bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of nestin after renal transplantation in the rat
Authors: Skwirba Michael , Zakrzewicz Anna , Atanasova Srebrena , Wilker Sigrid , Fuchs‐Moll Gabriele , Müller Dieter , Padberg Winfried , Grau Veronika
Published: April 2014

Chronic allograft injury (CAI) limits the long‐term success of renal transplantation. Nestin is a marker of progenitor cells, which probably contribute to its pathogenesis. We hypothesize that nestin is induced by ischemia/reperfusion injury and acute rejection, main risk factors for CAI. Syngeneic renal transplantation was performed in Lewis rats and allogeneic transplantation in the Fischer 344 to Lewis strain combination, which results in reversible acute rejection and in CAI in the long‐run. The Dark Agouti to Lewis rat strain combination was used to study fatal acute rejection. In untreated kidneys, nestin immunoreactivity was detected in glomeruli and in very few interstitial or microvascular cells. Syngeneic transplantation induced nestin expression within 4 days, which decreased until day 9 and returned to control levels on day 42. Nestin expression was strong during acute rejection and still detected during the pathogenesis of CAI on day 42. Nestin‐positive cells were identified as endothelial cells and interstitial fibroblast‐like cells co‐expressing alpha‐smooth muscle actin. A sub‐population of them expressed proliferating cell nuclear antigen. In conclusion, nestin is induced in renal grafts by ischemia/reperfusion injury and acute rejection. It is expressed by proliferating myofibroblasts and endothelial cells and probably contributes to the pathogenesis of CAI.
Histolopathologic approach to direct the management of the axilla in early breast cancer patients
Authors: Farid Rola M , Ahmed Naglaa S
Published: April 2014

Screening mammography improved early detection of breast cancer and since then, the percentage of patients with node involvement is declining. Sentinel lymph node biopsy (SLNB), although helpful in the diagnostic armamentarium of these patients, has consequential limitations. In these patients, moreover, lymphatic invasion (LI) is of utmost importance to determine the risk of local recurrence. To find an adjuvant histologic approach to assist in pre‐operative analysis of the patient's risk for having LI and thus sentinel ± non‐sentinel axillary lymph node metastasis, one hundred and twenty patients with early invasive duct carcinoma without axillary lymph node metastasis were evaluated. Logistic regression predictive models were built from 80 patients and validated in the remaining 40 patients. The final stepwise multi‐regression analysis identified four sensitive models. In the validation group, model 1 [applicable to tumors grade 3 having micropapillary differentiation (MPD)] correctly identified 92.31% of patients with LI and confirmed LI [positive predictive value (PPV) = 83%], but with moderate sensitivity. Model 2 [applicable to tumors without MPD], model 3 [applicable to tumors grade 1/2], and model 4 [applicable to tumors grade 1/2 having no MPD] all had moderate PPV and a high negative predictive value (NPV) rendering these models reliable negative tests. However, as they had high sensitivity, positive results confirm the presence of LI. Patient with tumors grade 3 and MPD might need SLNB and/or axillary lymph node dissection (ALND). Patients having tumors grade 1/2, size <2 cm, and no MPD nor extensive retraction artifact, SLNB and/or ALND could be omitted. In tumors grade 1/2 (model 2) and those without MPD (model 3), the proposed models are reliable negative tests rather than a definitive positive one.
Genotypic characteristics of multidrug‐resistant Escherichia coli isolates associated with urinary tract infections
Authors: Cao Xiaoli , Zhang Zhifeng , Shen Han , Ning Mingzhe , Chen Junhao , Wei Hongxia , Zhang Kui
Published: April 2014

Escherichia coli is an important pathogen involved in community‐acquired urinary tract infections (CA‐UTIs). In this study, we analyzed the prevalence of frequently occurring genes and the distribution of integrons in 51 multidrug‐resistant (MDR) E. coli isolates associated with CA‐UTIs. The clonality of these strains was investigated by phylogrouping, multi‐locus sequence typing, and pulsed‐field gel electrophoresis (PFGE). All these strains were found to produce two or more resistance determinants, ceftazidime‐hydrolyzing CTX‐M‐type extended‐spectrum β‐lactamases (ESBLs) and plasmid‐mediated quinolone resistance determinants were the most prevalent (92.2% and 51.0%, respectively). A sulfhydryl variable‐61‐producing E. coli strain was identified for the first time in China. The prevalence of class 1 integrons was 54.9%, class 2 integrons were detected in three isolates but no isolate contained a class 3 integron. Phylogenetic group D was the dominant, observed in 70.6% of the isolates. PFGE analysis revealed a high level of diversity. Twenty‐four distinctive sequence types (STs) including four major STs (ST648, ST224, ST38, and ST405) were identified. To our knowledge, this is the first report on the characterization of MDR E. coli isolates associated with CA‐UTIs in China; our results suggest that an MDR D‐ST648 clone producing CTX‐M‐ESBLs has emerged as a major clone in the community setting.
Smart Power Strategy: Recalibrating Indonesian Foreign Policy
Authors: Pitsuwan Fuadi
Published: April 2014

