bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive
Authors: Surampudi P. , Page S. T. , Swerdloff R. S. , Nya‐Ngatchou J. J. , Liu P. Y. , Amory J. K. , Leung A. , Hull L. , Blithe D. L. , Woo J. , Bremner W. J. , Wang C. 
Published: May 2014

SummaryThe novel androgen, dimethandrolone (DMA) has both androgenic and progestational activities, properties that may maximize gonadotropin suppression. We assessed the pharmacokinetics of dimethandrolone undecanoate (DMAU), an orally bioavailable, longer acting ester of DMA, for male contraceptive development. Our objective was to examine the safety and pharmacokinetics of single, escalating doses of DMAU (powder in capsule formulation) administered orally with or without food in healthy men. We conducted a randomized, double‐blind Phase 1 study. For each dose of DMAU (25–800 mg), 10 male volunteers received DMAU and two received placebo at two academic medical centres. DMAU was administered both fasting and after a high‐fat meal (200–800 mg doses). Serial serum samples were collected over 24 h following each dose. DMAU was well tolerated without significant effects on vital signs, safety laboratory tests or electrocardiograms. When administered while fasting, serum DMA (active compound) was detectable in only 4/10 participants after the 800 mg dose. When administered with a 50% fat meal, serum DMA was detectable in all participants given 200 mg DMAU and showed a dose‐incremental increase up to 800 mg, with peak levels 4–8 h after taking the dose. Serum gonadotropins and sex hormone concentrations were significantly suppressed 12 h after DMAU administration with food at doses above 200 mg. This first‐in‐man study demonstrated that a single, oral dose of DMAU up to 800 mg is safe. A high‐fat meal markedly improved DMAU/DMA pharmacokinetics.
Atrial Structure and Function 5 Years After Successful Ablation for Persistent Atrial Fibrillation: An MRI Study
Authors: COCHET HUBERT , SCHERR DANIEL , ZELLERHOFF STEPHAN , SACHER FREDERIC , DERVAL NICOLAS , DENIS ARNAUD , KNECHT SEBASTIEN , KOMATSU YUKI , MONTAUDON MICHEL , LAURENT FRANÇOIS , PIESKE BURKERT M. , HOCINI MÉLÈZE , HAÏSSAGUERRE MICHEL , JAÏS PIERRE 
Published: May 2014

Atrial Function After Persistent AF AblationIntroductionThe atrial outcome after extensive ablation is unknown. We sought to quantify atrial structure and function years after successful ablation for persistent atrial fibrillation (PsAF).Methods and ResultsWe studied after 80 ± 15 months 26 patients (54 ± 8 years, 1 woman) with PsAF successfully treated by ablation (2.2 ± 0.7 stepwise approach procedures, cumulative RF duration 126 ± 37 minutes). At follow‐up atrial scar burden and atrial outflows were quantified using delayed–enhanced and velocity‐encoded MRI, respectively. Cine imaging was used to quantify atrial conduit function (CF), active emptying fraction (AEF), expansion index (EI), and the inter‐appendage mechanical activation delay. Patients underwent exercise testing at baseline and follow‐up. LA and RA scar extent were 29 ± 6 and 4.3 ± 2.8%, respectively. LA and RA AEF were 10.0 ± 5.3 and 30 ± 8%. Mean inter‐appendage delay was 83 ± 47 ms [42–217]. Complete LAA isolation was found in 3 patients. A wave was absent in 9/26 patients. LA scar extent related to the number of procedures (R = 0.58, P = 0.002) and total RF duration (R = 0.56, P = 0.003). Among follow‐up characteristics, LA scar extent related to LAAEF (R = −0.73, P < 0.0001), LAEI (R = −0.64, P = 0.0003), A‐wave peak (R = −0.72, P < 0.0001), and inter‐appendage mechanical delay (R = 0.47, P = 0.02). At multivariable analysis, LA scar extent was independently related to LAAEF and LAEI. LAAEF and LA scar extent correlated with exercise capacity at follow‐up (R = 0.44, P = 0.02, and R = −0.40; P = 0.04).ConclusionLA contractility and compliance are markedly impaired years after successful PsAF ablation. LA dysfunction is closely related to scar burden.
EU Confidential: The European Parliament's Involvement in EU Security and Defence Policy
Authors: Rosén Guri 
Published: May 2014

