bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical utility of two human portable blood glucose meters in canine and feline practice
Authors: Domori Asuka , Sunahara Ayano , Tateno Morihiro , Miyama Takako Shimokawa , Setoguchi Asuka , Endo Yasuyuki 
Published: January 2014

BackgroundPortable blood glucose meters (PBGMs) are useful for serial measurements of blood glucose and creation of blood glucose curves in veterinary practice. However, it is necessary to validate PBGMs designed for people for veterinary use.ObjectivesOur objective was to evaluate the accuracy of 2 PBGMs designed for people for use in dogs and cats.MethodsThe blood glucose levels were determined in blood samples collected from 69 dogs and 26 cats admitted to the Kagoshima University Veterinary Teaching Hospital, using a MEDISAFE [PBGM‐T] and an Antsense III [PBGM‐H], and a FUJI DRI‐CHEM 7000V as reference method. The correlations and agreements among the results were statistically analyzed.ResultsSimple regression analyses revealed a high correlation between values from both PBGMs and the reference method in both dogs and cats. However, Passing–Bablok regression and Bland–Altman analyses revealed that the data from both PBGMs did not show statistical agreement with the reference values. Concordance correlated coefficients were moderate for the PBGM‐T and almost perfect for the PBGM‐H for canine samples, and were poor for the PBGM‐T and substantial for the PBGM‐H for feline samples. Hematocrit values significantly affected the results of the PBGM‐T, but not the PBGM‐H. Error grid analyses revealed that all measurements from both PBGMs would lead to acceptable treatment decisions.ConclusionsOur findings suggest that both PBGMs, especially the PBGM‐H, would be clinically useful in small animal practice, although there was a bias between each PBGM and the reference method.
Platelet count and plateletcrit in Cavalier King Charles Spaniels and Greyhounds using the Advia 120 and 2120
Authors: Kelley Jessica , Sharkey Leslie C. , Christopherson Pete W. , Rendahl Aaron 
Published: January 2014

BackgroundModels for the regulation of thrombopoiesis predict that platelet mass is the biologically regulated variable, yet clinical evaluations of thrombopoiesis are often based on platelet number. When thrombocytopenia and variation in platelet size occur concurrently, platelet count may poorly estimate total platelet mass, confounding clinical decision making.ObjectiveWe hypothesized that plateletcrit (PCT) provides clinically important information when platelet number is an incomplete representation of platelet mass, such as in genetic macrothrombocytopenia.MethodsWe retrospectively compared platelet count andPCTs with general reference intervals for 4 groups of dogs: sick Cavalier King Charles Spaniels (CKCS) and Greyhounds, presented for nonhematopoietic disease to the University of Minnesota (measured using an Advia 2120) and Auburn University Teaching Hospitals (measured using an Advia 120) over a 3‐year period.ResultsA caninePCTreference interval of 0.129–0.403% was established. None of the 4 sample groups had significantly more individuals below the reference interval for plateletcrit. For platelet count, only the 2 CKCS groups had significantly more individuals below the reference interval than predicted.ConclusionUse of thePCTas determined by the Advia 120/2120 appeared to avoid overestimation of low platelet mass in sick CKCS in a clinical setting. In contrast, thePCTperformed similarly to the platelet count in evaluation of platelet mass in sick Greyhounds. Evaluation of thePCTshould be considered in other conditions associated with increased mean platelet volume.
Increases in heart rate and serum cortisol concentrations in healthy dogs are positively correlated with an indoor waiting‐room environment
Authors: Perego Roberta , Proverbio Daniela , Spada Eva 
Published: January 2014

BackgroundFew studies have investigated the effect of veterinary clinical procedures on the welfare of dogs, with specific emphasis on the veterinary practice environment. Clinicopathologic variables have also not been assessed in these potentially stressful situations. Similar to human clinical studies, the veterinary clinical waiting room could present a significant stress factor for dogs.ObjectivesThe present study was designed to investigate the effect of waiting‐room environment on serum cortisol and glucose alterations as well as heart rate in privately owned healthy dogs.MethodsThe clinical trial included 24 healthy dogs that were divided into 2 groups: the clinical waiting‐room group (A) and the control group (B) that waited outside in a garden. During the entire experiment, 18 dogs (9 dogs per group) were monitored with a human heart rate monitor fastened around the chest. After 20 minutes of waiting, blood samples were collected from all of the dogs (24 dogs) to determine serum cortisol concentration.ResultsSerum cortisol concentration and mean, maximum, and minimum heart rate were significantly higher in group A compared with group B, but there was no statistical difference in serum glucose concentrations between the 2 study groups.ConclusionsResults of this study suggest that the waiting room is a potentially stressful situation for dogs in clinical veterinary practice, when compared with a garden, based on the assessment of adrenal cortex function and heart rate evaluation.
The Reach, Transferability, and Impact of the Evidence‐Based Practice Questionnaire: A Methodological and Narrative Literature Review
Authors: Upton Dominic , Upton Penney , Scurlock‐Evans Laura 
Published: January 2014