This article analyzes Indonesia's foreign policy by using the theoretical concept of “smart power” as proposed by Joseph S. Nye. The article begins by explaining Nye's smart power theory. It then delineates the most pressing foreign policy concerns of Indonesia. After that, it explores Indonesia's current hard power and soft power inventory. Finally, the article provides recommendations that form a smart power strategy for Indonesia. These recommendations, ranged from the easiest to most difficult to implement, suggest that the Indonesian government should: (i) engage nongovernmental organizations more vigorously; (ii) champion multilateralism and prioritize engagement with multilateral institutions; (iii) modernize and increase military capabilities; and (iv) improve domestic conditions to boost hard and soft power. For each aspect of these recommendations, the article delves into the specifics of how it addresses the main foreign policy challenges facing Indonesia.
Cyclo‐oxygenase‐2 inhibition and endothelium‐dependent vasodilation in younger vs. older healthy adults
Authors: Eisenach John H. , Gullixson Leah R. , Allen Alexander R. , Kost Susan L. , Nicholson Wayne T.
Published: April 2014

Aim

A major feature of endothelial dysfunction is reduced endothelium‐dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin, or nitric oxide (NO), or both.

Method

We tested this hypothesis in 12 younger (age 18–38 years, six women) and 12 older healthy adults (age 55–73 years, six post‐menopausal women). Endothelium‐dependent vasodilation was assessed by the forearm vascular conductance (FVC) response to intra‐arterial acetylcholine (ACh) (0.5, 1.0, 2.0, 4.0 μg dl−1 forearm tissue min−1) before and 90 min after inhibition of the enzyme cyclo‐oxygenase‐2 (COX‐2) with oral celecoxib (400 mg), followed by the addition of endothelial NO synthase inhibition with intra‐arterial NG‐monomethyl‐l arginine acetate (L‐NMMA).

Results

Ageing was associated with a significantly reduced FVC response to ACh (P = 0.009, age‐by‐dose interaction; highest dose FVC ± SEM in ageing: 11.2 ± 1.4 vs. younger: 17.7 ± 2.4 units, P = 0.02). Celecoxib did not reduce resting FVC or the responses to ACh in any group. L‐NMMA significantly reduced resting FVC and the responses to ACh in all groups, and absolute FVC values following L‐NMMA were similar between groups.

Conclusion

In healthy normotensive younger and older adults, there is minimal contribution of prostacyclin to ACh‐mediated vasodilation, yet the NO component of vasodilation is reduced with ageing. In the clinical context, these findings suggest that acute administration of medications that inhibit prostacyclin (i.e. COX‐2 inhibitors) evoke modest vascular consequences in healthy persons. Additional studies are necessary to test whether chronic use of COX‐2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors.
Patient participation in medication reviews is desirable but not evidence‐based: a systematic literature review
Authors: Willeboordse Floor , Hugtenburg Jacqueline G. , Schellevis François G. , Elders Petra J. M.
Published: April 2014

Aim

The aim of this systematic literature review is to investigate which types of patient participation in medication reviews have been practiced and what is known about the effects of patient participation within the medication review process.

Methods

A systematic literature review was performed in multiple databases using an extensive selection and quality assessment procedure.

Results

In total, 37 articles were included and most were assessed with a weak or moderate quality. In all studies patient participation in medication reviews was limited to the level of information giving by the patient to the professional, mainly on actual drug use. Nine studies showed limited results of effects of patient participation on the identification of drug related problems.

Conclusions

The effects of patient participation are not frequently studied and poorly described in current literature. Nevertheless, involving patients can improve patients' knowledge, satisfaction and the identification of drug related problems. Patient involvement is now limited to information sharing. The profit of higher levels of patient communication and shared decision making is until now, not supported by evidence of its effectiveness.
Preoperative serum cholesterol is an independent prognostic factor for patients with renal cell carcinoma (RCC)
Authors: de Martino Michela , Leitner Carmen V. , Seemann Christoph , Hofbauer Sebastian L. , Lucca Ilaria , Haitel Andrea , Shariat Shahrokh F. , Klatte Tobias
Published: April 2014

Objective

To assess the prognostic role of preoperative serum cholesterol in patients with renal cell carcinoma (RCC), as increasing evidence suggests that alterations in the lipid profile are associated with the development, progression and prognosis of various cancers.

Patients and Methods

We analysed 867 patients, who underwent radical or partial nephrectomy for RCC between 2002 and 2012. Preoperative total cholesterol levels were determined in serum using colorimetric analysis (CHOD‐PAP method). The association with cancer‐specific survival (CSS) was assessed with Cox models. Discrimination was quantified with the C‐index. The median follow‐up was 52 months.

