bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diastolic stress testing: similarities and differences between isometric handgrip and cycle echocardiography
Authors: Samuel T. Jake , Beaudry Rhys , Haykowsky Mark J. , Sarma Satyam , Nelson Michael D. 
Published: May 2018

Cycle echocardiography (CE) is recommended for noninvasive diagnosis of diastolic dysfunction but can be limited by respiratory and movement artifact. Isometric handgrip echocardiography (IHE) is also a robust diastolic discriminator, while avoiding the limitations associated with dynamic exercise. This study sought to compare these two diastolic stress testing approaches. Twelve elderly individuals were recruited from the community (age 71 ± 6 yr). Heart rate, arterial blood pressure, and left ventricular (LV) diastolic function (via echocardiography) were assessed at rest and in response to 3 min of IHE at 40% of their maximal voluntary contraction, followed by 3 min of CE at 20 W. Both IHE and CE caused a significant increase in heart rate and blood pressure, leading to similar increases in myocardial oxygen demand. Both stressors also evoked a similar rise in the ratio between early LV mitral inflow velocity to early lateral annular velocity, a surrogate measure of LV filling pressure. The underlying mechanisms leading to these changes, however, were inherently different. IHE increased mean arterial pressure, and impaired myocardial relaxation, to a greater extent than CE. In contrast, CE augmented cardiac index, and increased early mitral filling velocity, to a great extent than IHE. In conclusion, for the first time, these data highlight several important similarities and differences between IHE and CE. That IHE avoids respiratory and movement artifact, while still serving as a robust diastolic discriminator, supports IHE as a strong alternative to CE for diastolic stress testing. NEW & NOTEWORTHY This is the first study to compare the diastolic stress response between isometric handgrip exercise and conventional cycle exercise. The data suggest that isometric handgrip echocardiography is comparable to conventional cycle echocardiography, both in terms of its hemodynamic challenge and global diastolic stress response. That isometric handgrip echocardiography eliminates both respiratory and movement artifact and is low cost and incredibly portable supports its integration into routine echocardiography exams.
Protection against severe hypokalemia but impaired cardiac repolarization after intense rowing exercise in healthy humans receiving salbutamol
Authors: Atanasovska Tania , Smith Robert , Graff Claus , Tran Cao T. , Melgaard Jacob , Kanters Jørgen K. , Petersen Aaron C. , Tobin Antony , Kjeldsen Keld P. , McKenna Michael J. 
Published: May 2018

Intense exercise induces pronounced hyperkalemia, followed by transient hypokalemia in recovery. We investigated whether the β2agonist salbutamol attenuated the exercise hyperkalemia and exacerbated the postexercise hypokalemia, and whether hypokalemia was associated with impaired cardiac repolarization (QT hysteresis). Eleven healthy adults participated in a randomized, counterbalanced, double-blind trial receiving either 1,000 µg salbutamol (SAL) or placebo (PLAC) by inhalation. Arterial plasma potassium concentration ([K+]a) was measured at rest, during 3 min of intense rowing exercise, and during 60 min of recovery. QT hysteresis was calculated from ECG ( n = 8). [K+]aincreased above baseline during exercise (rest, 3.72 ± 0.7 vs. end-exercise, 6.81 ± 1.4 mM, P < 0.001, mean ± SD) and decreased rapidly during early recovery to below baseline; restoration was incomplete at 60 min postexercise ( P < 0.05). [K+]awas less during SAL than PLAC (4.39 ± 0.13 vs. 4.73 ± 0.19 mM, pooled across all times, P = 0.001, treatment main effect). [K+]awas lower after SAL than PLAC, from 2 min preexercise until 2.5 min during exercise, and at 50 and 60 min postexercise ( P < 0.05). The postexercise decline in [K+]awas correlated with QT hysteresis ( r = 0.343, n = 112, pooled data, P = 0.001). Therefore, the decrease in [K+]afrom end-exercise by ~4 mM was associated with reduced QT hysteresis by ~75 ms. Although salbutamol lowered [K+]aduring exercise, no additive hypokalemic effects occurred in early recovery, suggesting there may be a protective mechanism against severe or prolonged hypokalemia after exercise when treated by salbutamol. This is important because postexercise hypokalemia impaired cardiac repolarization, which could potentially trigger arrhythmias and sudden cardiac death in susceptible individuals with preexisting hypokalemia and/or heart disease.NEW & NOTEWORTHY Intense rowing exercise induced a marked increase in arterial potassium, followed by a pronounced decline to hypokalemic levels. The β2agonist salbutamol lowered potassium during exercise and late recovery but not during early postexercise, suggesting a protective effect against severe hypokalemia. The decreased potassium in recovery was associated with impaired cardiac QT hysteresis, suggesting a link between postexercise potassium and the heart, with implications for increased risk of cardiac arrhythmias and, potentially, sudden cardiac death.
Sweat from gland to skin surface: production, transport, and skin absorption
Authors: Gerrett Nicola , Griggs Katy , Redortier Bernard , Voelcker Thomas , Kondo Narihiko , Havenith George 
Published: May 2018