ABSTRACTBackgroundSince the 1990s, evidence‐based practice (EBP) has been increasingly emphasized in nursing, but its implementation is still sometimes met with confusion and resistance. Therefore, identifying factors affecting its implementation is crucial. The Evidence‐Based Practice Questionnaire (EBPQ) was published in 2006, addressing a need for a robust measure of nurses’ practice of, attitudes toward, and knowledge of EBP. The growing body of professionals using the questionnaire means that a review of its reach, transferability, and impact is timely.AimsThe aims of this review were threefold: (a) identify the situations in which the EBPQ has been used in both published and unpublished research internationally (Reach); (b) collate the psychometric properties of the EBPQ from the research reviewed (Transferability); and (c) discuss the study's findings to shed new light on issues facing professionals in implementing EBP, and possible future directions for research (Impact).MethodsLiterature searches on studies reported between 2006 and July 2012 inclusive were conducted using the terms “Evidence‐Based Practice Questionnaire” and “EBPQ.” Green, Johnson and Adams's guidelines for completing narrative literature reviews and Terwee et al.'s framework for reporting questionnaires’ psychometric properties were adopted to ensure rigor.FindingsTwenty‐seven studies were reviewed in which the EBPQ had been translated into five different languages and used with a variety of professional groups. The questionnaire demonstrated convergent and discriminant validity and good internal reliability. Research adopting the questionnaire identified a range of variables related to EBP implementation, including qualification route and job role.Linking Evidence to ActionAssessment of organizational culture and workforce training needs prior to developing educational interventions is crucial. The EBPQ has the potential to provide further understanding of these and other issues faced by professionals when implementing EBP.
The Establishment of Evidence‐Based Practice Competencies for Practicing Registered Nurses and Advanced Practice Nurses in Real‐World Clinical Settings: Proficiencies to Improve Healthcare Quality, Reliability, Patient Outcomes, and Costs
Authors: Melnyk Bernadette Mazurek , Gallagher‐Ford Lynn , Long Lisa English , Fineout‐Overholt Ellen 
Published: January 2014

ABSTRACTBackgroundAlthough it is widely known that evidence‐based practice (EBP) improves healthcare quality, reliability, and patient outcomes as well as reduces variations in care and costs, it is still not the standard of care delivered by practicing clinicians across the globe. Adoption of specific EBP competencies for nurses and advanced practice nurses (APNs) who practice in real‐world healthcare settings can assist institutions in achieving high‐value, low‐cost evidence‐based health care.AimThe aim of this study was to develop a set of clear EBP competencies for both practicing registered nurses and APNs in clinical settings that can be used by healthcare institutions in their quest to achieve high performing systems that consistently implement and sustain EBP.MethodsSeven national EBP leaders developed an initial set of competencies for practicing registered nurses and APNs through a consensus building process. Next, a Delphi survey was conducted with 80 EBP mentors across the United States to determine consensus and clarity around the competencies.FindingsTwo rounds of the Delphi survey resulted in total consensus by the EBP mentors, resulting in a final set of 13 competencies for practicing registered nurses and 11 additional competencies for APNs.Linking Evidence to ActionIncorporation of these competencies into healthcare system expectations, orientations, job descriptions, performance appraisals, and clinical ladder promotion processes could drive higher quality, reliability, and consistency of healthcare as well as reduce costs. Research is now needed to develop valid and reliable tools for assessing these competencies as well as linking them to clinician and patient outcomes.
Hypermuscular mice with mutation in the myostatin gene display altered calcium signalling
Authors: Bodnár Dóra , Geyer Nikolett , Ruzsnavszky Olga , Oláh Tamás , Hegyi Bence , Sztretye Mónika , Fodor János , Dienes Beatrix , Balogh Ágnes , Papp Zoltán , Szabó László , Müller Géza , Csernoch László , Szentesi Péter 
Published: January 2014

