanin is reportedly involved in collective cell invasion, which is independent from the epithelial–mesenchymal transition (EMT). We focused on the expression of podoplanin in esophageal squamous cell carcinomas (ESCC) and investigated the correlation of podoplanin and EMT‐related markers, and evaluated its prognostic significance. Five ESCC cell lines were subjected to western blot analysis for podoplanin and EMT markers. The effects of podoplanin on EMT and carcinoma invasion were evaluated with wound healing assays, invasion assays and 3‐D culture. Transfection of ectopic podoplanin into a podoplanin‐negative ESCC cell line (TE‐15) induced cell migration and invasive activity (P < 0.001 and P < 0.05, respectively) without downregulation of E‐cadherin. In contrast, transfection of si‐podoplanin RNA into a podoplanin‐positive ESCC cell line (TE‐13) reduced cell migration and invasive activity (P < 0.05). We reviewed 101 patients who had undergone esophagectomy for ESCC. Podoplanin expression was observed in 58 patients (57.4%), and positive expression was positively correlated with expression of E‐cadherin (P < 0.01), deeper wall invasion (P < 0.01), venous invasion (P < 0.05) and poorer prognosis (P < 0.01). Multivariate Cox analysis revealed that expression of podoplanin was a significant and independent unfavorable predictor of survival (P < 0.05). These data suggest that podoplanin is significantly associated with and likely contributes to ESCC invasion in the absence of EMT.
Barriers of delivering oral health care to older people experienced by dentists: a systematic literature review
Authors: Bots‐VantSpijker Pieternella C. , Vanobbergen Jacques N.O. , Schols Jos M.G.A. , Schaub Rob M.H. , Bots Casper P. , de Baat Cees
Published: October 2013

Objective

To identify barriers of delivering oral health care to older people experienced by dentists.

Methods

A comprehensive literature search was carried out for studies published in the period January 1990–December 2011, using free text and MESH term search strategies for PubMed (Medline), EMBASE and CINAHL.

Results

The initial search identified 236 potentially relevant publications: PubMed (Medline; n = 127), EMBASE (n = 108) and CINAHL (n = 1). After screening of titles and abstracts, 14 publications were revealed as relevant for further review. Seven articles, focusing on dentists delivering oral health care to older people in care homes, were suitable for this review, and seven articles did not meet the previously determined quality criteria. One of these articles also focused on barriers experienced by dentists working in their own practice and delivering oral health care to community‐dwelling older people.

Conclusions

The most common barriers of delivering oral health care to older people were identified respectively as: the lack of adequate equipment in a care home and no area for treatment available (n = 4) and the lack of adequate reimbursement for working in a care home (n = 5). In addition, the inadequate training and experience in delivering oral health care to older care home residents (n = 2) were mentioned. Four publications indicated the loss of time from private practice as a barrier to deliver oral health care in a care home. We suggest that additional research should be initiated to investigate more in detail the barriers dentists experience in delivering oral health care to older people in their own dental practices.
“The Cake and Custard is Good!” A Qualitative Study of Teenage Childrens' Experience of being in Prison
Authors: Holligan Chris
Published: October 2013

This qualitative study aims to uncover how young people, sentenced for violent offences, experience prison, something about which we know very little. It reports life history data from qualitative interviews with young male inmates aged 16–18 years convicted of violent assault. The findings indicate that the intrusive and inescapable challenges of incarceration are filtered through the boys' interpretations of previous critical incidents in their lives, in a way that can, it is argued, cause them additional harm. Respecting and attempting to understand the complex experiences of the participants, listening to the voices of these children, may help us to understand why a prison sentence seems to have limited impact on recidivism.
Alveolar Ridge and Maxillary Sinus Augmentation Using rhBMP‐2: A Systematic Review
Authors: de Freitas Rubens Moreno , Spin‐Neto Rubens , Junior Elcio Marcantonio , Pereira Luís Antônio Violin Dias , Wikesjö Ulf ME , Susin Cristiano
Published: October 2013

Purpose

The aim of this systematic review was to evaluate clinical and safety data for recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in an absorbable collagen sponge (ACS) carrier when used for alveolar ridge/maxillary sinus augmentation in humans.

Materials and Methods

Clinical studies/case series published 1980 through June 2012 using rhBMP‐2/ACS were searched. Studies meeting the following criteria were considered eligible for inclusion: >10 subjects at baseline and maxillary sinus or alveolar ridge augmentation not concomitant with implant placement.

