bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardin-Dependent Kv1.5 Channel Expression Prevents Phenotypic Modulation of Human Vessels in Organ Culture
Authors: Arévalo-Martínez Marycarmen , Cidad Pilar , García-Mateo Nadia , Moreno-Estar Sara , Serna Julia , Fernández Mirella , Swärd Karl , Simarro María , de la Fuente Miguel A. , López-López José R. , Pérez-García M. Teresa 
Published: October 2019

Objective:
We have previously described that changes in the expression of Kv channels associate to phenotypic modulation (PM), so that Kv1.3/Kv1.5 ratio is a landmark of vascular smooth muscle cells phenotype. Moreover, we demonstrated that the Kv1.3 functional expression is relevant for PM in several types of vascular lesions. Here, we explore the efficacy of Kv1.3 inhibition for the prevention of remodeling in human vessels, and the mechanisms linking the switch in Kv1.3 /Kv1.5 ratio to PM.

Approach and Results:
Vascular remodeling was explored using organ culture and primary cultures of vascular smooth muscle cells obtained from human vessels. We studied the effects of Kv1.3 inhibition on serum-induced remodeling, as well as the impact of viral vector-mediated overexpression of Kv channels or myocardin knock-down. Kv1.3 blockade prevented remodeling by inhibiting proliferation, migration, and extracellular matrix secretion. PM activated Kv1.3 via downregulation of Kv1.5. Hence, both Kv1.3 blockers and Kv1.5 overexpression inhibited remodeling in a nonadditive fashion. Finally, myocardin knock-down induced vessel remodeling and Kv1.5 downregulation and myocardin overexpression increased Kv1.5, while Kv1.5 overexpression inhibited PM without changing myocardin expression.

Conclusions:
We demonstrate that Kv1.5 channel gene is a myocardin-regulated, vascular smooth muscle cells contractile marker. Kv1.5 downregulation upon PM leaves Kv1.3 as the dominant Kv1 channel expressed in dedifferentiated cells. We demonstrated that the inhibition of Kv1.3 channel function with selective blockers or by preventing Kv1.5 downregulation can represent an effective, novel strategy for the prevention of intimal hyperplasia and restenosis of the human vessels used for coronary angioplasty procedures.
Electrical Stimulation of the Greater Auricular Nerve to Reduce Postoperative Atrial Fibrillation
Authors: Andreas Martin , Arzl Philipp , Mitterbauer Andreas , Ballarini Nicolas M. , Kainz Frieda-Maria , Kocher Alfred , Laufer Guenther , Wolzt Michael 
Published: October 2019

Background:
Postoperative atrial fibrillation (POAF) occurs in up to 40% of patients undergoing cardiac surgery. Invasive stimulation of the vagal nerve previously demonstrated a reduced risk of POAF. Therefore, we examined the antiarrhythmic and anti-inflammatory effects of noninvasive low-level transcutaneous electrical stimulation (LLTS) of the greater auricular nerve in a pilot trial including patients undergoing cardiac surgery.

Methods:
Patients were randomized into a sham (n=20) or a treatment group (n=20) for LLTS. After cardiac surgery, electrodes were applied in the triangular fossa of the ear. Stimulation (amplitude 1 mA, frequency 1 Hz for 40 minutes, followed by a 20 minutes break) was performed for up to 2 weeks after cardiac surgery. Heart rhythm was recorded continuously using an ECG during the observation period. CRP (C-reactive protein) and IL (interleukin)-6 plasma concentrations were measured immediately after surgery as well as on day 2 and 7 postsurgery.

Results:

Patients receiving LLTS had a significantly reduced occurrence of POAF (4 of 20) when compared with controls (11 of 20,
P
=0.022) during a similar mean Holter recording period. The median duration of POAF was comparable between the treatment and the control group (878 [249; 1660] minutes versus 489 [148; 1775] minutes;
P
=0.661). No effect of LLTS on CRP or IL-6 levels was detectable.

Conclusions:
LLTS of the greater auricular nerve may be a potential therapy for POAF. We demonstrated the feasibility to conduct a randomized trial of neurostimulation as an outlay for a multisite clinical trial.
Survival Outcomes After Heart Transplantation
Authors: Moayedi Yasbanoo , Fan Chun Po S. , Cherikh Wida S. , Stehlik Josef , Teuteberg Jeffrey J. , Ross Heather J. , Khush Kiran K. 
Published: October 2019

Background:
Currently, women represent <25% of heart transplant recipients. Reasons for this female underrepresentation have been attributed to selection and referral bias and potentially poorer outcomes in female recipients. The aim of this study was to compare long-term posttransplant survival between men and women, when matched for recipient and donor characteristics.