AbstractIn 2002, the European Parliament (EP) and the Council concluded an Interinstitutional Agreement that gave the EP privileged access to sensitive documents in the area of security and defence. It is argued that the Council let the EP become involved in this sensitive policy area because it accepted the legislature's argument for its right to access. In addition, the EP's bargaining strategy concretized the procedures and contributed to finalizing the deal after two years of negotiation. It is shown in this article that despite the EP's marginal powers in the area of security and defence and the traditional conception of this policy as an executive prerogative, it cannot be isolated from democratic principles. This article provides new evidence for previous claims that the EP's involvement in EU foreign policy is increasing due to legitimacy concerns. It also offers a theoretical account for why this is so.
Australian practice nursing: collaboration in context
Authors: Merrick Eamon , Fry Margaret , Duffield Christine 
Published: May 2014

Aims and objectivesTo explore whether or not the context of Australian practice nursing supports collaborative decision‐making about organisation and delivery of patient care.BackgroundPositive patient outcomes depend on Australian practice nurses participating in collaborative and interprofessional services, particularly for patients with chronic disease(s). It is unclear whether Australian practice nurses have the opportunity to collaborate in decision‐making or how traditional organisational structures may support or hinder collaboration.DesignThis is a descriptive exploratory study. Semi‐structured interviews were conducted using a purposive sample of practice nurses (n = 15). Thematic analysis was used to provide meaningful and contextual insights into how practice nurses participate in decision‐making.MethodAn interview tool, based on available literature, was developed and consisted of thirty open‐ended questions to direct discussion during telephone interviews. Transcribed data were imported into NVivotm for analysis and interpretation. The collection, analysis and thematic interpretation of data were an iterative process.FindingsParticipants fostered trusting interprofessional relationships, which enabled them to influence medical decision‐making and thereby advocate for patient need. Trusting interprofessional relationships were perceived to alter the relative roles of the medical practitioner and practice nurse and enhance the opportunities for collaborative decision‐making.Conclusions and relevance to clinical practiceCollaborative interprofessional care in Australian general practice must occur if increased demands for care are to be met. It is timely to consider how government policy, financial regulations and the organisation of Australian general practice can better support and enhance a collaborative contribution to care by practice nurses.
Fear of falling in robust community‐dwelling older people: results of a cross‐sectional study
Authors: Liu Justina YW 
Published: May 2014

Aims and objectivesTo identify the prevalence and risk factors for fear of falling among robust community‐dwelling older people.BackgroundDifferent models including various risk factors emerged when previous studies attempted to explore the factors’ multivariate associations with fear of falling. Attempting to detect fear of falling by a single question in some previous studies may not have been sufficiently sensitive, particularly in a robust population. Although some studies used a validated instrument to detect participants’ fear of falling, their self‐perceived efficacy in performing various activities was seldom reported. Information to provide an insight into the planning of well‐targeted interventions to reduce fear of falling has been lacking.DesignA cross‐sectional study of 445 robust community‐dwelling older people aged ≥65.MethodsBesides their demographic and fall‐related background, participants’ fear of falling level was assessed using the Chinese Fall Efficacy Scale–International. Other instruments included the timed up and go test, the Chinese Geriatric Depression Scale–Short Form, the Chinese Anxiety Disorder Scale, the Chinese Lubben Social Network Scale and the Chinese Personal Wellbeing Index, which were used to assess different variables that may be associated with fear of falling.ResultsOf the 64·73% of participants who had fear of falling, 65·63% had no history of fall but still had fear of falling. This result was higher than in most previous studies. Participants’ main concerns were walking on slippery/uneven surfaces, in crowded places and up/down a slope. Multivariate analyses showed that being female, suffering from poor vision and arthritis, poor performance in the timed up and go test, expressing more depressive and anxiety symptoms and low self‐perceived well‐being are multiply associated with fear of falling.ConclusionFear of falling is prevalent among robust community‐dwelling older people regardless of their fall history. They showed lack of self‐perceived efficacy in performing various outdoor activities.Relevance to clinical practiceThe findings can assist in developing multidimensional strategies for reducing fear of falling in robust community‐dwelling older people.
Person‐centred ward climate as experienced by mentally lucid residents in long‐term care facilities
Authors: Bergland Ådel , Hofoss Dag , Kirkevold Marit , Vassbø Tove , Edvardsson David 
Published: May 2014

