bluuebunny/crossref_metadata_2025 huggingface dataset:
Splenectomy Promotes Macrophage Polarization in a Mouse Model of Concanavalin A- (ConA-) Induced Liver Fibrosis
Authors: Wang Yongjuan , Guo Xiaopei , Jiao Guohui , Luo Lili , Zhou Lu , Zhang Jie , Wang Bangmao
Published: January 2019

Background. Splenectomy can improve liver function and survival in patients with autoimmune hepatitis (AIH) and liver cirrhosis. We investigated the underlying mechanism in a mouse model of concanavalin A- (ConA-) induced liver fibrosis. Methods. We used ConA to induce immune liver fibrosis in BALB/c mice. Splenectomy was performed alone or with the administration of dexamethasone (DEX). Changes in blood and liver tissues were evaluated. Results. Mice treated with ConA for 7 weeks developed advanced liver fibrosis, while splenectomy suppressed liver fibrosis. Although the populations of macrophages/monocytes and M1 macrophages decreased after splenectomy, the inflammatory factors associated with M2 macrophages increased after splenectomy. Furthermore, the population of circulating CD11b+Ly6Chigh myeloid-derived suppressor cells (MDSCs) increased after splenectomy. After ConA treatment, elevated levels of activated and total NF-kBp65/p50 combined with DNA were observed in hepatic tissues. In contrast, the levels of NF-κB p65/p50 decreased after splenectomy. Conclusions. Splenectomy may promote the polarization of CD11b+Ly6Chigh MDSCs and the differentiation of M2 macrophages while restricting the level of NF-κB p65-p50 heterodimers. These factors may suppress the progression of liver fibrosis.
Cardiac Arrest in the Airport Revealing Cocaine Body Packing: A Case Report
Authors: Resiere Dabor , Mehdaoui Hossein , Megarbane Bruno
Published: January 2019

Ingestion of large amounts of cocaine packages is a well-known method for cross-border transportation. Intestinal obstruction and life-threatening sympathomimetic toxidrome including seizures, ventricular dysrhythmia, and cardiac arrest resulting from the rupture of cocaine packages may occur. Here, we report a case of a 34-year-old pregnant woman who had a sudden cardiac arrest while waiting for her bags at Paris-Charles de Gaulle Airport, France. According to the flight attendants, the patient travelled from Brazil and complained of abdominal pain during the flight. After resuscitation, the patient presented sustained tachycardia and convulsions suggesting cocaine overdose caused by body packing. Once admitted to the hospital, laparotomy was performed allowing the extraction of 50 cocaine packages. Cardiac symptoms were attributed to the rupture of five of the packages. Prehospital and emergency physicians need to be aware of the possibility of cocaine overdose by body packing in patients presenting sudden cardiac arrest in airports.
Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells
Authors: Ceccarelli Simona , Megiorni Francesca , Bellavia Diana , Marchese Cinzia , Screpanti Isabella , Checquolo Saula
Published: January 2019

Notch signaling is frequently activated in ovarian cancer (OC) and contributes to the proliferation and survival of cultured OC cells as well as to tumor formation and angiogenesis in xenograft models. Several studies demonstrate that Notch3 expression renders cancer cells more resistant to carboplatin, contributing to chemoresistance and poor survival of OC-bearing patients. This suggests that Notch3 can represent both a biomarker and a target for therapeutic interventions in OC patients. Although it is still unclear how chemoresistance arises, different lines of evidence support a critical role of cancer stem cells (CSCs), suggesting that CSC targeting by innovative therapeutic approaches might represent a promising tool to efficiently reduce OC recurrence. To date, CSC-directed therapies in OC tumors are mainly targeted to the inhibition of CSC-related signaling pathways, including Notch. As it is increasingly evident the involvement of Notch signaling, and in particular of Notch3, in regulating stem-like cell maintenance and expansion in several tumors, here we provide an overview of the current knowledge of Notch3 role in CSC-mediated OC chemoresistance, finally exploring the potential design of innovative Notch3 inhibition-based therapies for OC treatment, aimed at eradicating tumor through the suppression of CSCs.
Emotion Processing and the Role of Compassion in Psychotherapy from the Perspective of Multiple Selves and the Compassionate Self
Authors: Asano Kenichi
Published: January 2019

Emotion processing is an important factor for successful psychotherapy. Clients tend to suffer from maladaptive emotions, which contribute to states of confusion, rumination, and stagnation. The therapist should demonstrate adequate empathy and understanding of the client’s complaints to help the client to recognize and respect their own emotions and desires. In most cases, there is more than one desire, and each desire should be confronted. The compassionate self exercises are helpful to distinguish and integrate confused states. In this report, the author introduces a case in which the therapist helped a client to process emotional experiences by leading the client to pay attention to her own emotional responses. The client accessed multiple desires for each emotion and recognized the context for each. To integrate multiple desires and contexts, the therapist used multiple selves exercises from Compassion Focused Therapy. The compassionate self exercises play a role in integrating complicated emotions and in directing the client toward making an adequate choice independently. On its own, processing emotional experiences can induce adaptive and healthy desires; however, using compassionate self exercises helps the client to integrate complicated emotions and to approach their own values in a more direct way.
A Framework for Analyzing Fog-Cloud Computing Cooperation Applied to Information Processing of UAVs
Authors: Pinto Milena F. , Marcato André L. M. , Melo Aurélio G. , Honório Leonardo M. , Urdiales Cristina
Published: January 2019

