bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection from chronic stress- and depressive symptom-induced vascular endothelial dysfunction in female rats is abolished by preexisting metabolic disease
Authors: Brooks Steven D. , Hileman Stanley M. , Chantler Paul D. , Milde Samantha A. , Lemaster Kent A. , Frisbee Stephanie J. , Shoemaker J. Kevin , Jackson Dwayne N. , Frisbee Jefferson C. 
Published: February 2018

While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent clinical evidence has identified correlations between the development of metabolic disease and depressive symptoms, creating a combined condition of severely elevated cardiovascular disease risk. In this study, we used the obese Zucker rat (OZRs) and the unpredictable chronic mild stress (UCMS) model to determine the impact of preexisting metabolic disease on the relationship between chronic stress/depressive symptoms and vascular function. Additionally, we determined the impact of metabolic syndrome on sex-based protection from chronic stress/depressive effects on vascular function in female lean Zucker rats (LZRs). In general, vasodilator reactivity was attenuated under control conditions in OZRs compared with LZRs. Although still impaired, conduit arterial and resistance arteriolar dilator reactivity under control conditions in female OZRs was superior to that in male or ovariectomized (OVX) female OZRs, largely because of better maintenance of vascular nitric oxide and prostacyclin levels. However, imposition of metabolic syndrome in combination with UCMS in OZRs further impaired dilator reactivity in both vessel subtypes to a similarly severe extent and abolished any protective effect in female rats compared with male or OVX female rats. The loss of vascular protection in female OZRs with UCMS was reflected in vasodilator metabolite levels, which closely matched those in male and OVX female OZRs subjected to UCMS. These results suggest that presentation of metabolic disease in combination with depressive symptoms can overwhelm the vasoprotection identified in female rats and, thereby, may reflect a severe impairment to normal endothelial function. NEW & NOTEWORTHY This study addresses the protection from chronic stress- and depression-induced vascular dysfunction identified in female compared with male or ovariectomized female rats. We determined the impact of preexisting metabolic disease, a frequent comorbidity of clinical depression in humans, on that vascular protection. With preexisting metabolic syndrome, female rats lost all protection from chronic stress/depressive symptoms and became phenotypically similar to male and ovariectomized female rats, with comparably poor vasoactive dilator metabolite profiles.
The HCM-linked W792R mutation in cardiac myosin-binding protein C reduces C6 FnIII domain stability
Authors: Smelter Dan F. , de Lange Willem J. , Cai Wenxuan , Ge Ying , Ralphe J. Carter 
Published: February 2018

Cardiac myosin-binding protein C (cMyBP-C) is a functional sarcomeric protein that regulates contractility in response to contractile demand, and many mutations in cMyBP-C lead to hypertrophic cardiomyopathy (HCM). To gain insight into the effects of disease-causing cMyBP-C missense mutations on contractile function, we expressed the pathogenic W792R mutation (substitution of a highly conserved tryptophan residue by an arginine residue at position 792) in mouse cardiomyocytes lacking endogenous cMyBP-C and studied the functional effects using three-dimensional engineered cardiac tissue constructs (mECTs). Based on complete conservation of tryptophan at this location in fibronectin type II (FnIII) domains, we hypothesized that the W792R mutation affects folding of the C6 FnIII domain, destabilizing the mutant protein. Adenoviral transduction of wild-type (WT) and W792R cDNA achieved equivalent mRNA transcript abundance, but not equivalent protein levels, with W792R compared with WT controls. mECTs expressing W792R demonstrated abnormal contractile kinetics compared with WT mECTs that were nearly identical to cMyBP-C-deficient mECTs. We studied whether common pathways of protein degradation were responsible for the rapid degradation of W792R cMyBP-C. Inhibition of both ubiquitin-proteasome and lysosomal degradation pathways failed to increase full-length mutant protein abundance to WT equivalence, suggesting rapid cytosolic degradation. Bacterial expression of WT and W792R protein fragments demonstrated decreased mutant stability with altered thermal denaturation and increased susceptibility to trypsin digestion. These data suggest that the W792R mutation destabilizes the C6 FnIII domain of cMyBP-C, resulting in decreased full-length protein expression. This study highlights the vulnerability of FnIII-like domains to mutations that alter domain stability and further indicates that missense mutations in cMyBP-C can cause disease through a mechanism of haploinsufficiency.NEW & NOTEWORTHY This study is one of the first to describe a disease mechanism for a missense mutation in cardiac myosin-binding protein C linked to hypertrophic cardiomyopathy. The mutation decreases stability of the fibronectin type III domain and results in substantially reduced mutant protein expression dissonant to transcript abundance.
Cognitive Function Declines Significantly during Haemodialysis in a Majority of Patients: A Call for Further Research
Authors: Dasgupta Indranil , Patel Mitesh , Mohammed Nuredin , Baharani Jyoti , Subramanian Thejasvi , Thomas G. Neil , Tadros George 
Published: February 2018