By combining galvanic skin conductance (GSC), stratum corneum hydration (HYD) and regional surface sweat rate (RSR) measurements at the arm, thigh, back and chest, we closely monitored the passage of sweat from gland to skin surface. Through a varied exercise-rest protocol, sweating was increased slowly and decreased in 16 male and female human participants (25.3 ± 4.7 yr, 174.6 ± 10.1 cm, 71.3 ± 12.0 kg, 53.0 ± 6.8 ml·kg−1·min−1). ∆GSC and HYD increased before RSR, indicating pre-secretory sweat gland activity and skin hydration. ∆GSC and HYD typically increased concomitantly during rest in a warm environment (30.1 ± 1.0°C, 30.0 ± 4.7% relative humidity) and only at the arm did ∆GSC increase before an increase in HYD. HYD increased before RSR, before sweat was visible on the skin, but not to full saturation, contradicting earlier hypotheses. Maximal skin hydration did occur, as demonstrated by a plateau in all regions. Post exercise rest resulted in a rapid decrease in HYD and RSR but a delayed decline in ∆GSC. Evidence for reabsorption of surface sweat into the skin following a decline in sweating, as hypothesized in the literature, was not found. This suggests that skin surface sweat, after sweating is decreased, may not diffuse back into the dermis, but is only evaporated. These data, showing distinctly different responses for the three measured variables, provide useful information about the fate of sweat from gland to surface that is relevant across numerous research fields (e.g., thermoregulation, dermatology, ergonomics and material design). NEW & NOTEWORTHY After sweat gland stimulation, sweat travels through the duct, penetrating the epidermis before appearing on the skin surface. We found that only submaximal stratum corneum hydration was required before surface sweating occurred. However, full hydration occurred only once sweat was on the surface. Once sweating reduces, surface sweat evaporation continues, but there is a delayed drying of the skin. This information is relevant across various research fields, including environmental ergonomics, dermatology, thermoregulation, and skin-interface interactions.
R-spondin3 Is Associated with Basal-Progenitor Behavior in Normal and Tumor Mammary Cells
Authors: Tocci Johanna M. , Felcher Carla M. , García Solá Martín E. , Goddio María Victoria , Zimberlin María Noel , Rubinstein Natalia , Srebrow Anabella , Coso Omar A. , Abba Martín C. , Meiss Roberto P. , Kordon Edith C. 
Published: May 2018

Abstract
R-spondin3 (RSPO3) is a member of a family of secreted proteins that enhance Wnt signaling pathways in diverse processes, including cancer. However, the role of RSPO3 in mammary gland and breast cancer development remains unclear. In this study, we show that RSPO3 is expressed in the basal stem cell–enriched compartment of normal mouse mammary glands but is absent from committed mature luminal cells in which exogenous RSPO3 impairs lactogenic differentiation. RSPO3 knockdown in basal-like mouse mammary tumor cells reduced canonical Wnt signaling, epithelial-to-mesenchymal transition-like features, migration capacity, and tumor formation in vivo. Conversely, RSPO3 overexpression, which was associated with some LGR and RUNX factors, highly correlated with the basal-like subtype among patients with breast cancer. Thus, we identified RSPO3 as a novel key modulator of breast cancer development and a potential target for treatment of basal-like breast cancers.
Significance: These findings identify RSPO3 as a potential therapetuic target in basal-like breast cancers.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4497/F1.large.jpg. Cancer Res; 78(16); 4497–511. ©2018 AACR.
Hepatic Overexpression of Endothelial Lipase Lowers High-Density Lipoprotein but Maintains Reverse Cholesterol Transport in Mice
Authors: Takiguchi Shunichi , Ayaori Makoto , Yakushiji Emi , Nishida Takafumi , Nakaya Kazuhiro , Sasaki Makoto , Iizuka Maki , Uto-Kondo Harumi , Terao Yoshio , Yogo Makiko , Komatsu Tomohiro , Ogura Masatsune , Ikewaki Katsunori 
Published: May 2018

Objective—
Reverse cholesterol transport (RCT) is a major mechanism by which HDL (high-density lipoprotein) protects against atherosclerosis. Endothelial lipase (EL) reportedly reduces HDL levels, which, in theory, would increase atherosclerosis. However, it remains unclear whether EL affects RCT in vivo.