Results

The median (interquartile range) serum cholesterol was 195 (166–232) mg/dL. Decreasing serum cholesterol was associated with more advanced T, N and M stages (P < 0.001), higher grades (P = 0.001) and presence of tumour necrosis (P = 0.002). Continuously coded cholesterol was associated with CSS in both univariable (hazard ratio [HR] 0.87, P < 0.001) and multivariable analyses (HR 0.93, P = 0.001). The discrimination of a multivariable base model increased significantly from 88.3% to 89.2% following inclusion of cholesterol (P = 0.006). In patients with clinically localised disease (T1–3N0/+M0), cholesterol remained associated with CSS in multivariable analysis (HR 0.90, P = 0.002) and increased the discrimination from 74.6% to 76.9% (P = 0.002).

Conclusions

Preoperative serum cholesterol is an independent prognostic factor for patients with RCC, with lower levels being associated with worse survival. Its use increases the discrimination of established prognostic factors. As cholesterol is a broadly available routine marker, its use may provide a meaningful adjunct in clinical practice. The biological rationale underlying this association remains to be clarified.
Drug effects on multiple and concurrent schedules of ethanol‐ and food‐maintained behaviour: context‐dependent selectivity
Authors: Ginsburg B C , Lamb R J
Published: April 2014

Background and Purpose

Drugs that more potently or effectively reduce ethanol‐maintained behaviour versus an alternative are considered selective and are considered promising pharmacotherapies for alcoholism. Such results are often obtained using separate groups or multiple schedules where ethanol and the alternative are available alone or sequentially. Recently, we observed that when ethanol and food were available sequentially under a multiple schedule, fluvoxamine and varenicline were selective; yet this selectivity disappeared when ethanol and food were concurrently available.

Experimental Approach

We examined the generality of these findings by comparing doses of several drugs required to decrease ethanol‐ and food‐maintained responding under a multiple schedule and under a concurrent schedule. Effects were determined for chlordiazepoxide, 2,5‐dimethoxy‐4‐iodoamphetamine (DOI), meta‐chlorophenylpiperazine (mCPP), morphine, naltrexone and d‐amphetamine.

Key Results

Under the multiple schedule, ED50 values for decreases in ethanol‐maintained responding were significantly different and lower than ED50s for decreases in food‐maintained responding (demonstrating selectivity) for each drug except for chlordiazepoxide (which was equipotent) and naltrexone (which did not affect responding). However, this selectivity vanished or even inverted under the concurrent schedule, such that ED50 values for decreasing ethanol‐ and food‐maintained responding were not different (or, following DOI, the ED50 for food‐maintained responding was lower than for ethanol‐maintained responding).

Conclusions and Implications

Results are consistent with those seen following fluvoxamine and varenicline administration, and suggest that selectivity is assay‐dependent. These results indicate the need for careful interpretation of selective drug effects, especially when obtained in situations where ethanol or the alternative is the only programmed reinforcement available.
Morphine‐induced internalization of the L83I mutant of the rat μ‐opioid receptor
Authors: Cooke A E , Oldfield S , Krasel C , Mundell S J , Henderson G , Kelly E
Published: April 2014

Background and Purpose

Naturally occurring single‐nucleotide polymorphisms (SNPs) within GPCRs can result in alterations in various pharmacological parameters. Understanding the regulation and function of endocytic trafficking of the μ‐opioid receptor (MOP receptor) is of great importance given its implication in the development of opioid tolerance. This study has compared the agonist‐dependent trafficking and signalling of L83I, the rat orthologue of a naturally occurring variant of the MOP receptor.

Experimental Approach

Cell surface elisa, confocal microscopy and immunoprecipitation assays were used to characterize the trafficking properties of the MOP‐L83I variant in comparison with the wild‐type receptor in HEK 293 cells. Functional assays were used to compare the ability of the L83I variant to signal to several downstream pathways.

Key Results

Morphine‐induced internalization of the L83I MOP receptor was markedly increased in comparison with the wild‐type receptor. The altered trafficking of this variant was found to be specific to morphine and was both G‐protein receptor kinase‐ and dynamin‐dependent. The enhanced internalization of L83I variant in response to morphine was not due to increased phosphorylation of serine 375, arrestin association or an increased ability to signal.

Conclusions and Implications

These results suggest that morphine promotes a specific conformation of the L83I variant that makes it more liable to internalize in response to morphine, unlike the wild‐type receptor that undergoes significantly less morphine‐stimulated internalization, providing an example of a ligand‐selective biased receptor. The presence of this SNP within an individual may consequently affect the development of tolerance and analgesic responses.