<b><i>Introduction:</i></b> Cognitive impairment (CI) is very common condition that occurs in haemodialysis patients and it is associated with reduced functional capacity and mortality. We assessed the change in cognitive function during haemodialysis and associated risk factors. <b><i>Methods:</i></b> All patients ≥50 years, on haemodialysis for ≥3 months, no dementia from 2 dialysis centres were selected. Cognition was assessed before and after a haemodialysis session using parallel versions of the Montreal Cognitive Assessment (MOCA) tool. Multiple regression was used to examine potential confounders. <b><i>Results:</i></b> Eight-two patients completed both tests – median age 73 (52–91) years, 59% male, dialysis vintage 41 (3–88) months. Sixty-two (76%) had CI at baseline. Cognition declined over dialysis (MOCA 21 ± 4.8 to 19.1 ± 4.1, <i>p</i> &#x3c; 0.001) and domains affected were attention, language, abstraction and delayed recall. Age and dialysis vintage were independently associated with decline. <b><i>Conclusion:</i></b> Cognitive function declines over a haemodialysis session and this has significant clinical implications over health literacy, self-management and tasks like driving. More research is needed to find the cause for this decline in cognition.
Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment
Authors: van Vugt Jeroen L.A. , Gaspersz Marcia P. , Vugts Jaynee , Buettner Stefan , Levolger Stef , de Bruin Ron W.F. , Polak Wojciech G. , de Jonge Jeroen , Willemssen François E.J.A. , Groot Koerkamp Bas , IJzermans Jan N.M. 
Published: February 2018

<b><i>Background:</i></b> Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. <b><i>Methods:</i></b> Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. <b><i>Results:</i></b> Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (<i>p</i> = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7–9.3) and high (HR 12.1, 95% CI 8.1–16.1) skeletal muscle density (<i>p</i> = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03–3.07, <i>p</i> = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44–1.07, <i>p</i> = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. <b><i>Conclusion:</i></b> A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.
Ten-Year Clinical Outcome After Circumferential Pulmonary Vein Isolation Utilizing the Hamburg Approach in Patients With Symptomatic Drug-Refractory Paroxysmal Atrial Fibrillation
Authors: Tilz Roland Richard , Heeger Christian-Hendrik , Wick Alexander , Saguner Ardan M. , Metzner Andreas , Rillig Andreas , Wohlmuth Peter , Reissmann Bruno , Lemeš Christine , Maurer Tilman , Santoro Francesco , Riedl Johannes , Sohns Christian , Mathew Shibu , Kuck Karl-Heinz , Ouyang Feifan 
Published: February 2018

Background:
Circumferential pulmonary vein isolation (CPVI) is increasingly performed for the treatment of symptomatic drug-refractory paroxysmal atrial fibrillation. Long-term data for >10 years after CPVI are sparse. We investigated the long-term clinical outcome and progression of paroxysmal atrial fibrillation after double-lasso and 3-dimensional electroanatomical mapping–guided CPVI.

Methods and Results:
From 2003 to 2004, 161 patients (mean age: 60±10 years) with symptomatic drug-refractory paroxysmal atrial fibrillation were prospectively enrolled and underwent electroanatomical mapping–guided CPVI. Right-sided and left-sided continuous circular lesions encircling the ipsilateral pulmonary veins were placed with irrigated radiofrequency energy. The procedural end point was the absence of pulmonary vein spikes 30 minutes after CPVI verified by 2 spiral catheters placed within the ipsilateral pulmonary veins (double-lasso technique). Major periprocedural complications occurred in 5 of 161 patients (3.1%). Follow-up was based on outpatient clinic visits, including Holter-ECGs and telephonic interviews. After a single procedure and median follow-up of 129.0 months (interquartile range, 124.7–133.1 months), stable sinus rhythm was present in 53 of 161 (32.9%) patients. Multiprocedural outcome after a mean of 1.73±0.9 procedures and a median follow-up of 123.4 months (interquartile range, 61.0–131.0 months) resulted in stable sinus rhythm in 101 of 161 patients (62.7%). Progression toward persistent atrial fibrillation was observed in 10 of 161 patients (6.2%).