Unmanned aerial vehicles (UAVs) are a relatively new technology. Their application can often involve complex and unseen problems. For instance, they can work in a cooperative-based environment under the supervision of a ground station to speed up critical decision-making processes. However, the amount of information exchanged among the aircraft and ground station is limited by high distances, low bandwidth size, restricted processing capability, and energy constraints. These drawbacks restrain large-scale operations such as large area inspections. New distributed state-of-the-art processing architectures, such as fog computing, can improve latency, scalability, and efficiency to meet time constraints via data acquisition, processing, and storage at different levels. Under these amendments, this research work proposes a mathematical model to analyze distribution-based UAVs topologies and a fog-cloud computing framework for large-scale mission and search operations. The tests have successfully predicted latency and other operational constraints, allowing the analysis of fog-computing advantages over traditional cloud-computing architectures.
Parallel Integral Equation-Based Nonoverlapping DDM for Solving Challenging Electromagnetic Scattering Problems of Two Thousand Wavelengths
Authors: Su Qin , Liu Yingyu , Zhao Xunwang , Gu Zongjing , Zhai Chang , Lin Zhongchao , Wu Weijun
Published: January 2019

In this paper, a parallel nonoverlapping and nonconformal domain decomposition method (DDM) is proposed for fast and accurate analysis of electrically large objects in the condition of limited resources. The formulation of nonoverlapping DDM for PEC bodies is derived from combined-field integral equation (CFIE), and an explicit boundary condition is applied to ensure the continuity of electric currents across the boundary. A parallel multilevel fast multipole algorithm (MLFMA) is extended to accelerate matrix-vector multiplications of subdomains as well as the coupling between them, and the coupling between different subdomains is computed in the manner of near field to avoid the storage of the mutual impedance. An improved adaptive direction partitioning scheme is applied to the oct-tree of MLFMA to achieve high parallel efficiency. Numerical examples demonstrate that the proposed method is able to simulate realistic problems with a maximum dimension greater than 2000 wavelengths.
A Randomized Crossover Pilot Study of Telemedicine Delivered via iPads in Parkinson’s Disease
Authors: Sekimoto Satoko , Oyama Genko , Hatano Taku , Sasaki Fuyuko , Nakamura Ryota , Jo Takayuki , Shimo Yasushi , Hattori Nobutaka
Published: January 2019

Background. We investigated the feasibility and safety of a video-based telemedicine system, delivered via a tablet, in Parkinson’s disease (PD).Methods. In a randomized, crossover, open-label pilot trial, we compared a telemedicine period (regular visits every two months with intermediate video calls via an iPad mini) with a control period (regular visits every two months), both lasting 6 months. We included 10 patients diagnosed with PD according to the British Brain Bank criteria, aged 20–75 years. The primary outcome was the PD questionnaire summary index (PDQ-39 SI). Secondary outcomes included the Hoehn and Yahr Stage and scores on the Unified PD Rating Scale (UPDRS) part I–IV, Beck Depression Inventory (BDI), and visual analog scale for satisfaction.Results. Both study periods were completed by 10 patients with PD. Friedman’s test revealed that there were no significant differences between the two periods in primary and secondary outcomes (p>0.05). With respect to visual analog scale scores for satisfaction, participants indicated high satisfaction with the telemedicine system. The number of extra hospital visits and phone calls did not differ between the periods. There were no adverse events or side effects.Conclusions. We observed that a telemedicine system delivered via a tablet could successfully be used by patients as a part of their care. Further studies investigating the use of telemedicine to replace in-person visits are warranted. This trial is registered withUMIN000015536.
Orostachys japonicusA. Berger Extracts Induce Immunity-Enhancing Effects on Cyclophosphamide-Treated Immunosuppressed Rats
Authors: Lee Hak Yong , Park Young Mi , Kim Jeong , Oh Hong Geun , Kim Kang Sung , Kang Hee Joo , Kim Ri Rang , Kim Min Jung , Kim Sang Hee , Yang Hye Jeong , Oh Jisun
Published: January 2019

In this study, we evaluated the immunity-enhancing effects ofOrostachys japonicusA. Berger (OJ). To examine the immune protective effect in vitro, primary mouse splenocytes were treated with water or ethanol extracts of OJ in the absence or presence of cyclophosphamide (CY), which is a cytotoxic, immunosuppressive agent. The extracts increased the propagation of splenocytes and inhibited CY-induced cytotoxicity. Further, to examine the immunostimulatory effectsin vivo, adult Wistar rats were orally administered OJ extracts with or without CY treatment. With the administration of OJ extracts, CY-treated immunosuppressed rats showed improved physical endurance, as assessed by the forced swim test. In addition, extract administration increased not only the number of immunity-related cells but also the levels of plasma cytokines. OJ extracts also recovered splenic histology in CY-treated rats. These findings suggest that an OJ regimen can enhance immunity by increasing immune cell propagation and specific plasma cytokine levels.
Isoflurane Preconditioning Attenuates Brain Injury Induced by Electromagnetic Pulse via the TLR4/NFκB Signaling Pathway
Authors: Li Jiang-Jing , Deng Bin , Zhang Xia-Jing , Lv Miao-Miao , Zhao Hui , Wang Jin , Liu Ji-Dong , Han Rui-Li , Sun Xu-De
Published: January 2019

