bluuebunny/crossref_metadata_2025_split huggingface dataset:
MitoBKCa channel is functionally associated with its regulatory β1 subunit in cardiac mitochondria
Authors: Balderas Enrique , Torres Natalia S. , Rosa‐Garrido Manuel , Chaudhuri Dipayan , Toro Ligia , Stefani Enrico , Olcese Riccardo 
Published: June 2019

Key points
Association of plasma membrane BKCa channels with BK‐β subunits shapes their biophysical properties and physiological roles; however, functional modulation of the mitochondrial BKCa channel (mitoBKCa) by BK‐β subunits is not established.
MitoBKCa‐α and the regulatory BK‐β1 subunit associate in mouse cardiac mitochondria.
A large fraction of mitoBKCa display properties similar to that of plasma membrane BKCa when associated with BK‐β1 (left‐shifted voltage dependence of activation, V1/2 = −55 mV, 12 µm matrix Ca2+).
In BK‐β1 knockout mice, cardiac mitoBKCa displayed a low Po and a depolarized V1/2 of activation (+47 mV at 12 µm matrix Ca2+)
Co‐expression of BKCa with the BK‐β1 subunit in HeLa cells doubled the density of BKCa in mitochondria.
The present study supports the view that the cardiac mitoBKCa channel is functionally modulated by the BK‐β1 subunit; proper targeting and activation of mitoBKCa shapes mitochondrial Ca2+ handling.
AbstractAssociation of the plasma membrane BKCa channel with auxiliary BK‐β1–4 subunits profoundly affects the regulatory mechanisms and physiological processes in which this channel participates. However, functional association of mitochondrial BK (mitoBKCa) with regulatory subunits is unknown. We report that mitoBKCa functionally associates with its regulatory subunit BK‐β1 in adult rodent cardiomyocytes. Cardiac mitoBKCa is a calcium‐ and voltage‐activated channel that is sensitive to paxilline with a large conductance for K+ of 300 pS. Additionally, mitoBKCa displays a high open probability (Po) and voltage half‐activation (V1/2 = −55 mV, n = 7) resembling that of plasma membrane BKCa when associated with its regulatory BK‐β1 subunit. Immunochemistry assays demonstrated an interaction between mitochondrial BKCa‐α and its BK‐β1 subunit. Mitochondria from the BK‐β1 knockout (KO) mice showed sparse mitoBKCa currents (five patches with mitoBKCa activity out of 28 total patches from n = 5 different hearts), displaying a depolarized V1/2 of activation (+47 mV in 12 µm matrix Ca2+). The reduced activity of mitoBKCa was accompanied by a high expression of BKCa transcript in the BK‐β1 KO, suggesting a lower abundance of mitoBKCa channels in this genotype. Accordingly, BK‐β1subunit increased the localization of BKDEC (i.e. the splice variant of BKCa that specifically targets mitochondria) into mitochondria by two‐fold. Importantly, both paxilline‐treated and BK‐β1 KO mitochondria displayed a more rapid Ca2+ overload, featuring an early opening of the mitochondrial transition pore. We provide strong evidence that mitoBKCa associates with its regulatory BK‐β1 subunit in cardiac mitochondria, ensuring proper targeting and activation of the mitoBKCa channel that helps to maintain mitochondrial Ca2+ homeostasis.
Parents’ prioritised outcomes for trials investigating treatments for paediatric severe infection: a qualitative synthesis
Authors: Woolfall Kerry , O’Hara Caitlin , Deja Elizabeth , Canter Ruth , Khan Imran , Mouncey Paul , Carter Anjali , Jones Nicola , Watkins Jason , Lyttle Mark David , Tume Lyvonne , Agbeko Rachel , Tibby Shane M , Pappachan John , Thorburn Kent , Rowan Kathryn M , Peters Mark John , Inwald David 
Published: June 2019