Conclusion:
Ten-year single-procedural outcome of CPVI in patients with paroxysmal atrial fibrillation resulted in stable sinus rhythm in 32.9% and in 62.7% of patients after multiple procedures. The progression rate to persistent AF was remarkably low.
Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin
Authors: Hanson Jacquelyn L.S. , Arvanitis Marios , Koch Clarissa M. , Berk John L. , Ruberg Frederick L. , Prokaeva Tatiana , Connors Lawreen H. 
Published: February 2018

Background:
Wild-type transthyretin amyloidosis (ATTRwt), an underappreciated cause of heart failure in older adults, is challenging to diagnose and monitor in the absence of validated, disease-specific biomarkers. We examined the prognostic use and survival association of serum TTR (transthyretin) concentration in ATTRwt.

Methods and Results:

Patients with biopsy-proven ATTRwt were retrospectively identified. Serum TTR, cardiac biomarkers, and echocardiographic parameters were assessed at baseline and follow-up evaluations. Statistical analyses included Kaplan–Meier method, Cox proportional hazard survival models, and receiver-operating characteristic curve analysis. Median serum TTR concentration at presentation was 23 mg/dL (n=116). Multivariate predictors of shorter overall survival were decreased TTR, left ventricular ejection fraction and elevated cTn-I (cardiac troponin I); an inclusive model demonstrated superior accuracy in 4-year survival prediction by receiver-operating characteristic curve analysis (area under the curve, 0.77). TTR values lower than the normal limit, <18 mg/dL, were associated with shorter survival (2.8 versus 4.1 years;
P
=0.03). Further, TTR values at 1- and 2-year follow-ups were significantly lower (
P
<0.001) in untreated patients (n=23) compared with those treated with TTR stabilizer, diflunisal (n=12), after baseline evaluation. During 2-year follow-up, unchanged TTR corresponded to increased cTn-I (
P
=0.006) in untreated patients; conversely, the diflunisal-treated group showed increased TTR (
P
=0.001) and stabilized cTn-I and left ventricular ejection fraction at 1 year.

Conclusions:
In this series of biopsy-proven ATTRwt, lower baseline serum TTR concentration was associated with shorter survival as an independent predictor of outcome. Longitudinal analysis demonstrated that decreasing TTR corresponded to worsening cardiac function. These data suggest that TTR may be a useful prognostic marker and predictor of outcome in ATTRwt.
Quantitative Flow Ratio Identifies Nonculprit Coronary Lesions Requiring Revascularization in Patients With ST-Segment–Elevation Myocardial Infarction and Multivessel Disease
Authors: Spitaleri Giosafat , Tebaldi Matteo , Biscaglia Simone , Westra Jelmer , Brugaletta Salvatore , Erriquez Andrea , Passarini Giulia , Brieda Alessandro , Leone Antonio Maria , Picchi Andrea , Ielasi Alfonso , Girolamo Domenico Di , Trani Carlo , Ferrari Roberto , Reiber Johan H.C. , Valgimigli Marco , Sabatè Manel , Campo Gianluca 
Published: February 2018

Background—
The nonculprit lesion (NCL) management in ST-segment–elevation myocardial infarction patients with multivessel disease is debated. We sought to assess whether quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, may be reliable in this scenario.