Methods and Results:

Using the International Society for Heart and Lung Transplantation Registry, we performed descriptive analyses and estimated overall freedom from posttransplant death stratified by sex using Kaplan-Meier survival methods. Male and female recipients were matched according to the Index for Mortality Prediction After Cardiac Transplantation and Donor Risk Index score using 1:1 propensity score matching. The study cohort comprised 34 198 heart transplant recipients (76.3% men, 23.7% women) between 2004 and 2014. Compared with men, women were more likely younger (51 [39–59] versus 55 [46–61] years;
P
<0.001) and had a different distribution of heart failure etiology (
P
<0.001). In general, the prevalence of comorbidities was lower in women than in men. Women were less likely to have diabetes mellitus (19.1% versus 26.2%;
P
<0.001), hypertension (40.7% versus 47.9%;
P
<0.001), peripheral vascular disease (2.4% versus 3.3%;
P
=0.002), tobacco use (36.5% versus 52.3%;
P
<0.001), and prior cardiovascular surgery (38.6% versus 50.7%;
P
<0.001). Women were more likely to have a history of malignancy (10.5% versus 5.3%;
P
<0.001), require intravenous inotropes (41.4% versus 37.2%;
P
<0.001), and were less likely supported by an intra-aortic balloon pump (3.3% versus 3.8%;
P
=0.03) or durable ventricular assist device (22% versus 31.5%;
P
<0.001). Transplanted male recipients had a higher Index for Mortality Prediction After Cardiac Transplantation score (5 [2–7] versus 4 [1–6];
P
<0.001). When male and female heart transplant recipients were matched for recipient and donor characteristics, there was no significant survival difference (
P
=0.57).

Conclusions:
Overall survival does not differ between men and women after cardiac transplantation. Women who survive to heart transplantation appear to have lower risk features than male recipients but receive hearts from higher risk donors.
Supplementation With the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension
Authors: Peng Jun , Vongpatanasin Wanpen , Sacharidou Anastasia , Kifer Domagoj , Yuhanna Ivan S. , Banerjee Subhashis , Tanigaki Keiji , Polasek Ozren , Chu Haiyan , Sundgren Nathan C. , Rohatgi Anand , Chambliss Ken L. , Lauc Gordan , Mineo Chieko , Shaul Philip W. 
Published: October 2019

Background:
Obesity-related hypertension is a common disorder, and attempts to combat the underlying obesity are often unsuccessful. We previously revealed that mice globally deficient in the inhibitory immunoglobulin G (IgG) receptor FcγRIIB are protected from obesity-induced hypertension. However, how FcγRIIB participates is unknown. Studies were designed to determine if alterations in IgG contribute to the pathogenesis of obesity-induced hypertension.

Methods:

Involvement of IgG was studied using IgG μ heavy chain–null mice deficient in mature B cells and by IgG transfer. Participation of FcγRIIB was interrogated in mice with global or endothelial cell–specific deletion of the receptor. Obesity was induced by high-fat diet (HFD), and blood pressure (BP) was measured by radiotelemetry or tail cuff. The relative sialylation of the Fc glycan on mouse IgG, which influences IgG activation of Fc receptors, was evaluated by
Sambucus nigra
lectin blotting. Effects of IgG on endothelial NO synthase were assessed in human aortic endothelial cells. IgG Fc glycan sialylation was interrogated in 3442 human participants by mass spectrometry, and the relationship between sialylation and BP was evaluated. Effects of normalizing IgG sialylation were determined in HFD-fed mice administered the sialic acid precursor N-acetyl-D-mannosamine (ManNAc).