ObjectiveTo identify parents’ prioritised outcomes by combining qualitative findings from two trial feasibility studies of interventions for paediatric suspected severe infection.DesignQualitative synthesis combining parent interview data from the Fluids in Shock (FiSh) and Fever feasibility studies. Parents had experience of their child being admitted to a UK emergency department or intensive care unit with a suspected infection.Participantsn=: 85 parents. FiSh study: n=41 parents, 37 mothers, 4 fathers, 7 were bereaved. Fever study: n=44 parents, 33 mothers, 11 fathers, 7 were bereaved.ResultsIn addition to survival, parents prioritised short-term outcomes including: organ and physiological functioning (eg, heart rate, breathing rate and temperature); their child looking and/or behaving more like their normal self; and length of time on treatments or mechanical support. Longer term prioritised outcomes included effects of illness on child health and development. We found that parents’ prioritisation of outcomes was influenced by their experience of their child’s illness, survival and the point at which they are asked about outcomes of importance in the course of their child’s illness.ConclusionsFindings provide insight into parent prioritised outcomes to inform the design of future trials investigating treatments for paediatric suspected or proven severe infection as well as core outcome set development work.
Electronic prescribing in paediatric secondary care: are harmful errors prevented?
Authors: Fox Andy , Portlock Jane , Brown David 
Published: June 2019

ObjectiveThe aim of this research was to ascertain the effectiveness of current electronic prescribing (EP) systems to prevent a standardised set of paediatric prescribing errors likely to cause harm if they reach the patient.DesignSemistructured survey.SettingUK hospitals using EP in the paediatric setting.Outcome measuresNumber and type of erroneous orders able to be prescribed, and the level of clinical decision support (CDS) provided during the prescribing process.Results90.7% of the erroneous orders were able to be prescribed across the seven different EP systems tested. Levels of CDS varied between systems and between sites using the same system.ConclusionsEP systems vary in their ability to prevent harmful prescribing errors in the hospital paediatric setting. Differences also occur between sites using the same system, highlighting the importance of how a system is set up and optimised.
How should clinicians rehabilitate patients after ACL reconstruction? A systematic review of clinical practice guidelines (CPGs) with a focus on quality appraisal (AGREE II)
Authors: Andrade Renato , Pereira Rogério , van Cingel Robert , Staal J Bart , Espregueira-Mendes João 
Published: June 2019

ObjectivesTo summarise recommendations and appraise the quality of international clinical practice guidelines (CPGs) for rehabilitation after ACL reconstruction.DesignSystematic review of CPGs (PROSPERO number: CRD42017020407).Data sourcesPubmed, EMBASE, Cochrane, SPORTDiscus, PEDro and grey literature databases were searched up to 30 September 2018.Eligibility criteriaEnglish-language CPGs on rehabilitation following ACL reconstruction that used systematic search of evidence to formulate recommendations.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to report the systematic review. Two appraisers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument to report comprehensiveness, consistency and quality of CPGs. We summarised recommendations for rehabilitation after ACL reconstruction.ResultsSix CPGs with an overall median AGREE II total score of 130 points (out of 168) and median overall quality of 63% were included. One CPG had an overall score below the 50% (poor quality score) and two CPGs scored above 80% (higher quality score). The lowest domain score was ‘applicability’ (can clinicians implement this in practice?) (29%) and the highest ‘scope and purpose’ (78%) and ‘clarity of presentation’ (75%). CPGs recommended immediate knee mobilisation and strength/neuromuscular training. Early full weight-bearing exercises, early open and closed kinetic-chain exercises, cryotherapy and neuromuscular electrostimulation may be used according individual circumstances. The CPGs recommend against continuous passive motion and functional bracing.ConclusionThe quality of the CPGs in ACL postoperative rehabilitation was good, but all CPGs showed poor applicability. Immediate knee mobilisation and strength/neuromuscular training should be used. Continuous passive motion and functional bracing should be eschewed.
The effects of alcohol pricing policies on consumption, health, social and economic outcomes, and health inequality in Australia: a protocol of an epidemiological modelling study
Authors: Jiang Heng , Room Robin , Livingston Michael , Callinan Sarah , Brennan Alan , Doran Christopher , Thorn Michael 
Published: June 2019