Electromagnetic pulse (EMP) is a unique type of electromagnetic radiation, and EMP exposure causes a series of biological effects. The nervous system is sensitive to EMP. We studied the neuroprotective effects of isoflurane preconditioning against EMP exposure and used hematoxylin-eosin staining (HE) to observe the effects of electromagnetic pulse and isoflurane preconditioning on neurons. Inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the expression of caspase-3, CD11b, TLR4, and NFκBp65. We found that after EMP exposure, the number of abnormal neurons had increased, and the expression of caspase-3, CD11b, TLR4, and NFκBp65 had also increased. Isoflurane preconditioning can reverse the above phenomenon. Moreover, we found that isoflurane preconditioning can reduce neuronal apoptosis and improve cognitive impairment induced by EMP. These findings indicate that isoflurane preconditioning can protect neurons in the cerebral cortex from EMP exposure, alleviate the inflammatory reaction and cell apoptosis, and improve cognitive impairment induced by EMP. These effects may occur through the downregulation of the TLR4/NFκB signaling pathway and the inhibition of microglial activation.
New Perspectives for Anatomical and Molecular Studies of Kisspeptin Neurons in the Aging Human Brain
Authors: Hrabovszky Erik , Takács Szabolcs , Göcz Balázs , Skrapits Katalin
Published: January 2019

The human infundibular nucleus (corresponding to the rodent arcuate nucleus) serves as an important integration center for neuronal signals and hormones released by peripheral endocrine organs. Kisspeptin (KP)-producing neurons of this anatomical site, many of which also synthesize neurokinin B (NKB), are critically involved in sex hormone signaling to gonadotropin-releasing hormone (GnRH) neurons. In recent years, the basic topography, morphology, neuropeptide content, and connectivity of human KP neurons have been investigated with in situ hybridization and immunohistochemistry on postmortem tissues. These studies revealed that human KP neurons differ neurochemically from their rodent counterparts and show robust aging-related plasticity. Earlier immunohistochemical experiments also provided evidence for temporal changes in the hypothalamus of aging men whose NKB and KP neurons undergo hypertrophy, increase in number, exhibit increased neuropeptide mRNA expression and immunoreactivity and give rise to higher numbers of immunoreactive fibers and afferent contacts onto GnRH neurons. Increasing percentages of KP-expressing NKB perikarya, NKB axons, and NKB inputs to GnRH neurons raise the intriguing possibility that a significant subset of NKB neurons begins to cosynthesize KP as aging advances. Although use of postmortem tissues is technically challenging, recently available single-cell anatomical and molecular approaches discussed in this review provide promising new tools to investigate the aging-related anatomical and functional plasticity of the human KP neuronal system.
A arquitetura moderna e o Condephaat no desafio das práticas seletivas
Authors: Nascimento Flávia Brito do
Published: January 2019

O presente artigo discute a proteção à arquitetura moderna pelo Conselho de Defesa do Patrimônio Histórico, Artístico, Arqueológico e Turístico do Estado de São Paulo (Condephaat) em perspectiva histórica, procurando problematizar a compreensão de modernidade e as atribuições de valor à arquitetura do século XX. Trataremos neste artigo das ações que o órgão estadual paulista fará aos bens imóveis modernos discutindo sua relação com o legado discursivo da historiografia da arquitetura. Entendendo que a arquitetura moderna é parte integrante dos cânones do patrimônio nacional, pergunta-se em que medida o moderno no órgão estadual paulista foi capaz de romper com a lógica do foco na arquitetura olhada a partir da crítica e de seus atributos estéticos ou estilísticos. Debateremos o papel da tradição do grupo de arquitetos modernos nas práticas na valoração das obras modernas paulistas, compreendendo de que maneira as progressivas mudanças no patrimônio nos anos 1970, e claramente 1980, trarão para a preservação da arquitetura moderna na ação do órgão estadual paulista, chegando até os tombamentos mais recentes nos anos 2000.
Breve contribuição a um debate sobre a construção do patrimônio imaterial paulista, 2010-2014
Authors: Silva Mario Augusto Medeiros da
Published: January 2019

O objetivo deste artigo é apresentar, brevemente, alguns tópicos a respeito do debate ocorrido há alguns anos sobre o tema do patrimônio imaterial no órgão de preservação cultural do estado de São Paulo, o Conselho de Defesa do Patrimônio Histórico, Arqueológico, Artístico e Turístico (Condephaat). Explicitam-se alguns casos de referência, um percurso da discussão, a construção do texto legal e alguns dos caminhos percorridos posteriormente, sugerindo a necessidade de pesquisa maior sobre o assunto.
Os desafios contemporâneos do patrimônio cultural paulista
Authors: Neves Deborah Regina Leal , Chinelato Zagato José Antônio
Published: January 2019

O presente artigo traz uma análise panorâmica da atuação do Conselho de Defesa do Patrimônio Histórico, Arqeuológico, Artístico e Turístico (Condephaat) entre 2006 e 2018, sob o ponto de vista de jovens profissionais que ingressaram em seu corpo técnico na Unidade de Preservação do Patrimônio Histórico (UPPH) em momento de transformação do órgão. A partir de casos considerados emblemáticos no período, a atuação do conselho paulista de patrimônio é avaliada criticamente, colocando-se em perspectiva os principais desafios, inovações e abordagens interdisciplinares para a preservação e difusão do patrimônio cultural pelo estado de São Paulo. O objetivo é demonstrar a complexidade e importância do trabalho técnico, os debates e interação com o Colegiado e a aproximação com os anseios da sociedade.
A retextualização interlingual de fábulas: um estudo de caso
Authors: Rosas Clarissa , Cintrão Heloísa Pezza
Published: January 2019

