bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myopathy in older people receiving statin therapy: a systematic review and meta‐analysis
Authors: Iwere Roli B. , Hewitt Jonathan 
Published: May 2015

ObjectiveThe aim of the present study was to determine the risk of myopathy in older people receiving statin therapy.MethodsEligible studies were identified searching Ovid Medline, EMBASE, Scopus, CINAHL, Cochrane and PSYCHINFO databases (1987 to July 2014). The selection criteria comprised randomized controlled studies that compared the effects of statin monotherapy and placebo on muscle adverse events in the older adult (65+ years). Data were extracted and assessed for validity by the authors. Odds ratios and 95% confidence intervals (CIs) were used to calculate binary outcomes. Evidence from included studies were pooled in a meta‐analysis using Revman 5.3.ResultsThe trials assessed in the systematic review showed little or no evidence of a difference in risks between treatment and placebo groups, with myalgia [odds ratio (OR) 1.03, 95% CI 0.90, 1.17; I2 = 0%; P = 0.66] and combined muscle adverse events (OR 1.03, 95% CI 0.91, 1.18; I2 = 0%; P = 0.61) (myopathy). No evidence was found for an increased risk of rhabdomyolysis (OR 2.93, 95% CI 0.30, 28.18; I2 = 0%; P = 0.35) in the seven trials that reported this. No trials reported mortality due to a muscle‐related event. Discontinuations due to an adverse effect were reduced in the treatment group compared with placebo (OR 0.74, 95% CI 0.50, 1.09; I2 = 0%; P = 0.13).ConclusionThe results obtained from the present review suggest that statins are relatively safe, even in older people. There was no evidence to suggest an increased risk of myopathy in older adults receiving statin therapy. There is slightly increased seen with rhabdomyolysis when compared with the general population, although the event is relatively rare. Statins should be prescribed to elderly people who need it, and not withheld, as its myopathy safety profile is tolerable.
The FNTB promoter polymorphism rs11623866 as a potential predictive biomarker for lonafarnib treatment of ovarian cancer patients
Authors: Bachmann Hagen Sjard , Meier Werner , du Bois Andreas , Kimmig Rainer , Kuhlmann Jan Dominik , Siffert Winfried , Sehouli Jalid , Wollschlaeger Kerstin , Huober Jens , Hillemanns Peter , Burges Alexander , Schmalfeldt Barbara , Aminossadati Behnaz , Wimberger Pauline 
Published: May 2015

AimDespite promising preclinical findings regarding clinical utility of farnesyltransferase inhibitors (FTI), such as lonafarnib, success of clinical trials is limited. A multicentre AGO‐OVAR‐15 phase II trial reported an unfavourable effect of lonafarnib on the outcome of patients with advanced ovarian cancer. This study was performed as a genetic subgroup analysis of the AGO‐OVAR‐15 trial, and investigated the utility of the promoter polymorphism rs11623866 of the farnesyltransferase ß‐subunit gene (FNTB) in predicting the clinical effectiveness of lonafarnib.MethodsThe influence of rs11623866 (c.‐609G > C) on FNTB promoter activity was investigated by electrophoretic‐mobility‐shift assay, luciferase‐reporter assay and RT‐qPCR. A total of 57 out of 105 patients from the AGO‐OVAR‐15 trial, treated with carboplatin and paclitaxel ± lonafarnib, was genotyped for rs11623866 by restriction fragment length polymorphism analysis. Genotype‐dependent survival analysis was performed by Kaplan–Meier analysis.ResultsThe presence of the G allele was associated with increased FNTB promoter activity compared with the C allele. An unfavourable effect of lonafarnib was limited to patients carrying a GG genotype (HRPFS 6.2, 95%CI = 2.01, 19.41, P = 0.002; HROS 9.6, 95%CI = 1.89, 48.54, P = 0.006). Median progression free survival (PFS) for patients with the GG genotype in the lonafarnib treated arm was 10 months, whereas median PFS without FTI‐treatment was 40 months. Median overall survival (OS) in the lonafarnib‐treated group was 19 months, whereas median OS was not reached in the untreated group.ConclusionsDiscrepancies between preclinical success and clinical failure may be due to the patients' genetic variability of FNTB. Therefore, our results may encourage retrospective evaluation of FNTB polymorphisms in previous FTI studies, especially those reporting positive FTI response.
Temperature rises in the round window caused by various light sources during insertion of rigid endoscopes: an experimental animal study
Authors: Dundar R. , Bulut H. , Yükkaldiran A. , Güler O.K. , Demirtaş Y. , Iynen İ. , Bozkuş F. , Soy F.K. 
Published: May 2015