Linked Articles

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
IL‐6 in diabetes and cardiovascular complications
Authors: Qu Dan , Liu Jian , Lau Chi Wai , Huang Yu
Published: April 2014

IL‐6 is a pleiotropic cytokine that participates in normal functions of the immune system, haematopoiesis, metabolism, as well as in the pathogenesis of metabolic and cardiovascular diseases. Both pro‐ and anti‐inflammatory roles of IL‐6 have been described, which are distinguished by different cascades of signalling transduction, namely classic and trans‐signalling. The present review summarizes the basic principles of IL‐6 signalling and discusses its roles in diabetes and associated cardiovascular complications, with emphasis on the different outcomes mediated by the two modes of IL‐6 signalling and the value of developing therapeutic strategies to specifically target the deleterious trans‐signalling of IL‐6.
Prevalence and penetrance of ZFPM2 mutations and deletions causing congenital diaphragmatic hernia
Authors: Longoni M. , Russell M.K. , High F.A. , Darvishi K. , Maalouf F.I. , Kashani A. , Tracy A.A. , Coletti C.M. , Loscertales M. , Lage K. , Ackerman K.G. , Woods S.A. , Ward‐Melver C. , Andrews D. , Lee C. , Pober B.R. , Donahoe P.K.
Published: April 2014

Zinc finger protein, FOG2 family member 2 (ZFPM2) (previously named FOG2) gene defects result in the highly morbid congenital diaphragmatic hernia (CDH) in humans and animal models. In a cohort of 275 CDH patient exomes, we estimated the prevalence of damaging ZFPM2 mutations to be almost 5%. Genetic analysis of a multigenerational family identified a heritable intragenic ZFPM2 deletion with an estimated penetrance of 37.5%, which has important implications for genetic counseling. Similarly, a low penetrance ZFPM2 frameshift mutation was observed in a second multiplex family. Isolated CDH was the predominant phenotype observed in our ZFPM2 mutation patients. Findings from the patients described herein indicate that ZFPM2 point mutations or deletions are a recurring cause of CDH.
Regional‐Level Analysis of Oligopsony Power in the Ukrainian Dairy Industry
Authors: Perekhozhuk Oleksandr , Glauben Thomas , Teuber Ramona , Grings Michael
Published: April 2014

Transition was characterized by massive structural changes in most economic sectors in Ukraine. This is especially true for the dairy sector. Several countervailing developments took place under transition that affected the dairy industry. Interregional trade became feasible, the importance of milk delivered by households increased significantly, and most dairies became investor‐owned companies. The latter point and the fact that the Antimonopoly Committee of Ukraine detected several price cartels in the industry lead us to offer that after transition, dairies were able to exercise oligopsony power toward dairy producers at the regional level. This paper estimates market structure models for raw milk in Ukraine using a translog production function for the processing sector at the national and regional level. The results suggest the existence of oligopsony power in three of 25 administrative regions in Ukraine, coupled with a potential deviation of procurement prices for raw milk from the value marginal product of raw milk ranging from 24.6% to 49.4%.
Scale‐dependent effects of landscape variables on gene flow and population structure in bats
Authors: Razgour Orly , Rebelo Hugo , Puechmaille Sébastien J. , Juste Javier , Ibáñez Carlos , Kiefer Andreas , Burke Terry , Dawson Deborah A. , Jones Gareth
Published: April 2014

Aim

A common pattern in biogeography is the scale‐dependent effect of environmental variables on the spatial distribution of species. We tested the role of climatic and land cover variables in structuring the distribution of genetic variation in the grey long‐eared bat, Plecotus austriacus, across spatial scales. Although landscape genetics has been widely used to describe spatial patterns of gene flow in a variety of taxa, volant animals have generally been neglected because of their perceived high dispersal potential.

Location

England and Europe.

Methods

We used a multiscale integrated approach, combining population genetics with species distribution modelling and geographical information under a causal modelling framework, to identify landscape barriers to gene flow and their effect on population structure and conservation status. Genotyping involved 23 polymorphic microsatellites and 259 samples from across the species' range.

Results

We identified distinct population structure shaped by geographical barriers and evidence of population fragmentation at the northern edge of the range. Habitat suitability (as captured by species distribution models, SDMs) was the most important landscape variable affecting genetic connectivity at the broad spatial scale, while at the fine scale, lowland unimproved grasslands, the main foraging habitat of P. austriacus, played a pivotal role in promoting genetic connectivity.