Results

Seven of 69 publications were eligible for review. rhBMP‐2/ACS yielded clinically meaningful bone formation for maxillary sinus augmentation that would allow placement of regular dental implants without consistent differences between rhBMP‐2 concentrations. Nevertheless, the statistical analysis showed that sinus augmentation following autogenous bone graft was significantly greater (mean bone height: 1.6 mm, 95% CI: 0.5–2.7 mm) than for rhBMP‐2/ACS (rhBMP‐2 at 1.5 mg/mL). In extraction sockets, rhBMP‐2/ACS maintained alveolar ridge height while enhancing alveolar ridge width. Safety reports did not represent concerns for the proposed indications.

Conclusions

rhBMP‐2/ACS appears a promising alternative to autogenous bone grafts for alveolar ridge/maxillary sinus augmentation; dose and carrier optimization may expand its efficacy, use, and clinical application.
A Real Options Approach for the Investment Decisions of a Farm‐Based Anaerobic Digester
Authors: Anderson Robert C. , Weersink Alfons
Published: October 2013

The profitability of anaerobic digesters (ADs) for Ontario dairy farmers are examined using real options under current and proposed government pricing policies and investment uncertainty. In the case of a renewable energy initiative such as an AD with large sunk costs and volatile returns, the value of deferring investment may be significant enough to offset the returns suggested by the net present value (NPV) approach. For a 150 cow herd, net revenues should be approximately $1.1 million before the AD is installed using the real options approach as compared to $0.5 million with the NPV approach. An AD is close to generating a positive NPV for a 600 cow herd if for either a 1% increase in the electrical price or decrease in the cost. However, farmers need not invest today and there is a value to delaying this decision from potential improvements in the technology that increase the efficiency and/or decrease operating costs of the AD. The real options analysis indicates that this option to delay investment has a value of approximately $300,000 for a typical Ontario dairy farm. Thus, either significant grant funding or higher feed‐in‐tariff rates are required to induce the increased adoption of AD technology in Ontario today even for the largest of dairy farms. Considering the probability of government support potentially ending, increases the value of investing today but a significant option value to defer still exists.
Effects of Crop Prices, Nuisance Costs, and Wetland Regulation on Saskatchewan NAWMP Implementation Goals
Authors: De Laporte Aaron
Published: October 2013

Current Saskatchewan wetland regulation may be insufficient to meet North American Waterfowl Management Plan (NAWMP) preservation and restoration goals in a climate of increasing demand for grains and nuisance costs. Therefore, the purpose of this paper is to ascertain the effects that crop prices, nuisance costs, and alternate wetland regulation have on these goals. An integrated geographic information system and economic farm‐level model that assesses the net present value of drainage projects in the Whitesand River Watershed is employed. If prices eventually reach historical highs observed in the early 1970s, more than 85% of the wetland area in the study area could be drained, making NAWMP goals impossible to achieve. In this scenario, nuisance costs have little effect on drainage outcomes because they are dwarfed by the magnitude of agricultural revenue. If prices remain at the current higher levels observed from 2007 to 2012, the use of a binding permit could help achieve NAWMP goals. In this case, nuisance costs play a large role in determining the drainage of marginal, comparatively larger wetlands. If prices return to the recent lower levels observed from 1999 to 2006, current Saskatchewan regulation is sufficient. In this scenario, agricultural returns are low and nuisance costs are not high enough to cause wetland drainage. Both wetland regulation and nuisance costs can play an important role in agricultural wetland drainage, but that role depends critically upon the price of agricultural products.
Canadian Hog Supply Response: A Provincial Level Analysis
Authors: Rude James , Surry Yves
Published: October 2013

Canada's hog sector has faced two decades of tumultuous growth, yet there are no recent estimates of supply response. This study uses state‐space methods to account for a multiplicity of autonomous structural changes impacting the sector and determines if the fundamental relationship between supply response and hog prices has changed from previous estimates. The results are consistent with prior research but offer the reader previously unavailable estimates of supply response with respect to feed prices and the variability of hog and feed prices. Feed price elasticities are somewhat larger than hog price elasticities. The effects of price risk for supply response appear quite muted but the impacts of feed price risk are greater than for hog price risk.
Prognostic significance of extramural vascular invasion in T4 rectal cancer
Authors: Bhangu A. , Fitzgerald J. E. F. , Slesser A. , Northover J. M. , Faiz O. , Tekkis P.
Published: October 2013

Aim

Extramural vascular invasion (EMVI) has been proposed as an adverse prognostic indicator in colorectal cancer, although its use remains both variable and controversial. This study aimed to determine the survival effect of EMVI in T4 rectal cancer.