Results:
Mice deficient in B cells were protected from obesity-induced hypertension. Compared with IgG from control chow–fed mice, IgG from HFD-fed mice was hyposialylated, and it raised BP when transferred to recipients lacking IgG; the hypertensive response was absent if recipients were FcγRIIB-deficient. Neuraminidase-treated IgG lacking the Fc glycan terminal sialic acid also raised BP. In cultured endothelial cells, via FcγRIIB, IgG from HFD-fed mice and neuraminidase-treated IgG inhibited vascular endothelial growth factor activation of endothelial NO synthase by altering endothelial NO synthase phosphorylation. In humans, obesity was associated with lower IgG sialylation, and systolic BP was inversely related to IgG sialylation. Mice deficient in FcγRIIB in endothelium were protected from obesity-induced hypertension. Furthermore, in HFD-fed mice, ManNAc normalized IgG sialylation and prevented obesity-induced hypertension.

Conclusions:
Hyposialylated IgG and FcγRIIB in endothelium are critically involved in obesity-induced hypertension in mice, and supportive evidence was obtained in humans. Interventions targeting these mechanisms, such as ManNAc supplementation, may provide novel means to break the link between obesity and hypertension.
Work‐Family Conflict and Ideal Cardiovascular Health Score in the ELSA‐Brasil Baseline Assessment
Authors: Rocco Priscila T. P. , Bensenor Isabela M. , Griep Rosane H. , Barreto Sandhi M. , Moreno Arlinda B. , Alencar Airlane P. , Lotufo Paulo A. , Santos Itamar S. 
Published: October 2019

Background

There are few data about the association between work‐related stress and the American Heart Association ideal cardiovascular health (
CVH
) metrics. We studied the association between work‐family conflict (
WFC
) and ideal
CVH
scores in the
ELSA
‐Brasil (Brazilian Longitudinal Study of Adult Health) baseline study.

Methods and Results

We analyzed data of active workers (5424 men and 5967 women), aged 35 to 74 years, from 2008 to 2010. Ideal
CVH
scores were calculated based on the lifestyle and health metrics proposed by the American Heart Association, using data from questionnaires and clinical and laboratory examinations from the
ELSA
‐Brasil study baseline. The
WFC
questionnaire was based on the Frone model, validated for Brazilian Portuguese.
WFC
domains (time and strain‐based work interference with family, family interference with work, and lack of time for personal care and leisure) and frequency (never to rarely, sometimes, or frequently) were self‐reported. Main models were adjusted for age, sex, race, educational level, income, and study site. Positive relative predicted score differences (
rPSDs
) indicate higher predicted scores. We found lower lifestyle ideal
CVH
scores among men (
rPSD
, −5.7%;
P
=0.002) and women (
rPSD,
−10.2%;
P
<0.001) with frequent lack of time for personal care and leisure. We found lower lifestyle ideal
CVH
scores among women with frequent strain‐based work interference with family (
rPSD,
−5.1%;
P
=0.002), and family interference with work (
rPSD
, −8.6%;
P
=0.001). We found higher health ideal
CVH
scores among men with frequent
WFC
, which may be attributable to reverse causation.

Conclusions

We found significant associations between
WFC
and ideal
CVH
scores. These associations were heterogeneous according to sex.
Short‐Term Changes in Cardiorespiratory Fitness in Response to Exercise Training and the Association with Long‐Term Cardiorespiratory Fitness Decline: The STRRIDE Reunion Study
Authors: Pandey Ambarish , Johnson Johanna L. , Slentz Cris A. , Ross Leanna M. , Agusala Vijay , Berry Jarett D. , Kraus William E. 
Published: October 2019

Background
Substantial heterogeneity exists in the cardiorespiratory fitness (CRF) change in response to exercise training, and its long‐term prognostic implication is not well understood. We evaluated the association between the short‐term supervised training‐related changes in CRF and CRF levels 10 years later.

Methods and Results

STRRIDE (Studies of a Targeted Risk Reduction Intervention Through Defined Exercise) trial participants who were originally randomized to exercise training for 8 months and participated in the 10‐year follow‐up visit were included. CRF levels were measured at baseline, after training (8 months), and at 10‐year follow‐up as peak oxygen uptake (
vo
2
, mL/kg per min) using the maximal treadmill test. Participants were stratified into low, moderate, and high CRF response groups according to the training regimen–specific tertiles of CRF change. The study included 80 participants (age: 52 years; 35% female). At 10‐year follow‐up, the high‐response CRF group had the least decline in CRF compared with the moderate‐ and low‐response CRF groups (−0.35 versus −2.20 and −4.25 mL/kg per minute, respectively;
P
=0.02). This result was largely related to the differential age‐related changes in peak oxygen pulse across the 3 groups (0.58, −0.23, and −0.86 mL/beat, respectively;
P
=0.03) with no difference in the peak heart rate change. In adjusted linear regression analysis, high response was significantly associated with greater CRF at follow‐up independent of other baseline characteristics (high versus low [reference] CRF response: standard β=0.25;
P
=0.004).

