bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Glucose‐6‐Phosphate Dehydrogenase Could Enhance 1,4‐Benzoquinone‐Induced Oxidative Damage in K562 Cells
Authors: Zhang Juan , Cao Meng , Yang Wenwen , Sun Fengmei , Xu Cheng , Yin Lihong , Pu Yuepu
Published: August 2016

Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose‐6‐phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4‐benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure.
Molecular Diversity of Sapovirus Infection in Outpatients Living in Nanjing, China (2011–2013)
Authors: Zhang Hong-ying , Qiao Meng-kai , Wang Xuan , He Min , Shi Li-min , Xie Guo-xiang , Jin Hei-ying
Published: August 2016

Aim. To gain insight into the molecular diversity of sapovirus in outpatients with acute gastroenteritis in Nanjing, China.Methods. The specimens from outpatients clinically diagnosed as acute gastroenteritis were detected by real-time PCR; RT-PCR was then performed to amplify part of VP1 sequences. The PCR products were cloned into pGEM-T Easy vector and bidirectionally sequenced. All sequences were edited and analyzed. A phylogenetic tree was drawn with the MEGA 5.0 software.Results. Between 2011 and 2013, 16 sapovirus positive cases were confirmed by real-time PCR. The infected cases increased from two in 2011 and six in 2012 to eight in 2013. The majority was children and the elderly (15, 93.75%) and single infections (15, 93.75%). Of the 16 real-time positive specimens, 14 specimens had PCR products and the analysis data of the 14 nucleic sequences showed that there was one GI genogroup with four genotypes, two GI.2 in 2011, three GI.2, and one GI.1 in 2012 and one GI.2, three GI.1, two GI.3, and two GI.5 in 2013.Conclusion. Our data confirmed continuous existing of GI genogroup and GI.2 genotype from 2011 to 2013 in Nanjing and the successive appearance of different genotypes from outpatients with gastroenteritis.
Apigenin Attenuates Oxidative Injury in ARPE‐19 Cells thorough Activation of Nrf2 Pathway
Authors: Xu Xinrong , Li Min , Chen Weiwei , Yu Haitao , Yang Yan , Hang Li
Published: August 2016

The current study was aimed at evaluating the therapeutic implication of apigenin and to elucidate the underlying mechanism. The tert‐butyl hydroperoxide (t‐BHP) at 200 μM was used to induce oxidative stress‐associated injury in ARPE‐19 cells. Apigenin at concentrations less than 800 μM did not cause cytotoxic effects on ARPE‐19 cells. Cell viability assay showed that apigenin at 200 μM significantly promoted cell survival in t‐BHP‐treated ARPE‐19 cells. Additionally, apigenin at 100 μM significantly protected ARPE‐19 cells from t‐BHP‐induced apoptosis. Molecular examinations demonstrated that apigenin at 400 μM significantly upregulated the mRNA and protein expression of Nrf2 and stimulated its nuclear translocation in ARPE‐19 cells treated with or without t‐BHP. Apigenin 400 μM also significantly elevated the expression of HO‐1, NQO1, and GCLM at both mRNA and protein levels in the presence or absence of t‐BHP. Furthermore, apigenin at 400 μM significantly increased the activities of SOD, CAT, GSH‐PX, and T‐AOC and reduced the levels of ROS and MDA in t‐BHP‐treated ARPE‐19 cells. However, these effects of apigenin were all abolished by being transfected with Nrf2 siRNA. Collectively, our current data indicated that apigenin exerted potent antioxidant properties in ARPE‐19 cells challenged with t‐BHP, which were dependent on activation of Nrf2 signaling.
Certificates of Optimality for Mixed Integer Linear Programming Using Generalized Subadditive Generator Functions
Authors: Cheung Kevin K. H. , Moazzez Babak
Published: August 2016

We introduce generalized subadditive generator functions for mixed integer linear programs. Our results extend Klabjan’s work from pure integer programs with nonnegative entries to general MILPs. These functions suffice to achieve strong subadditive duality. Several properties of the functions are shown. We then use this class of functions to generate certificates of optimality for MILPs. We have performed a computational test study on knapsack problems to investigate the efficiency of the certificates.
Traumatic Rupture of A Posterior Mediastinal Teratoma following Motor-Vehicle Accident
Authors: Bell Christopher , Domingo Fernando , Miller Ashley D. , Smith Jeremiah S. , Headrick James R.
Published: August 2016

We report a case of a posterior mediastinal mature cystic teratoma with rupture secondary to blunt chest trauma in a 20-year-old male involved in a motor-vehicle accident. Initial treatment was guided by Advanced Trauma Life Support and a tube thoracostomy was performed for presumed hemothorax. The heterogeneous collection within the thoracic cavity was discovered to be the result of a ruptured cystic mass. Pathologic findings confirmed the mass consistent with a mature cystic teratoma. As mediastinal teratomas are most commonly described arising from the anterior mediastinum, the posterior location of the teratoma described in this report is exceedingly rare.
On the Existence of Infinitely Many Solutions for Nonlocal Systems with Critical Exponents
Authors: Khiddi M. , Echarghaoui R.
Published: August 2016