Method

Patients undergoing surgery with curative intent for primary T4 rectal cancer between 1971 and 2011 were included from two prospectively collected rectal cancer databases. The main end‐point was 3‐year survival.

Results

From 1142 patients undergoing resection of rectal cancer during the study period, 126 (11.0%) had T4 rectal cancer and were included in the study group. Sphincter preservation was performed in 61 (48%) and a pathologically negative resection margin (R0) was achieved in 104 patients (82.5%). EMVI was present in 51 patients (40.5%) and was an independent predictor of positive lymph node status (adjusted odds ratio 2.66, P = 0.013). Considering all patients, EMVI was associated with reduced overall survival (P = 0.007) and disease‐free survival (P = 0.002), but not local recurrence‐free survival (P = 0.198). In only those undergoing R0 resection, EMVI predicted reduced disease‐free survival with positive nodal status (P = 0.021); it did not predict survival with negative nodal status.

Conclusion

Overall, EMVI was a strong prognostic marker of survival. However, after complete surgical resection in patients with node‐negative disease, EMVI did not predict local recurrence.
Correlation between myocardial fibrosis and restrictive cardiac physiology in patients undergoing retransplantation
Authors: Kobashigawa Jon A. , Itagaki Brandon K. , Razi Rabia R. , Patel Jignesh K. , Chai Wanxing , Kawano Matthew A. , Goldstein Zachary , Kittleson Michelle M. , Fishbein Michael C.
Published: October 2013

After cardiac transplant, there is often development of restrictive cardiac physiology. Little is known about the factors that contribute to this physiology and its correlation with pathology. Heart retransplantation provides a valuable opportunity to further understand this relationship. In this study, we investigated the correlation of myocardial fibrosis and restrictive physiology, and possible risk factors utilizing data from all retransplants at our center. A retrospective review of the 30 patients who underwent retransplantation at our institution between 1994 and 2004 was performed. Hemodynamic and imaging data were reviewed for the presence of restrictive physiology. Pathology reports were reviewed for the presence of myocardial fibrosis in the explanted hearts. The cohort with restrictive physiology preceding redo heart transplant had significantly more patients exhibiting myocardial fibrosis compared with the non‐restrictive physiology group (94.1% vs. 15.4%, p < 0.001). We found no difference in the immunosuppressive regimen, history of rejection, and reason for transplant. In our study, we observed that myocardial fibrosis is an important contributor to the development of restrictive physiology. Further work needs to be done for risk stratification and the mechanism of fibrosis development.
Parallel development of ERP and behavioural measurements of visual segmentation
Authors: van den Boomen Carlijn , Lamme Victor A.F. , Kemner Chantal
Published: October 2013

Visual segmentation, a process in which elements are integrated into a form and segregated from the background, is known to differ from adults at infancy. The further developmental trajectory of this process, and of the underlying brain mechanisms, during childhood and adolescence is unknown. The aim of the study was to investigate the developmental trajectory of ERP reflections of visual segmentation, and to relate this to behavioural performance. One hundred and eleven typically developing children from 7 to 18 years of age were divided into six age groups. Each child performed two visual tasks. In a texture segmentation task, the difference in event‐related potential (ERP) response to homogeneous (no visual segmentation) and checkered stimuli (visual segmentation) was investigated. In addition, behavioural performance on integration of elements into contours was measured. Both behavioural and ERP measurements of visual segmentation differed from adults in 7–12 year‐old children. Behaviourally, young children were less able to integrate elements into a contour than older children. In addition, a developmental change was present in the ERP pattern evoked by homogeneous versus checkered stimuli. The largest differences in behaviour and ERPs were found between 7–8‐ and 9–10‐, and between 11–12‐ and 13–14‐year‐old children, indicating the strongest development between those age groups. Behavioural as well as ERP measurements at 13–14 years of age showed similar results to those of adults. These results reveal that visual segmentation continues to develop until early puberty. Only by 13–14 years of age, children do integrate and segregate visual information as adults do. These results can be interpreted in terms of functional connectivity within the visual cortex.
Positivity for islet cell autoantibodies in patients with monogenic diabetes is associated with later diabetes onset and higher HbA1c level
Authors: Urbanová J. , Rypáčková B. , Procházková Z. , Kučera P. , Černá M. , Anděl M. , Heneberg P.
Published: October 2013

Aims

Islet cell autoantibodies are associated with autoimmune insulitis and belong to the diagnostic criteria of Type 1 diabetes mellitus. However, growing evidence suggests that autoantibodies are present in other types of diabetes. Here, we focus on the autoantibody incidence in Czech patients with maturity‐onset diabetes of the young and analyse their functional relevance in terms of diabetes onset and control.