Approach and Results—

Adenoviral vectors expressing EL or luciferase were intravenously injected into mice, and a macrophage RCT assay was performed. As expected, hepatic EL overexpression markedly reduced HDL levels. In parallel, plasma
3
H-cholesterol counts from the EL-expressing mice decreased by 85% compared with control. Surprisingly, there was no difference in fecal
3
H-cholesterol excretion between the groups. Kinetic studies revealed increased catabolism/hepatic uptake of
3
HDL-cholesteryl ether, resulting in no change in fecal HDL-cholesteryl ester excretion in the mice. To explore underlying mechanisms for the preservation of RCT despite low HDL levels in the EL-expressing mice, we investigated the effects of hepatic SR-BI (scavenger receptor class B type I) knockdown. RCT assay revealed that knockdown of SR-BI alone reduced fecal excretion of macrophage-derived
3
H-cholesterol. Interestingly, hepatic EL overexpression under SR-BI inhibition further attenuated fecal tracer counts as compared with control. Finally, we observed that EL overexpression enhanced in vivo RCT under pharmacological inhibition of hepatic ABCA1 (ATP-binding cassette transporter A1) by probucol.

Conclusions—
Hepatic EL expression compensates for reduced macrophage-derived cholesterol efflux to plasma because of low HDL levels by promoting cholesterol excretion to bile/feces via an SR-BI pathway, maintaining overall RCT in vivo. In contrast, EL-modified HDL might negatively regulate RCT via hepatic ABCA1. Despite extreme hypoalphalipoproteinemia, RCT is maintained in EL-expressing mice via SR-BI/ABCA1-dependent pathways.
Does High-Intensity Endurance Training Increase the Risk of Atrial Fibrillation?
Authors: Opondo Mildred A. , Aiad Norman , Cain Matthew A. , Sarma Satyam , Howden Erin , Stoller Douglas A. , Ng Jason , van Rijckevorsel Pieter , Hieda Michinari , Tarumi Takashi , Palmer M. Dean , Levine Benjamin D. 
Published: May 2018

Background:
Exercise mitigates many cardiovascular risk factors associated with atrial fibrillation. Endurance training has been associated with atrial structural changes which can increase the risk for atrial fibrillation. The dose of exercise training required for these changes is uncertain. We sought to evaluate the impact of exercise on left atrial (LA) mechanical and electrical function in healthy, sedentary, middle-aged adults.

Methods:
Sixty-one adults (52±5 years) were randomized to either 10 months of high-intensity exercise training or yoga. At baseline and post-training, all participants underwent maximal exercise stress testing to assess cardiorespiratory fitness, P-wave signal-averaged electrocardiography for filtered P-wave duration and atrial late potentials (root mean square voltage of the last 20 ms), and echocardiography for LA volume, left ventricular end-diastolic volume, and mitral inflow for assessment of LA active emptying. Post-training data were compared with 14 healthy age-matched Masters athletes.

RESULTS:

LA volume, Vo
2
max, and left ventricular end-diastolic volume increased in the exercise group (15%, 17%, and 16%, respectively) with no change in control (
P
<0.0001). LA active emptying decreased post-exercise versus controls (5%;
P
=0.03). No significant changes in filtered P-wave duration or root mean square voltage of the last 20 ms occurred after exercise training. LA and left ventricular volumes remained below Masters athletes. The athletes had longer filtered P-wave duration but no difference in the frequency of atrial arrhythmia.

Conclusions:
Changes in LA structure, LA mechanical function, and left ventricular remodeling occurred after 10 months of exercise but without significant change in atrial electrical activity. A longer duration of training may be required to induce electrical changes thought to cause atrial fibrillation in middle-aged endurance athletes.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique Identifier: NCT02039154.
Radiotracer Imaging Allows for Noninvasive Detection and Quantification of Abnormalities in Angiosome Foot Perfusion in Diabetic Patients With Critical Limb Ischemia and Nonhealing Wounds
Authors: Alvelo Jessica L. , Papademetris Xenophon , Mena-Hurtado Carlos , Jeon Sangchoon , Sumpio Bauer E. , Sinusas Albert J. , Stacy Mitchel R. 
Published: May 2018

Background:
Single photon emission computed tomography (SPECT)/computed tomography (CT) imaging allows for assessment of skeletal muscle microvascular perfusion but has not been quantitatively assessed in angiosomes, or 3-dimensional vascular territories, of the foot. This study assessed and compared resting angiosome foot perfusion between healthy subjects and diabetic patients with critical limb ischemia (CLI). Additionally, the relationship between SPECT/CT imaging and the ankle–brachial index—a standard tool for evaluating peripheral artery disease—was assessed.

