Use of α2-Adrenergic Agonists to Improve Surgical Field Visibility in Endoscopy Sinus Surgery: A Systematic Review of Randomised Controlled Trials

Publication date: Available online 18 December 2017
Source:Clinical Therapeutics
Author(s): Maria Angeles Quijada-Manuitt, Yolanda Escamilla, Antonio Vallano, Alda Cardesín, Manuel Bernal-Sprekelsen, Caridad Pontes
PurposeWe assessed the evidence for the use of α2-adrenergic agonists (A2AAs) in bleeding control and field quality in endoscopic sinus surgery.MethodsWe systematically reviewed randomized clinical trials (RCTs) assessing A2AAs in endoscopic sinus surgery. Abstracts were reviewed by 2 investigators for eligibility, and selected articles were fully reviewed. Data on study design, population, A2AA drug and control groups, bleeding and surgical field quality outcomes, and adverse effects were extracted and synthesized.FindingsA total of 13 RCTs that included 896 individuals (7 double-blind trials, 5 single-blind trials, and 1 open-label trial) were selected that assessed the efficacy of clonidine (6 RCTs, 407 patients), dexmedetomidine (6 RCT, 423 patients), or both (1 RCT, 66 patients). Clonidine was compared with placebo (3 RCTs), midazolam (1 RCT), and remifentanil (2 RCTs). Dexmedetomidine was compared with esmolol (2 RCTs), remifentanil (2 RCTs), nitroglycerin and esmolol (1 RCT), and magnesium sulfate (1 RCT). Clonidine and dexmedetomidine were compared in 1 RCT. Clonidine reduced the proportion of individuals with an impaired surgical field by 23% vs placebo (number needed to treat = 4). Clonidine was better than midazolam and remifentanil in 2 trials, and dexmedetomidine was better than magnesium sulfate and esmolol in 2 trials but was not superior to esmolol, remifentanil, or nitroglycerin in 4 trials. Dexmedetomidine produced significantly better differences in bleeding outcomes versus clonidine. Adverse events were infrequent and mainly caused by hypotension or bradycardia.ImplicationsRCTs consistently report that A2AAs reduce bleeding and improve surgical field quality during endoscopic sinus surgery. Adverse event reporting was often omitted in RCTs. Well-designed RCTs with appropriate sample sizes are desirable to identify the best A2AAs and confirm their potential effects on clinical outcomes.



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Editors, contents and cover information

Publication date: January 2018
Source:Trends in Biochemical Sciences, Volume 43, Issue 1





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TCR Signaling: Mechanisms of Initiation and Propagation

Publication date: Available online 18 December 2017
Source:Trends in Biochemical Sciences
Author(s): Adam H. Courtney, Wan-Lin Lo, Arthur Weiss
The mechanisms by which a T cell detects antigen using its T cell antigen receptor (TCR) are crucial to our understanding of immunity and the harnessing of T cells therapeutically. A hallmark of the T cell response is the ability of T cells to quantitatively respond to antigenic ligands derived from pathogens while remaining inert to similar ligands derived from host tissues. Recent studies have revealed exciting properties of the TCR and the behaviors of its signaling effectors that are used to detect and discriminate between antigens. Here we highlight these recent findings, focusing on the proximal TCR signaling molecules Zap70, Lck, and LAT, to provide mechanistic models and insights into the exquisite sensitivity and specificity of the TCR.



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Forecasting Faces in the Cortex

Publication date: Available online 18 December 2017
Source:Trends in Cognitive Sciences
Author(s): Lucy S. Petro, Lars Muckli
Although theories of predictive coding in the brain abound, we lack key pieces of neuronal data to support these theories. Recently, Schwiedrzik and Freiwald found neurophysiological evidence for predictive codes throughout the face-processing hierarchy in macaque cortex. We highlight how these data enhance our knowledge of cortical information processing, and the impact of this more broadly.



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Alterations in comprehensive geriatric assessment decrease survival of elderly patients with cancer

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): M. Frasca, P. Soubeyran, C. Bellera, M. Rainfray, K. Leffondre, S. Mathoulin-Pélissier
IntroductionA comprehensive geriatric assessment (CGA) evaluating several domains of health is recommended for elderly patients with cancer. Effects of altered domains on the risk of death in this population need to be clarified. The aim of this study was to estimate the independent association of each CGA domain to overall survival (OS).MethodPatients included in the ONCODAGE cohort completed a CGA at baseline. Cox models (one per domain) estimated the hazard ratio (HR) of death for each CGA domain. Directed Acyclic Graphs (DAGs) selected specific sets of adjustment factors for each model.ResultsThe analysis included 1264 patients (mean age: 78 years, women: 70%). Median follow-up was 5.2 years, and 446 patients died. Each altered domain had a detrimental effect on survival, sometimes dependent on gender, age, education or time from inclusion. Nutritional status had a time-varying effect, with higher mortality rates if altered only within the first 3 years of follow-up. In case of altered mobility, the risk of death was higher only for the youngest patients and, in case of altered autonomy, only for the youngest women. An altered neurological state led to higher mortality rates; this effect increased with the level of education. Patients with altered psychological status or more than four comorbidities at baseline had also higher mortality rates.ConclusionsPatients with an altered CGA domain have a higher risk of death than those without any alteration. The effect of some alterations is different in some subgroups or at a given time of the treatments.