Methods

Autoantibodies against glutamic acid decarboxylase (GAD) 65 and protein tyrosine phosphatase islet antigen 2 (IA‐2) were measured in a cohort of 28 Czech patients with maturity‐onset diabetes of the young, all confirmed by genetic testing. Selected clinical data were correlated to the status and kinetics of autoantibodies.

Results

One quarter of patients with maturity‐onset diabetes of the young examined (7/28; 25%) was positive for GAD or IA‐2 autoantibodies. GAD autoantibodies were more prevalent (7/7) than IA‐2 autoantibodies (1/7). The incidence of autoantibodies did not correlate with human leukocyte antigen status. The patients who were positive for the autoantibodies developed diabetes later than those who were autoantibody‐negative, but had worse glycaemic control (increased HbA1c). Expression of autoantibodies decreased with any improvement of diabetes compensation. Only one patient did not correspond to the above and displayed signs of combined signs of maturity‐onset diabetes of the young and Type 1 diabetes.

Conclusions

The data suggest transient but highly prevalent islet cell autoantibody expression in Czech patients with maturity‐onset diabetes of the young. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. As improvement of glycaemic control was associated with a decrease in levels of autoantibodies, their presence may reflect the kinetics of β‐cell destruction induced by causes other than autoimmune ones.
Thyroid autoimmunity in Type 1 diabetes: systematic review and meta‐analysis
Authors: Shun C. B. , Donaghue K. C. , Phelan H. , Twigg S. M. , Craig M. E.
Published: October 2013

Aims

To review the incidence and evidence for screening for thyroid autoimmunity and thyroid dysfunction in Type 1 diabetes.

Methods

Systematic review and meta‐analysis. Inclusion criteria were prospective cohort studies screening for thyroid autoimmunity and/or dysfunction (defined as an abnormal thyroid‐stimulating hormone level) in Type 1 diabetes. Exclusion criteria included pregnancy and thyroid dysfunction before diabetes onset. Outcomes examined were: incidence of thyroid autoimmunity and/or dysfunction; association between thyroid autoimmunity and dysfunction; and cost‐effectiveness. Data sources wereMEDLINE,EMBASE, the Cochrane Library, manual searching and contact with authors, with limitations to English language and human studies. Meta‐analysis was performed using random effects models.

Results

We identified 14 eligible studies, involving 2972 young people and 789 adults with Type 1 diabetes. Follow‐up ranged from 1–18 years. None of the studies were of good methodological quality (Newcastle Ottowa Scale score > 7). The incidence of thyroid dysfunction (11 studies) ranged from 27 (95% CI15–45) to 246 (95% CI118–453) per 10 000 patient‐years and thyroid autoimmunity (four studies) from 13 (95% CI0.3–71) to 326 (95% CI194–510). The risk of thyroid dysfunction was higher in those with thyroid autoimmunity: summary risk ratio 25 (95% CI9–71) and was higher in children (49, 95% CI16–150) compared with adults (7, 95% CI3–13). No studies examined cost‐effectiveness of screening.

Conclusions

There is a markedly increased risk of thyroid dysfunction in people with Type 1 diabetes and thyroid autoimmunity. The optimal method or frequency of screening could not be determined from available data. Future studies should examine whether screening improves clinical outcomes in this population.
The Impact of Segmental Volumetric Changes on Functional Mitral Regurgitation: A Study Using Three‐Dimensional Regional Time‐Volume Analysis Combined with Low‐Dose Dobutamine
Authors: Chen Xiaofeng , Hsiung Ming‐Chon , Mu Yuming
Published: October 2013

Purpose

Using transthoracic three‐dimensional (3D) echo regional volume analysis combined with low‐dose dobutamine to investigate the effects on regional volume, mitral configuration and functional mitral regurgitation (FMR).

Methods

Fifty‐six patients with ischemic cardiomyopathy (ICM) were included in this study. The effective regurgitant orifice area (EROA) of FMR secondary to ICM with depressed left ventricular ejection fraction was compared with mitral tenting area and coaptation height (CH) before and after low‐dose dobutamine (10 μg/kg per min). Using 3‐DQ software we measured and calculated regional stroke‐volumes (rSV), the ratio of the rSV to the whole left ventricular stroke volume (rgSVratio) in all 17 segments and the average rgSVratio of 4 anterior‐PM attached segments (rgSVratio‐aver anter‐PM), 4 posterior‐PM attached segments (rgSVratio‐aver post‐PM), 8 PMs attached segments (rgSVratio‐aver PMs) and all 17 segments before and after dobutamine.

