bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are happy people healthier? An instrumental variable approach using data from Greece
Authors: Kyriopoulos Ilias , Athanasakis Kostas , Kyriopoulos John 
Published: July 2018

BackgroundFrom a theoretical perspective, several studies indicate that happiness and health are—in some extent—interrelated. Despite the mechanisms explaining the relationship between happiness and health, there is still no consensus regarding this link. Using recently collected primary data, this study aims to examine the relationship between happiness and health, and identify potential heterogeneity in the association depending on socioeconomic status (SES).MethodsThis study draws on data from a nationally representative cross-sectional survey, conducted by the Greek National School of Public Health in 2015. We applied an instrumental variable (IV) approach to address the endogeneity, arising from the simultaneous determination of happiness and health. Controlling for several confounders (ie, socioeconomic, demographic, lifestyle, social capital variables) we employed several IV models, including two-stage least squares, IV probit and bivariate probit models.ResultsWe report strong evidence of a relationship between happiness and health. This association remains strong after correcting for endogeneity, and is robust across different specifications. Further, we find a positive relationship between happiness and self-rated health (SRH) for low educated, but not for high educated. Similarly, we find a strong relationship between happiness and health for the lower socioeconomic strata, but not for the higher ones.ConclusionsOverall, we show that happiness is positively associated with health. Further, happiness significantly influences SRH in low-SES individuals, but this association wanes for the higher socioeconomic strata. This finding has significant implications for health promotion, prevention and public health, and suggests that policymakers have a wider array of choices for improving health and tackling health inequalities.
Bacteria-free minicircle DNA system to generate integration-free CAR-T cells
Authors: Cheng Chen , Tang Na , Li Jiaxin , Cao Shiwei , Zhang Tongtong , Wei Xiaofei , Wang Haoyi 
Published: July 2018

BackgroundChimeric antigen receptor T (CAR-T) cells engineered with lentiviral and retroviral vectors have been successfully applied to treat patients with B cell malignancy. However, viral integration in T cells has the potential risk of mutagenesis, and viral vector production demands effort and is costly. Using non-integrative episomal vector such as minicircle vector to generate integration-free CAR-T cells is an attractive option.Methods and resultsWe established a novel method to generate minicircle vector within a few hours using simple molecular biology techniques. Since no bacteria is involved, we named these vectors bacteria-free (BF) minicircle. In comparison with plasmids, BF minicircle vector enabled higher transgene expression and improved cell viability in human cell line, stem cells and primary T cells. Using BF minicircle vector, we generated integration-free CAR-T cells, which eliminated cancer cells efficiently both in vitro and in vivo.ConclusionBF minicircle vector will be useful in basic research as well as in clinical applications such as CAR-T and gene therapy. Although the transgene expression of minicircle vector lasts apparently shorter than that of insertional lentivirus, multiple rounds of BF minicircle CAR-T cell infusion could eliminate cancer cells efficiently. On the other hand, a relatively shorter CAR-T cell persistence provides an opportunity to avoid serious side effects such as cytokine storm or on-target off-tumour toxicity.
Normal patterns of thoracic aortic wall shear stress measured using four-dimensional flow MRI in a large population
Authors: Callaghan Fraser M. , Grieve Stuart M. 
Published: July 2018

Wall shear stress (WSS) plays a governing role in vascular remodeling and a pathogenic role in vessel wall diseases. However, little is known of the normal WSS patterns in the aorta as there is currently no practical means to routinely measure WSS and no normal ranges derived from population data exist. WSS measurements were made on the aorta of 224 subjects with normal anatomy using four-dimensional flow MRI with multiple encoding velocities and an optimized postprocessing routine. The spatial and temporal variation in WSS and oscillatory shear index was analyzed using a flat map representation of the unfolded aorta. The influence of aortic shape and velocity on WSS was evaluated using regression analysis. WSS in the thoracic aorta is dominated by axial flow. Average peak systolic WSS was 1.79 ± 0.71 Pa in the aortic arch and was significantly higher at 2.23 ± 1.04 Pa in the descending aorta, with a strong negative correlation with advancing age. The spatial distribution of WSS is highly heterogeneous, with a localized region of elevated WSS along the length of the anterior wall seen across all individuals. Our data demonstrate that accurate four-dimensional flow-derived WSS measurement is feasible, and we further provide a standardized parametric approach for presentation and analysis. We present a normal range for WSS across the lifespan, demonstrating a decrease in WSS with advancing age as well as illustrating the high degree of spatial and temporal variation. NEW & NOTEWORTHY With the use of four-dimensional flow MRI and postprocessing, accurate direct measurement of wall shear stress (WSS) was performed in a population of normal thoracic aortas ( n = 224). WSS was higher in the descending aorta compared with the aortic arch and decreased with age. A heterogeneous pattern of elevated WSS along the length of the aorta anterior wall was consistent across the population. This work provides normal data across the adult age range, permitting comparison with pathology.
Astrocyte-produced carbon monoxide and the carbon monoxide donor CORM-A1 protect against cerebrovascular dysfunction caused by prolonged neonatal asphyxia
Authors: Parfenova Helena , Pourcyrous Massroor , Fedinec Alex L. , Liu Jianxiong , Basuroy Shyamali , Leffler Charles W. 
Published: July 2018