Conclusions
Greater CRF improvement in response to short‐term training is associated with higher CRF levels 10 years later. Lack of CRF improvements in response to short‐term training may identify individuals at risk for exaggerated CRF decline with aging.
Mortality Benefit of Alirocumab: A Bayesian Perspective
Authors: Labos Christopher , Brophy James M. , Sniderman Allan , Thanassoulis George 
Published: October 2019

Background
The ODYSSEY OUTCOMES (Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome) trial demonstrated that alirocumab reduced major cardiovascular events. However, because of the hierarchical testing strategy used for the multiple outcomes examined, the observed reduction in all‐cause mortality was labeled “nominally significant” which has clouded its interpretation.

Methods and Results

We re‐analyzed data from
ODYSSEY
OUTCOMES using Bayesian methods and generated various prior probabilities by incorporating mortality data from previous similar
PCSK
9 (proprotein convertase subtilisin‐kexin type 9) inhibitor trials. We first used data from the
ODYSSEY
OUTCOMES trial with a non‐informative prior, then sequentially added data from
ODYSSEY
LONG TERM and the
FOURIER
trial, giving
FOURIER
full weight, 50% weight and 10%. The posterior probability of a mortality reduction using only the
ODYSSEY
OUTCOMES data was hazard ratio 0.85 (95% CI 0.74–0.99) which corresponded to a 98.4% probability of a mortality benefit. When the
ODYSSEY
LONG TERM data were added to the analysis, the posterior probability was hazard ratio 0.84 (95% CI 0.72–0.97) with a 99.9% probability of mortality reduction, and when the
FOURIER
data were added to the analysis the posterior probability was hazard ratio 0.94 (95% CI 0.85–1.04) with an 89.1% probability of a mortality reduction. When the
FOURIER
trial was given only 50% or 10% weight, the probability of a mortality reduction rose 95.4% and 98.7%, respectively. We estimate that the probability of >1% absolute risk reduction ranges from 8% to 24%, while the probability of >0.5% absolute risk reduction ranges from 66% to 89%.

Conclusions
Our analysis demonstrates a high likelihood that alirocumab confers a reduction in all‐cause mortality, despite the equivocal interpretation of the data in the original ODYSSEY OUTCOMES publication.
Implementing Caregiver Support Programs in a Regional Stroke System
Authors: Tseung Victrine , Jaglal Susan B. , Salbach Nancy M. , Cameron Jill I. 
Published: October 2019

Background and Purpose—
Family caregivers play a central role in the recovery of people with stroke. They need support to optimize the care they provide and their own health and well-being. Despite support from the literature and best practice recommendations, healthcare systems are not formally adopting caregiver programs. This study aimed to describe system-level facilitators and barriers to caregiver support program implementation in a regional stroke system.

Methods—
Using a qualitative descriptive study design, focus groups were conducted with regional rehabilitation specialists, education coordinators, community and long-term care specialists, and regional/district program directors. Semi-structured interviews were conducted with regional medical directors, health professionals providing stroke care in acute care, rehabilitation and community settings, regional health executives, and primary care leaders. Data were analyzed using inductive thematic analysis.

Results—
Four focus groups (n=43) and 29 interviews were conducted. We identified 4 themes related to caregiver program implementation: (1) establishing the need for caregiver education and support in an integrated healthcare system; (2) incorporating caregiver programs into the system of care across the care continuum; (3) uncertainty regarding ownership and responsibility for implementation; and (4) addressing regional variations related to access, availability, and culture.