ObjectivesThe instruments used in endoscopic surgery include rigid endoscopes of different diameters and angles, sources of light and monitors. In this study, we explored temperature rises in the round window caused by insertion of rigid endoscopes of different diameters into the middle ear; the endoscopes were fitted with different light sources.DesignAn experimental animal study.SettingWe subjected seven guinea pigs to simulate otological surgery at room temperature. We monitored body temperatures, along with temperature rises caused by the use of 0° rigid endoscopes of diameters 3 or 4 mm, fitted with light sources including a halogen light, a light‐emitting diode (LED) and a xenon light. Data were collected every second from a sensor placed in the round window.ParticipantsAn experimental study on 7 guinea pigs.Main Outcome MeasuresRise of the temperature on round window.ResultsRigid endoscopes caused the temperature of the tympanum to rise when xenon and halogen light sources were used, regardless of endoscope diameter. However, the temperature rise was less when a LED light source was employed.ConclusionThe endoscopic instruments used in middle ear surgery caused the temperature of the round window to rise. The rise varied with endoscope diameter and the type of light source used.
Charcot neuroarthropathy after simultaneous pancreas–kidney transplantation: risk factors, prevalence, and outcome
Authors: García Barrado Fernando , Kuypers Dirk R. , Matricali Giovanni A. 
Published: May 2015

AbstractWe retrospectively analyzed outcome and risk factors of developing Charcot foot (CF) in 100 patients with type 1 diabetes mellitus who underwent a simultaneous pancreas–kidney (SPK) transplantation. Patients who developed CF after SPK transplantation had significantly higher mortality (56% vs. 18%) and more frequently graft failure (44% vs. 13%). Recipients with CF also experienced acute rejections more frequently (78% vs. 41%). They furthermore had higher pre‐transplant values of HbA1c, received cyclosporine and azathioprine more often, and had significantly higher cumulative corticosteroid use. Patients transplanted in an earlier era (1992–1998) received cyclosporine and azathioprine more often and had a significantly higher cumulative corticosteroid use with the higher prevalence of CF. Conversely, patients with diabetes transplanted more recently (1999–2012) received lower doses of corticosteroids as part of their tacrolimus‐based immunosuppressive therapy, resulting in fewer CF attacks. In conclusion, development of CF after SPK is associated with poor patient and graft outcome. Poor pre‐transplant diabetic control and the use of high‐dose corticosteroids are risk factors for the development of CF. We recommend reduction in or even total avoidance of corticosteroids after SPK transplantation. Given the importance of the diagnosis of CF on outcome, a systematic examination of SPK patients' feet is recommended.
Self‐reported diabetes self‐management competence and support from healthcare providers in achieving autonomy are negatively associated with diabetes distress in adults with Type 1 diabetes
Authors: Mohn J. , Graue M. , Assmus J. , Zoffmann V. , B. Thordarson H. , Peyrot M. , Rokne B. 
Published: May 2015

AbstractAimTo investigate the associations of self‐perceived competence in diabetes management and autonomy support from healthcare providers with diabetes distress in adults with Type 1 diabetes mellitus that is not optimally controlled [HbA1c ≥ 64 mmol/mol (8.0%)].MethodsThis cross‐sectional study comprised blood sampling and three self‐report questionnaires, the Problem Areas in Diabetes scale, the Perceived Competence in Diabetes Scale and a measure of autonomy support by healthcare providers, the Health Care Climate Questionnaire. We fitted blockwise linear regression models to assess the associations between Problem Areas in Diabetes score and the variables of interest (autonomy support and perceived diabetes competence), controlling for clinical and sociodemographic variables.ResultsOf the study sample [n = 178; mean age 36.7 (±10.7) years], 31.5% had long‐term complications and 43.2% reported elevated (≥40) Problem Areas in Diabetes scores. A significant negative association was found between autonomy support and Problem Areas in Diabetes score (B = ‐3.61, P = 0.001), indicating that lower autonomy support was associated with greater diabetes distress. When perceived competence was controlled, it mediated the association of autonomy support with diabetes distress, reducing it to non‐significance. There was a significant negative association between perceived competence and Problem Areas in Diabetes score (B = ‐8.89, P < 0.001), indicating that lower perceived competence was associated with greater perceived distress.ConclusionsThere was an indirect (fully mediated) relationship between autonomy support and diabetes distress; autonomy support was associated with increased perceived competence, which, in turn, was associated with reduced distress. Healthcare providers' communication styles enhancing perceived competence through autonomy support may contribute to effective treatment for people with Type 1 diabetes and suboptimum glycaemic control.
A novel mutation of the hGR gene causing Chrousos syndrome
Authors: Nicolaides Nicolas C. , Geer Eliza B. , Vlachakis Dimitrios , Roberts Michael L. , Psarra Anna‐Maria G. , Moutsatsou Paraskevi , Sertedaki Amalia , Kossida Sophia , Charmandari Evangelia 
Published: May 2015

