bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre‐ischaemic mitochondrial substrate constraint by inhibition of malate‐aspartate shuttle preserves mitochondrial function after ischaemia–reperfusion
Authors: Jespersen Nichlas Riise , Yokota Takashi , Støttrup Nicolaj Brejnholt , Bergdahl Andreas , Pælestik Kim Bolther , Povlsen Jonas Agerlund , Dela Flemming , Bøtker Hans Erik 
Published: January 2017

Key points
Pre‐ischaemic administration of aminooxiacetate (AOA), an inhibitor of the malate‐aspartate shuttle (MAS), provides cardioprotection against ischaemia–reperfusion injury. The underlying mechanism remains unknown.
We examined whether transient inhibition of the MAS during ischaemia and early reperfusion by AOA treatment could prevent mitochondrial damage at later reperfusion.
The AOA treatment preserved mitochondrial respiratory capacity with reduced mitochondrial oxidative stress during late reperfusion to the same extent as ischaemic preconditioning (IPC).
However, AOA treatment, but not IPC, reduced the myocardial interstitial concentration of tricarboxylic acid cycle intermediates at the onset of reperfusion.
The results obtained in the present study demonstrate that metabolic regulation by inhibition of the MAS at the onset of reperfusion may be beneficial for the preservation of mitochondrial function during late reperfusion in an IR‐injured heart.
AbstractMitochondrial dysfunction plays a central role in ischaemia–reperfusion (IR) injury. Pre‐ischaemic administration of aminooxyacetate (AOA), an inhibitor of the malate‐aspartate shuttle (MAS), provides cardioprotection against IR injury, although the underlying mechanism remains unknown. We hypothesized that a transient inhibition of the MAS during ischaemia and early reperfusion could preserve mitochondrial function at later phase of reperfusion in the IR‐injured heart to the same extent as ischaemic preconditioning (IPC), which is a well‐validated cardioprotective strategy against IR injury. In the present study, we show that pre‐ischaemic administration of AOA preserved mitochondrial complex I‐linked state 3 respiration and fatty acid oxidation during late reperfusion in IR‐injured isolated rat hearts. AOA treatment also attenuated the excessive emission of mitochondrial reactive oxygen species during state 3 with complex I‐linked substrates during late reperfusion, which was consistent with reduced oxidative damage in the IR‐injured heart. As a result, AOA treatment reduced infarct size after reperfusion. These protective effects of MAS inhibition on the mitochondria were similar to those of IPC. Intriguingly, the protection of mitochondrial function by AOA treatment appears to be different from that of IPC because AOA treatment, but not IPC, downregulated myocardial tricarboxilic acid (TCA)‐cycle intermediates at the onset of reperfusion. MAS inhibition thus preserved mitochondrial respiratory capacity and decreased mitochondrial oxidative stress during late reperfusion in the IR‐injured heart, at least in part, via metabolic regulation of TCA cycle intermediates in the mitochondria at the onset of reperfusion.
Presynaptic inhibition of transient receptor potential vanilloid type 1 (TRPV1) receptors by noradrenaline in nociceptive neurons
Authors: Chakraborty Saikat , Elvezio Vincent , Kaczocha Martin , Rebecchi Mario , Puopolo Michelino 
Published: January 2017