Key points
Hypermuscularity associated with naturally occurring mutations in the myostatin gene as found in Compact mice results in increased muscle mass but reduced specific force.
The calcium sensitivity of the contractile apparatus as assessed on chemically skinned skeletal muscle fibres under isometric conditions is not altered in these animals.
While the resting calcium concentration remains unaffected, depolarization‐evoked increases in intracellular calcium concentration are suppressed.
Spontaneous calcium release events from sarcoplasmic reticulum are also decreased in frequency, amplitude and spatial spread.
Our results suggest that mutations in the myostatin gene are accompanied by alterations in excitation contraction coupling, which manifest as a reduction in sarcoplasmic calcium release.
AbstractMyostatin, a member of the transforming growth factor β family, is a potent negative regulator of skeletal muscle growth, as myostatin‐deficient mice show a great increase in muscle mass. Yet the physical performance of these animals is reduced. As an explanation for this, alterations in the steps in excitation–contraction coupling were hypothesized and tested for in mice with the 12 bp deletion in the propeptide region of the myostatin precursor (MstnCmpt‐dl1Abc or Cmpt). In voluntary wheel running, control C57BL/6 mice performed better than the mutant animals in both maximal speed and total distance covered. Despite the previously described lower specific force of Cmpt animals, the pCa–force relationship, determined on chemically permeabilized fibre segments, did not show any significant difference between the two mouse strains. While resting intracellular Ca2+ concentration ([Ca2+]i) measured on single intact flexor digitorum brevis (FDB) muscle fibres using Fura‐2 AM was similar to control (72.0 ± 1.7 vs. 78.1 ± 2.9 nm, n = 38 and 45), the amplitude of KCl‐evoked calcium transients was smaller (360 ± 49 vs. 222 ± 45 nm, n = 22) in the mutant strain. Similar results were obtained using tetanic stimulation and Rhod‐2 AM, which gave calcium transients that were smaller (2.42 ± 0.11 vs. 2.06 ± 0.10 ΔF/F0, n = 14 and 13, respectively) on Cmpt mice. Sarcoplasmic reticulum (SR) calcium release flux calculated from these transients showed a reduced peak (23.7 ± 3.0 vs. 15.8 ± 2.1 mMs−1) and steady level (5.7 ± 0.7 vs. 3.7 ± 0.5 mm s−1) with no change in the peak‐to‐steady ratio. The amplitude and spatial spread of calcium release events detected on permeabilized FDB fibres were also significantly smaller in mutant mice. These results suggest that reduced SR calcium release underlies the reduced muscle force in Cmpt animals.
Genetic ablation of ryanodine receptor 2 phosphorylation at Ser‐2808 aggravates Ca2+‐dependent cardiomyopathy by exacerbating diastolic Ca2+ release
Authors: Liu Bin , Ho Hsiang‐Ting , Velez‐Cortes Florencia , Lou Qing , Valdivia Carmen R. , Knollmann Bjorn C. , Valdivia Hector H. , Gyorke Sandor 
Published: January 2014

Key points
Phosphorylation at Ser‐2808 is suggested to result in RyR2 hyperactivity, i.e. ‘leakiness’, thus contributing to the pathology of cardiac diseases.
We studied the effect of disabling phosphorylation at Ser‐2808 of RyR2 in a genetic model of Ca2+‐dependent cardiomyopathy, which was caused by leaky RyR2.
RyR2 phosphorylation was high at Ser‐2808 in myocytes expressing wild‐type (WT) RyR2; protein phosphatase increased RyR2 leakiness in cells expressing WT, but not in mutant RyR2s with disabled Ser‐2808 phosphorylation sites.
Rather than alleviating cardiac disease, ablation of the Ser‐2808 exacerbated the disease phenotype by reducing survival, impairing in vivo cardiac function and enhancing RyR2 Ca2+ leak and mitochondrial damage.
These results suggest a novel mode of RyR2 regulation via dephosphorylation at Ser‐2808 in normal and diseased hearts.
AbstractPhosphorylation of the cardiac ryanodine receptor (RyR2) by protein kinase A (PKA) at Ser‐2808 is suggested to mediate the physiological ‘fight or flight’ response and contribute to heart failure by rendering the sarcoplasmic reticulum (SR) leaky for Ca2+. In the present study, we examined the potential role of RyR2 phosphorylation at Ser‐2808 in the progression of Ca2+‐dependent cardiomyopathy (CCM) by using mice genetically modified to feature elevated SR Ca2+ leak while expressing RyR2s that cannot be phosphorylated at this site (S2808A). Surprisingly, rather than alleviating the disease phenotype, constitutive dephosphorylation of Ser‐2808 aggravated CCM as manifested by shortened survival, deteriorated in vivo cardiac function, exacerbated SR Ca2+ leak and mitochondrial injury. Notably, the deteriorations of cardiac function, myocyte Ca2+ handling, and mitochondria integrity were consistently worse in mice with heterozygous ablation of Ser‐2808 than in mice with complete ablation. Wild‐type (WT) and CCM myocytes expressing unmutated RyR2s exhibited a high level of baseline phosphorylation at Ser‐2808. Exposure of these CCM cells to protein phosphatase 1 caused a transitory increase in Ca2+ leak attributable to partial dephosphorylation of RyR2 tetramers at Ser‐2808 from more fully phosphorylated state. Thus, exacerbated Ca2+ leak through partially dephosphorylated RyR2s accounts for the prevalence of the disease phenotype in the heterozygous S2808A CCM mice. These results do not support the importance of RyR2 hyperphosphorylation in Ca2+‐dependent heart disease, and rather suggest roles for the opposite process, the RyR2 dephosphorylation at this residue in physiological and pathophysiological Ca2+ signalling.
Adult spinal motoneurones are not hyperexcitable in a mouse model of inherited amyotrophic lateral sclerosis
Authors: Delestrée Nicolas , Manuel Marin , Iglesias Caroline , Elbasiouny Sherif M. , Heckman C. J. , Zytnicki Daniel 
Published: January 2014