IntroductionAlcohol use and misuse are associated with substantial health and social issues in Australia and internationally. Pricing policy is considered as one of the most effective means to reduce risky drinking and related harms. This protocol paper describes a study that will model and estimate the effects, effectiveness and cost–benefit of alcohol pricing policy initiatives in reducing risky drinking, health and social harms, and health inequalities among subpopulations in Australia.Methods and analysisThe study is a modelling and epidemiological study using data from various resources, such as survey, previous literatures and response agencies. A number of statistical procedures will be undertaken to evaluate the impact of different alcohol pricing policy initiatives on various outcomes, including alcohol consumption in population subgroups, and health and social problems, and to measure health inequalities and cost-effectiveness of those proposed pricing policies, such as a 10% tax increase on all alcohol beverages or introduction of a minimum unit price.Ethics and disseminationThe ethics approval of this study was obtained from the College Human Ethics Sub-Committee of the La Trobe University on 9 November 2017 (Ref: S17-206). While examining the heterogeneous effects of price policy across population subgroups, this study will provide the first comprehensive estimates of the likely impacts of alcohol price changes on health inequalities. The study will also provide sophisticated economic analyses of the impact of price policy changes, which is critical information for policy makers and will assist policy makers in directing resources to a more efficient alcohol strategy. Results will be made available to communities and societies, health departments and other researchers.
Penetrating thoracic injuries: a retrospective analysis from a French military trauma centre
Authors: Swiech Astree , Boddaert G , Daban J-L , Falzone E , Ausset S , Boutonnet M 
Published: June 2019

BackgroundPenetrating thoracic injuries (PTIs) is a medicosurgical challenge for civilian and military trauma teams. In civilian European practice, PTIs are most likely due to stab wounds and mostly require a simple chest tube drainage. On the battlefield, combat casualties suffer severe injuries, caused by high-lethality wounding agents.The aim of this study was to analyse and compare the demographics, injury patterns, surgical management and clinical outcomes of civilian and military patients with PTIs.MethodsAll patients with PTIs admitted to a Level I Trauma Centre in France or to Role-2 facilities in war theatres between 1 January 2004 and 31 May 2016 were included. Combat casualties’ data were analysed from Role-2 medical charts. The hospital manages military casualties evacuated from war theatres who had already received primary surgical care, but also civilian patients issued from the Paris area. During the study period, French soldiers were deployed in Afghanistan, in West Africa and in the Sahelo-Saharan band since 2013.Results52 civilian and 17 military patients were included. Main mechanisms of injury were stab wounds for civilian patients, and gunshot wounds and explosive fragments for military casualties. Military patients suffered more severe injuries and needed more thoracotomies. In total, 29 (33%) patients were unstable or in cardiac arrest on admission. Thoracic surgery was performed in 38 (55%) patients (25 thoracotomies and 13 thoracoscopies). Intrahospital mortality was 18.8%.ConclusionWar PTIs are associated with extrathoracic injuries and higher mortality than PTIs in the French civilian area. In order to reduce the mortality of PTIs in combat, our study highlights the need to improve tactical en route care with transfusion capabilities and the deployment of forward surgical units closer to the combatants. In the civilian area, our results indicated that video-assisted thoracoscopic surgery is a reliable diagnostic and therapeutic technique for haemodynamically stable patients.
Soil quality and land capability of reclaimed oil and gas well pads in southern Alberta: long-term legacy effects
Authors: Janz A. , Whitson I.R. , Lupardus R. 
Published: June 2019

Since 1963 approximately 100 000 oil and gas well pads have been officially certified as reclaimed in Alberta, yet follow-up monitoring programs have not been established to assure provincial environmental desired outcomes such as equivalent land capability are met at these certified well pads. The Ecological Recovery Monitoring Project was designed to determine long-term recovery of environmental quality at certified, reclaimed oil and gas well pads. Our study used soil data from 25 oil and gas well pads that were certified as reclaimed between 1964 and 2011. The objective of this study was to determine if well pad reclamation had long-term legacy effects on soil parameters and land capability as measured with the land suitability rating system (LSRS). We used multivariate covariance generalized linear models to determine effects of recovery time and reclamation on well pad soil parameters pH, bulk density (Db), total organic carbon (TOC), and electrical conductivity relative to reference soils. We also determined effects of reclamation on capability ratings using the LSRS. We concluded that soil quality and LSRS indices on well pads were lower than references due to adverse effects on pH, Db, and TOC. Long-term legacy effects on cultivated soils are significant and not well aligned with intended provincial outcomes. Further monitoring of reclaimed sites is strongly recommended.
Mapping Uncertainty
Authors: Lovejoy Henry B. 
Published: June 2019