Key points
The transient receptor potential vanilloid type 1 (TRPV1) receptor is a polymodal molecular integrator in the pain pathway expressed in Aδ‐ and C‐fibre nociceptors and is responsible for the thermal hyperalgesia associated with inflammatory pain.
Noradrenaline strongly inhibited the activity of TRPV1 channels in dorsal root ganglia neurons. The effect of noradrenaline was reproduced by clonidine and antagonized by yohimbine, consistent with contribution of α2 adrenergic receptors.
The inhibitory effect of noradrenaline on TRPV1 channels was dependent on calcium influx and linked to calcium/calmodulin‐dependent protein kinase II.
In spinal cord slices, clonidine reduced the frequency of capsaicin‐induced miniature EPSCs in the presence of tetrodotoxin and ω‐conotoxin‐MVIIC, consistent with inhibition of presynaptic TRPV1 channels by α2 adrenergic receptors.
We suggest that modulation of presynaptic TRPV1 channels in nociceptive neurons by descending noradrenergic inputs may constitute a mechanism for noradrenaline to modulate incoming noxious stimuli in the dorsal horn of the spinal cord.
AbstractThe transient receptor potential vanilloid type 1 (TRPV1) receptor is a well‐known contributor to nociceptor excitability. To address whether noradrenaline can down‐regulate TRPV1 channel activity in nociceptors and reduce their synaptic transmission, the effects of noradrenaline and clonidine were tested on the capsaicin‐activated current recorded from acutely dissociated small diameter (<27 μm) dorsal root ganglia (DRG) neurons and on miniature (m)EPSCs recorded from large lamina I neurons in horizontal spinal cord slices. Noradrenaline or clonidine inhibited the capsaicin‐activated current by ∼60%, and the effect was reversed by yohimbine, confirming that it was mediated by activation of α2 adrenergic receptors. Similarly, clonidine reduced the frequency of capsaicin‐induced mEPSCs by ∼60%. Inhibition of capsaicin‐activated current by noradrenaline was mediated by GTP binding proteins, and was highly dependent on calcium influx. The inhibitory effect of noradrenaline on the capsaicin‐activated current was not affected either by blocking the activity of protein kinase A with H89, or by blocking the activity of protein kinase C with bisindolylmaleimide II. In contrast, when the calcium/calmodulin‐dependent protein kinase II (CaMKII) was blocked with KN‐93, the inhibitory effect of noradrenaline on the capsaicin‐activated current was greatly reduced, suggesting that activation of adrenergic receptors in DRG neurons is preferentially linked to CaMKII activity. We suggest that modulation of TRPV1 channels by noradrenaline in nociceptive neurons is a mechanism whereby noradrenaline may suppress incoming noxious stimuli at the primary synaptic afferents in the dorsal horn of the spinal cord.
A Pilot Study Using Entropy as a Noninvasive Assessment of Running
Authors: Murray Andrew M. , Ryu Joong Hyun , Sproule John , Turner Anthony P. , Graham-Smith Phil , Cardinale Marco 
Published: January 2017

Purpose:Running performance is influenced by the interaction of biomechanical and physiological factors. Miniaturized accelerometers worn by athletes can be used to quantify mechanical aspects of running and as a noninvasive tool to assess training status and progression. The aim of this study was to define and validate a method to assess running regularity and allow the estimation of an individual’s oxygen uptake (V̇O2) and/or blood lactate—[La]b—based on data collected with accelerometers and heart rate.Methods:Male adolescent endurance athletes completed an incremental submaximal aerobic stage test where V̇O2 and [La]b were measured. The test was terminated when [La]b concentration at the end of the stage exceeded 4 mmol/L. Two wireless triaxial accelerometers were placed on participants’ right shank and lower back throughout the test. The root mean square (RMS) and sample entropy (SampEn) were calculated for the vertical, mediolateral, and anteroposterior components of acceleration.Results:There were significant positive correlations of acceleration and entropy variables with [La]b and V̇O2, with moderate to high coefficients (r = .43–.87). RMS of the shank acceleration was the most highly related with both physiological variables. When the accelerometer was attached on the trunk, SampEn of the vertical acceleration had the strongest relationship with V̇O2 (r = .76, P < .01).Conclusions:The described method analyzing running complexity may allow an assessment of gait variability, which noninvasively tracks V̇O2 and/or [La]b, allowing monitoring of fatigue or training readiness for trained adolescent individuals.
Impaired Player–Coach Perceptions of Exertion and Recovery During Match Congestion
Authors: Doeven Steven H. , Brink Michel S. , Frencken Wouter G.P. , Lemmink Koen A.P.M. 
Published: January 2017

During intensified phases of competition, attunement of exertion and recovery is crucial to maintain performance. Although a mismatch between coach and player perceptions of training load is demonstrated, it is unknown if these discrepancies also exist for match exertion and recovery.
Purpose:To determine match exertion and subsequent recovery and to investigate the extent to which the coach is able to estimate players’ match exertion and recovery.
Methods:Rating of perceived exertion (RPE) and total quality of recovery (TQR) of 14 professional basketball players (age 26.7 ± 3.8 y, height 197.2 ± 9.1 cm, weight 100.3 ± 15.2 kg, body fat 10.3% ± 3.6%) were compared with observations of the coach. During an in-season phase of 15 matches within 6 wk, players gave RPEs after each match. TQR scores were filled out before the first training session after the match. The coach rated observed exertion (ROE) and recovery (TQ-OR) of the players.
Results:RPE was lower than ROE (15.6 ± 2.3 and 16.1 ± 1.4; P = .029). Furthermore, TQR was lower than TQ-OR (12.7 ± 3.0 and 15.3 ± 1.3; P < .001). Correlations between coach- and player-perceived exertion and recovery were r = .25 and r = .21, respectively. For recovery within 1 d the correlation was r = .68, but for recovery after 1–2 d no association existed.
Conclusion:Players perceive match exertion as hard to very hard and subsequent recovery reasonable. The coach overestimates match exertion and underestimates degree of recovery. Correspondence between coach and players is thus not optimal. This mismatch potentially leads to inadequate planning of training sessions and decreases in performance during fixture congestion in basketball.
Paediatric ED BiPAP continuous quality improvement programme with patient analysis: 2005–2013
Authors: Abramo Thomas , Williams Abby , Mushtaq Samaiya , Meredith Mark , Sepaule Rawle , Crossman Kristen , Burney Jones Cheryl , Godbold Suzanne , Hu Zhuopei , Nick Todd 
Published: January 2017