We study a class of semilinear nonlocal elliptic systems posed on settings without compact Sobolev embedding. By employing critical point theory and concentration estimates, we prove the existence of infinitely many solutions for values of the dimensionN, whereN>6s,provided0<s<1.
Endoleak Assessment Using Computational Fluid Dynamics and Image Processing Methods in Stented Abdominal Aortic Aneurysm Models
Authors: Lu Yueh-Hsun , Mani Karthick , Panigrahi Bivas , Hsu Wen-Tang , Chen Chia-Yuan
Published: August 2016

Endovascular aortic aneurysm repair (EVAR) is a predominant surgical procedure to reduce the risk of aneurysm rupture in abdominal aortic aneurysm (AAA) patients. Endoleak formation, which eventually requires additional surgical reoperation, is a major EVAR complication. Understanding the etiology and evolution of endoleak from the hemodynamic perspective is crucial to advancing the current posttreatments for AAA patients who underwent EVAR. Therefore, a comprehensive flow assessment was performed to investigate the relationship between endoleak and its surrounding pathological flow fields through computational fluid dynamics and image processing. Six patient-specific models were reconstructed, and the associated hemodynamics in these models was quantified three-dimensionally to calculate wall stress. To provide a high degree of clinical relevance, the mechanical stress distribution calculated from the models was compared with the endoleak positions identified from the computed tomography images of patients through a series of imaging processing methods. An endoleak possibly forms in a location with high local wall stress. An improved stent graft (SG) structure is conceived accordingly by increasing the mechanical strength of the SG at peak wall stress locations. The presented analytical paradigm, as well as numerical analysis using patient-specific models, may be extended to other common human cardiovascular surgeries.
VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma
Authors: Baitello Maria Eduarda Lopes , Tenani Graciele Domitila , Ferreira Rafael Fernandes , Nogueira Victor , Pinhel Marcela Augusta de Souza , da Silva Rita de Cássia Martins Alves , Silva Renato Ferreira da , Fucuta Patrícia da Silva , de Godoy Moacir Fernandes , Souza Dorotéia Rossi Silva
Published: August 2016

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association ofVEGF-A(C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P>0.05). In G1, 23% of the patients died, with no relation to genetic profile (P>0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele ofVEGF-C936T andVEGF-A1154G, respectively, and compared with the wild-type genotype (P=0.0285;P=0.0284, resp.) as well as G1 versus G2 and G3 forVEGF-C936T and G1 versus G2 forVEGF-A1154G (P<0.05for both). In conclusion, there is a relationship between mutant alleles ofVEGF-C936T andVEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC.
An Aqueous Extract of Marine Microalgae Exhibits Antimetastatic Activity through Preferential Killing of Suspended Cancer Cells and Anticolony Forming Activity
Authors: Somasekharan Syam Prakash , El-Naggar Amal , Sorensen Poul H. , Wang Yuzhuo , Cheng Hongwei
Published: August 2016

Research on marine natural products as potential anticancer agents is still limited. In the present study, an aqueous extract of a Canadian marine microalgal preparation was assessed for anticancer activities using various assays and cell lines of human cancers, including lung, prostate, stomach, breast, and pancreatic cancers, as well as an osteosarcoma. In vitro, the microalgal extract exhibited marked anticolony forming activity. In addition, it was more toxic, as indicated by increased apoptosis, to nonadherent cells (grown in suspension) than to adherent cells. In vivo, an antimetastatic effect of the extract was observed in NOD‐SCID mice carrying subrenal capsule xenografts of PC3 prostate cancer cells. The results of the present study suggest that the antimetastatic effect of the aqueous microalgal extract is based on inhibition of colony forming ability of cancer cells and the preferential killing of suspended cancer cells. Further research aimed at identification of the molecular basis of the anticancer activities of the microalgal extract appears to be warranted.
MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer
Authors: Zhang Li , Wang Jianghua , Wang Yongquan , Zhang Yiqun , Castro Patricia , Shao Longjiang , Sreekumar Arun , Putluri Nagireddy , Guha Nilanjan , Deepak Saligrama , Padmanaban Arunkumar , Creighton Chad J. , Ittmann Michael
Published: August 2016

Incidence and mortality rates for prostate cancer are higher in African-American (AA) men than in European-American (EA) men, but the biologic basis for this disparity is unclear. We carried out a detailed analysis of gene expression changes in prostate cancer compared with their matched benign tissues in a cohort of AA men and compared them with existing data from EA men. In this manner, we identified MNX1 as a novel oncogene upregulated to a relatively greater degree in prostate cancer from AA men. Androgen and AKT signaling play a central role in the pathogenesis of prostate cancer and we found that both of these signaling pathways increased MNX1 expression. MNX1 in turn upregulated lipid synthesis by stimulating expression of SREBP1 and fatty acid synthetase. Our results define MNX1 as a novel targetable oncogene increased in AA prostate cancer that is associated with aggressive disease. Cancer Res; 76(21); 6290–8. ©2016 AACR.
Histone H3K27 Trimethylation Modulates 5-Fluorouracil Resistance by Inhibiting PU.1 Binding to the DPYD Promoter
Authors: Wu Rentian , Nie Qian , Tapper Erin E. , Jerde Calvin R. , Dunlap Garrett S. , Shrestha Shikshya , Elraiyah Tarig A. , Offer Steven M. , Diasio Robert B.
Published: August 2016