Results

Compared with the resting condition, the SVr and rgSVratio on the basal and mid segments of anterior, lateral, inferior, and posterior walls were increased after dobutamine infusion (P < 0.05). EROA at rest was associated with tenting area, CH and rgSVratio‐aver of PMs and the reduction in EROA caused by dobutamine was associated with reductions in tenting area, CH and increases in rgSVratio‐aver of PMs. Tenting area was associated with rgSVratio‐aver of PMs and reduction caused by dobutamine was associated with increases in rgSVratio‐aver of PMs.

Conclusions

The FMR decreasing during low‐dose dobutamine is quantitatively associated with the regional LV volume change of attached PMs. Real time transthoracic three‐dimensional echocardiography may provide a simple and noninvasive approach to assess regional LV time‐volume characteristic during FMR.
Abnormal Agitated Saline Study Results after Tetralogy of Fallot Repair
Authors: Tunks Robert D. , Barker Piers C.A. , Johnson Jason N. , Campbell Michael J.
Published: October 2013

Residual intracardiac or extracardiac shunting is frequently seen in patients with repaired congenital heart disease and can cause systemic hypoxemia. We present the case of an adult with tetralogy of Fallot who underwent two corrective surgical procedures as a child with subsequent pulmonary valve replacement due to residual pulmonary insufficiency. Further details of her operative history were otherwise unknown. After being lost to follow‐up for many years, she presented with unexplained cyanosis and a markedly abnormal agitated saline study on transthoracic echocardiography in which only the left heart filled after contrast administration. We review the differential diagnosis for such a presentation and discuss the utility of cardiac magnetic resonance imaging (MRI) to define the etiology. Cardiac MRI, a frequently used imaging modality to longitudinally assess adult patients with congenital heart disease, provides excellent image quality of cardiac structures and the ability to perform angiography in a variety of imaging planes. These advantages render cardiac MRI, a useful modality to determine the etiology of unexplained cyanosis in these patients as both intracardiac and extracardiac shunts can be detected.
Right Ventricular Wall‐Motion Changes after Infant Open Heart Surgery—A Tissue Doppler Study
Authors: Pauliks Linda B. , Valdes‐Cruz Lilliam M. , Perryman Richard , Scholl Frank G.
Published: October 2013

Background

Right ventricular (RV) dysfunction is a well‐recognized complication of cardiopulmonary bypass surgery (CPB) in adults. Infants and neonates may also be at high risk for this due to immature myocardium. Conventional assessment of RV function is just qualitative, but novel tissue Doppler echocardiographic (TDI) markers including peak systolic strain rate (SR) and isovolumic contraction acceleration (IVA) permit noninvasive quantitation of RV function. This study assessed myocardial velocities, IVA and SR in infants and neonates undergoing open heart surgery using TDI to study regional myocardial function perioperatively.

Methods

Transthoracic TDI data were obtained in the OR before and 24 hours post‐CPB on 53 consecutive infants (age 0.39 ± 0.23 years). They were followed with TDI through hospital discharge.

Results

Mean CPB time was 87 ± 49 min (cross‐clamp 52 ± 26 min). Peak systolic (STDI) and diastolic myocardial velocities (ETDI, ATDI), IVA, and peak SR were recorded in RV and LV from standard views for offline analysis. Postoperatively, LV systolic function and diastolic longitudinal function were unchanged or improved from baseline. LV radial velocities were increased postoperatively indicating adequate support. In contrast, RV longitudinal systolic and diastolic function was significantly diminished after CPB. RV changes persisted through hospital discharge.

Conclusions

In infants and neonates, perioperative measurements of systolic and diastolic tissue Doppler parameters are feasible and revealed significant RV systolic and diastolic dysfunction post‐CPB with preserved LV function. As such, TDI provides a sensitive tool to monitor the infant heart after CPB and may potentially be useful to assess different myocardial protection strategies.
Proposed score for survival of patients with myelodysplastic syndromes
Authors: Sperr Wolfgang R. , Kundi Michael , Wimazal Friedrich , Nösslinger Thomas , Schönmetzler‐Makrai Anabel , Stauder Reinhard , Krieger Otto , Neukirchen Judith , Germing Ulrich , Pfeilstöcker Michael , Valent Peter
Published: October 2013

Background

Patient selection for various therapies in myelodysplastic syndromes (MDS) is based on prognostic factors, scoring systems and the individual life expectancy. However, most established risk scores include mainly disease‐related parameters and thus focus on leukaemia‐transformation rather than survival.