Aims and objectivesTo assess the content validity and reliability of the Person‐centred Climate Questionnaire‐Patient version in long‐term care facilities, to describe residents' perceptions of the extent to which their ward climate was person‐centred and to explore whether person‐centredness was associated with facility and resident characteristics, such as facility and ward size, having a sensory garden and having a primary caregiver.BackgroundThe importance of the physical environment to persons with dementia has been investigated. However, research is lacking regarding the extent to which mentally lucid residents experience their physical and psycho‐social ward climate as person‐centred and the factors influencing their experience.DesignCross‐sectional survey design.MethodsThe Person‐centred Climate Questionnaire–Patient version was translated into Norwegian with forward and backward translation. The content validity index for scales was assessed. The Person‐centred Climate Questionnaire –Patient version was completed by 145 mentally lucid residents in 17 Norwegian long‐term care facilities. Reliability was assessed by Cronbach's α and item–total correlations. Test–retest reliability was assessed by paired samples t‐test and Spearman's correlation. To explore differences based on facility and resident characteristics, independent‐samples t‐test and one‐way anova were used.ResultsThe content validity index for scales was satisfactory. The Person‐centred Climate Questionnaire–Patient version was internally consistent and had satisfactory test–retest reliability. The climate was experienced as highly person‐centred. No significant differences were found, except that residents in larger facilities experienced the climate as more person‐centred in relation to everyday activities (subscale 2) than residents in smaller facilities.ConclusionThe Norwegian version of the Person‐centred Climate Questionnaire–Patient version can be regarded as reliable in a long‐term care facility context. Perceived degree of person‐centredness was not associated with facility or resident characteristics, such as the number of residents, having a sensory garden or knowing that one has a primary caregiver.Relevance to clinical practiceA person‐centred climate can be attained in different kinds of long‐term care facilities.
Genetic diagnosis of familial hypercholesterolaemia by targeted next‐generation sequencing
Authors: Maglio C. , Mancina R. M. , Motta B. M. , Stef M. , Pirazzi C. , Palacios L. , Askaryar N. , Borén J. , Wiklund O. , Romeo S. 
Published: May 2014

AbstractObjectivesThe aim of this study was to combine clinical criteria and next‐generation sequencing (pyrosequencing) to establish a diagnosis of familial hypercholesterolaemia (FH).Design, setting and subjectsA total of 77 subjects with a Dutch Lipid Clinic Network score of ≥3 (possible, probable or definite FH clinical diagnosis) were recruited from the Lipid Clinic at Sahlgrenska Hospital, Gothenburg, Sweden. Next‐generation sequencing was performed in all subjects using SEQPRO LIPO RS, a kit that detects mutations in the low‐density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLR adapter protein 1 (LDLRAP1) genes; copy‐number variations in the LDLR gene were also examined.ResultsA total of 26 mutations were detected in 50 subjects (65% success rate). Amongst these, 23 mutations were in the LDLR gene, two in the APOB gene and one in the PCSK9 gene. Four mutations with unknown pathogenicity were detected in LDLR. Of these, three mutations (Gly505Asp, Ile585Thr and Gln660Arg) have been previously reported in subjects with FH, but their pathogenicity has not been proved. The fourth, a mutation in LDLR affecting a splicing site (exon 6–intron 6) has not previously been reported; it was found to segregate with high cholesterol levels in the family of the proband.ConclusionsUsing a combination of clinical criteria and targeted next‐generation sequencing, we have achieved FH diagnosis with a high success rate. Furthermore, we identified a new splicing‐site mutation in the LDLR gene.
Antitumour activity of melatonin in a mouse model of human prostate cancer: relationship with hypoxia signalling
Authors: Paroni Rita , Terraneo Laura , Bonomini Francesca , Finati Elena , Virgili Eleonora , Bianciardi Paola , Favero Gaia , Fraschini Franco , Reiter Russel J. , Rezzani Rita , Samaja Michele 
Published: May 2014