The antimetabolite 5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs. Dihydropyrimidine dehydrogenase (DPD) is a major determinant of 5-FU response and toxicity. Although DPYD variants may affect 5-FU metabolism, they do not completely explain the reported variability in DPD function or the resultant differences in treatment response. Here, we report that H3K27 trimethylation (H3K27me3) at the DPYD promoter regulated by Ezh2 and UTX suppresses DPYD expression by inhibiting transcription factor PU.1 binding, leading to increased resistance to 5-FU. Enrichment of H3K27me3 at the DPYD promoter was negatively correlated with both DPYD expression and DPD enzyme activity in peripheral blood specimens from healthy volunteers. Lastly, tumor expression data suggest that DPYD repression by Ezh2 predicts poor survival in 5-FU–treated cancers. Collectively, the findings of the present article suggest that a previously uncharacterized mechanism regulates DPD expression and may contribute to tumor resistance to 5-FU. Cancer Res; 76(21); 6362–73. ©2016 AACR.
Accuracy of Gene Scores when Pruning Markers by Linkage Disequilibrium
Authors: Dudbridge Frank , Newcombe Paul J.
Published: August 2016

Objective: Gene scores are often used to model the combined effects of genetic variants. When variants are in linkage disequilibrium, it is common to prune all variants except the most strongly associated. This avoids duplicating information but discards information when variants have independent effects. However, joint modelling of correlated variants increases the sampling error in the gene score. In recent applications, joint modelling has offered only small improvements in accuracy over pruning. We aimed to quantify the relationship between pruning and joint modelling in relation to sample size. Methods: We derived the coefficient of determination R2 for a gene score constructed from pruned markers, and for one constructed from correlated markers with jointly estimated effects. Results: Pruned scores tend to have slightly lower R2 than jointly modelled scores, but the differences are small at sample sizes up to 100,000. If the proportion of correlated variants is high, joint modelling can obtain modest improvements asymptotically. Conclusions: The small gains observed to date from joint modelling can be explained by sample size. As studies become larger, joint modelling will be useful for traits affected by many correlated variants, but the improvements may remain small. Pruning remains a useful heuristic for current studies.
Retrospective Association Analysis of Binary Traits: Overcoming Some Limitations of the Additive Polygenic Model
Authors: Jiang Duo , Mbatchou Joelle , McPeek Mary Sara
Published: August 2016

Case-control genetic association analysis is an extremely common tool in human complex trait mapping. From a statistical point of view, the analysis of binary traits poses somewhat different challenges from the analysis of quantitative traits. Desirable features of a binary trait mapping approach would include (1) phenotype modeled as binary, with appropriate dependence between the mean and variance; (2) appropriate correction for relevant covariates; (3) appropriate correction for sample structure of various types, including related individuals, admixture and other types of population structure; (4) both fast and accurate computations; (5) robustness to ascertainment and other types of phenotype model misspecification, and (6) ability to leverage partially missing data to increase power. We review these challenges and argue, both theoretically and in simulations, for the value of retrospective association analysis as a way to overcome some of the limitations of the phenotype model, including model misspecification due to ascertainment. We give an overview of two recent retrospective methods, CARAT and CERAMIC, that are designed to meet criteria 1-6.
Giant Esophageal Lipoma as an Uncommon Cause of Diverticula
Authors: Yekeler Erdal , Yazicioglu Alkin , Subasi Mahmut , Boztepe Hacer
Published: August 2016

Esophageal lipoma is an uncommon benign tumor of the esophagus and accounts for only 0.4% of all benign neoplasms of the gastrointestinal system. The majority of these are located in the cervical part; only very few are located in the lower third of the esophagus. We discuss the case of a 37-year-old female who presented with dysphagia and an esophageal lipoma located in the lower third of the esophagus. The patient underwent right mini-thoracotomy and enucleation of lipoma. Histopathologic examination revealed adipose tissue with a collection of matured adipose tissue. We present the case because of the atypical localization of an esophageal lipoma and development of a diverticulum, which was caused by the lipoma and required an additional surgical procedure.
The Use of the Linear Mixed Model in Human Genetics
Authors: Dandine-Roulland Claire , Perdry Hervé
Published: August 2016

We give a short but detailed review of the methods used to deal with linear mixed models (restricted likelihood, AIREML algorithm, best linear unbiased predictors, etc.), with a few original points. Then we describe three common applications of the linear mixed model in contemporary human genetics: association testing (pathways analysis or rare variants association tests), genomic heritability estimates, and correction for population stratification in genome-wide association studies. We also consider the performance of best linear unbiased predictors for prediction in this context, through a simulation study for rare variants in a short genomic region, and through a short theoretical development for genome-wide data. For each of these applications, we discuss the relevance and the impact of modeling genetic effects as random effects.
Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study
Authors: van Bezooijen Ji Sun , Balak Deepak M.W. , van Doorn Martijn B.A. , Looman Caspar W.N. , Schreurs Marco W.J. , Koch Birgit C.P. , van Gelder Teun , Prens Errol P.
Published: August 2016