Main conclusions

The importance of lowland unimproved grasslands in determining the biogeography and genetic connectivity in P. austriacus highlights the importance of their conservation as part of a wider landscape management for fragmented edge populations. This study illustrates the value of using SDMs in landscape genetics and highlights the need for multiscale approaches when studying genetic connectivity in volant animals or taxa with similar dispersal abilities.
Training‐induced recovery of low‐level vision followed by mid‐level perceptual improvements in developmental object and face agnosia
Authors: Lev Maria , Gilaie‐Dotan Sharon , Gotthilf‐Nezri Dana , Yehezkel Oren , Brooks Joseph L. , Perry Anat , Bentin Shlomo , Bonneh Yoram , Polat Uri
Published: April 2014

Long‐term deprivation of normal visual inputs can cause perceptual impairments at various levels of visual function, from basic visual acuity deficits, through mid‐level deficits such as contour integration and motion coherence, to high‐level face and object agnosia. Yet it is unclear whether training during adulthood, at a post‐developmental stage of the adult visual system, can overcome such developmental impairments. Here, we visually trained LG, a developmental object and face agnosic individual. Prior to training, at the age of 20, LG's basic and mid‐level visual functions such as visual acuity, crowding effects, and contour integration were underdeveloped relative to normal adult vision, corresponding to or poorer than those of 5–6 year olds (Gilaie‐Dotan, Perry, Bonneh, Malach & Bentin, 2009). Intensive visual training, based on lateral interactions, was applied for a period of 9 months. LG's directly trained but also untrained visual functions such as visual acuity, crowding, binocular stereopsis and also mid‐level contour integration improved significantly and reached near‐age‐level performance, with long‐term (over 4 years) persistence. Moreover, mid‐level functions that were tested post‐training were found to be normal in LG. Some possible subtle improvement was observed in LG's higher‐order visual functions such as object recognition and part integration, while LG's face perception skills have not improved thus far. These results suggest that corrective training at a post‐developmental stage, even in the adult visual system, can prove effective, and its enduring effects are the basis for a revival of a developmental cascade that can lead to reduced perceptual impairments.
A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position
Authors: Giorda C. B. , Nada E. , Tartaglino B. , Marafetti L. , Gnavi R.
Published: April 2014

The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re‐emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30‐fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug‐related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT‐2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase‐4 (DPP‐4) inhibitors, and GLP‐1 receptor agonists. To date, however, a clear‐cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use.
Clinical Settings Leading to Presystolic Tricuspid Regurgitation
Authors: Szymański Piotr , Lipczyńska Magdalena , Klisiewicz Anna , Hoffman Piotr
Published: April 2014

Purpose

Few studies describe diastolic (presystolic) tricuspid regurgitation (DTR) mainly in the context of atrioventricular conduction abnormalities. Little is known about its occurrence in the other clinical settings.

Methods

We identified patients with DTR recorded during routine echocardiographic examinations. DTR was defined as low velocity backward flow through the tricuspid valve orifice during end‐diastole recorded with a continuous and/or pulsed‐wave Doppler and/or color‐coded M‐mode Doppler echocardiography.

Results

Diastolic tricuspid regurgitation was present in a wide variety of clinical entities. Of the 23 patients with DTR 6 patients had ischemic and 10 dilated cardiomyopathy. Others had clinical conditions including: inappropriate pacemaker settings, decompensated hypertrophic cardiomyopathy, biventricular dysfunction following orthotropic heart transplantation, torrential aortic regurgitation, low ejection fraction aortic stenosis, advanced endocardial fibroelastosis, and complex congenital heart disease. Twenty of 23 patients had significantly impaired right ventricle (RV) systolic function. Systolic tricuspid regurgitation was estimated as moderate or severe in 13 cases and mild in the remaining 10 cases. RV systolic pressure was significantly elevated in all but 2 cases. In all but 4 cases DTR was transient. The persistence of DTR was associated with severe pulmonary hypertension, severe biventricular failure, and persistent severe pulmonary regurgitation.

Conclusions

Diastolic tricuspid regurgitation may be encountered in a variety of clinical settings and should be sought for especially in patients with advanced RV systolic dysfunction, pulmonary hypertension, pulmonary regurgitation, or conduction abnormalities. Significant systolic regurgitation is not prerequisite for the development of DTR.
Three‐Dimensional Transesophageal Echocardiography for Guiding Percutaneous Fontan Fenestration Closure
Authors: Giannakoulas George , Thanopoulos Vasilios
Published: April 2014

Mini Abstract

The presented case highlights the important complementary role of real time 3D transesophageal echocardiography in the guidance of transcatheter closure of a surgically created fenestration after Fontan operation.
Atrial Mechanics after Surgical Repair of Tetralogy of Fallot
Authors: Hou Jia , Yu Hong‐kui , Wong Sophia J. , Cheung Yiu‐fai
Published: April 2014

Background

Ventricular diastolic dysfunction in patients with repaired tetralogy of Fallot (TOF) may affect atrial mechanics. This study aimed to explore right atrial (RA) and left atrial (LA) mechanics in repaired TOF patients and their relationship with ventricular diastolic function.

Methods

Fifty‐four patients (36 males), aged 17.8 ± 8.3 years, who had undergone TOF repair at 3.9 ± 3.3 years and 40 healthy subjects aged 16.9 ± 6.3 years (P = 0.57) were studied. Right and LA peak positive, peak negative, and total strain, strain rate at ventricular systole (SRs), early diastole (SRed), and atrial contraction (SRac), and electromechanical delay were determined using speckle tracking echocardiography (STE). Ventricular diastolic function was assessed by tissue Doppler imaging and STE. Ventricular volumes and pulmonary regurgitant volume were derived from 3D echocardiography.