AbstractBackgroundNatural mutations in the human glucocorticoid receptor (hGR, NR3C1) gene cause Chrousos syndrome, a rare condition characterized by generalized, partial, target‐tissue insensitivity to glucocorticoids.ObjectiveTo present a new case of Chrousos syndrome caused by a novel mutation in the hGR gene, and to elucidate the molecular mechanisms through which the natural mutant receptor affects glucocorticoid signal transduction.Design and ResultsThe index case presented with hirsutism, acne, alopecia, anxiety, fatigue and irregular menstrual cycles, but no clinical manifestations suggestive of Cushing's syndrome. Endocrinologic evaluation revealed elevated 08:00 h plasma adrenocorticotropic hormone, serum cortisol and androstenedione concentrations and increased urinary free cortisol excretion. The patient harbored a novel A > G transition at nucleotide position 2177, which resulted in histidine (H) to arginine (R) substitution at amino acid position 726 of the receptor (c.2177A > G, p.H726R). Compared with the wild‐type receptor, the mutant receptor hGRαH726R demonstrated decreased ability to transactivate glucocorticoid‐responsive genes and to transrepress the nuclear factor‐κB signalling pathway, displayed 55% lower affinity for the ligand and a four‐fold delay in nuclear translocation, and interacted with the glucocorticoid receptor‐interacting protein 1 coactivator mostly through its activation function‐1 domain. Finally, a 3‐dimensional molecular modelling study of the H726R mutation revealed a significant structural shift in the rigidity of helix 10 of the receptor, which resulted in reduced flexibility and decreased affinity of the mutant receptor for binding to the ligand.ConclusionsThe natural mutant receptor hGRαH726R impairs multiple steps of glucocorticoid signal transduction, thereby decreasing tissue sensitivity to glucocorticoids.
Factors influencing recruitment of walleye and white bass to three distinct early ontogenetic stages
Authors: DeBoer Jason A. , Pope Kevin L. 
Published: May 2015

AbstractDetermining the factors that influence recruitment to sequential ontogenetic stages is critical for understanding recruitment dynamics of fish and for effective management of sportfish, particularly in dynamic and unpredictable environments. We sampled walleye (Sander vitreus) and white bass (Morone chrysops) at 3 ontogenetic stages (age 0 during spring: ‘age‐0 larval’; age 0 during autumn: ‘age‐0 juvenile’; and age 1 during autumn: ‘age‐1 juvenile’) from 3 reservoirs. We developed multiple linear regression models to describe factors influencing age‐0 larval, age‐0 juvenile and age‐1 juvenile walleye and white bass abundance indices. Our models explained 40–80% (68 ± 9%; mean ± SE) and 71%–97% (81 ± 6%) of the variability in catch for walleye and white bass respectively. For walleye, gizzard shad were present in the candidate model sets for all three ontogenetic stages we assessed. For white bass, there was no unifying variable in all three stage‐specific candidate model sets, although walleye abundance was present in two of the three white bass candidate model sets. We were able to determine several factors affecting walleye and white bass year‐class strength at multiple ontogenetic stages; comprehensive analyses of factors influencing recruitment to multiple early ontogenetic stages are seemingly rare in the literature. Our models demonstrate the interdependency among early ontogenetic stages and the complexities involved with sportfish recruitment.
Fish species incidence patterns in naturally fragmented Chihuahuan Desert streams
Authors: Miyazono Seiji , Taylor Christopher M. 
Published: May 2015