Key points
Intrinsic hyperexcitability of spinal motoneurones is thought to contribute to excitotoxicity during amyotrophic lateral sclerosis (ALS), but it has never been demonstrated that adult motoneurones become hyperexcitable before disconnection from their muscle fibres.
We found an increased input conductance in motoneurones recorded in a mouse model of ALS. Yet, most cells retained normal excitability as measured by current onset for firing and input–output gain. This indicates successful regulation of excitability, compensating for the increase in conductance.
In contrast, some cells became hypoexcitable, losing their ability to fire repetitively to quasi‐stationary inputs before denervation. Hypoexcitability might therefore be an early marker of disease progression.
We thereby demonstrate that, if excitotoxicity is indeed a mechanism leading to degeneration in ALS, it is not caused by changes in the intrinsic electrical properties of the motoneurones but most probably by extrinsic factors such as excessive synaptic excitation.
AbstractIn amyotrophic lateral sclerosis (ALS), an adult onset disease in which there is progressive degeneration of motoneurones, it has been suggested that an intrinsic hyperexcitability of motoneurones (i.e. an increase in their firing rates), contributes to excitotoxicity and to disease onset. Here we show that there is no such intrinsic hyperexcitability in spinal motoneurones. Our studies were carried out in an adult mouse model of ALS with a mutated form of superoxide dismutase 1 around the time of the first muscle fibre denervations. We showed that the recruitment current, the voltage threshold for spiking and the frequency–intensity gain in the primary range are all unchanged in most spinal motoneurones, despite an increased input conductance. On its own, increased input conductance would decrease excitability, but the homeostasis for excitability is maintained due to an upregulation of a depolarizing current that is activated just below the spiking threshold. However, this homeostasis failed in a substantial fraction of motoneurones, which became hypoexcitable and unable to produce sustained firing in response to ramps of current. We found similar results both in lumbar motoneurones recorded in anaesthetized mice, and in sacrocaudal motoneurones recorded in vitro, indicating that the lack of hyperexcitability is not caused by anaesthetics. Our results suggest that, if excitotoxicity is indeed a mechanism leading to degeneration in ALS, it is not caused by the intrinsic electrical properties of motoneurones but by extrinsic factors such as excessive synaptic excitation.
Deficiency of slow skeletal muscle troponin T causes atrophy of type I slow fibres and decreases tolerance to fatigue
Authors: Wei Bin , Lu Yingru , Jin J.‐P. 
Published: January 2014