Conclusions—
This study provides a comprehensive understanding of organization and system-level considerations for implementing caregiver programs in a regional stroke system. Program implementation requires evidence to establish the need for caregiver programs, practical strategies, and establishing ownership to incorporate programs into existing healthcare systems, and consideration of regional variations across healthcare systems. Ultimately, adopting programs to support caregivers will improve recovery in people with stroke and caregiver well-being.
Population dynamics and host range of Paratylenchus bukowinensis
Authors: Schmidt Jan H. , Seeger Judith N. , von Grafenstein Katharina , Wintzer Jenny , Finckh Maria R. , Hallmann Johannes 
Published: October 2019

Summary
The plant-parasitic nematode, Paratylenchus bukowinensis, occurs ubiquitously in arable fields. Economic damage has been reported from, among others, cabbage, parsley, and celery, but other crops might be affected as well. Management of P. bukowinensis is difficult. Resistant cultivars are not available and chemical control is prohibited in most European countries. In addition, sustainable management is often hindered by a lack of information regarding the biology and host range of P. bukowinensis. To improve the management of P. bukowinensis in the future, a good understanding of the life cycle and host plant-nematode interactions is required. We investigated the host range, life cycle and natural decline of P. bukowinensis in five glasshouse experiments. A total of 26 plant genotypes comprising 22 plant species from eight plant families were studied. Plant species within the families Brassicaceae and Apiaceae were confirmed as good hosts, while plant species within the families Fabaceae, Asteraceae, Amaryllidaceae, Solanaceae, Amaranthaceae and Poaceae can be considered non-hosts or poor hosts. In roots of good hosts, P. bukowinensis completed its life cycle within 3-4 weeks. In the absence of a host plant, P. bukowinensis declined by 40% within the first 4 weeks, but then remained at this level until the experiment was terminated after 14 weeks. Overall, the host range of P. bukowinensis seems to be smaller than for other species within the genus Paratylenchus, such as P. projectus or P. similis. Control of P. bukowinensis using crop rotation should be feasible by rotating good hosts belonging to the families Brassicaceae and Apiaceae with non-hosts or poor hosts.
Use of Force in Somatic Treatment of Adults in Denmark
Authors: Adolphsen Caroline 
Published: October 2019

Abstract
The article provides a critical analysis of the new Danish Act on Use of Force in Somatic Treatment of Adults with a Permanently Impaired Ability to Give Consent (FTAC, Act no. 655 of 8 June 2017), which covers adults unable to give an informed consent. The rules in the Act are included in the legal framework governing medical treatment with and without consent in Denmark, and the article draws on international human rights in connection with the subject matter. The aim of the article is also to highlight the grey areas that still exist despite the new rules and to provide legal argumentation for solutions to the issues that can arise in these legal grey areas.
Antichresis: a comparative study of classical Roman law and the contractual praxis from Roman Egypt
Authors: Bobbink R. , Mauer Q. 
Published: October 2019

Summary
The authors examine how papyrological sources from Roman Egypt written in Greek on antichresis relate to classical Roman law. Antichresis attested in papyrological antichretic contracts had a lot in common with antichresis emerging from Roman dispute resolutions. There was only one substantive difference: in classical Roman law, protection of the debtor was emphasized, whereas in the Greek papyrological antichretic contracts the position of the creditor was favoured. Given the similarities found, the authors conclude that antichretic loan both as an independent legal institution and as a pactum antichreticum was a pan-Mediterranean legal concept.
The Cross-Fertilization of UNCLOS, Custom and Principles Relating to Procedure in the Jurisprudence of UNCLOS Courts and Tribunals
Authors: Ivanova Elena 
Published: October 2019

Cross-fertilization of international law entails interaction of norms in international law and can occur in the context of interaction between different sources of law; different branches of international law or different subject-matter areas; and interaction between a treaty norm belonging to a one area of international law and a customary norm arising from another area of international law. There are different avenues for cross-fertilization of international law: it can result from the application of Art. 31 (3) (c) of the Vienna Convention on the Law of Treaties (VCLT)1 in the process of interpreting a particular treaty, from the application of other rules of international law together with a particular treaty or from reference to the jurisprudence of other international courts or tribunals by adhering to the approach adopted in this jurisprudence.
This article examines the question of cross-fertilization of international law in the context of the jurisprudence of the courts and tribunals operating within the dispute settlement system established under the UN Convention on the Law of the Sea (hereinafter ‘UNCLOS’ or ‘Convention’).2 It will demonstrate how these adjudicatory bodies have employed Art. 31 (3) (c) VCLT, Art. 293 UNCLOS which explicitly enables them to apply other rules of international law not incompatible with the Convention, and the international jurisprudence in order to interpret and apply the UNCLOS while situating it the broader context of international law. Note will be taken of UNCLOS provisions incorporating or referring to other rules of international law which also contribute to the cross-fertilization of international law.