AbstractWe investigated how stream fragmentation affects local fish species persistence and extinction from three Rio Grande systems (Texas, USA) stream reaches with different levels of natural fragmentation. We examined species–volume (SV) relationships of fish assemblages in 42 pools across the watersheds and predicted greater fragmentation would correspond to an increase in the slope of the SV relationship due to decreased within‐reach rescue effects. In addition, we examined relationships among tributary‐specific nested subset patterns, local habitat features and spatial position of the reaches relative to the Rio Grande mainstem to better understand the importance of local and regional processes on fish species richness patterns in the stream reaches. Slopes of the SV curves did not differ among the stream reaches, but the intercepts of the SV curves were significantly different. These results indicated rescue effects among habitats within a stream reach were not apparent; however, rescue effects from the mainstem largely determined the species richness of a given stream reach. The nested subset patterns in all stream reaches were related to several local environmental factors, and large, deep pools provided important aquatic refugia in all three systems. We suggest declines in mainstem and tributary flows will likely continue to impact local and regional fish assemblage attributes. High flow events are important for dispersal and can reset tributary fish communities for the next extinction‐driven, successional cycle.
The GIRK2 subunit is involved in IS‐like seizures induced by GABAB receptor agonists
Authors: Blichowski Monica , Shephard Alexander , Armstrong Jessica , Shen Liqing , Cortez Miguel A. , Eubanks James H. , Snead O. Carter 
Published: May 2015

SummaryObjectiveInfantile spasms (or IS) is a catastrophic childhood epilepsy that is particularly prevalent in children with Down syndrome. Previously, we have shown that the Ts65Dn (Ts) mouse model of Down syndrome is a useful substrate upon which to develop an animal model of infantile spasms. Specifically, the Ts mouse is exquisitely sensitive to the electroencephalography (EEG) and behavioral effects of γ‐aminobutyric acid (GABA) B receptor (GABABR) agonists with a resultant phenotype that bears behavioral, EEG, and pharmacologic semblance to infantile spasms in humans. The G protein–coupled inward rectifying potassium channel subunit 2 (GIRK2) gene, KCNJ6, is overexpressed in Ts mice, and the GABABR‐mediated GIRK2 current is significantly increased in these mutant animals as well. Therefore, we formulated the hypothesis that the GIRK2 channel plays a significant role in the behavioral (measured by acute extensor spasms quantification) and EEG (measured by the electrodecremental response duration) phenotype induced in the Ts mice by GABABR agonists.MethodsGIRK2−/−, +/−, and +/+ mice were treated with γ‐butyrolactone (GBL), a pro‐drug of the GABABR agonist γ‐hydroxybutyric acid, and the specific GABABR agonist baclofen (BAC) under continuous EEG monitoring. These drugs induce epileptiform bursts, extensor spasms, and an electrodecremental response (EDR) in Ts mice at low doses, and in wild‐type mice at high doses. A dose–response curve was ascertained with two treatment groups: GBL (100, 200, and 400 mg/kg) and BAC (4, 8, 12, and 16 mg/kg). We determined the baseline, the presence and duration of electrodecremental epochs (EDEs), and quantified acute epileptic extensor spasms.ResultsAnalysis of EEG and behavior of GIRK2−/−, +/−, and +/+ mice after treatment with GABABR agonists and antagonists, indicate that GIRK2−/− mice are highly resistant to GABABR agonist–induced EEG and behavioral changes.SignificanceThese data increase the possibility that GIRK2 channel function plays a major role in the genesis of infantile spasms.
What are the minimum requirements for ketogenic diet services in resource‐limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy
Authors: Kossoff Eric H. , Al‐Macki Nabil , Cervenka Mackenzie C. , Kim Heung D. , Liao Jianxiang , Megaw Katherine , Nathan Janak K. , Raimann Ximena , Rivera Rocio , Wiemer‐Kruel Adelheid , Williams Emma , Zupec‐Kania Beth A. 
Published: May 2015