Results

Compared with controls, patients had significantly lower RA and LA peak positive and total strain, SRs, SRed, and SRac (all P < 0.001). The timing of RA (178 ± 33 msec vs. 152 ± 17 msec, P < 0.001) and LA (170 ± 32 msec vs. 152 ± 24 msec, P = 0.006) electromechanical coupling (EMC) was significantly longer in patients than in controls. The RA total strain, SRs, SRed, SRac, and EMC correlated positively with corresponding LA parameters (all P < 0.001). The RA and LA total strain and SRed were associated positively with diastolic annular velocities and strain rates of respective ventricles (all P < 0.05). The LA SRed correlated negatively with pulmonary regurgitant volume (r = −0.33, P = 0.016) and RV end‐diastolic volume (r = −0.33, P = 0.015).

Conclusion

Mechanics of both atria are impaired in patients after repair of TOF and are associated with diastolic performance of the respective ventricles.
Back to basics: could behavioural therapy be a good treatment option for youth depression? A critical review
Authors: Hetrick Sarah E. , Cox Georgina R. , Fisher Caroline A. , Bhar Sunil S. , Rice Simon M. , Davey Christopher G. , Parker Alexandra G.
Published: April 2014

Aim

Recent findings from systematic reviews and primary research studies have shown more modest effects of cognitive behavioural therapy (CBT) for youth depression than previously shown, highlighting the need to further enhance the effectiveness of this intervention, or components of this intervention. Therefore, the aim of this review is to summarize the work that has been done to identify the different components of CBT and their varying effectiveness for young people with depression.

Methods

Narrative overview of English language reviews/meta‐analyses and primary intervention studies retrieved from searches of computerized databases as well as ancestry searches.

Results

Reviews of intervention studies of adults as well as young people with depression have shown that behavioural approaches are equally as effective as cognitive approaches in reducing depression symptoms. Post‐hoc analyses of large studies in youth depression have also shown that behavioural approaches might be more suitable for young people.

Conclusions

Behaviourally based approaches appear promising in treating youth depression; however, further research is required. This research will represent an essential step towards refining interventions for youth depression, and enabling interventions to be targeted to particular subgroups, to optimize their effectiveness.
Teacher Education and Curriculum Change in Scotland
Authors: Donaldson Graham
Published: April 2014

The dynamic forces shaping education in the 21st century have led countries across the world to pursue sweeping educational reforms. Despite significant investment and radical approaches including system and organisational restructuring, managerialism and marketisation, evidence of sustained impact in the classroom remains elusive. Using the example of an emerging systemic approach to educational change in Scotland, this article analyses an aligned approach to improvement, encompassing teaching, leadership, curriculum, self evaluation and related structural support. In this context, it becomes necessary to re‐imagine the profession of teaching as one in which teachers are active as authors and drivers of educational change and career‐long professional growth is the norm. The emerging approach to reform in Scotland reflects this interpretation of effective reform. Its curriculum reform, ‘Curriculum for Excellence’, focuses on the development of capacities in young people and is much less prescriptive than traditional forms of curriculum development. Scotland's now well‐established approach to inspection and self‐evaluation provides a further pillar in the overall reform programme. More recently, major developments have been set in train in relation to teacher education and school leadership. Following a fundamental review of teacher education, a radical and systemic programme of reform of the teaching profession is now under way. The article outlines the main features of the approach and considers the main factors which will influence its likelihood of success.
Implications of Research on Effective Learning Environments for Initial Teacher Education
Authors: Conner Lindsey , Sliwka Anne
Published: April 2014

As a result of multi‐disciplinary research on learning, a consistent and comprehensive body of knowledge on effective learning environments is currently emerging (OECD 2010). While this evidence is increasingly influencing the academic and policy discourse on the improvement and innovation of schools, its impact on the design principles of effective initial teacher education has been limited so far. In this paper, the seven transversal learning principles published in the 2010 OECD publication The Nature of Learning: Using Research to Inspire Practice serve as a framework for systematic reflections on how learning research on effective learning environments can inform initial teacher education and how the seven transversal learning principles can contribute to greater coherence and alignment in initial teacher education programs. We consider the implications of The Nature of Learning and other research on teacher education, alongside international examples of next practice, concluding that initial teacher education should model effective student learning.
Fractographic features of glass‐ceramic and zirconia‐based dental restorations fractured during clinical function
Authors: Øilo Marit , Hardang Anne D. , Ulsund Amanda H. , Gjerdet Nils R.
Published: April 2014