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A randomised phase II trial of docetaxel versus docetaxel plus carboplatin in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy: The RECARDO trial

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): Esther W. Bouman-Wammes, H. Pieter van den Berg, Linda de Munck, Aart Beeker, Carolien H. Smorenburg, Walter L. Vervenne, Juleon L.L.M. Coenen, Henk M.W. Verheul, Winald R. Gerritsen, Alfons J.M. Van den Eertwegh
BackgroundDocetaxel is standard first-line chemotherapy for patients with metastatic castration–resistant prostate carcinoma (mCRPC). Docetaxel re-challenge has never been tested in a prospective randomised controlled study. As some studies support the addition of carboplatin to docetaxel, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel re-treatment in docetaxel pre-treated mCRPC patients.MethodsPatients with mCRPC with a progression-free interval of ≥3 months after initial docetaxel treatment were randomised between docetaxel 75 mg/m² or docetaxel 60 mg/m² plus carboplatin AUC4. The primary end-point was progression-free survival (PFS; PSA/RECIST).ResultsOwing to insufficient recruitment, the study was discontinued early after inclusion of 75 patients (targeted 150) PFS and overall survival (OS) were comparable between both groups (median PFS 12.7 months (95% CI 9.9–17.5 months) with docetaxel monotherapy and 11.7 months (95% CI 8.5–21.0 months) with combination therapy (p = 0.98); OS 18.5 months (95% CI 11.8–24.5 months) versus 18.9 months (95% CI 16.0–23.7 months) (p = 0.79). An interim analysis (SEQTEST) showed that the null hypothesis could already be excepted, and no significant difference between both study arms was expected if inclusion would be completed. The incidence of grade 3–4 infections and gastrointestinal side-effects was numerical higher in the carboplatin arm (p = 0.056).ConclusionThis early terminated study suggests no benefit from the addition of carboplatin to docetaxel re-treatment in patients with mCRPC, whereas the combination resulted in more toxicity. Re-treatment with docetaxel monotherapy appears to be feasible, save and effective for patients with mCRPC and an initial good response to docetaxel.Trial registrationNTR3070.



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Methylglyoxal displays colorectal cancer-promoting properties in the murine models of azoxymethane and CT26 isografts

Publication date: Available online 18 December 2017
Source:Free Radical Biology and Medicine
Author(s): Jer-An Lin, Chi-Hao Wu, Gow-Chin Yen
Methylglyoxal (MG), a highly reactive carbonyl species (RCS) with pro-oxidant and proinflammatory properties, may be a colon tumor-promoting factor in food and biological systems. In the present study, we found that consumption of MG significantly deteriorated azoxymethane (AOM)-induced colonic preneoplastic lesions in ICR mice, in which biomarkers of oxidative stress and inflammation within the body and feces induced by MG-fueled carbonyl stress may have played important roles. Interestingly, exposure to MG also led to increases in the serum low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio and fecal bile acid levels in mice, which may be critical factors involved in MG-induced colonic lesions. Additionally, MG treatment (50mg/kg body weight (BW); intraperitoneally) promoted tumor growth of CT26 isografts in mice partly by carbonyl stress-evoked protumorigenic responses, including low-grade inflammation and oxidative stress. Furthermore, primary tumor cells isolated from mice with MG-induced CT26 isografts had greater proliferative and migratory activities as well as stem-like properties compared to those isolated from the vehicle controls. Excitingly, enhanced expression or activation of proteins that modulate cell survival, proliferation, or migration/invasion was also observed in those cells. In conclusion, it is conceivable that MG-induced carbonyl stress may be the pivotal promoter involved in colon cancer progression.

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PKCδ-dependent p47phox activation mediates methamphetamine-induced dopaminergic neurotoxicity

Publication date: Available online 18 December 2017
Source:Free Radical Biology and Medicine
Author(s): Duy-Khanh Dang, Eun-Joo Shin, Dae-Joong Kim, Hai-Quyen Tran, Ji Hoon Jeong, Choon-Gon Jang, Ole Petter Ottersen, Seung-Yeol Nah, Jau-Shyong Hong, Toshitaka Nabeshima, Hyoung-Chun Kim
Protein kinase C (PKC) has been recognized to activate NADPH oxidase (PHOX). However, the interaction between PKC and PHOX in vivo remains elusive. Treatment with methamphetamine (MA) resulted in a selective increase in PKCδ expression out of PKC isoforms. PKCδ co-immunoprecipitated with p47phox, and facilitated phosphorylation and membrane translocation of p47phox. MA-induced increases in PHOX activity and reactive oxygen species were attenuated by knockout of p47phox or PKCδ. In addition, MA-induced impairments in the Nrf-2-related glutathione synthetic system were also mitigated by knockout of p47phox or PKCδ. Glutathione-immunoreactivity was co-localized in Iba-1-labeled microglial cells and in NeuN-labeled neurons, but not in GFAP-labeled astrocytes, reflecting the necessity for self-protection against oxidative stress by mainly microglia. Buthionine-sulfoximine, an inhibitor of glutathione biosynthesis, potentiated microglial activation and pro-apoptotic changes, leading to dopaminergic losses. These neurotoxic processes were attenuated by rottlerin, a pharmacological inhibitor of PKCδ, genetic inhibitions of PKCδ [i.e., PKCδ knockout mice (KO) and PKCδ antisense oligonucleotide (ASO)], or genetic inhibition of p47phox (i.e., p47phox KO or p47phox ASO). Rottlerin did not exhibit any additive effects against the protective activity offered by genetic inhibition of p47phox. Therefore, we suggest that PKCδ is a critical regulator for p47phox activation induced by MA, and that Nrf-2-dependent GSH induction via inhibition of PKCδ or p47phox, is important for dopaminergic protection against MA insult.