SummaryDespite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow‐up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost‐effective recommendations for new ketogenic diet centers in resource‐limited regions of the world.
Structure of a thermophilic F1‐ATPase inhibited by an ε‐subunit: deeper insight into the ε‐inhibition mechanism
Authors: Shirakihara Yasuo , Shiratori Aya , Tanikawa Hiromi , Nakasako Masayoshi , Yoshida Masasuke , Suzuki Toshiharu 
Published: May 2015

F1‐ATPase (F1) is the catalytic sector in FoF1‐ATPsynthase that is responsible forATPproduction in living cells. In catalysis, its three catalytic β‐subunits undergo nucleotide occupancy‐dependent and concerted open–close conformational changes that are accompanied by rotation of the γ‐subunit. Bacterial and chloroplast F1are inhibited by their own ε‐subunit. In the ε‐inhibitedEscherichia coliF1structure, the ε‐subunit stabilizes the overall conformation (half‐closed, closed, open) of the β‐subunits by inserting its C‐terminal helix into the α3β3cavity. The structure of ε‐inhibited thermophilic F1is similar to that ofE. coliF1, showing a similar conformation of the ε‐subunit, but the thermophilic ε‐subunit stabilizes another unique overall conformation (open, closed, open) of the β‐subunits. The ε‐C‐terminal helix 2 and hook are conserved between the two structures in interactions with target residues and in their positions. Rest of the ε‐C‐terminal domains are in quite different conformations and positions, and have different modes of interaction with targets. This region is thought to serve ε‐inhibition differently. For inhibition, the ε‐subunit contacts the second catches of some of the β‐ and α‐subunits, the N‐ and C‐terminal helices, and some of the Rossmann fold segments. Those contacts, as a whole, lead to positioning of those β‐ and α‐ second catches in ε‐inhibition‐specific positions, and prevent rotation of the γ‐subunit. Some of the structural features are observed even inIF1inhibition in mitochondrial F1.DatabaseStructural data are available in the Worldwide Protein Data Bank database under the accession number4XD7
Non–animal collagens as new options for cosmetic formulation
Authors: Peng Y. Y. , Stoichevska V. , Vashi A. , Howell L. , Fehr F. , Dumsday G. J. , Werkmeister J. A. , Ramshaw J. A. M. 
Published: May 2015

SynopsisObjectiveTo examine the potential of non‐animal collagens as a new option for cosmetic applications.MethodsNon‐animal collagens from three species,Streptococcus pyogenes,Solibacter usitatusandMethylobacteriumsp 4‐46, have been expressed as recombinant proteins inEscherichia coliusing a cold‐shock, pCold, expression system. The proteins were purified using either metal affinity chromatography or a simple process based on precipitation and proteolytic digestion of impurities, which is suitable for large‐scale production. Samples were examined using a range of analytical procedures.ResultsAnalyses by gel electrophoresis and mass spectrometry were used to examine the purity and integrity of the products. Circular dichroism spectroscopy showed stabilities around 38°C, and calculated pIvalues were from 5.4 to 8.6.UV‐visible light spectroscopy showed the clarity of collagen solutions. The collagens were soluble at low ionic strength between pH5 and pH8, but were less soluble under more acidic conditions. At lower pH, the insoluble material was well dispersed and did not form the fibrous associations and aggregates found with animal collagens. The materials were shown to be non‐cytotoxic to cells in culture.ConclusionsThese novel, non‐animal collagens may be potential alternatives to animal collagens for inclusion in cosmetic formulations.
A model of sustainable household technology acceptance
Authors: Ahn Mira , Kang Jiyun , Hustvedt Gwendolyn 
Published: May 2015

AbstractThere is an expanding range of technologies used in a residential setting to enable sustainable living, including ‘smart’ technology that uses learning and connectivity to modify household behaviours. Understanding what drives the adoption of sustainable household technology will allow product developers, marketers and policy makers to use technology to reduce the environmental impact of homes. Based on the United Theory of Acceptance and Use of Technology, a model that explains predictors of intention to adopt sustainable household technology was developed and tested via an online survey of 592 US consumers. The results from structural equation modelling demonstrate that product attributes of sustainable household technology including performance, compatibleness and hedonic expectancy as well as consumer characteristics, in specific, sustainable innovativeness significantly predicts adoption intent. Conversely, the model testing shows that effort expectancy as well as social pressure and environmentalism are not significant predictors of adoption intention Theoretical and practical implications are discussed.