O presente trabalho, que constitui parte de uma pesquisa maior, apresenta um estudo de caso sobre uma fábula do espanhol Tomás de Iriarte, publicada em 1782 e traduzida à língua portuguesa em diferentes momentos ao longo dos séculos XVIII e XX. O artigo inicia tratando da formação do conceito de literatura infantil e da evolução histórica desse gênero, chegando à inserção da fábula na literatura infantil. A partir daí, apresenta o modelo descritivo de tradução proposto por Lambert e Van Gorp (2011[1985]) e o trabalho de Genette (2009[1987]) acerca dos paratextos editoriais, com vistas a esquematizar alguns pontos para análise. Em seguida, dá início ao estudo de caso, que analisa duas retextualizações interlinguísticas (espanhol-português) da fábula “El Pato y la Serpiente” em relação a seu texto-fonte.
Terminologia do Licenciamento Ambiental Brasileiro em Português e Inglês
Authors: Chichorro Caroline Lúcia Costa Moia , Reuillard Patrícia Chittoni Ramos
Published: January 2019

Esta pesquisa objetivou repertoriar os termos do licenciamento ambiental brasileiro e oferecer seus equivalentes em língua inglesa. Foram utilizados dois corpora, nos idiomas português e inglês. Baseia-se nos pressupostos da Teoria Comunicativa da Terminologia (CABRÉ, 1999a), da Linguística de Corpus (SARDINHA, 2004) e no conceito de equivalência funcional (GÉMAR, 1998; SARCEVIC, 1997). Os corpora foram analisados com o programa AntConc (ANTHONY, 2014), com apoio da árvore de domínio e dos fluxogramas do licenciamento ambiental elaborados. Foram validados 371 termos do domínio do licenciamento ambiental. Dadas as diferenças jurídicas e culturais existentes entre as línguas selecionadas, evidenciadas na terminologia estudada, observou-se não ser possível oferecer um equivalente funcional para todos os termos repertoriados, reforçando a necessidade em prosseguir com a pesquisa.
O perfil do Tradutor Público e Intérprete Comercial: um estudo sobre competências tradutórias
Authors: Nanetti Jonatã José Roberto Cardoso , Gumushian Felipini Leila Maria
Published: January 2019

A profissão de Tradutor Público e Intérprete Comercial é a única regulamentada na área da tradução. Uma vez que os documentos que constituem a sua regulamentação se limitam a descrever as atividades realizadas pelos profissionais e como essas devem ser cumpridas perante a Lei, o presente estudo teve o intuito de estabelecer um perfil recomendado aos Tradutores Públicos e Intérpretes Comerciais, por meio de levantamento bibliográfico, documental e exploratório. A teoria utilizada contempla Aubert (1987, 1996, 1998, 2005), Aubert e Tagnin (2004), Pagano (2013), Alves (2013) e Albir (2005). Foi possível identificar que a formação formal fornece ao tradutor a otimização das subcompetências tradutórias responsáveis pelo bom desenvolvimento profissional, embora a maioria dos tradutores em atuação hoje em dia não possua tal formação.
Targeting NLRP3 (Nucleotide-Binding Domain, Leucine-Rich–Containing Family, Pyrin Domain–Containing-3) Inflammasome in Cardiovascular Disorders
Authors: Wang Zheng , Hu Wei , Lu Chenxi , Ma Zhiqiang , Jiang Shuai , Gu Chunhu , Acuña-Castroviejo Darío , Yang Yang
Published: January 2019

Inflammation is an important innate immune response to infection or tissue damage. Inflammasomes are involved in the onset and development of inflammation. The NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3) inflammasome is the best-characterized inflammasome. Recent evidence has indicated the importance of the NLRP3 inflammasome in the pathophysiology of cardiovascular disorders. To further understand the roles of the NLRP3 inflammasome in the cardiovascular system, we provide a comprehensive overview and discuss the remaining questions. First, a summary of NLRP3 inflammasome in the cardiovascular system is introduced. Then, the associations between NLRP3 inflammasome and cardiovascular disorders are presented. Finally, we discuss existing problems and potential directions with this issue. The information compiled here summarizes recent progress, thus potentially aiding in the understanding of the NLRP3 inflammasome in cardiovascular disorders, designing experimental and clinical research about the NLRP3 inflammasome, and promoting therapeutics for cardiovascular disorders.
Prognostic Significance of PR Interval Prolongation in Adult Patients With Total Correction of Tetralogy of Fallot
Authors: Kimura Yoshitaka , Fukuda Koji , Nakano Makoto , Hasebe Yuhi , Fukasawa Kyoshiro , Chiba Takahiko , Miki Keita , Tatebe Shunsuke , Miyata Satoshi , Ota Hideki , Kimura Masato , Adachi Osamu , Saiki Yoshikatsu , Shimokawa Hiroaki
Published: January 2019

Background:

Several studies have demonstrated the importance of mechanoelectrical interaction in patients with surgically corrected tetralogy of Fallot. However, the significance of atrioventricular conduction disturbance, that is PR interval prolongation, on adverse cardiac events in those patients remains to be elucidated.

Methods:

We examined electrocardiograms at baseline and their temporal change in a total of 176 patients with repaired tetralogy of Fallot (49% men; median age, 17.4 years). Then, we evaluated their correlation with right ventricular volume and function measured by cardiac magnetic resonance and the significance as a risk factor of adverse cardiac events: lethal ventricular arrhythmias, atrial arrhythmias, heart failure hospitalization, complete atrioventricular block (AVB), and all-cause death.