Abstract
This historical GIS experiment attempts to map the collapse of the kingdom of Oyo alongside the departure of slave ships from the Bight of Benin. The achievements and drawbacks of mapping Africa’s pre-colonial past require an overview of the sources and methods used to illustrate the dissolution and formation of inland places during an intense period of intra-African conflict. By collating geopolitical data, it is possible to represent on annual maps the likely origins and migrations of diverse groups of enslaved people who were involved in the warfare in the Bight of Benin hinterland between 1816 and 1836. During this period, an unknown number of captives were enslaved and forced into an internal slave trade, most especially into the Sokoto Caliphate, while over 75,000 individuals involuntarily boarded European slave ships leaving for Brazil, Cuba and, due to British abolition efforts, Sierra Leone.
Rapid Decline of Total Antarctic Sea Ice Extent during 2014–16 Controlled by Wind-Driven Sea Ice Drift
Authors: Wang Zhaomin , Turner John , Wu Yang , Liu Chengyan 
Published: June 2019

AbstractBetween 2014 and 2016 the annual mean total extent of Antarctic sea ice decreased by a record, unprecedented amount of 1.6 × 106 km2, the largest in a record starting in the late 1970s. The mechanisms behind such a rapid decrease remain unknown. Using the outputs of a high-resolution, global ocean–sea ice model we show that the change was predominantly a result of record atmospheric low pressure systems over sectors of the Southern Ocean in 2016, with the associated winds inducing strong sea ice drift. Regions of large positive and negative sea ice extent anomaly were generated by both thermal and dynamic effects of the wind anomalies. Although the strong wind forcing also generated the warmest ocean surface state from April to December 2016, we show that enhanced northward sea ice drift and hence increased melting at lower latitudes driven by strong winds made the dominant contribution to the large decrease in total Antarctic sea ice extent between 2014 and 2016.
Leukocytosis and thrombosis in essential thrombocythemia and polycythemia vera: a systematic review and meta-analysis
Authors: Carobbio Alessandra , Ferrari Alberto , Masciulli Arianna , Ghirardi Arianna , Barosi Giovanni , Barbui Tiziano 
Published: June 2019

AbstractIn the last years, a growing amount of evidence has been produced regarding the role of leukocytosis as a risk factor for thrombosis in patients with myeloproliferative neoplasms, predominantly in polycythemia vera (PV) and essential thrombocythemia (ET). Results from epidemiologic studies on this issue, however, are inconclusive. We conducted a systematic review and meta-analysis of articles published in the last 12 years addressing the issue, according to a predefined protocol. Forty-one articles analyzing &gt;30 000 patients met our inclusion criteria and were deemed of acceptable methodologic quality. In addition to data on thrombosis, data were collected on bleeding, hematologic evolution, secondary cancer, and death. The relative risk (RR) of thrombosis in the presence of leukocytosis was 1.59 (95% CI, 1.40-1.80), mainly accounted for by ET (RR, 1.65; 95% CI, 1.43-1.91) and arterial thrombosis (RR, 1.45; 95% CI, 1.13-1.86) subgroups; the effect was not significant in venous thrombosis alone. Sensitivity analyses considering recurrent events as well as white blood cell estimates adjusted or unadjusted for confounding factors confirmed the primary results. In addition, the pooled RR of studies that tested white blood cell counts in time-dependent models suggested a causative effect of leukocytes in the mechanism that triggers thrombosis. The effect of leukocytosis on bleeding (RR, 1.87; 95% CI, 1.26-2.77) and death (RR, 1.89; 95% CI, 1.59-2.23) was confirmed, whereas conclusions on hematologic evolutions and solid tumors were uncertain. To confirm the accuracy of these results, an investigation on individual patient data in a large collective archive of homogeneous patients is warranted.
Development and Implementation of Survivorship Tools to Enable Medical Follow-Up After Childhood Cancer Treatment in Southern Sweden
Authors: Petersson-Ahrholt Magnus , Wiebe Thomas , Hjorth Lars , Relander Thomas , Linge Helena M. 
Published: June 2019

PURPOSE Survival rates after childhood cancer have increased from 20% to 80% since the 1970s. The increased number of survivors emphasizes the importance of late effects and their monitoring. Late effects may have a strong impact on quality of life in survivors. The purpose of this study was to make key data in a quality registry available for direct clinical use, enabling health care professionals to perform efficient and appropriate long-term medical follow-up after childhood cancer treatment. METHODS The population-based quality registry upon which this study is centered contains data on all individuals diagnosed with childhood cancer (diagnosed at 18 years of age or younger) in southern Sweden since January 1, 1970, and treatment data on 5-year survivors. Web tools, which were developed and implemented in a health care setting, generate a personalized treatment summary for each patient and enable risk group stratification of survivors. RESULTS Generation of a personalized treatment summary and risk group stratification of survivors led to identification of women at risk for developing breast cancer as a consequence of childhood cancer treatment. Three novel cases of previously undiagnosed breast cancer were identified. CONCLUSION The registry, together with the developed tools, enabled health care professionals to perform medical follow-up in this at-risk patient population.
Horizontal Crank Position Affects Economy and Upper Limb Kinematics of Recumbent Handcyclists
Authors: STONE BENJAMIN , MASON BARRY S. , WARNER MARTIN B. , GOOSEY-TOLFREY VICTORIA L. 
Published: June 2019