Background: Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. Objective: To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. Methods: Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. Results: In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. Conclusion: Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability.
Understanding Bidirectional Mother-Infant Affective Displays across Contexts: Effects of Maternal Maltreatment History and Postpartum Depression and PTSD Symptoms
Authors: Morelen Diana , Menke Rena , Rosenblum Katherine Lisa , Beeghly Marjorie , Muzik Maria
Published: August 2016

Background: This study examined the bidirectional nature of mother-infant positive and negative emotional displays during social interactions across multiple tasks among postpartum women accounting for childhood maltreatment severity. Additionally, effects of maternal postpartum psychopathology on maternal affect and effects of task and emotional valence on dyadic emotional displays were evaluated. Sampling and Methods: A total of 192 mother-infant dyads (51% male infants) were videotaped during free play and the Still-Face paradigm at 6 months postpartum. Mothers reported on trauma history and postpartum depression and posttraumatic stress disorder (PTSD) symptoms. Reliable, masked coders scored maternal and infant positive and negative affect from the videotaped interactions. Results: Three path models evaluated whether dyadic affective displays were primarily mother driven, infant driven, or bidirectional in nature, adjusting for mothers' maltreatment severity and postpartum psychopathology. The bidirectional model had the best fit. Child maltreatment severity predicted depression and PTSD symptoms, and maternal symptoms predicted affective displays (both positive and negative), but the pattern differed for depressive symptoms compared to PTSD symptoms. Emotional valence and task altered the nature of bidirectional affective displays. Conclusions: The results add to our understanding of dyadic affective exchanges in the context of maternal risk (childhood maltreatment history, postpartum symptoms of depression and PTSD). Findings highlight postpartum depression symptoms as one mechanism of risk transmission from maternal maltreatment history to impacted parent-child interactions. Limitations include reliance on self-reported psychological symptoms and that the sample size prohibited testing of moderation analyses. Developmental and clinical implications are discussed.
Case of Six-Year Disease-Free Survival with Undifferentiated Carcinoma of the Pancreas
Authors: Saito Hiroyuki , Kashiyama Hiroshi , Murohashi Takashi , Sasaki Kazunari , Misawa Ryosuke , Ohwada Susumu
Published: August 2016

Undifferentiated carcinoma of the pancreas (UDC) is rare and has a dismal prognosis. Here, we report a case of 6-year disease-free survival with a mixed type of UDC and UDC with osteoclast-like giant cells, with a high mitotic index as well as perineural, lymphatic, vessel, and diaphragmatic invasion. The patient underwent radical distal pancreatectomy and was subsequently treated with adjuvant chemotherapy using gemcitabine plus S-1 followed by maintenance chemotherapy with oral tegafur-uracil. The patient has been doing well with no evidence of recurrence for more than 6 years after surgery.
Investigación etnográfica sobre experiencias de trabajo infantil en el noreste argentino
Authors: Frasco-Zuker Laura
Published: August 2016

(descriptivo): El artículo tiene como objetivo caracterizar la infancia de quienes trabajan y/o trabajaron en contextos familiares en un barrio de una localidad de Misiones. Se parte de una concepción de la infancia como categoría socio-histórica y se realiza una indagación antropológica en perspectiva del actor sobre experiencias de trabajo infantil en integrantes de tres unidades domésticas. El método de investigación es el trabajo de campo etnográfico. Los resultados preliminares muestran que las distintas trayectorias de trabajo en la infancia se vinculan a sentidos esperables en esta etapa de la vida que modelan prácticas específicas según generaciones, géneros e historias familiares. La articulación entre datos de campo y discusión teórica sobre trabajo infantil permite discutir nociones universales sobre las que se legisla y reflexionar sobre sus alcances y limitaciones.
Outcomes of Redo Transcatheter Aortic Valve Replacement for the Treatment of Postprocedural and Late Occurrence of Paravalvular Regurgitation and Transcatheter Valve Failure
Authors: Barbanti Marco , Webb John G. , Tamburino Claudia , Van Mieghem Nicolas M. , Makkar Raj R. , Piazza Nicolò , Latib Azeem , Sinning Jan-Malte , Won-Keun Kim , Bleiziffer Sabine , Bedogni Francesco , Kapadia Samir , Tchetche Didier , Rodés-Cabau Josep , Fiorina Claudia , Nombela-Franco Luis , De Marco Federico , de Jaegere Peter P. , Chakravarty Tarun , Vaquerizo Beatriz , Colombo Antonio , Svensson Lars , Lange Rüdiger , Nickenig Georg , Möllmann Helge , Walther Thomas , Della Rosa Francesco , Elhmidi Yacine , Dvir Danny , Brambilla Nedy , Immè Sebastiano , Sgroi Carmelo , Gulino Simona , Todaro Denise , Pilato Gerlando , Petronio Anna Sonia , Tamburino Corrado
Published: August 2016

Background—

Transcatheter aortic valves can degenerate in a manner similar to surgical bioprostheses.