Patients and Methods

To establish a risk score optimized for prediction of survival, we analysed international prognostic scoring system (IPSS)‐related and IPSS‐independent variables in 400 patients with primary MDS (median age: 71 years; range 18–91) of the Austrian MDS platform. Patients were randomly split into a learning sample (60%) and validation sample (40%). External validation was performed on 93 patients from the Heinrich Heine University (Duesseldorf/Germany).

Results

By multivariate analysis, IPSS, ferritin, age and comorbidities were found to be independent predictive variables concerning survival. Based on weighing these prognostic parameters against each other, we established a novel survival score employing IPSS, ferritin (< 900 ng/mL = 0; ≥ 900 ng/mL = 1), age (< 70 years = 0; 70–79 years = 1; ≥ 80 years = 1·5) and HCT‐CI comorbidity (low/intermediate = 0; high = 0·5). Using this score, four prognostic risk groups could be discriminated in the validation sample, with highly significant differences in life expectancy [median survival: LowS (score 0), not reached; Int‐1S (score 0·5–1·0), 3·84 years; Int‐2S (score 1·5–2·0): 2·72 years; and HighS (score > 2·0): 0·80 years; P < 0·0001].

Conclusions

Our newly proposed score may be a useful tool for survival prediction in MDS and helpful in patient selection for various therapies in daily practice and clinical trials.
Flexural impact force absorption of mouthguard materials using film sensor system
Authors: Reza Fazal , Churei Hiroshi , Takahashi Hidekazu , Iwasaki Naohiko , Ueno Toshiaki
Published: October 2013

Purpose

Several methods have been used to measure the impact force absorption capacities of mouthguard materials; however, the relationships among these measurement systems have not been clearly determined. The purpose of the present study was to evaluate the impact force‐absorbing capability of materials using a drop‐ball system with film sensors and load cells to clarify the relationship between these two sensor systems.

Materials and methods

Disk‐shaped specimens (1, 2, and 3 mm thick) were prepared using three commercial thermoplastic mouthguard materials (Bioplast, Impact Guard, MG 21) and one experimental mouthguard material [mixture of Poly (ethyl methacrylate)]. Impact force was applied by letting a stainless steel ball drop free‐fall onto the specimens and then measuring the impact load under each specimen using a film sensor system and a load cell sensor system.

Results

The total load measured with the film sensor system decreased with an increase in mouthguard thickness, while almost none of the transmitted impact forces measured with the load cell system were statistically different.

Conclusions

The film sensor system was considered to be superior to the load cell system because the maximum stress and stress area could be determined.
The impact of age on the diagnosis and therapy of myelodysplastic syndromes: results from a retrospective multicenter analysis in Germany
Authors: Gattermann Norbert , Kündgen Andrea , Kellermann Lenka , Zeffel Matti , Paessens Bernadette , Germing Ulrich
Published: October 2013

Myelodysplastic syndromes (MDS) is a disease of predominantly elderly patients with a median age of >70 yrs. However, data on the management of these patients outside of clinical trials are scarce. To assess patterns of MDS management in routine patient care with regard to the impact of age, we conducted a multicenter, representative survey of MDS health services in Germany. Data of 269 patients treated at 57 institutions were collected from preplanned chart reviews and were analyzed retrospectively. At diagnosis, median age was 70 yrs, 50% of patients had a Karnofsky index (KI) of 90%, and 12% had a comorbidity index ≥ 3 according to Sorror et al. (J Clin Oncol, 25, 2007, 4246). Cytogenetic analysis and International Prognostic Scoring System (IPSS) risk assessment were performed significantly less frequently in patients >75 yrs than in patients ≤75 yrs (P < 0.001 and P = 0.019). In bivariate analysis, potential predictors for performing IPSS risk assessment were age ≤75 yrs (y/n, P = 0.019), diagnosis at a university hospital (y/n, P = 0.001), WHO subtypes RCUD (y/n, P = 0.028), RARS (y/n, P = 0.002), or RAEB II (y/n, P = 0.037). Patients ≤75 yrs were more likely to receive active therapies (i.e., chemotherapy, immunomodulatory therapy, or epigenetic therapy) than patients >75 yrs (51% vs. 37%, P = 0.007). In bivariate analysis age ≤75 yrs (y/n, P = 0.007) was a significant predictor for active treatment with no correlation with the other predictors [IPSS risk score int‐2 or high (y/n, P = 0.005), WHO subtypes RCUD (y/n, P < 0.001), RCMD (y/n, P = 0.003), RAEB II (y/n, P < 0.001), or CMML I (y/n, P = 0.020)]. This survey confirms the impact of age on the thoroughness of MDS diagnosis and the decision for active treatment. As cytogenetic analysis and risk assessment are essential for the choice of appropriate therapy, elderly patients in particular may not be receiving adequate treatment.
Synaptic vesicle protein 2A: basic facts and role in synaptic function
Authors: Mendoza‐Torreblanca Julieta Griselda , Vanoye‐Carlo América , Phillips‐Farfán Bryan Víctor , Carmona‐Aparicio Liliana , Gómez‐Lira Gisela
Published: October 2013