ABSTRACT

Purpose
To determine the effects of horizontal crank position on economy and upper limb kinematics in recumbent handcycling.

Methods
Fifteen trained handcyclists performed trials at 50% and 70% of their peak aerobic power output (POPeak), determined during a maximal exercise test, in each horizontal crank position. Four horizontal crank positions, 94%, 97%, 100%, and 103% of arm length, were investigated. Horizontal crank positions were defined as the distance between the acromion angle to the center of the handgrip, while the crank arm was parallel to the floor and pointing away from the participant. Economy and upper limb kinematics were calculated during the final minute of each 3-min trial.

Results
Horizontal crank position significantly affected handcycling economy at 70% POPeak (P < 0.01) but not at 50% POPeak (P = 0.44). The 97% horizontal crank position (16.0 [1.5] mL·min−1·W−1) was significantly more economical than the 94% (16.7 (1.9) mL·min−1·W−1) (P = 0.04) and 103% (16.6 (1.7) mL·min−1·W−1) (P < 0.01) positions. The 100% horizontal crank position (16.2 (1.7) mL·min−1·W−1) was significantly more economical than the 103% position (P < 0.01). Statistical parametric mapping indicated that an increase in horizontal crank position, from 94% to 103%, caused a significant increase in elbow extension, shoulder flexion, adduction, internal rotation, scapular internal rotation, wrist flexion, clavicle depression and clavicle protraction between 0% and 50% (0°–180°) of the cycle (P < 0.05).

Conclusions
Positioning the cranks at 97% to 100% of the athletes’ arm length improved handcycling economy at 70% POPeak as, potentially, the musculature surrounding the joints of the upper limb were in a more favorable position to produce force economically.
Assessment of Na+/K+ ATPase Activity in Small Rodent and Human Skeletal Muscle Samples
Authors: JANNAS-VELA SEBASTIAN , BROWNELL STUART , PETRICK HEATHER L. , HEIGENHAUSER GEORGE J. F. , SPRIET LAWRENCE L. , HOLLOWAY GRAHAM P. 
Published: June 2019

ABSTRACT

Introduction
In skeletal muscle, the Na+/K+ ATPase (NKA) plays essential roles in processes linked to muscle contraction, fatigue, and energy metabolism; however, very little information exists regarding the regulation of NKA activity. The scarcity of information regarding NKA function in skeletal muscle likely stems from methodological constraints, as NKA contributes minimally to total cellular ATP utilization, and therefore contamination from other ATPases prevents the assessment of NKA activity in muscle homogenates. Here we introduce a method that improves accuracy and feasibility for the determination of NKA activity in small rodent muscle samples (5–10 mg) and in human skeletal muscle.

Methods
Skeletal muscle homogenates from mice (n = 6) and humans (n = 3) were used to measure NKA and sarcoplasmic reticulum Ca2+ ATPase (SERCA) activities with the addition of specific ATPase inhibitors to minimize “background noise.”

Results
We observed that myosin ATPase activity was the major interfering factor for estimation of NKA activity in skeletal muscle homogenates, as the addition of 25 μM of blebbistatin, a specific myosin ATPase inhibitor, considerably minimized “background noise” (threefold) and enabled the determination of NKA maximal activity with values three times higher than previously reported. The specificity of the assay was demonstrated after the addition of 2 mM ouabain, which completely inhibited NKA. On the other hand, the addition of blebbistatin did not affect the ability to measure SERCA function. The coefficient of variation for NKA and SERCA assays were 6.2% and 4.4%, respectively.

Conclusion
The present study has improved the methodology to determine NKA activity. We further show the feasibility of measuring NKA and SERCA activities from a common muscle homogenate. This methodology is expected to aid in our long-term understanding of how NKA affects skeletal muscle metabolic homeostasis and contractile function in diverse situations.