Results:

First-degree AVB was noted in 25 patients (14%). During a median follow-up of 10.0 (5.0–14.2) years, there was a progressive prolongation of PR interval (2.00±3.99 ms/y). Importantly, there were significant correlations between PR interval prolongation and right ventricular enlargement or right ventricular dysfunction. In contrast, in patients who underwent pulmonary valve replacement (n=23), significant shortening of PR interval by pulmonary valve replacement was noted (204±32 versus 176±34 ms;
P
=0.007). Cox regression analysis showed that first-degree AVB was an independent risk factor for lethal ventricular arrhythmias (hazard ratio, 5.479; 95% CI, 1.181–25.42;
P
=0.030) and complete AVB (hazard ratio, 27.67; 95% CI, 4.152–184.3;
P
<0.001) and had a tendency for heart failure hospitalization (hazard ratio, 3.301; 95% CI, 0.864–11.80;
P
=0.069). In addition, PR interval prolongation >2 ms/y was also a significant risk factor for lethal ventricular arrhythmias, regardless of the presence or absence of first-degree AVB at enrollment (hazard ratio, 24.18; 95% CI, 2.080–281.1;
P
=0.011).

Conclusions:

These results indicate that progressive atrioventricular conduction disturbance is correlated with right ventricular enlargement and could be a useful predictor for increased risk of lethal ventricular arrhythmias in patients with repaired tetralogy of Fallot.
Tissue-Specific Differential Expression of Novel Genes and Long Intergenic Noncoding RNAs in Humans With Extreme Response to Evoked Endotoxemia
Authors: Ferguson Jane F. , Xue Chenyi , Gao Yuanfeng , Tian Tian , Shi Jianting , Zhang Xuan , Wang Ying , Li Yuhuang D. , Wei Zhi , Li Mingyao , Zhang Hanrui , Reilly Muredach P.
Published: January 2019

Background:

Cytokine responses to activation of innate immunity differ between individuals, yet the genomic and tissue-specific transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that tissue-specific mRNA and long intergenic noncoding RNA (lincRNA) induction differs between individuals with divergent evoked inflammatory responses.

Methods:

In the GENE Study (Genetics of Evoked Response to Niacin and Endotoxemia), we performed an inpatient endotoxin challenge (1 ng/kg lipopolysaccharide [LPS]) in healthy humans. We selected individuals in the top (high responders) and bottom (low responders) extremes of inflammatory responses and applied RNA sequencing to CD14 monocytes (N=15) and adipose tissue (N=25) before and after LPS administration.

Results:

Although only a small number of genes were differentially expressed at baseline, there were clear differences in the magnitude of the transcriptional response post-LPS between high and low responders, with a far greater number of genes differentially expressed by endotoxemia in high responders. Furthermore, tissue responses differed during inflammation, and we found a number of tissue-specific differentially expressed lincRNAs post-LPS, which we validated. Relative to nondifferentially expressed lincRNAs, differentially expressed lincRNAs were equally likely to be nonconserved as conserved between human and mouse, indicating that conservation is not a predictor of lincRNAs associated with human inflammatory pathophysiology. Differentially expressed genes also were enriched for signals with inflammatory and cardiometabolic disease in published genome-wide association studies.
CTB-41I6.2
(
AC002091.1
), a nonconserved human-specific lincRNA, is one of the top lincRNAs regulated by endotoxemia in monocytes, but not in adipose tissue. Knockdown experiments in THP-1 monocytes suggest that this lincRNA enhances LPS-induced interleukin 6 (
IL6
) expression in monocytes, and we now refer to this as monocyte LPS-induced lincRNA regulator of IL6 (
MOLRIL6
).

Conclusions:

We highlight mRNAs and lincRNAs that represent novel candidates for modulation of innate immune and metabolic responses in humans.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00953667.
Biomarker Glycoprotein Acetyls Is Associated With the Risk of a Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients
Authors: Kettunen Johannes , Ritchie Scott C. , Anufrieva Olga , Lyytikäinen Leo-Pekka , Hernesniemi Jussi , Karhunen Pekka J. , Kuukasjärvi Pekka , Laurikka Jari , Kähönen Mika , Lehtimäki Terho , Havulinna Aki S. , Salomaa Veikko , Männistö Satu , Ala-Korpela Mika , Perola Markus , Inouye Michael , Würtz Peter
Published: January 2019

Background:

Integration of systems-level biomolecular information with electronic health records has led to recent interest in the glycoprotein acetyls (GlycA) biomarker—a serum- or plasma-derived nuclear magnetic resonance spectroscopy signal that represents the abundance of circulating glycated proteins. GlycA predicts risk of diverse outcomes, including cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality; however, the underlying detailed associations of GlycA’s morbidity and mortality risk are currently unknown.

Methods:

We used 2 population-based cohorts totaling 11 861 adults from the Finnish general population to test for an association with 468 common incident hospitalization and mortality outcomes during an 8-year follow-up. Further, we utilized 900 angiography patients to test for GlycA association with mortality risk and potential utility for mortality risk discrimination during 12-year follow-up.

Results:

New associations with GlycA and incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthropathies, and hypertension were uncovered, and known incident disease associations were replicated. GlycA associations for incident disease outcomes were in general not attenuated when adjusting for hsCRP (high-sensitivity C-reactive protein). Among 900 patients referred to angiography, GlycA had hazard ratios of 4.87 (95% CI, 2.45–9.65) and 5.00 (95% CI, 2.38–10.48) for 12-year risk of mortality in the fourth and fifth quintiles by GlycA levels, demonstrating its prognostic potential for identification of high-risk individuals. When modeled together, both hsCRP and GlycA were attenuated but remained significant.