Fractures during clinical function have been reported as the major concern associated with all‐ceramic dental restorations. The aim of this study was to analyze the fracture features of glass‐ceramic and zirconia‐based restorations fractured during clinical use. Twenty‐seven crowns and onlays were supplied by dentists and dental technicians with information about type of cement and time in function, if available. Fourteen lithium disilicate glass‐ceramic restorations and 13 zirconia‐based restorations were retrieved and analyzed. Fractographic features were examined using optical microscopy to determine crack initiation and crack propagation of the restorations. The material comprised fractured restorations from one canine, 10 incisors, four premolars, and 11 molars. One crown was not categorized because of difficulty in orientation of the fragments. The results revealed that all core and veneer fractures initiated in the cervical margin and usually from the approximal area close to the most coronally placed curvature of the margin. Three cases of occlusal chipping were found. The margin of dental all‐ceramic single‐tooth restorations was the area of fracture origin. The fracture features were similar for zirconia, glass‐ceramic, and alumina single‐tooth restorations. Design features seem to be of great importance for fracture initiation.
Simulation of clinical fractures for three different all‐ceramic crowns
Authors: Øilo Marit , Kvam Ketil , Gjerdet Nils R.
Published: April 2014

Comparison of fracture strength and fracture modes of different all‐ceramic crown systems is not straightforward. Established methods for reliable testing of all‐ceramic crowns are not currently available. Published in‐vitro tests rarely simulate clinical failure modes and are therefore unsuited to distinguish between the materials. The in‐vivo trials usually lack assessment of failure modes. Fractographic analyses show that clinical crowns usually fail from cracks initiating in the cervical margins, whereas in‐vitro specimens fail from contact damage at the occlusal loading point. The aim of this study was to compare three all‐ceramic systems using a clinically relevant test method that is able to simulate clinical failure modes. Ten incisor crowns of three types of all‐ceramic systems were exposed to soft loading until fracture. The initiation and propagation of cracks in these crowns were compared with those of a reference group of crowns that failed during clinical use. All crowns fractured in a manner similar to fracture of the clinical reference crowns. The zirconia crowns fractured at statistically significantly higher loads than alumina and glass‐ceramic crowns. Fracture initiation was in the core material, cervically in the approximal areas.
In vivo ketogenic diet treatment attenuates pathologic sharp waves and high frequency oscillations in in vitro hippocampal slices from epileptic Kv1.1α knockout mice
Authors: Simeone Timothy A. , Samson Kaeli K. , Matthews Stephanie A. , Simeone Kristina A.
Published: April 2014

The ketogenic diet (KD) is an effective therapy for pediatric refractory epilepsies; however, whether the KD changes the pathologic network oscillations generated by an epileptic brain remains unknown. We have reported that hippocampal CA3 regions of epileptic Kv1.1α knockout (KO) mice generate pathologic sharp waves (SPWs) and high‐frequency oscillations (HFOs) that have higher incidence, longer duration, and fast ripples compared to wild‐type (WT). Synaptic activity of hyperexcitable KO mossy fibers significantly decreased CA3 principal cell spike‐timing reliability, which contributed to this network pathology. In addition, we have demonstrated that the KD reduces seizures by 75% in KO mice. Here, we determined whether 10‐ to 14‐day in vivo KD treatment exerts disease‐modifying effects that alter the spontaneous SPW‐HFO complexes generated by the hippocampal CA3 region of KO mice in vitro using extracellular multielectrode array recordings. We found that KD treatment significantly attenuated the pathologic features of KO SPWs and ripples and reduced the incidence of fast ripples. The KD also improved spike‐timing reliability of KO CA3 principal cells, decreased mossy fiber excitability, increased mossy fiber‐CA3 paired‐pulse ratios, and reduced coupling of field excitatory postsynaptic potentials and population spikes in the CA3 region. Collectively, these data indicate that KD treatment modulates CA3‐generated pathologic oscillations by dampening hyperactive mossy fiber synapses.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Impaired cognitive function in idiopathic generalized epilepsy and unaffected family members: An epilepsy endophenotype
Authors: Chowdhury Fahmida A. , Elwes Robert D. C. , Koutroumanidis Michaelis , Morris Robin G. , Nashef Lina , Richardson Mark P.
Published: April 2014

Objective

Idiopathic generalized epilepsy (IGE) has a strong genetic component, and patients with IGE show deficits in a range of frontal lobe functions. Previous studies provide hints that unaffected siblings of people with IGE may share some of these cognitive deficits, suggesting that these deficits may be genetically determined endophenotypes. Establishment of a neurocognitive endophenotype of IGE would contribute to genetic studies and increase our understanding of the pathophysiology of IGE. To identify potential neurocognitive endophenotypes of IGE, this study aimed to measure neuropsychological performance in patients with IGE, their unaffected relatives, and healthy controls.

Methods

Thirty‐six patients with IGE, 38 first‐degree relatives, and 40 healthy controls were examined using a battery of neuropsychological tests sensitive to frontal lobe dysfunction (executive function, nonverbal reasoning, verbal generativity, response inhibition, attention, and working memory). Subject groups were compared using robust Bonferroni‐corrected statistics.