ObjectiveIn paediatric moderate-to-severe asthmatics, there is significant bronchospasm, airway obstruction, air trapping causing severe hyperinflation with more positive intraplural pressure preventing passive air movement. These effects cause an increased respiratory rate (RR), less airflow and shortened inspiratory breath time. In certain asthmatics, aerosols are ineffective due to their inadequate ventilation. Bilevel positive airway pressure (BiPAP) in acute paediatric asthmatics can be an effective treatment. BiPAP works by unloading fatigued inspiratory muscles, a direct bronchodilation effect, offsetting intrinsic PEEP and recruiting collapsed alveoli that reduces the patient's work of breathing and achieves their total lung capacity quicker. Unfortunately, paediatric emergency department (PED) BiPAP is underused and quality analysis is non-existent. A PED BiPAP Continuous Quality Improvement Program (CQIP) from 2005 to 2013 was evaluated using descriptive analytics for the primary outcomes of usage, safety, BiPAP settings, therapeutics and patient disposition.InterventionsPED BiPAP CQIP descriptive analytics.SettingAcademic PED.Participants1157 patients.InterventionsA PED BiPAP CQIP from 2005 to 2013 for the usage, safety, BiPAP settings, therapeutic response parameters and patient disposition was evaluated using descriptive analytics.Primary and secondary outcomesSafety, usage, compliance, therapeutic response parameters, BiPAP settings and patient disposition.Results1157 patients had excellent compliance without complications. Only 6 (0.5%) BiPAP patients were intubated. BiPAP median settings: IPAP 18 (16,20) cm H2O range 12–28; EPAP 8 cmH2O (8,8) range 6–10; inspiratory-to-expiratory time (I:E) ratio 1.75 (1.5,1.75). Pediatric Asthma Severity score and RR decreased (p<0.001) while tidal volume increased (p<0.001). Patient disposition: 325 paediatric intensive care units (PICU), 832 wards, with 52 of these PED ward patients were discharged home with only 2 hours of PED BiPAP with no returning to the PED within 72 hours.ConclusionsBiPAP is a safe and effective therapeutic option for paediatric patients with asthma presenting to a PED or emergency department. This BiPAP CQIP showed significant patient compliance, no complications, improved therapeutics times, very low intubations and decreased PICU admissions. CQIP analysis demonstrated that using a higher IPAP, low EPAP with longer I:E optimises the patient's BiPAP settings and showed a significant improvement in PAS, RR and tidal volume. BiPAP should be considered as an early treatment in the PED severe or non-responsive moderate asthmatics.
Development and validation of a prediction model for gestational hypertension in a Ghanaian cohort
Authors: Antwi Edward , Groenwold Rolf H H , Browne Joyce L , Franx Arie , Agyepong Irene A , Koram Kwadwo A , Klipstein-Grobusch Kerstin , Grobbee Diederick E 
Published: January 2017

ObjectiveTo develop and validate a prediction model for identifying women at increased risk of developing gestational hypertension (GH) in Ghana.DesignA prospective study. We used frequencies for descriptive analysis, χ2test for associations and logistic regression to derive the prediction model. Discrimination was estimated by the c-statistic. Calibration was assessed by calibration plot of actual versus predicted probability.SettingPrimary care antenatal clinics in Ghana.Participants2529 pregnant women in the development cohort and 647 pregnant women in the validation cohort. Inclusion criterion was women without chronic hypertension.Primary outcomeGestational hypertension.ResultsPredictors of GH were diastolic blood pressure, family history of hypertension in parents, history of GH in a previous pregnancy, parity, height and weight. The c-statistic of the original model was 0.70 (95% CI 0.67–0.74) and 0.68 (0.60 to 0.77) in the validation cohort. Calibration was good in both cohorts. The negative predictive value of women in the development cohort at high risk of GH was 92.0% compared to 94.0% in the validation cohort.ConclusionsThe prediction model showed adequate performance after validation in an independent cohort and can be used to classify women into high, moderate or low risk of developing GH. It contributes to efforts to provide clinical decision-making support to improve maternal health and birth outcomes.
Burden of disease associated with lower levels of income among US adults aged 65 and older
Authors: Lubetkin Erica I , Jia Haomiao 
Published: January 2017