Methods and Results—

The present proof-of-concept study is based on a 3-step process: (1) identification of the QFR reproducibility in NCLs assessment (cohort A, n=31); (2) prospective validation of QFR diagnostic accuracy in respect to fractional flow reserve (cohort B, n=45); and (3) investigation of long-term clinical outcomes of NCLs stratified according to QFR (cohort C, n=110). A blinded core laboratory computed QFR values for all NCLs. Cohort A showed a good correlation and agreement between QFR values at index (acute) and at staged (subacute, 3–4 days later) procedures (
r
=0.98; 95% confidence interval, 0.96–0.99; mean difference, 0.004 [−0.027 to 0.34]). The inter-rater agreement was κ=0.9. In cohort B, fractional flow reserve and QFR identified 16 (33%) and 17 (35%) NCLs potentially flow limiting. Sensitivity, specificity, negative, and positive predictive values were 88%, 97%, 94%, and 94%. The area under the receiver operating characteristics curve was 0.96 (95% confidence interval, 0.89–0.99). Finally, in cohort C, we identified 110 ST-segment–elevation myocardial infarction patients where at least 1 NCL was left untreated. Patients with NCLs showing a QFR value ≤0.80 were at higher risk of adverse events (hazard ratio, 2.3; 95% confidence interval, 1.2–4.5;
P
=0.01).

Conclusions—
In a limited and selected study population, our study showed that QFR computation may be a safe and reliable tool to guide coronary revascularization of NCLs in ST-segment–elevation myocardial infarction patients.
Novel Patient‐Centered Approach to Facilitate Same‐Day Discharge in Patients Undergoing Elective Percutaneous Coronary Intervention
Authors: Amin Amit P. , Crimmins‐Reda Patricia , Miller Samantha , Rahn Brandon , Caruso Mary , Pierce Andrew , Dennis Brandy , Pendegraft Marissa , Sorensen Katrine , Kurz Howard I. , Lasala John M. , Zajarias Alan , Bach Richard G. , Kulkarni Hemant , Singh Jasvindar 
Published: February 2018

Background

Same‐day discharge (
SDD
) after elective percutaneous coronary intervention is safe, less costly, and preferred by patients, but it is usually performed in low‐risk patients, if at all. To increase the appropriate use of
SDD
in more complex patients, we implemented a “patient‐centered” protocol based on risk of complications at Barnes‐Jewish Hospital.

Methods and Results

Our objectives were as follows: (1) to evaluate time trends in
SDD
; (2) to compare (a) mortality, bleeding, and acute kidney injury, (b) patient satisfaction, and (c) hospital costs by
SDD
versus no SDD (
NSDD
); and (3) to compare
SDD
eligibility by our patient‐centered approach versus Society for Cardiovascular Angiography and Interventions guidelines. Our patient‐centered approach was based on prospectively identifying personalized bleeding, mortality, and acute kidney injury risks, with a personalized safe contrast limit and mitigating those risks. We analyzed Barnes‐Jewish Hospital's National Cardiovascular Data Registry Cath
PCI
Registry data from July 1, 2009 to September 30, 2015 (N=1752).
SDD
increased rapidly from 0% to 77% (
P
<0.001), independent of radial access. Although
SDD
patients were comparable to
NSDD
patients,
SDD
was not associated with adverse outcomes (0% mortality, 0% bleeds, and 0.4% acute kidney injury). Patient satisfaction was high with
SDD
. Propensity score–adjusted costs were $7331 lower/
SDD
patient (
P
<0.001), saving an estimated $1.8 million annually. Only 16 patients (6.95%) met the eligibility for
SDD
by Society for Cardiovascular Angiography and Interventions guidelines, implying our patient‐centered approach markedly increased
SDD
eligibility.

Conclusions

With a patient‐centered approach,
SDD
rapidly increased and was safe in 75% of patients undergoing elective percutaneous coronary intervention, despite patient complexity. Patient satisfaction was high, and hospital costs were lower. Patient‐centered decision making to facilitate
SDD
is an important opportunity to improve the value of percutaneous coronary intervention.
Differential Clinical Outcomes Between Angiographic Complete Versus Incomplete Coronary Revascularization, According to the Presence of Chronic Kidney Disease in the Drug‐Eluting Stent Era
Authors: Kim Jihoon , Lee Joo Myung , Choi Ki Hong , Rhee Tae‐Min , Hwang Doyeon , Park Jonghanne , Ahn Chul , Park Taek Kyu , Yang Jeong Hoon , Song Young Bin , Choi Jin‐Ho , Hahn Joo‐Yong , Choi Seung‐Hyuk , Gwon Hyeon‐Cheol 
Published: February 2018

Background

There are limited data regarding the prognostic impact of angiographic complete revascularization (
CR
) in patients with chronic kidney disease (
CKD
). We sought to investigate the differential prognostic impact of angiographic
CR
over incomplete revascularization (
IR
), according to the presence of
CKD
in the drug‐eluting stent era.