Neonatal asphyxia leads to cerebrovascular disease and neurological complications via a mechanism that may involve oxidative stress. Carbon monoxide (CO) is an antioxidant messenger produced via a heme oxygenase (HO)-catalyzed reaction. Cortical astrocytes are the major cells in the brain that express constitutive HO-2 isoform. We tested the hypothesis that CO, produced by astrocytes, has cerebroprotective properties during neonatal asphyxia. We developed a survival model of prolonged asphyxia in newborn pigs that combines insults of severe hypoxia, hypercapnia, and acidosis while avoiding extreme hypotension and cerebral blood flow reduction. During the 60-min asphyxia, CO production by brain and astrocytes was continuously elevated. Excessive formation of reactive oxygen species during asphyxia/reventilation was potentiated by the HO inhibitor tin protoporphyrin, suggesting that endogenous CO has antioxidant effects. Cerebral vascular outcomes tested 24 and 48 h after asphyxia demonstrated the sustained impairment of cerebral vascular responses to astrocyte- and endothelium-specific vasodilators. Postasphyxia cerebral vascular dysfunction was aggravated in newborn pigs pretreated with tin protoporphyrin to inhibit brain HO/CO. The CO donor CO-releasing molecule-A1 (CORM-A1) reduced brain oxidative stress during asphyxia/reventilation and prevented postasphyxia cerebrovascular dysfunction. The antioxidant and antiapoptotic effects of HO/CO and CORM-A1 were confirmed in primary cultures of astrocytes from the neonatal pig brain exposed to glutamate excitotoxicity. Overall, prolonged neonatal asphyxia leads to neurovascular injury via an oxidative stress-mediated mechanism that is counteracted by an astrocyte-based constitutive antioxidant HO/CO system. We propose that gaseous CO or CO donors can be used as novel approaches for prevention of neonatal brain injury caused by prolonged asphyxia. NEW & NOTEWORTHY Asphyxia in newborn infants may lead to lifelong neurological disabilities. Using the model of prolonged asphyxia in newborn piglets, we propose novel antioxidant therapy based on systemic administration of low doses of a carbon monoxide donor that prevent loss of cerebral blood flow regulation and may improve the neurological outcome of asphyxia.
FGF23 impairs peripheral microvascular function in renal failure
Authors: Verkaik Melissa , Juni Rio P. , van Loon Ellen P. M. , van Poelgeest Erik M. , Kwekkeboom Rick F. J. , Gam Zeineb , Richards William G. , ter Wee Pieter M. , Hoenderop Joost G. , Eringa Etto C. , Vervloet Marc G. ,   the NIGRAM Consortium
Published: July 2018