Conclusions:

GlycA was predictive of myriad incident diseases across many major internal organs and stratified mortality risk in angiography patients. Both GlycA and hsCRP had shared and independent contributions to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings.
Noninvasive Multimodality Imaging for the Diagnosis of Constrictive Pericarditis
Authors: Alajaji Wissam , Xu Bo , Sripariwuth Apichaya , Menon Vivek , Kumar Arnav , Schleicher Mary , Isma’eel Hussain , Cremer Paul C. , Bolen Michael A. , Klein Allan L.
Published: January 2019

There is a need to review the multimodality imaging techniques, as well as the emerging role of the newer noninvasive imaging modalities in the field of constrictive pericarditis (CP). Therefore, the aim of this review is to summarize the current available techniques that are useful for the diagnosis and differentiation of CP from restrictive cardiomyopathy. Also, we provide illustrative images and videos of typical CP noninvasive imaging findings, as well as a diagnostic and management algorithm. CP is a challenging diagnosis; therefore, cardiologists need adequate knowledge about the application of multimodality noninvasive imaging in a systematic and guideline-oriented fashion whenever CP is suspected.
Impact of Preexisting Left Bundle Branch Block in Transcatheter Aortic Valve Replacement Recipients
Authors: Fischer Quentin , Himbert Dominique , Webb John G. , Eltchaninoff Helene , Muñoz-García Antonio J. , Tamburino Corrado , Nombela-Franco Luis , Nietlispach Fabian , Moris Cesar , Ruel Marc , Dager Antonio E. , Serra Vicenç , Cheema Asim N. , Amat-Santos Ignacio J. , de Brito Fabio Sandoli , Ribeiro Henrique , Abizaid Alexandre , Sarmento-Leite Rogério , Dumont Eric , Barbanti Marco , Durand Eric , Alonso Briales Juan H. , Bouleti Claire , Immè Sebastiano , Maisano Francesco , del Valle Raquel , Miguel Benitez Luis , García del Blanco Bruno , Côté Mélanie , Philippon François , Urena Marina , Rodés-Cabau Josep
Published: January 2019

Background:

The impact of preexisting left bundle branch block (LBBB) in transcatheter aortic valve replacement (TAVR) recipients is unknown. The aim of this study was to determine the impact of preexisting LBBB on clinical outcomes after TAVR.

Methods and Results:

This multicenter study evaluated 3404 TAVR candidates according to the presence or absence of LBBB on baseline ECG. TAVR complications and causes of death were defined according to Valve Academic Research Consortium-2 definitions. Follow-up outpatient visits or telephone interviews were conducted at 30 days, 12 months, and yearly thereafter. Echocardiography examinations were performed at baseline, at hospital discharge, and at 1-year follow-up. Preexisting LBBB was present in 398 patients (11.7%) and was associated with an increased risk of permanent pacemaker implantation (PPI; 21.1% versus 14.8%; adjusted odds ratio, 1.51; 95% CI, 1.12–2.04) but not death (7.3% versus 5.5%; adjusted odds ratio, 1.33; 95% CI, 0.84–2.12) at 30 days. At a mean follow-up of 22±21 months, there were no differences between patients with and without preexisting LBBB in overall mortality (adjusted hazard ratio, 0.94; 95% CI, 0.75–1.18) and cardiovascular mortality (adjusted hazard ratio, 0.90; 95% CI, 0.68–1.21). In a subanalysis of 2421 patients without PPI at 30 days and with complete follow-up about the PPI, preexisting LBBB was not associated with an increased risk of PPI or sudden cardiac death. Patients with preexisting LBBB had a lower left ventricular ejection fraction (LVEF) at baseline and at 1-year follow-up (
P
<0.001 for both), but those with low LVEF exhibited a similar increase in LVEF over time after TAVR compared with patients with no preexisting LBBB (
P
=0.327).

Conclusions:

Preexisting LBBB significantly increased the risk of early (but not late) PPI after TAVR, without any significant effect on overall mortality or cardiovascular mortality. Preexisting LBBB was associated with lower LVEF pre-TAVR but did not prevent an increase in LVEF post-TAVR similar to patients without LBBB.
Serial Fractional Flow Reserve Measurements Post Coronary Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Karamasis Grigoris V. , Kalogeropoulos Andreas S. , Mohdnazri Shah R. , Al-Janabi Firas , Jones Richard , Jagathesan Rohan , Aggarwal Rajesh K. , Clesham Gerald J. , Tang Kare H. , Kelly Paul A. , Davies John R. , Werner Gerald S. , Keeble Thomas R.
Published: January 2019

Background

The aim of this study was to evaluate the functional result of chronic total occlusion percutaneous coronary intervention (PCI) measured by fractional flow reserve (FFR) immediately post the index procedure and at short-term follow-up.

Methods and Results

This was a prospective single-center observational study. Consecutive patients with right coronary artery chronic total occlusion scheduled for elective PCI were included. FFR measurements were performed immediately after successful PCI and at 4 months follow-up. Twenty-six patients completed baseline and follow-up measurements. Mean age was 61.2±9.7 years, 88.5% of the patients were male, and 19.2% were diabetic. The mean FFR immediately after successful chronic total occlusion PCI was 0.82±0.10 and significantly increased to 0.89±0.07 at 4 months (
P
<0.001). The FFR increased in 77% of the patients with a mean absolute increase of 0.07±0.08. The incidence of FFR ≤0.80 immediately after PCI was significantly higher amongst patients with subintimal versus intraplaque recanalization (23% versus 12%;
P
=0.03). At 4 months, FFR ≤0.80 was found only in 2 patients with subintimal recanalization. At follow-up, 42.7% of the patients continued to have an FFR <0.90.