Methods and Results—

Clinical and echocardiographic outcomes of patients who underwent redo transcatheter aortic valve replacement (TAVR) procedures >2 weeks post procedure were collected from 14 centers. Among 13 876 patients, 50 (0.4%) underwent redo TAVR procedure at participating centers. Indications for redo TAVR were moderate–severe prosthetic aortic valve stenosis (n=10, 21.7%), moderate–severe central prosthetic aortic valve regurgitation (n=13, 28.3%), and moderate–severe paraprosthetic aortic valve regurgitation (n=25, 50.0%). The index TAVR was most commonly a Medtronic CoreValve (N=38, 76.0%), followed by Edwards SAPIEN-type valves (n=12, 24.0%) and Portico (n=1, 2.0%). The redo TAVR device was most commonly a CoreValve/Evolut R (n=29, 58.0%), followed by a SAPIEN-type valve (n=20,40.0%) or a Boston Lotus valve (n=1, 2.0%). In 40 patients (80.0%), redo TAVR was performed using the identical device type or that of the succeeding generation. Valve performance was uniformly good after redo TAVR (mean transvalvular gradient post redo TAVR: 12.5±6.1 mm Hg). At hospital discharge, all patients remained alive, with 1 nondisabling stroke (2.0%) and 1 life-threatening bleed (2.0%). Permanent pacemaker implantation was required in 3 out of 35 patients without a prior pacemaker (8.6%). Late survival was 85.1% at a median follow-up of 1589 days (range: 31–3775) after index TAVR and 635 days (range: 8–2460) after redo TAVR.

Conclusions—

Redo TAVR for the treatment of postprocedural and late occurrence of paravalvular regurgitation and transcatheter aortic valve prosthesis failure seems to be safe, and it is associated with favorable acute and midterm clinical and echocardiographic outcomes.
Long-Term Survival Among Patients With Myocardial Infarction Before Age 50 Compared With the General Population
Authors: Schmidt Morten , Szépligeti Szimonetta , Horváth-Puhó Erzsébet , Pedersen Lars , Bøtker Hans Erik , Sørensen Henrik Toft
Published: August 2016

Background—

The long-term prognosis for young myocardial infarction (MI) survivors remains poorly understood.

Methods and Results—

We conducted a nationwide population-based cohort study using prospectively collected medical data from all hospitals in Denmark during 1980 to 2009. We examined 30-year cause-specific death rates among 21 693 MI patients <50 years versus 216 930 sex- and age-matched people from the general population. We calculated mortality rate ratios (MRRs) based on Cox regression. Between 1980 to 1989 and 2000 to 2009, MI mortality declined from 12.5% to 3.2% within 30 days, 5.1% to 1.6% within 31 to 365 days, and 24.2% to 8.9% within 1 to 10 years. Compared with the general population, the MRR adjusted for sex, age, and cardiovascular and noncardiovascular comorbidity decreased 4.5-fold within 30 days (from 468 to 97), 3-fold within 31 to 365 days (from 11.32 to 3.70), and 2.5-fold within 1 to 10 years (from 4.77 to 1.89). The remaining 1.89-fold increased mortality rate among 1-year survivors in 2000 to 2009 corresponded to 6 additional deaths each year per 1000 patients compared with the general population. Long-term causes of death were primarily because of cardiovascular and chronic pulmonary diseases. The excess 10-year MRR among 1-year survivors was consistent within MI subtypes, did not differ substantially between comorbidity categories, but was higher for women than men (3-fold versus 1.7-fold).

Conclusions—

The long-term mortality rate after MI before age 50 has decreased remarkably over the last 3 decades, but remains increased relative to the general population, mainly because of deaths from ischemic heart disease and other smoking-related diseases.
Genetically Encoded Biosensors Reveal PKA Hyperphosphorylation on the Myofilaments in Rabbit Heart Failure
Authors: Barbagallo Federica , Xu Bing , Reddy Gopireddy R. , West Toni , Wang Qingtong , Fu Qin , Li Minghui , Shi Qian , Ginsburg Kenneth S. , Ferrier William , Isidori Andrea M. , Naro Fabio , Patel Hemal H. , Bossuyt Julie , Bers Donald , Xiang Yang K.
Published: August 2016

Rationale:

In heart failure, myofilament proteins display abnormal phosphorylation, which contributes to contractile dysfunction. The mechanisms underlying the dysregulation of protein phosphorylation on myofilaments is not clear.

Objective:

This study aims to understand the mechanisms underlying altered phosphorylation of myofilament proteins in heart failure.

Methods and Results:

We generate a novel genetically encoded protein kinase A (PKA) biosensor anchored onto the myofilaments in rabbit cardiac myocytes to examine PKA activity at the myofilaments in responses to adrenergic stimulation. We show that PKA activity is shifted from the sarcolemma to the myofilaments in hypertrophic failing rabbit myocytes. In particular, the increased PKA activity on the myofilaments is because of an enhanced β
2
adrenergic receptor signal selectively directed to the myofilaments together with a reduced phosphodiesterase activity associated with the myofibrils. Mechanistically, the enhanced PKA activity on the myofilaments is associated with downregulation of caveolin-3 in the hypertrophic failing rabbit myocytes. Reintroduction of caveolin-3 in the failing myocytes is able to normalize the distribution of β
2
adrenergic receptor signal by preventing PKA signal access to the myofilaments and to restore contractile response to adrenergic stimulation.