Key points
Loss of slow skeletal muscle troponin T (ssTnT) due to a nonsense mutation in codon Glu180 causes a lethal form of recessively inherited nemaline myopathy.
We studied the phenotypes of partial and total loss of ssTnT in the diaphragm and soleus muscles of Tnnt1 gene targeted mice.
ssTnT deficiency resulted in significant decreases in other slow fibre‐specific myofilament proteins whereas fast fibre‐specific myofilament proteins were increased correspondingly.
ssTnT deficiency produced significantly smaller type I slow fibres and compensatory growth of type II fast fibres with significantly reduced contractile force and tolerance to fatigue.
ssTnT‐deficient soleus muscle exhibited a significant numbers of small‐sized central nuclei type I fibres, indicating regeneration.
The data support the critical role of ssTnT in skeletal muscle function and the causal effect of its loss on the pathogenesis of nemaline myopathy.
AbstractThe total loss of slow skeletal muscle troponin T (ssTnT encoded by TNNT1 gene) due to a nonsense mutation in codon Glu180 causes a lethal form of recessively inherited nemaline myopathy (Amish nemaline myopathy, ANM). To investigate the pathogenesis and muscle pathophysiology of ANM, we studied the phenotypes of partial and total loss of ssTnT in Tnnt1 gene targeted mice. An insertion of neomycin resistance cassette in intron 10 of Tnnt1 gene caused an approximately 60% decrease in ssTnT protein expression whereas cre‐loxP‐mediated deletion of exons 11–13 resulted in total loss of ssTnT, as seen in ANM muscles. In diaphragm and soleus muscles of the knockdown and knockout mouse models, we demonstrated that ssTnT deficiency resulted in significantly decreased levels of other slow fibre‐specific myofilament proteins whereas fast fibre‐specific myofilament proteins were increased correspondingly. Immunohistochemical studies revealed that ssTnT deficiency produced significantly smaller type I slow fibres and compensatory growth of type II fast fibres. Along with the slow fibre atrophy and the changes in myofilament protein isoform contents, ssTnT deficiency significantly reduced the tolerance to fatigue in soleus muscle. ssTnT‐deficient soleus muscle also contains significant numbers of small‐sized central nuclei type I fibres, indicating active regeneration. The data provide strong support for the essential role of ssTnT in skeletal muscle function and the causal effect of its loss in the pathology of ANM. This observation further supports the hypothesis that the function of slow fibres can be restored in ANM patients if a therapeutic supplement of ssTnT is achieved.
Purinergic signalling contributes to chemoreception in the retrotrapezoid nucleus but not the nucleus of the solitary tract or medullary raphe
Authors: Sobrinho Cleyton R. , Wenker Ian C. , Poss Erin M. , Takakura Ana C. , Moreira Thiago S. , Mulkey Daniel K. 
Published: January 2014

Key points
Several brain regions are thought to sense changes in tissue CO2/H+ to regulate breathing (i.e. central chemoreceptors) including the nucleus of the solitary tract (NTS), medullary raphe and retrotrapezoid nucleus (RTN).
Mechanism(s) underlying RTN chemoreception involve direct activation of RTN neurons by H+‐mediated inhibition of a resting K+ conductance and indirect activation of RTN neurons by purinergic signalling, most likely from CO2/H+‐sensitive astrocytes.
Here, we confirm that activation of P2 receptors in the RTN stimulates cardiorespiratory activity, and we show at the cellular and systems level that purinergic signalling is not essential for CO2/H+ sensing in the NTS or medullary raphe.
These results support the possibility that purinergic signalling is a unique feature of RTN chemoreception.
AbstractSeveral brain regions are thought to function as important sites of chemoreception including the nucleus of the solitary tract (NTS), medullary raphe and retrotrapezoid nucleus (RTN). In the RTN, mechanisms of chemoreception involve direct H+‐mediated activation of chemosensitive neurons and indirect modulation of chemosensitive neurons by purinergic signalling. Evidence suggests that RTN astrocytes are the source of CO2‐evoked ATP release. However, it is not clear whether purinergic signalling also influences CO2/H+ responsiveness of other putative chemoreceptors. The goals of this study are to determine if CO2/H+‐sensitive neurons in the NTS and medullary raphe respond to ATP, and whether purinergic signalling in these regions influences CO2 responsiveness in vitro and in vivo. In brain slices, cell‐attached recordings of membrane potential show that CO2/H+‐sensitive NTS neurons are activated by focal ATP application; however, purinergic P2‐receptor blockade did not affect their CO2/H+ responsiveness. CO2/H+‐sensitive raphe neurons were unaffected by ATP or P2‐receptor blockade. In vivo, ATP injection into the NTS increased cardiorespiratory activity; however, injection of a P2‐receptor blocker into this region had no effect on baseline breathing or CO2/H+ responsiveness. Injections of ATP or a P2‐receptor blocker into the medullary raphe had no effect on cardiorespiratory activity or the chemoreflex. As a positive control we confirmed that ATP injection into the RTN increased breathing and blood pressure by a P2‐receptor‐dependent mechanism. These results suggest that purinergic signalling is a unique feature of RTN chemoreception.