Conclusions

Post chronic total occlusion PCI, FFR increased significantly at short-term follow-up compared with measurements post index procedure. Because FFR remained <0.90 in many cases, further efforts should be made to optimize procedural results.
Fish Oil and Perioperative Bleeding
Authors: Akintoye Emmanuel , Sethi Prince , Harris William S. , Thompson Paul A. , Marchioli Roberto , Tavazzi Luigi , Latini Roberto , Pretorius Mias , Brown Nancy J. , Libby Peter , Mozaffarian Dariush
Published: January 2019

Background

Fish oil is among the most common natural supplements for treatment of hypertriglyceridemia or prevention of cardiovascular disease. However, concerns about theoretical bleeding risk have led to recommendations that patients should stop taking fish oil before surgery or delay in elective procedures for patients taking fish oil by some health care professionals.

Methods and Results

We tested the effect of fish oil supplementation on perioperative bleeding in a multinational, placebo-controlled trial involving 1516 patients who were randomized to perioperative fish oil (eicosapentaenoic acid+docosahexaenoic acid; 8–10 g for 2–5 days preoperatively, and then 2 g/d postoperatively) or placebo. Primary outcome was major perioperative bleeding as defined by the Bleeding Academic Research Consortium. Secondary outcomes include perioperative bleeding per thrombolysis in myocardial infarction and International Society on Thrombosis and Hemostasis definitions, chest tube output, and total units of blood transfused. Participants’ mean (SD) age was 63 (13) years, and planned surgery included coronary artery bypass graft (52%) and valve surgery (50%). The primary outcome occurred in 92 patients (6.1%). Compared with placebo, risk of Bleeding Academic Research Consortium bleeding was not higher in the fish oil group: odds ratio, 0.81; 95% CI, 0.53–1.24; absolute risk difference, 1.1% lower (95% CI, −3.0% to 1.8%). Similar findings were seen for secondary bleeding definitions. The total units of blood transfused were significantly lower in the fish oil group compared with placebo (mean, 1.61 versus 1.92;
P
<0.001). Evaluating achieved plasma phospholipid omega-3 polyunsaturated fatty acids levels with supplementation (on the morning of surgery), higher levels were associated with lower risk of Bleeding Academic Research Consortium bleeding, with substantially lower risk in the third (odds ratio, 0.30 [95% CI, 0.11–0.78]) and fourth (0.36 [95% CI, 0.15–0.87]) quartiles, compared with the lowest quartile.

Conclusions

Fish oil supplementation did not increase perioperative bleeding and reduced the number of blood transfusions. Higher achieved n-3-PUFA levels were associated with lower risk of bleeding. These novel findings support the need for reconsideration of current recommendations to stop fish oil or delay procedures before cardiac surgery.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00970489.
GDF11 Decreases Pressure Overload–Induced Hypertrophy, but Can Cause Severe Cachexia and Premature Death
Authors: Harper Shavonn C. , Johnson Jaslyn , Borghetti Giulia , Zhao Huaqing , Wang Tao , Wallner Markus , Kubo Hajime , Feldsott Eric A. , Yang Yijun , Joo Yunichel , Gou Xinji , Sabri Abdel Karim , Gupta Priyanka , Myzithras Maria , Khalil Ashraf , Franti Michael , Houser Steven R.
Published: January 2019

Rationale:

Possible beneficial effects of GDF11 (growth differentiation factor 11) on the normal, diseased, and aging heart have been reported, including reversing aging-induced hypertrophy. These effects have not been well validated. High levels of GDF11 have also been shown to cause cardiac and skeletal muscle wasting. These controversies could be resolved if dose-dependent effects of GDF11 were defined in normal and aged animals as well as in pressure overload-induced pathological hypertrophy.

Objective:

To determine dose-dependent effects of GDF11 on normal hearts and those with pressure overload-induced cardiac hypertrophy.

Methods and Results:

Twelve- to 13-week-old C57BL/6 mice underwent transverse aortic constriction (TAC) surgery. One-week post-TAC, these mice received rGDF11 (recombinant GDF11) at 1 of 3 doses: 0.5, 1.0, or 5.0 mg/kg for up to 14 days. Treatment with GDF11 increased plasma concentrations of GDF11 and p-SMAD2 in the heart. There were no significant differences in the peak pressure gradients across the aortic constriction between treatment groups at 1 week post-TAC. Two weeks of GDF11 treatment caused dose-dependent decreases in cardiac hypertrophy as measured by heart weight/tibia length ratio, myocyte cross-sectional area, and left ventricular mass. GDF11 improved cardiac pump function while preventing TAC-induced ventricular dilation and caused a dose-dependent decrease in interstitial fibrosis (in vivo), despite increasing markers of fibroblast activation and myofibroblast transdifferentiation (in vitro). Treatment with the highest dose (5.0 mg/kg) of GDF11 caused severe body weight loss, with significant decreases in both muscle and organ weights and death in both sham and TAC mice.