Conclusions:

In hypertrophic rabbit myocytes, selectively enhanced β
2
adrenergic receptor signaling toward the myofilaments contributes to elevated PKA activity and PKA phosphorylation of myofilament proteins. Reintroduction of caveolin-3 is able to confine β
2
adrenergic receptor signaling and restore myocyte contractility in response to β adrenergic stimulation.
Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study
Authors: Resor Charles D. , Nathan Ashwin , Kereiakes Dean J. , Yeh Robert W. , Massaro Joseph M. , Cutlip Donald E. , Gabriel Steg P. , Hsieh Wen-Hua , Mauri Laura
Published: August 2016

Background:

Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown.

Methods:

The DAPT (Dual Antiplatelet Therapy) Study, a double-blind trial, randomly assigned 11 648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use in patients with an American College of Cardiology/American Heart Association class I indication for each medication. Per protocol, all patients were treated with 75 to 325 mg aspirin daily. End points included myocardial infarction, major adverse cardiovascular and cerebrovascular events, and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate or severe bleeding events.

Results:

Of 11 643 randomly assigned patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced myocardial infarction in comparison with placebo in both groups (on OMT 2.1% versus 3.3%, hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.48–0.86;
P
=0.003; off OMT 2.2% versus 5.2%, HR, 0.41; CI, 0.29–0.58;
P
<0.001; interaction
P
=0.103). Comparing continued thienopyridine versus placebo, rates of major adverse cardiovascular and cerebrovascular events were 4.2% versus 5.0% among patients on OMT (HR, 0.82; CI, 0.66–1.02;
P
=0.077) and 4.5% versus 7.0% among those off OMT (HR, 0.63; CI, 0.49–0.82;
P
<0.001; interaction
P
=0.250); rates of bleeding for thienopyridine versus placebo in patients on OMT were 2.2% versus 1.0% (HR, 2.13; CI, 1.43–3.17;
P
<0.001), and in patients off OMT were 2.8% versus 2.2% (HR, 1.30; CI, 0.88–1.92;
P
=0.189; interaction
P
=0.073). Overall, patients on OMT had lower rates of myocardial infarction (2.7% versus 3.7%,
P
=0.003), major adverse cardiovascular and cerebrovascular events (4.6% versus 5.7%,
P
=0.007), and bleeding (1.6% versus 2.5%,
P
<0.001) in comparison with patients off OMT. Rates of stent thrombosis (0.8% versus 1.0%,
P
=0.171) and death (1.6% versus 1.9%,
P
=0.155) did not differ.

Conclusions:

Continued thienopyridine therapy reduced the rate of myocardial infarction regardless of OMT status and had consistent effects on reduction in major adverse cardiovascular and cerebrovascular events and increased bleeding.

Clinical Trial Registration:

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00977938.
Prasugrel Versus Ticagrelor in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention
Authors: Motovska Zuzana , Hlinomaz Ota , Miklik Roman , Hromadka Milan , Varvarovsky Ivo , Dusek Jaroslav , Knot Jiri , Jarkovsky Jiri , Kala Petr , Rokyta Richard , Tousek Frantisek , Kramarikova Petra , Majtan Bohumil , Simek Stanislav , Branny Marian , Mrozek Jan , Cervinka Pavel , Ostransky Jiri , Widimsky Petr
Published: August 2016

Background:

No randomized head-to-head comparison of the efficacy and safety of ticagrelor and prasugrel has been published in the 7 years since the higher efficacy of these newer P2Y
12
inhibitors were first demonstrated relative to clopidogrel.

Methods:

This academic study was designed to compare the efficacy and safety of prasugrel and ticagrelor in acute myocardial infarction treated with primary or immediate percutaneous coronary intervention. A total of 1230 patients were randomly assigned across 14 sites to either prasugrel or ticagrelor, which was initiated before percutaneous coronary intervention. Nearly 4% were in cardiogenic shock, and 5.2% were on mechanical ventilation. The primary end point was defined as death, reinfarction, urgent target vessel revascularization, stroke, or serious bleeding requiring transfusion or prolonging hospitalization at 7 days (to reflect primarily the in-hospital phase). This analysis presents data from the first 30 days (key secondary end point). The total follow-up will be 1 year for all patients and will be completed in 2017.

Results:

The study was prematurely terminated for futility. The occurrence of the primary end point did not differ between groups receiving prasugrel and ticagrelor (4.0% and 4.1%, respectively; odds ratio, 0.98; 95% confidence interval, 0.55–1.73;
P
=0.939). No significant difference was found in any of the components of the primary end point. The occurrence of key secondary end point within 30 days, composed of cardiovascular death, nonfatal myocardial infarction, or stroke, did not show any significant difference between prasugrel and ticagrelor (2.7% and 2.5%, respectively; odds ratio, 1.06; 95% confidence interval, 0.53–2.15;
P
=0.864).

Conclusions:

This head-to-head comparison of prasugrel and ticagrelor does not support the hypothesis that one is more effective or safer than the other in preventing ischemic and bleeding events in the acute phase of myocardial infarction treated with a primary percutaneous coronary intervention strategy. The observed rates of major outcomes were similar but with broad confidence intervals around the estimates. These interesting observations need to be confirmed in a larger trial.