Methods and Results

Between 2003 and 2011 at Samsung Medical Center, consecutive patients with multivessel disease were stratified by the presence of
CKD
(estimated glomerular filtration rate <60 mL/min per 1.73 m
2
) and classified according to angiographic
CR
(residual
SYNTAX
score=0) or
IR
. Clinical outcomes were compared between angiographic
CR
and
IR
, stratified by the presence of
CKD
. Primary outcome was patient‐oriented composite outcomes (
POCO
, a composite of all‐cause death, myocardial infarction, any revascularization) at 3 years. Inverse probability weighting was performed between the
CR
and
IR
groups. A total of 3224 patients were eligible for analysis: 2295 without
CKD
; 929 with
CKD
. Among non‐
CKD
patients, angiographic
CR
showed a significantly lower risk of
POCO
than
IR
(17.2% versus 21.7%, adjusted hazard ratio 0.76, 95% confidence interval, 0.62–0.95,
P
=0.014), mainly driven by a significantly lower risk of any revascularization. Among
CKD
patients, however, angiographic
CR
was associated with a significantly higher risk of
POCO
than
IR
(37.7% versus 28.4%, adjusted hazard ratio 1.42, 95% confidence interval, 1.08%–1.85%,
P
=0.011), mainly driven by a significantly higher risk of nonfatal target vessel myocardial infarction.

Conclusions

Angiographic
CR
was associated with reduced risk of
POCO
than
IR
in patients without
CKD
; however, it was associated with a significantly higher risk of
POCO
and nonfatal myocardial infarction in
CKD
patients.
A Legal Obligation to Restore Wetlands by Environmental Water Allocations
Authors: Jensen Jeanette , Gardner Alex 
Published: February 2018

Abstract
Wetlands worldwide require significant restoration, especially through environmental water allocations. This article examines the Ramsar Convention (Ramsar) and the Convention on Biological Diversity (cbd) to ascertain whether they require an obligation to restore wetlands by such means. While both conventions contain a general obligation to restore, that obligation appears too uncertain, due to either the disputable status of the language of the text (Ramsar) or the qualifying language expressing it (cbd). The Ramsar obligation, arguably, amounts to a legal obligation that is potentially enforceable in the icj against another contracting party. The article recognizes that the obligation is practically difficult to enforce because: the Convention does not provide a formal dispute settlement procedure; the obligation is derived from guidance in numerous Conference of the Parties resolutions, and is subject to certain exceptions. Further, there is a judicial reluctance to find that the facts prove a breach of the obligations and warrant a remedy. The authors argue, however, that restoration goals are, in fact, achievable through Convention amendments or by an additional protocol.
Quantifying the Relative Importance of Direct and Indirect Biophysical Effects of Deforestation on Surface Temperature and Teleconnections
Authors: Devaraju N. , de Noblet-Ducoudré Nathalie , Quesada Benjamin , Bala G. 
Published: February 2018

Abstract
In this study, the authors linearize the surface energy budget equation that disentangles indirect effects (resulting from changes in downward shortwave and longwave radiation and air temperature) from direct biophysical effects (resulting from changes in surface albedo, evapotranspiration, and roughness length) of deforestation on land surface temperature. This formulation is applied to idealized deforestation simulations from two climate models and to realistic land-use and land-cover change (LULCC) simulations from 11 models, and the contribution of each underlying mechanism to surface temperature change is quantified. It is found that the boreal region experiences dominant indirect effects and the tropics experience dominant direct effects in all seasons in idealized deforestation simulations. The temperate region response differs in the two models. However, five out of seven models in response to realistic historical LULCC show a dominance of indirect effects in the temperate region. In response to future LULCC, three out of four models confirm the dominance of direct effects in the tropical region. It is found that indirect effects are always largely attributable to air temperature feedback and direct effects are essentially driven by changes in roughness length in both idealized and realistic simulations. Furthermore, teleconnections are shown to exist between deforested regions and the rest of the world, associated with the indirect effects. The study also shows that the partitioning between direct and indirect effects is highly model dependent, which may explain part of the intermodel spread found in previous studies comparing the total biophysical effects across models.