Conclusions:

Although GDF11 treatment can reduce pathological cardiac hypertrophy and associated fibrosis while improving cardiac pump function in pressure overload, high doses of GDF11 cause severe cachexia and death. Use of GDF11 as a therapy could have potentially devastating actions on the heart and other tissues.
Macrophage Inflammation, Erythrophagocytosis, and Accelerated Atherosclerosis in
Jak2

V617F

Mice
Authors: Wang Wei , Liu Wenli , Fidler Trevor , Wang Ying , Tang Yang , Woods Brittany , Welch Carrie , Cai Bishuang , Silvestre-Roig Carlos , Ai Ding , Yang Yong-Guang , Hidalgo Andres , Soehnlein Oliver , Tabas Ira , Levine Ross L. , Tall Alan R. , Wang Nan
Published: January 2019

Rationale:

The mechanisms driving atherothrombotic risk in individuals with
JAK2

V617F

(
Jak2

VF

) positive clonal hematopoiesis or myeloproliferative neoplasms are poorly understood.

Objective:

The goal of this study was to assess atherosclerosis and underlying mechanisms in hypercholesterolemic mice with hematopoietic
Jak2

VF

expression.

Methods and Results:

Irradiated low-density lipoprotein receptor knockout (
Ldlr
−/−
) mice were transplanted with bone marrow from wild-type or
Jak2

VF

mice and fed a high-fat high-cholesterol Western diet. Hematopoietic functions and atherosclerosis were characterized. After 7 weeks of Western diet,
Jak2

VF

mice showed increased atherosclerosis. Early atherosclerotic lesions showed increased neutrophil adhesion and content, correlating with lesion size. After 12 weeks of Western diet,
Jak2

VF

lesions showed increased complexity, with larger necrotic cores, defective efferocytosis, prominent iron deposition, and costaining of erythrocytes and macrophages, suggesting erythrophagocytosis.
Jak2

VF

erythrocytes were more susceptible to phagocytosis by wild-type macrophages and showed decreased surface expression of CD47, a “don’t-eat-me” signal. Human JAK2VF erythrocytes were also more susceptible to erythrophagocytosis.
Jak2

VF

macrophages displayed increased expression and production of proinflammatory cytokines and chemokines, prominent inflammasome activation, increased p38 MAPK (mitogen-activated protein kinase) signaling, and reduced levels of MerTK (c-Mer tyrosine kinase), a key molecule mediating efferocytosis. Increased erythrophagocytosis also suppressed efferocytosis.

Conclusions:

Hematopoietic
Jak2

VF

expression promotes early lesion formation and increased complexity in advanced atherosclerosis. In addition to increasing hematopoiesis and neutrophil infiltration in early lesions,
Jak2

VF

caused cellular defects in erythrocytes and macrophages, leading to increased erythrophagocytosis but defective efferocytosis. These changes promote accumulation of iron in plaques and increased necrotic core formation which, together with exacerbated proinflammatory responses, likely contribute to plaque instability.
A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse
Authors: Hulsmans Maarten , Aguirre Aaron D. , Bonner Matthew D. , Bapat Aneesh , Cremer Sebastian , Iwamoto Yoshiko , King Kevin R. , Swirski Filip K. , Milan David J. , Weissleder Ralph , Nahrendorf Matthias
Published: January 2019

Rationale:

Cardiac pacing is a critical technology for the treatment of arrhythmia and heart failure. The impact of specific pacing strategies on myocardial function is an area of intense research and high clinical significance. Mouse models have proven extremely useful for probing mechanisms of heart disease, but there is currently no reliable technology for long-term pacing in the mouse.

Objective:

We sought to develop a device for long-term pacing studies in mice. We evaluated the device for (1) treating third-degree atrioventricular block after macrophage depletion, (2) ventricular pacing-induced cardiomyopathy, and (3) high-rate atrial pacing.

Methods and Results:

We developed a mouse pacemaker by refashioning a 26 mm×6.7 mm clinical device powered by a miniaturized, highly efficient battery. The electrode was fitted with a single flexible lead, and custom software extended the pacing rate to up to 1200 bpm. The wirelessly programmable device was implanted in the dorsal subcutaneous space of 39 mice. The tunneled lead was passed through a left thoracotomy incision and attached to the epicardial surface of the apex (for ventricular pacing) or the left atrium (for atrial pacing). Mice tolerated the implantation and both long-term atrial and ventricular pacing over weeks. We then validated the pacemaker’s suitability for the treatment of atrioventricular block after macrophage depletion in
Cd11b

DTR

mice. Ventricular pacing increased the heart rate from 313±59 to 550 bpm (
P
<0.05). In addition, we characterized tachypacing-induced cardiomyopathy in mice. Four weeks of ventricular pacing resulted in reduced left ventricular function, fibrosis, and an increased number of cardiac leukocytes and endothelial activation. Finally, we demonstrated the feasibility of chronic atrial pacing at 1200 bpm.

Conclusions:

Long-term pacing with a fully implantable, programmable, and battery-powered device enables previously impossible investigations of arrhythmia and heart failure in the mouse.
Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis
Authors: Sorokin Alexander V. , Kotani Kazuhiko , Elnabawi Youssef A. , Dey Amit K. , Sajja Aparna P. , Yamada Shingo , Ueda Masashi , Harrington Charlotte L. , Baumer Yvonne , Rodante Justin A. , Gelfand Joel M. , Chen Marcus Y. , Joshi Aditya A. , Playford Martin P. , Remaley Alan T. , Mehta Nehal N.
Published: January 2019

Rationale:

Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis.

Objective:

To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis.

Methods and Results:

Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased
body mass index
, and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL;
P
<0.05 for all) with significant association of oxidized LDL (β=0.10;
P
=0.020) and oxHDL (β=−0.11;
P
=0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82;
P
=0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03;
P
<0.001) and with a concomitant decrease in NCB at 1 year (1.04±0.44 versus 0.95±0.32;
P
=0.03).

Conclusions:

Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.