Clinical Trial Registration:

URL:
http://www.ClinicalTrials.gov
. Unique identifier: NCT02808767.
Physical Activity, Parental History of Premature Coronary Heart Disease, and Incident Atherosclerotic Cardiovascular Disease in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Florido Roberta , Zhao Di , Ndumele Chiadi E. , Lutsey Pamela L. , McEvoy John W. , Windham B. Gwen , Pankow James S. , Guallar Eliseo , Michos Erin D.
Published: August 2016

Background

The effects of some atherosclerotic cardiovascular disease (
ASCVD
) risk factors vary according to whether an individual has a family history (
FH
x) of premature coronary heart disease (
CHD
). Physical activity (
PA
) is associated with reduced risk of
ASCVD
, but whether this association varies by
FH
x status is not well established.

Methods and Results

We evaluated 9996 participants free of
ASCVD
at baseline.
FH
x of premature
CHD
was defined as
CHD
occurring in a father before age 55 or mother before age 60.
PA
, assessed by a Baecke questionnaire, was converted into minutes/week of moderate or vigorous exercise and categorized per American Heart Association guidelines as recommended, intermediate, or poor. Incident
ASCVD
was defined as incident myocardial infarction, fatal
CHD
, or stroke. Multivariable‐adjusted Cox hazard models were used. The mean age was 54±6 years, 56% were women, and 21% of black race. Participants with and without a
FH
x of premature
CHD
reported similar levels of
PA
at baseline (423 versus 409 metabolic equivalents of task×min/week, respectively,
P
=0.852), and ≈40% of both groups met American Heart Association recommended
PA
levels. Over a mean follow−up of 20.9 years, there were 1723 incident
ASCVD
events. Compared to those with poor
PA
adherence to American Heart Association guidelines, participants who reported
PA
at recommended levels had significantly lower risk of incident
ASCVD
after adjustment for demographics and lifestyle factors (hazard ratio 0.84, 95%
CI
0.74–0.94), but this association was not modified by
FH
x status (
P
−interaction=0.680).

Conclusions

PA
was associated with a reduced risk of
ASCVD
among individuals with and without a
FH
x of premature
CHD
.
Gut Microbiota Promote Angiotensin II–Induced Arterial Hypertension and Vascular Dysfunction
Authors: Karbach Susanne H. , Schönfelder Tanja , Brandão Ines , Wilms Eivor , Hörmann Nives , Jäckel Sven , Schüler Rebecca , Finger Stefanie , Knorr Maike , Lagrange Jeremy , Brandt Moritz , Waisman Ari , Kossmann Sabine , Schäfer Katrin , Münzel Thomas , Reinhardt Christoph , Wenzel Philip
Published: August 2016

Background

The gut microbiome is essential for physiological host responses and development of immune functions. The impact of gut microbiota on blood pressure and systemic vascular function, processes that are determined by immune cell function, is unknown.

Methods and Results

Unchallenged germ‐free mice (
GF
) had a dampened systemic T helper cell type 1 skewing compared to conventionally raised (
CONV
‐R) mice. Colonization of
GF
mice with regular gut microbiota induced lymphoid
mRNA
transcription of T‐box expression in T cells and resulted in mild endothelial dysfunction. Compared to
CONV
‐R mice, angiotensin
II
(Ang
II
; 1 mg/kg per day for 7 days) infused
GF
mice showed reduced reactive oxygen species formation in the vasculature, attenuated vascular
mRNA
expression of monocyte chemoattractant protein 1 (
MCP
‐1), inducible nitric oxide synthase (iNOS) and
NADPH
oxidase subunit Nox2, as well as a reduced upregulation of retinoic‐acid receptor‐related orphan receptor gamma t (Rorγt), the signature transcription factor for interleukin (IL)‐17 synthesis. This resulted in an attenuated vascular leukocyte adhesion, less infiltration of Ly6G
+
neutrophils and Ly6C
+
monocytes into the aortic vessel wall, protection from kidney inflammation, as well as endothelial dysfunction and attenuation of blood pressure increase in response to Ang
II
. Importantly, cardiac inflammation, fibrosis and systolic dysfunction were attenuated in
GF
mice, indicating systemic protection from cardiovascular inflammatory stress induced by AngII.

Conclusion

Gut microbiota facilitate Ang
II
‐induced vascular dysfunction and hypertension, at least in part, by supporting an
MCP
‐1/
IL
‐17 driven vascular immune cell infiltration and inflammation.
Anabaenopsis morphospecies (Cyanobacteria, Nostocales) from Los Patos shallow lake (Province of Buenos Aires, Argentina)
Authors: AGUILERA ANABELLA , KOMÁREK JIŘĺ , ECHENIQUE RICARDO O.
Published: August 2016