Methods and Results:

Healthy subjects (n=9) and diabetic patients with CLI and nonhealing ulcers (n=42) underwent SPECT/CT perfusion imaging of the feet. CT images were segmented into angiosomes for quantification of relative radiotracer uptake, expressed as standardized uptake values. Standardized uptake values were assessed in ulcerated angiosomes of patients with CLI and compared with whole-foot standardized uptake values in healthy subjects. Serial SPECT/CT imaging was performed to assess uptake kinetics of technetium-99m-tetrofosmin. The relationship between angiosome perfusion and ankle–brachial index was assessed via correlational analysis. Resting perfusion was significantly lower in CLI versus healthy subjects (
P
=0.0007). Intraclass correlation coefficients of 0.95 (healthy) and 0.93 (CLI) demonstrated excellent agreement between serial perfusion measurements. Correlational analysis, including healthy and CLI subjects, demonstrated a significant relationship between ankle–brachial index and SPECT/CT (
P
=0.01); however, this relationship was not significant for diabetic CLI patients only (
P
=0.2).

Conclusions:
SPECT/CT imaging assesses regional foot perfusion and detects abnormalities in microvascular perfusion that may be undetectable by conventional ankle–brachial index in patients with diabetes mellitus. SPECT/CT may provide a novel approach for evaluating responses to targeted therapies.
Frequency, Reasons, and Impact of Premature Ticagrelor Discontinuation in Patients Undergoing Coronary Revascularization in Routine Clinical Practice
Authors: Zanchin Thomas , Temperli Fabrice , Karagiannis Alexios , Zanchin Christian , Räsänen Markus , Koskinas Konstantinos C. , Stortecky Stefan , Hunziker Lukas , Praz Fabien , Blöchlinger Stefan , Moro Christina , Moschovitis Aris , Seiler Christian , Billinger Michael , Heg Dik , Pilgrim Thomas , Valgimigli Marco , Windecker Stephan , Räber Lorenz 
Published: May 2018

Background—
Although ticagrelor has improved clinical outcomes among patients with acute coronary syndrome compared with clopidogrel, adherence to this new antiplatelet agent in real-world practice has not been fully investigated.

Methods and Results—

Between November 2011 and June 2014, 1278 of 4831 consecutive patients (26.5%) undergoing percutaneous coronary intervention at a tertiary care center were treated with ticagrelor. Premature ticagrelor cessation was categorized into (1) change, when ticagrelor was replaced by prasugrel; (2) de-escalation, when ticagrelor was replaced by clopidogrel; and (3) premature discontinuation, when ticagrelor was discontinued without P2Y12 inhibitor replacement. Of 1278 patients treated with ticagrelor, premature treatment cessation occurred in 212 patients (17%). De-escalation to clopidogrel was the most frequent scenario (57%; n=120), followed by premature discontinuation (28%; n=60) and change to prasugrel (15%; n=32). Reasons for ticagrelor cessation included adverse effects (49%), initiation of oral anticoagulation (19%), and unspecified general practitioner preference (10%). Most frequent adverse effects leading to premature ticagrelor cessation were bleeding (41%), dyspnea (29%), and gastrointestinal symptoms (18%). Premature ticagrelor cessation was not associated with an increased risk of cardiac death, myocardial infarction, or stroke (hazard ratio, 0.73; 95% confidence interval: 0.40–1.32;
P
=0.29).

Conclusions—
Premature ticagrelor cessation in routine clinical practice occurred in 1 of 6 patients and was primarily related to adverse effects among which bleeding and dyspnea were the most frequent. Although premature ticagrelor cessation was not associated with adverse cardiovascular outcomes, this finding requires careful interpretation in view of the modest sample size.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02241291.
Risk Factors and Temporal Trends of Complications Associated With Transvenous Implantable Cardiac Defibrillator Leads
Authors: Koneru Jayanthi N. , Jones Paul W. , Hammill Eric F. , Wold Nicholas , Ellenbogen Kenneth A. 
Published: May 2018

Background

The transvenous implantable cardioverter‐defibrillator (
ICD
) lead is the most common source of complications in a traditional
ICD
system. This investigation aims to determine the incidence, predictors, and costs associated with these complications using a large insurance database.