AbstractMelatonin is known to exert antitumour activity in several types of human cancers, but the underlying mechanisms as well as the efficacy of different doses of melatonin are not well defined. Here, we test the hypothesis whether melatonin in the nanomolar range is effective in exerting antitumour activity in vivo and examine the correlation with the hypoxia signalling mechanism, which may be a major molecular mechanism by which melatonin antagonizes cancer. To test this hypothesis, LNCaP human prostate cancer cells were xenografted into seven‐wk‐old Foxn1nu/nu male mice that were treated with melatonin (18 i.p. injections of 1 mg/kg in 41 days). Saline‐treated mice served as control. We found that the melatonin levels in plasma and xenografted tissue were 4× and 60× higher, respectively, than in control samples. Melatonin tended to restore the redox imbalance by increasing expression of Nrf2. As part of the phenotypic response to these perturbations, xenograft microvessel density was less in melatonin‐treated animals, indicative of lower angiogenesis, and the xenograft growth rate was slower (P < 0.0001). These changes were accompanied by a reduced expression of Ki67, elevated expression of HIF‐1α and increased phosphorylation of Akt in melatonin than saline‐treated mice. We conclude that the beneficial effect of melatonin in reducing cancer growth in vivo was evident at melatonin plasma levels as low as 4 nm and was associated with decreased angiogenesis. Higher HIF‐1α expression in xenograft tissue indicates that the antitumour effect cannot be due to a postulated antihypoxic effect, but may stem from lower angiogenesis potential.
The effect of season and track condition on injury rate in racing greyhounds
Authors: Iddon J. , Lockyer R. H. , Frean S. P. 
Published: May 2014

OBJECTIVESTo identify environmental and management factors affecting injury rate in racing greyhounds.METHODSSurveys of racing injuries at two greyhound tracks in the UK were conducted using injury data collected by track veterinary surgeons. At Track A the relative frequency of common injuries was determined and compared with previously published studies conducted in the UK. At Track B the effects of month of the year, ambient temperature and track condition (“going”) on injury rate were determined.RESULTSComparison of common injuries at Track A with previous studies suggested a change in the relative frequency of some injury types following a change in track surface from grass to sand. Estimated injury rates suggest improved track safety with the change in track surface. At Track B, injury rate increased significantly with faster track conditions. Time of year and ambient temperature had no significant effect on injury rate.CLINICAL SIGNIFICANCEChanges in track maintenance resulting in a slower track may reduce injury rate in racing greyhounds, with associated welfare benefits.
Diversification of an emerging pathogen in a biodiversity hotspot: Leptospira in endemic small mammals of Madagascar
Authors: Dietrich Muriel , Wilkinson David A. , Soarimalala Voahangy , Goodman Steven M. , Dellagi Koussay , Tortosa Pablo 
Published: May 2014