The genus Anabaenopsis comprises about 20 morphospecies distributed in plankton of tropical, subtropical and temperate regions during warm periods. The morphological diversity and population dynamics of Anabaenopsis species from one artificial shallow lake from the Province of Buenos Aires, Argentina, was studied during summer 2005 and 2006; and from April 2012 to May 2014. The most common and abundant species were identified as A. elenkinii and A. cf. cunningtonii (first report in Argentina). Anabaenopsis circularis and A. milleri (first report in the American continent and Argentina) were less common, whereas A. nadsonii was rarely observed. Almost all species contributed to algal blooms during warm periods. However, some species were registered even under the lowest temperatures recorded (7.5 °C) and sustained biovolume also during winter (A. milleri, A. elenkinii and A. cf. cunningtonii). These results indicate that some species of the genus are capable of growing at temperatures much lower than 20°C. The species richness noted in this study suggests that there is likely much more diversity remaining on this genus to be reported in Argentina.
Dendrocalamus jinghongensis (Poaceae, Bambusoideae), another new woody bamboo from Yunnan, China
Authors: WANG PING-YUAN , ZHANG YU-XIAO , LI DE-ZHU , LIU WEN-JIE
Published: August 2016

Dendrocalamus jinghongensis, another new species of woody bamboos endemic to southern Yunnan, China, is described and illustrated. It can be distinguished from closely related species by the following morphological characters: branching from the nodes around 2 m above the ground; culm sheath 1/2 as long as the internode, culm sheath ligule 10–20 mm long; leaf sheath ligule 3–13 mm long; filaments free, or attached together only at the lower portion, and ca. 14 mm long.
Mapping Rainfall Feedback to Reveal the Potential Sensitivity of Precipitation to Biological Aerosols
Authors: Morris Cindy E. , Soubeyrand Samuel , Bigg E. Keith , Creamean Jessie M. , Sands David C.
Published: August 2016

The aerosols that influence the initiation and amount of precipitation are cloud condensation nuclei (CCN), giant CCN, and ice nuclei. Aerosols are ever-present, their properties are variable, and their abundance is dynamic. Therefore, the extent of their impact on the outcome of meteorological contexts that are favorable for rain are difficult to specify. Rainfall can generate aerosols. Those of biological origin that are generated after rainfall can accumulate in a persistent manner over several weeks. Based on a recently developed index of rainfall feedback that focuses on persistent feedback effects and that represents the a priori sensitivity of rainfall to aerosols— of biological origin in particular—we mapped the intensity and patterns of rainfall feedback at 1,250 sites in the western United States where 100-year daily rainfall data were available and where drought is critically severe. This map reveals trends in feedback related to orographic context, geographical location, and season, among other trends. We describe an open-access tool (http://w3.avignon.inra.fr/rainfallfeedback/index.html) for mapping rainfall feedback on a planetary scale to provide a framework for future research to generate hypotheses and to establish rationale to choose field sites for experimentation. This will contribute to the long-term goal of developing a robust understanding of specific and contextual aerosol effects on rainfall applicable to forecasting and to land-use management.
Closure Schemes for Stably Stratified Atmospheric Flows without Turbulence Cutoff
Authors: Li Dan , Katul Gabriel G. , Zilitinkevich Sergej S.
Published: August 2016

Two recently proposed turbulence closure schemes are compared against the conventional Mellor–Yamada (MY) model for stably stratified atmospheric flows. The Energy- and Flux-Budget (EFB) approach solves the budgets of turbulent momentum and heat fluxes and turbulent kinetic and potential energies. The Cospectral Budget (CSB) approach is formulated in wavenumber space and integrated across all turbulent scales to obtain flow variables in physical space. Unlike the MY model, which is subject to a “critical gradient Richardson number,” both EFB and CSB models allow turbulence to exist at any gradient Richardson number and predict a saturation of flux Richardson number () at sufficiently large . The CSB approach further predicts the value of and reveals a unique expression linking the Rotta and von Kármán constants. Hence, all constants in the CSB model are nontunable and stability independent. All models agree that the dimensionless sensible heat flux decays with increasing . However, the decay rate and subsequent cutoff in the MY model appear abrupt. The MY model further exhibits an abrupt cutoff in the turbulent stress normalized by vertical velocity variance, while the CSB and EFB models display increasing trends. The EFB model produces a rapid increase in the ratio of turbulent potential energy and vertical velocity variance as is approached, suggesting a strong self-preservation mechanism. Vertical anisotropy in the turbulent kinetic energy is parameterized in different ways in MY and EFB, but this consideration is not required in CSB. Differences between EFB and CSB model predictions originate from how the vertical anisotropy is specified in the EFB model.
The Relationship between Soil Moisture and LAI in Different Types of Soil in Central Eastern China
Authors: Liu Li , Zhang Renhe , Zuo Zhiyan
Published: August 2016

As important parameters in the land–atmosphere system, both soil moisture (SM) and vegetation play a significant role in land–atmosphere interactions. Using observational data from clay and sand stations over central eastern China, the relationship between leaf area index (LAI) and SM (LAI–SM) in different types of soil was investigated. The results show that the LAI–SM correlation is significantly positive in clay but not significant in sand. The physical causes for the discrepant LAI–SM correlations in different types of soil were explored from the perspectives of evapotranspiration (ET) and soil water retention. In clay stations, increasing LAI is associated with greater soil-water-retention capacity. Although the increasing LAI corresponds to increasing ET, the impact of ET on SM is weak because of the small particle size of soil. Consequently, the LAI–SM relationship in clay is significantly positive. In sand stations, ET is negatively correlated with SM owing to the large soil particle size, resulting in a negative LAI–SM correlation in sand. However, soil water retention is weakened by the increased LAI, which may be an important factor causing the insignificant LAI–SM correlation in sand.