Results

Patients with IGE showed deficits in nonverbal reasoning, verbal generativity, attention, and working memory. Relatives exhibited a parallel profile of cognitive abilities, with significant deficits in these tasks. Patients tended to show greater impairment than relatives in these tasks.

Significance

This study shows that measures of nonverbal reasoning, verbal generativity, sustained attention, and working memory are endophenotypes of IGE and offer the potential for aiding molecular genetic studies and elucidating the pathophysiology of IGE. Patients tended to demonstrate greater impairment in these tasks, possibly because of a greater genetic contribution and/or disease‐related factors.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Sexual History Affects Mating Behavior and Mate Choice in the Crayfish Orconectes limosus
Authors: Mellan Dane , Warren Allyson , Buckholt Michael A. , Mathews Lauren M.
Published: April 2014

Because mating entails both costs and potential benefits to both sexes, males and females should be under selection to make optimal choices from among available potential mates. For example, in some cases, individuals may benefit by using information on potential mates' previous sexual histories to make mate choices. In such cases, the form and direction of these benefits may vary both between the sexes and based on the sexual history of the choosing individuals themselves. We investigated the effects of recent previous sexual history on the mate choice and mating behavior of both males and females of the crayfish Orconectes limosus. In one experiment, we found that opposite‐sex dyads comprising crayfish that had both mated 7–8 d previously with other conspecifics were significantly less likely to mate than dyads in which at least one crayfish was unmated. In a second experiment, we found that, when presented with a choice of tethered (but free to move) opposite‐sex conspecifics, only virgin females discriminated between males based on sexual history, showing a preference for virgin males over recently mated males. Mated females, mated males, and virgin males showed no preferences based on the sexual histories of potential mates. We discuss the implications of these inferences in the context of what was previously known about mating behavior and potential sperm limitation in crustaceans and other taxa.
Nitrogen limitation of the phytobenthos in Alpine lakes: results from nutrient‐diffusing substrata
Authors: Lepori Fabio , Robin Joël
Published: April 2014

In the Alps, as in other mountainous regions across the world, nitrogen (N) enrichment of ecosystems via atmospheric deposition is a major environmental concern. Nitrogen enrichment can cause acidification in poorly buffered lakes and streams, but here we assessed the less well‐known effects of eutrophication on the phytobenthos of lakes and its consequences for grazing.

To simulate the effects of N deposition, we conducted experimental nutrient additions (N and N+P) in two lakes in the French Alps, in summer 2012. In each lake, we deployed nutrient‐diffusing substrata for 22 days. The substrata were placed within cages that either allowed or prevented access by macrograzers. We tested the hypotheses that N enrichment: (i) increases phytobenthic biomass, (ii) alters phytobenthic taxonomic composition and (iii) reduces benthic grazing.

Supporting the first hypothesis, at the end of the experiments N‐enriched substrata had a greater phytobenthic biomass than unenriched substrata, indicating N limitation. Supporting the second hypothesis, the taxonomic composition of the phytobenthos differed between N‐enriched and control substrata. Green algae, including filamentous forms, were favoured by N enrichment to a greater extent than diatoms and cyanobacteria. By contrast, the third hypothesis was not supported. Grazing had the same effect on the biomass of the phytobenthos regardless of nutrient treatment.

Our results highlight the sensitivity of Alpine lakes to deposition of atmospheric N. Its ecological effects are not limited to acidification, but also include increased biomass (eutrophication) and altered taxonomic composition of the phytobenthos. Because filamentous green algae favoured by N enrichment are usually unpalatable to macrograzers, inputs of atmospheric N could reduce the efficiency of transfer of energy from the phytobenthos up through the food web.
Process‐based models not always better than empirical models for simulating budburst of Norway spruce and birch in Europe
Authors: Olsson Cecilia , Jönsson Anna Maria
Published: April 2014

Budburst models have mainly been developed to capture the processes of individual trees, and vary in their complexity and plant physiological realism. We evaluated how well eleven models capture the variation in budburst of birch and Norway spruce in Germany, Austria, the United Kingdom and Finland. The comparison was based on the models performance in relation to their underlying physiological assumptions with four different calibration schemes. The models were not able to accurately simulate the timing of budburst. In general the models overestimated the temperature effect, thereby the timing of budburst was simulated too early in the United Kingdom and too late in Finland. Among the better performing models were three models based on the growing degree day concept, with or without day length or chilling, and an empirical model based on spring temperatures. These models were also the models least influenced by the calibration data. For birch the best calibration scheme was based on multiple sites in either Germany or Europe, and for Norway spruce the best scheme included multiple sites in Germany or cold years of all sites. Most model and calibration combinations indicated greater bias with higher spring temperatures, mostly simulating earlier than observed budburst.