Cardiovascular diseases account for ~50% of mortality in patients with chronic kidney disease (CKD). Fibroblast growth factor 23 (FGF23) is independently associated with endothelial dysfunction and cardiovascular mortality. We hypothesized that CKD impairs microvascular endothelial function and that this can be attributed to FGF23. Mice were subjected to partial nephrectomy (5/6Nx) or sham surgery. To evaluate the functional role of FGF23, non-CKD mice received FGF23 injections and CKD mice received FGF23-blocking antibodies after 5/6Nx surgery. To examine microvascular function, myocardial perfusion in vivo and vascular function of gracilis resistance arteries ex vivo were assessed in mice. 5/6Nx surgery blunted ex vivo vasodilator responses to acetylcholine, whereas responses to sodium nitroprusside or endothelin were normal. In vivo FGF23 injections in non-CKD mice mimicked this endothelial defect, and FGF23 antibodies in 5/6Nx mice prevented endothelial dysfunction. Stimulation of microvascular endothelial cells with FGF23 in vitro did not induce ERK phosphorylation. Increased plasma asymmetric dimethylarginine concentrations were increased by FGF23 and strongly correlated with endothelial dysfunction. Increased FGF23 concentration did not mimic impaired endothelial function in the myocardium of 5/6Nx mice. In conclusion, impaired peripheral endothelium-dependent vasodilatation in 5/6Nx mice is mediated by FGF23 and can be prevented by blocking FGF23. These data corroborate FGF23 as an important target to combat cardiovascular disease in CKD.NEW & NOTEWORTHY In the present study, we provide the first evidence that fibroblast growth factor 23 (FGF23) is a cause of peripheral endothelial dysfunction in a model of early chronic kidney disease (CKD) and that endothelial dysfunction in CKD can be prevented by blockade of FGF23. This pathological effect on endothelial cells was induced by long-term exposure of physiological levels of FGF23. Mechanistically, increased plasma asymmetric dimethylarginine concentrations were strongly associated with this endothelial dysfunction in CKD and were increased by FGF23.
Ventricular Arrhythmias Underlie Sudden Death in Rats With Heart Failure and Preserved Ejection Fraction
Authors: Cho Jae Hyung , Zhang Rui , Aynaszyan Stephan , Holm Kevin , Goldhaber Joshua I. , Marbán Eduardo , Cingolani Eugenio 
Published: July 2018

Background:
Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly common clinically, now rivaling or exceeding HF with reduced ejection fraction. Sudden death is the leading mode of exodus in patients with HFpEF, but the underlying causes are largely unknown. Using ambulatory recordings in a rat model, we test the hypothesis that ventricular arrhythmias (VA) underlie sudden death in HFpEF.

Methods:
Dahl salt-sensitive rats (7 weeks of age) were fed a high-salt diet to induce HFpEF (n=13) or a normal-salt diet (controls, n=9). Transthoracic echocardiography was performed to check systolic and diastolic function at 14 to 18 weeks of age. Telemetric electrocardiographic recordings were analyzed for QT interval duration, burden of premature ventricular contractions, spontaneous VA, and heart rate variability. Survival was monitored twice daily.

Results:

High-salt–fed rats with clear diastolic dysfunction, preserved ejection fraction, and HF signs were diagnosed with HFpEF at 14 to 15 weeks of age. QT and QTc intervals were prolonged in HFpEF rats compared with controls. Heart rate variability was reduced in HFpEF rats compared with controls. Spontaneous VA were more prevalent in HFpEF rats (6/13=46.1% versus 0/9=0% in controls;
P
<0.05), and sudden death was observed in 4 of 13 HFpEF rats. Three of the 4 sudden deaths were associated with VA as the terminal rhythm.

Conclusions:
In this rat model with phenotypically verified HFpEF, sudden death was common and generally associated with VA. Further clinical studies are warranted to determine whether these insights translate to sudden death in HFpEF patients.
Acute Enhancement of Cardiac Function by Phosphodiesterase Type 1 Inhibition
Authors: Hashimoto Toru , Kim Grace E. , Tunin Richard S. , Adesiyun Tolulope , Hsu Steven , Nakagawa Ryo , Zhu Guangshuo , O’Brien Jennifer J. , Hendrick Joseph P. , Davis Robert E. , Yao Wei , Beard David , Hoxie Helen R. , Wennogle Lawrence P. , Lee Dong I. , Kass David A. 
Published: July 2018

Background:
Phosphodiesterase type-1 (PDE1) hydrolyzes cAMP and cGMP and is constitutively expressed in the heart, although cardiac effects from its acute inhibition in vivo are largely unknown. Existing data are limited to rodents expressing mostly the cGMP-favoring PDE1A isoform. Human heart predominantly expresses PDE1C with balanced selectivity for cAMP and cGMP. Here, we determined the acute effects of PDE1 inhibition in PDE1C-expressing mammals, dogs, and rabbits, in normal and failing hearts, and explored its regulatory pathways.