In recent years, there has been considerable interest in determining the function of synaptic vesicle protein 2A and its role as a target for antiepileptic drugs. Although it is known that synaptic vesicle protein 2A is involved in normal synaptic vesicle function, its participation in synaptic vesicle cycling and neurotransmitter release in normal and pathological conditions is unclear. However, the experimental evidence suggests that synaptic vesicle protein 2A could be a vesicular transporter, regulate synaptic exocytosis as a gel matrix, or modulate synaptotagmin‐1 activity. This review describes and discusses the participation of synaptic vesicle protein 2A in synaptic modulation in normal and pathological conditions.
Different TRPV1‐mediated brain responses to intragastric infusion of capsaicin and capsiate
Authors: Tsurugizawa Tomokazu , Nogusa Yoshihito , Ando Yumi , Uneyama Hisayuki
Published: October 2013

Capsaicin and capsiate, which is an analogue of capsaicin, are agonists of capsaicin‐binding transient potential vanilloid 1 (TRPV1) receptors. However, their physiological effects are different. Capsaicin induces thermogenesis and nociception, while the different kinetics of capsiate result in thermogenesis without nociception in the oral cavity. In the present study, using functional magnetic resonance imaging, we compared the brain activation after intragastric infusion of non‐nociceptive levels of capsaicin and capsiate in wild‐type and TRPV1‐knockout (KO) mice. Capsaicin activated several brain regions, such as the periaqueductal grey (PAG), thalamic nuclei and hypothalamus, including the medial preoptic area (mPOA) and ventromedial hypothalamus (VMH). Most of these areas were not activated in TRPV1‐KO mice. Capsiate activated several regions, including the thalamic nuclei, mPOA and VMH but not PAG in wild‐type mice. Most of the activated areas were not activated by intragastric capsiate infusion in TRPV1‐KO mice. These results demonstrate that TRPV1 is critical for the induction of activation in the hypothalamus by capsaicin and capsiate, and these distinct brain activations could help to explain the individual physiological reactions of capsaicin and capsiate.
Rethinking the Priority of Practical Reason inKant
Authors: Mudd Sasha
Published: October 2013

Throughout the critical periodKant enigmatically insists that reason is a ‘unity’, thereby suggesting that both our theoretical and practical endeavors are grounded in one and the same rational capacity. HowKant's unity thesis ought to be interpreted and whether it can be substantiated remain sources of controversy in the literature. According to the strong reading of this claim, reason is a ‘unity’ because all our reasoning, including our theoretical reasoning, functions practically. Although several prominent commentators endorse this view, it is widely thought to lack exegetical support. This paper seeks to strengthen the case for this reading by showing how theoretical reason's positive function, asKant presents it in theAppendix to theTranscendentalDialectic, may be construed as fundamentally practical. I argue that reason's supreme regulative principle ought to be understood as a categorical practical imperative. This interpretation, I suggest, resolves the apparent inconsistencies that blightKant's account of the principle in theAppendix, while bringing greater overall coherence to his account of theoretical reason's regulative function.
Population incidence of Guillain−Barré syndrome in parts of China: three large populations in Jiangsu province, 2008–2010
Authors: Chen Y. , Ma F. , Zhang J. , Chu X. , Xu Y.
Published: October 2013

Background and purpose

It is important to have an estimate of the incidence of Guillain−Barré syndrome (GBS) because of the expansion of vaccination programs and the associated risks of vaccine‐related GBS. Incidence information in Asia, especially in China, is scarce. This study attempts to describe GBS incidence in large Chinese populations located in three geographically different and moderately distant areas of the same province.

Methods

The surveyed areas were Nanjing, Yancheng and Xuzhou, which are three cities in Jiangsu province in China. Nanjing is in the south of Jiangsu province, Yancheng is in the middle and Xuzhou is in the north. The survey was carried out in regions that might have received patients meeting the case definition from 2008 to 2010. The population numbers came from the local Bureau of Statistics. Data analysis was conducted in 2011.

Results

The incidence of GBS was 0.59 cases per 100 000 person‐years. The GBS incidence increased with age amongst people <80 years old. Males had a higher incidence of GBS than females. GBS incidence in Nanjing was the highest amongst the three regions.