Methods and Results

Data from the OptumLabs™ Data Warehouse, which include diagnosis, physician and procedure codes, and claims from patient hospitalizations, were analyzed. Patients with a de novo
ICD
or cardiac resynchronization therapy defibrillator implanted from January 1, 2003, through June 30, 2015, were included; those who did not have continuous coverage beginning 1 year before implantation were excluded, resulting in 40 837 patients followed up over an average of 2.3±2.1 years. Patients were followed up until they had the procedure or their last active date in the database. Of 20 580 device procedures, 2165 (5.3%) and 771 (1.9%) had mechanical and infectious complications, respectively. The 5‐year rate of freedom from mechanical complication was 92.0% and 89.3% for
ICD
s and cardiac resynchronization therapy defibrillators, respectively. Infectious complications were more likely in patients with a history of atrial fibrillation, diabetes mellitus, and renal disease, and the risk increased with subsequent device procedures. Younger age, female sex, lack of comorbidities, and implantations between 2003 and 2008 were associated with more mechanical complications.

Conclusions

Incidence of mechanical and infectious complications of transvenous
ICD
leads over long‐term follow‐up is much higher in the real world than in clinical studies. In our study cohort, 1 of 4 transvenous
ICD
leads had mechanical complications when followed up to 10 years. The high rate of reintervention leads to additional complications.
The Internal Generation of the Atlantic Ocean Interdecadal Variability
Authors: Arzel Olivier , Huck Thierry , Colin de Verdière Alain 
Published: May 2018

AbstractNumerical simulations of a realistic ocean general circulation model forced by prescribed surface fluxes are used to study the origin and structure of intrinsic interdecadal variability of the ocean circulation. When eddy-induced turbulent diffusivities are low enough, spontaneous oscillations of the Atlantic meridional overturning circulation (AMOC) with periods O(20) yr and amplitude O(1) Sv (1 Sv ≡ 106 m3 s−1) emerge. The transition from the steady to the oscillatory regime is shown to be consistent with a supercritical Hopf bifurcation of the horizontal Peclet number. Adding atmospheric thermal damping is shown to have a very limited influence on the domain of existence of intrinsic variability. The spatial structure of the mode consists of a dipole of sea surface temperature (SST)/sea surface height (SSH) anomalies centered at about 50°N with stronger variance in the western part of the subpolar gyre, in agreement with the observed Atlantic multidecadal oscillation (AMO) signature in this region. Specific features include a westward propagation of temperature anomalies from the source region located on the western flank of the North Atlantic Current (NAC) and a one-quarter phase lag between surface and subsurface (800 m) temperature anomalies. Local linear stability calculations including viscous and diffusive effects confirm that the North Atlantic Current is baroclinically unstable on scales of O(1000) km with growth rates of O(1) yr−1. Both the spatial structure of the mode and the period agree in magnitude with in situ measurements in the North Atlantic, suggesting that this intrinsic ocean mode participates in the observed Atlantic bidecadal climate variability.
Parallel Direct Solution of the Covariance-Localized Ensemble Square Root Kalman Filter Equations with Matrix Functions
Authors: Steward Jeffrey L. , Roman Jose E. , Daviña Alejandro Lamas , Aksoy Altuǧ 
Published: May 2018

Abstract
Recently, the serial approach to solving the square root ensemble Kalman filter (ESRF) equations in the presence of covariance localization was found to depend on the order of observations. As shown previously, correctly updating the localized posterior covariance in serial requires additional effort and computational expense. A recent work by Steward et al. details an all-at-once direct method to solve the ESRF equations in parallel. This method uses the eigenvectors and eigenvalues of the forward observation covariance matrix to solve the difficult portion of the ESRF equations. The remaining assimilation is easily parallelized, and the analysis does not depend on the order of observations. While this allows for long localization lengths that would render local analysis methods inefficient, in theory, an eigenpair-based method scales as the cube number of observations, making it infeasible for large numbers of observations. In this work, we extend this method to use the theory of matrix functions to avoid eigenpair computations. The Arnoldi process is used to evaluate the covariance-localized ESRF equations on the reduced-order Krylov subspace basis. This method is shown to converge quickly and apparently regains a linear scaling with the number of observations. The method scales similarly to the widely used serial approach of Anderson and Collins in wall time but not in memory usage. To improve the memory usage issue, this method potentially can be used without an explicit matrix. In addition, hybrid ensemble and climatological covariances can be incorporated.