Methods:
Conscious dogs chronically instrumented for pressure-volume relations were studied before and after tachypacing-induced heart failure (HF). A selective PDE1 inhibitor (ITI-214) was administered orally or intravenously±dobutamine. Pressure-volume analysis in anesthetized rabbits tested the role of β-adrenergic and adenosine receptor signaling on ITI-214 effects. Sarcomere and calcium dynamics were studied in rabbit left ventricular myocytes.

Results:

In normal and HF dogs, ITI-214 increased load-independent contractility, improved relaxation, and reduced systemic arterial resistance, raising cardiac output without altering systolic blood pressure. Heart rate increased, but less so in HF dogs. ITI-214 effects were additive to β-adrenergic receptor agonism (dobutamine). Dobutamine but not ITI-214 increased plasma cAMP. ITI-214 induced similar cardiovascular effects in rabbits, whereas mice displayed only mild vasodilation and no contractility effects. In rabbits, β-adrenergic receptor blockade (esmolol) prevented ITI-214–mediated chronotropy, but inotropy and vasodilation remained unchanged. By contrast, adenosine A
2B
-receptor blockade (MRS-1754) suppressed ITI-214 cardiovascular effects. Adding fixed-rate atrial pacing did not alter the findings. ITI-214 alone did not affect sarcomere or whole-cell calcium dynamics, whereas β-adrenergic receptor agonism (isoproterenol) or PDE3 inhibition (cilostamide) increased both. Unlike cilostamide, which further enhanced shortening and peak calcium when combined with isoproterenol, ITI-214 had no impact on these responses. Both PDE1 and PDE3 inhibitors increased shortening and accelerated calcium decay when combined with forskolin, yet only cilostamide increased calcium transients.

Conclusions:
PDE1 inhibition by ITI-214 in vivo confers acute inotropic, lusitropic, and arterial vasodilatory effects in PDE1C-expressing mammals with and without HF. The effects appear related to cAMP signaling that is different from that provided via β-adrenergic receptors or PDE3 modulation. ITI-214, which has completed phase I trials, may provide a novel therapy for HF.
Early Regenerative Capacity in the Porcine Heart
Authors: Ye Lei , D’Agostino Giuseppe , Loo Sze Jie , Wang Chen Xu , Su Li Ping , Tan Shi Hua , Tee Gui Zhen , Pua Chee Jian , Pena Edgar Macabe , Cheng Redmond Belen , Chen Way Cherng , Abdurrachim Desiree , Lalic Janise , Tan Ru San , Lee Teck Hock , Zhang JianYi , Cook Stuart Alexander 
Published: July 2018

Background:
The adult mammalian heart has limited ability to repair itself after injury. Zebrafish, newts, and neonatal mice can regenerate cardiac tissue, largely by cardiac myocyte (CM) proliferation. It is unknown whether hearts of young large mammals can regenerate.

Methods:
We examined the regenerative capacity of the pig heart in neonatal animals (ages 2, 3, or 14 days postnatal) after myocardial infarction or sham procedure. Myocardial scar and left ventricular function were determined by cardiac magnetic resonance imaging and echocardiography. Bromodeoxyuridine pulse-chase labeling, histology, immunohistochemistry, and Western blotting were performed to study cell proliferation, sarcomere dynamics, and cytokinesis and to quantify myocardial fibrosis. RNA-sequencing was also performed.

Results:
After myocardial infarction, there was early and sustained recovery of cardiac function and wall thickness in the absence of fibrosis in 2-day-old pigs. In contrast, older animals developed full-thickness myocardial scarring, thinned walls, and did not recover function. Genome-wide analyses of the infarct zone revealed a strong transcriptional signature of fibrosis in 14-day-old animals that was absent in 2-day-old pigs, which instead had enrichment for cytokinesis genes. In regenerating hearts of the younger animals, up to 10% of CMs in the border zone of the myocardial infarction showed evidence of DNA replication that was associated with markers of myocyte division and sarcomere disassembly.