AbstractBiodiversity hotspots and associated endemism are ideal systems for the study of parasite diversity within host communities. Here, we investigated the ecological and evolutionary forces acting on the diversification of an emerging bacterial pathogen, Leptospira spp., in communities of endemic Malagasy small mammals. We determined the infection rate with pathogenic Leptospira in 20 species of sympatric rodents (subfamily Nesomyinae) and tenrecids (family Tenrecidae) at two eastern humid forest localities. A multilocus genotyping analysis allowed the characterization of bacterial diversity within small mammals and gave insights into their genetic relationships with Leptospira infecting endemic Malagasy bats (family Miniopteridae and Vespertilionidae). We report for the first time the presence of pathogenic Leptospira in Malagasy endemic small mammals, with an overall prevalence of 13%. In addition, these hosts harbour species of Leptospira (L. kirschneri, L. borgpetersenii and L. borgpetersenii group B) which are different from those reported in introduced rats (L. interrogans) on Madagascar. The diversification of Leptospira on Madagascar can be traced millions of years into evolutionary history, resulting in the divergence of endemic lineages and strong host specificity. These observations are discussed in relation to the relative roles of endemic vs. introduced mammal species in the evolution and epidemiology of Leptospira on Madagascar, specifically how biodiversity and biogeographical processes can shape community ecology of an emerging pathogen and lead to its diversification within native animal communities.
Bridging physiological and evolutionary time‐scales in a gene regulatory network
Authors: Marchand Gwenaëlle , Huynh‐Thu Vân Anh , Kane Nolan C. , Arribat Sandrine , Varès Didier , Rengel David , Balzergue Sandrine , Rieseberg Loren H. , Vincourt Patrick , Geurts Pierre , Vignes Matthieu , Langlade Nicolas B. 
Published: May 2014

Summary

Gene regulatory networks (GRNs) govern phenotypic adaptations and reflect the trade‐offs between physiological responses and evolutionary adaptation that act at different time‐scales. To identify patterns of molecular function and genetic diversity in GRNs, we studied the drought response of the common sunflower, Helianthus annuus, and how the underlying GRN is related to its evolution.

We examined the responses of 32 423 expressed sequences to drought and to abscisic acid (ABA) and selected 145 co‐expressed transcripts. We characterized their regulatory relationships in nine kinetic studies based on different hormones. From this, we inferred a GRN by meta‐analyses of a Gaussian graphical model and a random forest algorithm and studied the genetic differentiation among populations (FST) at nodes.

We identified two main hubs in the network that transport nitrate in guard cells. This suggests that nitrate transport is a critical aspect of the sunflower physiological response to drought. We observed that differentiation of the network genes in elite sunflower cultivars is correlated with their position and connectivity.

This systems biology approach combined molecular data at different time‐scales and identified important physiological processes. At the evolutionary level, we propose that network topology could influence responses to human selection and possibly adaptation to dry environments.
Investigation of Central Nervous System Dysfunction in Chronic Pelvic Pain Using Magnetic Resonance Spectroscopy and Noninvasive Brain Stimulation
Authors: Simis Marcel , Reidler Jay S. , Duarte Macea Debora , Moreno Duarte Ingrid , Wang Xiaoen , Lenkinski Robert , Petrozza John C. , Fregni Felipe 
Published: May 2014

AbstractBackgroundRecent studies demonstrate that chronic pelvic pain is associated with altered afferent sensory input resulting in maladaptive changes in the neural circuitry of pain. To better understand the central changes associated with chronic pelvic pain, we investigated the contributions of critical pain‐related neural circuits using single‐voxel proton magnetic resonance spectroscopy (MRS) and transcranial direct current stimulation (tDCS).MethodsWe measured concentrations of neural metabolites in 4 regions of interest (thalamus, anterior cingulate cortex, primary motor, and occipital cortex [control]) at baseline and after 10 days of active or sham tDCS in patients with chronic pelvic pain. We then compared our results to those observed in healthy controls, matched by age and gender.ResultsWe observed a significant increase in pain thresholds after active tDCS compared with sham conditions. There was a correlation between metabolite concentrations at baseline and quantitative sensory assessments. Chronic pelvic pain patients had significantly lower levels of NAA/Cr in the primary motor cortex compared with healthy patients.ConclusionstDCS increases pain thresholds in patients with chronic pelvic pain. Biochemical changes in pain‐related neural circuits are associated with pain levels as measured by objective pain testing. These findings support the further investigation of targeted cortical neuromodulatory interventions for chronic pelvic pain.