BackgroundPersons aged 65 years and older represent a heterogeneous group whose prevalence in the USA is expected to markedly increase. Few investigations have examined the total burden of disease attributable to lower levels of income in a single number that accounts for morbidity and mortality.MethodsWe ascertained respondents' health-related quality of life (HRQOL) scores and mortality status from the 2003 to 2004, 2005 to 2006, 2007 to 2008 and 2009 to 2010 cohorts of the National Health and Nutrition Examination Survey (NHANES) with mortality follow-up through 31 December 2011. A mapping algorithm based on respondents' age and answers to the 4 core Healthy Days questions was used to obtain values of a preference-based measure of HRQOL, the EuroQol five dimensions questionnaire (EQ-5D) index, which enables quality-adjusted life years (QALYs) to be calculated. We included only respondents aged 65 years and older at the baseline, yielding a total sample size of 4952. We estimated mean QALYs according to different categories of income based on the percentage of Federal Poverty Level (FPL).ResultsAfter adjusting for age, gender and education, the remaining QALYs decreased with each successive decrement of category of income, ranging from 18.4 QALY (≥500% FPL) to 8.6 QALY (<100% FPL). Compared with participants with a mean income of ≥250% FPL, participants with an income <250% FPL had significant losses in QALY for most of the sociodemographic groups examined. In contrast, persons with a lower educational attainment did not show a corresponding loss in QALY according to income category.ConclusionsThis study confirmed the association between lower income category and greater burden of disease, as measured by QALYs lost, among the US population aged 65 years and older. Our findings provide additional evidence of the role played by other key determinants of health and how factors not traditionally addressed by the healthcare system impact the life cycle of individuals and communities.
Percutaneous PFO closure for cryptogenic stroke in the setting of a systematic cardiac and neurological screening and a standardised follow-up protocol
Authors: Noble Stéphane , Bonvini Robert F , Rigamonti Fabio , Sztajzel Roman , Perren Fabienne , Meyer Philippe , Müller Hajo , Roffi Marco 
Published: January 2017

BackgroundThere are no uniform workup and follow-up (FU) protocols for patients presenting with cryptogenic embolism (CE) who undergo percutaneous closure of a patent foramen ovale (PFO).MethodsWe prospectively performed a systematic cardiac and neurological FU protocol in all patients who underwent percutaneous PFO closure in order to assess the incidence of subsequent cardiac and neurological adverse events. All patients received dual antiplatelet therapy for 6 months and were systematically included in a 12-month standardised FU protocol including: clinical evaluation—transthoracic and transoesophageal echocardiography, 24-hour Holter monitoring and/or 1-week R-test, and transcranial Doppler. Late FU (>12 months) was performed by reviewing medical records.ResultsOver a 10-year period, 221 consecutive patients underwent PFO closure for CE and 217 of them (98%) completed the 12-month FU. Ischaemic event recurrence at 12-month and late FU (mean time 69±35 months, median time 65 months, Q1:38 months, Q3:98 months) was observed in 6 (2.8%) and 3 patients (1.4%), respectively. The initial diagnosis of CE was reconsidered in 17 cases (7.8%), as the clinical and paraclinical FU exams showed possible alternative aetiologies for the initial event: 13 patients (6.0%) presented at least 1 episode of atrial fibrillation, while in 4 cases (1.8%) a non-ischaemic origin of the initial symptoms was identified.ConclusionsAlternative diagnoses explaining the initial symptoms are rarely detected with an in-depth screening for alternative diagnoses before PFO closure. Despite extensive screening, atrial fibrillation is the most frequently observed alternative aetiology for cryptogenic stroke.
Cardiac mechanics and dysfunction with anthracyclines in the community: results from the PREDICT study
Authors: Narayan Hari K , Wei Wei , Feng Ziding , Lenihan Daniel , Plappert Ted , Englefield Virginia , Fisch Michael , Ky Bonnie 
Published: January 2017