Conclusions:
Hearts of large mammals have regenerative capacity, likely driven by cardiac myocyte division, but this potential is lost immediately after birth.
The prevalence of Amblyopia in a young Population
Authors: Hashemi Hassan , Saatchi Mohammad , Ali Babak , Yekta Abbasali , Asharlous Amir , Ostadimoghaddam Hadi , Heravian Javad , Khabazkhoob Mehdi 
Published: July 2018

Purpose: The aim of this study was to determine the prevalence of amblyopia and its determinants in Iranian students above 18 years. Methods: In this university-based cross-sectional study, multi-stage cluster sampling was used to select participants. After selecting the students, visual acuity, objective, and subjective refraction were measured and the best-corrected visual acuity was determined. Results: We evaluated 1462 individuals with a mean age of 22.8 ± 3.1 years in this study, of whom 73% were female. The prevalence of amblyopia was 2.19% (95% confidence interval [CI]: [1.43, 2.93]), of which 6.2% was strabismic, 71.8% was refractive (isometropic and anisometropic), and 22.0% was mix (strabismic and anisometropic). No difference was observed in the prevalence of amblyopia between boys and girls ( p value = 0.315). The prevalence of amblyopia was 3.93%, 1.71%, 3.79%, and 0% in the age group 18–20, 21–25, 26–30, and above 30 years, respectively ( p value = 0.071). Conclusion: The results of this study, as the first study investigating the prevalence of amblyopia in Iranian adults, showed a rather higher prevalence of amblyopia in Iranian university students compared to other studies on adults in other countries. Moreover, similar to some other studies, refractive amblyopia had a higher prevalence than other types.
Percutaneous cholecystostomy for biliary decompression in patients with cholangitis and pancreatitis
Authors: Park Jin Myung , Kang Chang Don , Lee Minjong , Park Sung Chul , Lee Sung Joon , Jeon Yong Hwan , Cho Seong Whi 
Published: July 2018

Objective This study was performed to assess the effectiveness and safety of percutaneous cholecystostomy (PC) for biliary decompression. Methods We retrospectively analyzed our institution’s PC database from March 2015 to August 2017 and selected patients with biliary obstruction. The primary outcomes were the technical and clinical success rates. As secondary outcomes, adverse events and pain after PC were compared with those of patients who underwent PC for acute cholecystitis during the same period. Results Twenty patients underwent PC for biliary obstruction (cholangitis, 19; pancreatitis, 1). The technical and clinical success rates were 100%. The median serum total bilirubin level decreased considerably from 4.5 to 1.4 mg/dL after PC. An adverse event (catheter migration) occurred in 1 patient, and 17 patients developed pain after PC. During the same period, 104 patients underwent PC for cholecystitis. Adverse events occurred in 7 patients, and 62 developed pain. There was no significant difference in the adverse event rate between the cholangitis/pancreatitis and cholecystitis groups (5.0% vs. 6.7%, respectively), but pain occurred considerably more frequently in the cholangitis/pancreatitis group (94.4% vs. 63.9%, respectively). Conclusions PC is an effective and safe method for biliary decompression in selected patients. However, attention should be paid to postoperative pain.
Intergenerational differences in the personal and professional values of nurses
Authors: Şenyuva Emine 
Published: July 2018

Objectives: This study was conducted descriptively for the purpose of determining the differences in the personal and professional values of nurses according to their generation. Methods: The study was planned according to the descriptive research method. The population of the research consisted of nurses carrying out their duties in Istanbul, and the sample consisted of 718 nurses. The number of nurses to be included in the sample was determined by stratified sampling, and the nurses to be included in the sample were determined through random sampling. The data were collected using an information form, the Value Preferences Scale, Professional Value Order of Priority Scale, and the Nurses’ Professional Values Scale. Ethical considerations: Ethics committee approval for the study was received from the Ethics Committee Presidency of the I.U. Cerrahpasa Medical Faculty of Clinical Studies. The study began after the participants were informed that they could decide to withdraw from the study at any time during the data collection process. In order to use the Nurses Professional Values Scale, written permission was received from Nuray Sahin Orak. Findings: The primary value preference is social value for nurses from the Baby Boomers generation, Y and Z generations, and political value for nurses from X generation. It is the nurses from every generation who prioritized human dignity among professional values, which is follow by activation and responsibility. It is determined that a great majority of nurses from the Baby Boomers generation, X, Y, and Z generations prioritized human dignity among professional values, which was followed by the values of equality, justice, and freedom. Conclusion: These results indicate that nurses from all generations agree on the professional values required by their profession and thus carry out their duties in accordance with the ethical principles and the values of their profession.