Conclusions

The incidence rates in parts of Jiangsu province were lower than those in Europe and North America. There was one peak in incidence amongst older adults (70–80 years). Geographical differences in GBS incidence rates may be related to socioeconomic status. There were no significant seasonal variations of incidence in Jiangsu.
Linking Behavior and Community Ecology: Interspecific Aggression Provides Evidence for Competition Between a Migrant and Resident Warbler
Authors: Toms Judith D.
Published: October 2013

Intraspecific aggression is known to be an important behavior structuring bird communities, but interspecific aggression has been studied less frequently. Because of a high degree of similarity in foraging niches, I hypothesized that American redstarts (Setophaga ruticilla) and Adelaide's warblers (S. adelaidae) would interact aggressively during the non‐breeding season in southwest Puerto Rico. I used a crossover experiment to determine whether these species were aggressive to heterospecifics, presenting decoys and vocalizations of these two species, along with a control, to individuals and observing their vocal and physical responses. However, the study used only a single playback and decoy for each species, limiting the generality of the conclusions. Both species responded aggressively to decoys of conspecifics and heterospecifics, while no individual responded to the control. Responses to conspecifics were stronger than responses to heterospecifics as hypothesized, although the differences were significant only in Adelaide's warblers. The interspecific aggression observed in this study, combined with previous studies showing a high degree of overlap in space use and foraging niches and probable food limitation, strongly suggests that these species are competing for food during the non‐breeding season.
Male Ornamentation in the European Minnow (Phoxinus phoxinus) Signals Swimming Performance
Authors: Lai Yi‐Te , Kekäläinen Jukka , Kortet Raine
Published: October 2013

The association between male secondary sexual ornamentation and male quality has been under intensive study for decades. It has been shown that male ornaments in fish indicate a variety of physical and genetic qualities. However, only few studies have investigated whether male ornaments signal locomotor performance, a trait that is expected to be vital for individual fitness in the nature. In this study, we sampled two populations of European minnow (Phoxinus phoxinus), a cyprinid fish species with spectacular and colourful male breeding ornamentation, and examined the association between male ornaments (tubercle number, lateral darkness and abdominal redness), swimming performance, and three fitness‐related traits, body length (LT), condition factor (K) and gonadosomatic index (GI). We found that male tubercle number and abdominal redness were positively correlated with their swimming performance. In addition, these two ornaments were correlated with male fitness‐related traits, which in turn were also directly associated with the swimming performance. In general, these results suggest that in the European minnow male ornamentation may act as an honest signal of several fitness‐related traits and locomotor performance in the nature.
G‐protein coupled receptor 56 promotes myoblast fusion through serum response factor‐ and nuclear factor of activated T‐cell‐mediated signalling but is not essential for muscle development in vivo
Authors: Wu Melissa P. , Doyle Jamie R. , Barry Brenda , Beauvais Ariane , Rozkalne Anete , Piao Xianhua , Lawlor Michael W. , Kopin Alan S. , Walsh Christopher A. , Gussoni Emanuela
Published: October 2013

Mammalian muscle cell differentiation is a complex process of multiple steps for which many of the factors involved have not yet been defined. In a screen to identify the regulators of myogenic cell fusion, we found that the gene for G‐protein coupled receptor 56 (GPR56) was transiently up‐regulated during the early fusion of human myoblasts. Human mutations in the gene for GPR56 cause the disease bilateral frontoparietal polymicrogyria; however, the consequences of receptor dysfunction on muscle development have not been explored. Using knockout mice, we defined the role of GPR56 in skeletal muscle. GPR56−/− myoblasts have decreased fusion and smaller myotube sizes in culture. In addition, a loss of GPR56 expression in muscle cells results in decreases or delays in the expression of myogenic differentiation 1, myogenin and nuclear factor of activated T‐cell (NFAT)c2. Our data suggest that these abnormalities result from decreased GPR56‐mediated serum response element and NFAT signalling. Despite these changes, no overt differences in phenotype were identified in the muscle of GPR56 knockout mice, which presented only a mild but statistically significant elevation of serum creatine kinase compared to wild‐type. In agreement with these findings, clinical data from 13 bilateral frontoparietal polymicrogyria patients revealed mild serum creatine kinase increase in only two patients. In summary, targeted disruption of GPR56 in mice results in myoblast abnormalities. The absence of a severe muscle phenotype in GPR56 knockout mice and human patients suggests that other factors may compensate for the lack of this G‐protein coupled receptor during muscle development and that the motor delay observed in these patients is likely not a result of primary muscle abnormalities.