BackgroundOur objective was to determine the relevance of changes in myocardial mechanics in diagnosing and predicting cancer therapeutics-related cardiac dysfunction (CTRCD) in a community-based population treated with anthracyclines.MethodsQuantitative measures of cardiac mechanics were derived from 493 echocardiograms in 165 participants enrolled in the PREDICT study (A Multicenter Study inPatients Undergoing AnthRacycline-Based Chemotherapy to Assess theEffectiveness of Using Biomarkers toDetect andIdentifyCardiotoxicity and DescribeTreatment). Echocardiograms were obtained primarily at baseline (prior to anthracyclines), 6 and 12 months. Predictors included changes in strain; strain rate; indices of contractile function derived from the end-systolic pressure–volume relationship (end-systolic elastance (Eessb) and the left ventricular (LV) volume at an end-systolic pressure of 100 mm Hg (V100)); total arterial load (effective arterial elastance (Ea)) and ventricular–arterial coupling (Ea/Eessb). Logistic regression models determined the diagnostic and prognostic associations of changes in these measures and CTRCD, defined as a LV ejection fraction decline ≥10 to <50%.ResultsBy 12 months, 31 participants developed CTRCD. Longitudinal and circumferential strain and strain rate, V100, Ea, and Ea/Eessbeach demonstrated significant diagnostic associations, with a 1–7% increased odds of CTRCD (p<0.05). Changes in longitudinal strain rate (area under the curve (AUC) 0.719 (95% CI 0.595 to 0.843)), V100(AUC 0.796 (95% CI 0.686 to 0.903)) and Ea (AUC 0.742 (95% CI 0.632 to 0.852)) from baseline to 6 months were individually predictive of CTRCD at 12 months.ConclusionsChanges in non-invasively derived measures of myocardial mechanics are diagnostic and predictive of cardiac dysfunction with anthracycline chemotherapy in community populations. Our findings support the non-invasive assessment of measures of myocardial mechanics more broadly in clinical practice and emphasise the role of serial assessments of these measures during and after cardiotoxic cancer therapy.Trial registration numberNCT01032278; Pre-results.
Tectonostratigraphic framework and depositional history of the Cretaceous–Danian succession of the Danish Central Graben (North Sea) – new light on a mature area
Authors: van Buchem F. S. P. , Smit F. W. H. , Buijs G. J. A. , Trudgill B. , Larsen P.-H. 
Published: January 2017

Abstract
An integrated tectonic and sequence stratigraphic analysis of the Cretaceous and Danian of the Danish Central Graben has led to significant new insights critical for our understanding of the chalk facies as a unique cool-water carbonate system, as well as for the evaluation of its potential remaining economic significance.
A major regional unconformity in the middle of the Upper Cretaceous chalk has been dated as being of early Campanian age. It separates two distinctly different basin types: a thermal contraction early post-rift basin (Valanginian–Santonian), which was succeeded by an inversion tectonics-affected basin (Campanian–Danian). The infill patterns for these two basin types are dramatically different as a result of the changing influence of the tectonic, palaeoceanographic and eustatic controlling factors.
Several new insights are reported for the Lower Cretaceous: a new depositional model for chalk deposition along the basin margins on shallow shelves, which impacts reservoir quality trends; recognition of a late Aptian long-lasting sea-level lowstand (which hosts lowstand sandstone reservoirs in other parts of the North Sea Basin); and, finally, the observation that Barremian–Aptian sequences can be correlated from the Boreal to the Tethyan domain. In contrast, the Late Cretaceous sedimentation patterns have a strong synsedimentary local tectonic overprint (inversion) that influenced palaeoceanography through the intensification of bottom currents and, as a result, the depositional facies. In this context, four different chalk depositional systems are distinguished in the Chalk Group, with specific palaeogeography, depositional features and sediment composition.
The first formalization of the lithostratigraphic subdivision of the Chalk Group in the Danish Central Graben is proposed, as well as an addition to the Cromer Knoll Group.
From a Formalized Parallel Action Language to Its Efficient Code Generation
Authors: Llopard Ivan , Fabre Christian , Cohen Albert 
Published: January 2017

Modeling languages propose convenient abstractions and transformations to handle the complexity of today’s embedded systems. Based on the formalism of the Hierarchical State Machine, they enable the expression of hierarchical control parallelism. However, they face two important challenges when it comes to modeling data-intensive applications: no unified approach that also accounts for data-parallel actions and no effective code optimization and generation flows.
We propose a modeling language extended with parallel action semantics and hierarchical indexed-state machines suitable for computationally intensive applications. Together with its formal semantics, we present an optimizing model compiler aiming for the generation of efficient data-parallel implementations.