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NADPH Oxidase 4 and Endothelial Nitric Oxide Synthase Contribute to Endothelial Dysfunction Mediated by Histone Methylations in Metabolic Memory

Publication date: Available online 18 December 2017
Source:Free Radical Biology and Medicine
Author(s): Yunfei Liao, Luoning Gou, Lulu Chen, Xueyu Zhong, Dongxue Zhang, Hangang Zhu, Xiaodan Lu, Tianshu Zeng, Xiuling Deng, Yuming Li
"Metabolic memory" is identified as a phenomenon that transient hyperglycemia can be remembered by vasculature for quite a long term even after reestablishment of normoglycemia. NADPH oxidases (Noxs) and endothelial nitric oxide synthase (eNOS) are important enzymatic sources of reactive oxygen species (ROS) in diabetic vasculature. The aim of this study is to explore the roles of epigenetics and ROS derived from Noxs and eNOS in the metabolic memory. In this study, we demonstrated that vascular ROS was continuously activated in endothelium induced by transient high glucose, as well as sustained vascular endothelial dysfunction. The Nox4 and uncoupled eNOS are the major sources of ROS, while inhibition of Nox4 and eNOS significantly attenuated oxidative stress and almost recovered the endothelial function in metabolic memory. Furthermore, the aberrant histone methylation (H3K4me1, H3K9me2, and H3K9me3) at promoters of Nox4 and eNOS are the main causes for the persistent up-regulation of these two genes. Modifying the histone methylation could reduce the expression levels of Nox4 and eNOS, thus obviously attenuating endothelial dysfunction. These results indicate that histone methylation of Nox4 and eNOS play a key role in metabolic memory and may be the potential intervention targets for metabolic memory.

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Detection of Intra-Articular Screw Penetration of Proximal Humerus Fractures

Publication date: Available online 18 December 2017
Source:Academic Radiology
Author(s): Xiaoyang Jia, Yanxi Chen, Minfei Qiang, Kun Zhang, Haobo Li, Yuchen Jiang, Yijie Zhang
Rationale and ObjectiveScrew penetration is the common complication of proximal humerus fractures treated with locking plates. This study compared postoperative plain radiography to computed tomography (CT) for their abilities in determining screw penetration, and was to evaluate whether advanced imaging modalities (two-dimensional [2D] CT; three-dimensional [3D] CT) could increase surgeons' level of confidence regarding their diagnoses.Materials and MethodsTwo observers reviewed radiological images of 134 patients who sustained proximal humerus fractures treated with locking plates. The observers were asked to answer two questions: (1) Is there screw penetrating into glenohumeral joint for this patient (Yes/No)? and (2) On a scale from 0 to 10, how confident are you about this diagnosis: (0–10) (0 = not at all confident; 10 = very confident)? Three evaluations were performed: (1) plain radiography alone, (2) radiography and 2D CT 4 weeks later, and (3) radiography in combination with 2D and 3D CT after that. This process was then repeated for intraobserver analysis.ResultsCT obtained almost perfect interobserver and intraobserver agreement (0.818–0.961), which was higher than radiography (0.377–0.655). For incidence of screw penetration, the significant difference was found between radiographs and CT images (P < .0125), but not between 2D and 3D CT images (P > .05). For confidence of diagnosis, the differences between imaging modalities were significant (all P < .001).ConclusionsWe suggest that postoperative CT scans (especially 3D CT images) should be used to evaluate the intra-articular screw penetration of proximal humerus fractures, especially when surgeons have not enough confidence in determining screw penetration using radiography alone.



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Ambient nanoparticles/nanominerals and hazardous elements from coal combustion activity: implications on energy challenges and health hazards

Publication date: Available online 18 December 2017
Source:Geoscience Frontiers
Author(s): Binoy K. Saikia, Jyotilima Saikia, ShahadevRabha, Luis F.O. Silva, Robert Finkelman
Coal is the most abundant fossil fuel in the world. Because of the growth of coal mining, coal-fired power plants, and coal-burning industries the increase of the emission of particulates (coarse, fine or ultrafine) is of great concern. There is a relationship between increasing human morbidity and mortality and progressive environmental air pollution caused by these types of particles. Thus, the knowledge of the physico-chemical composition and ambient concentrations of coal-derived nanoparticles will improve pollution control strategy. Given the current importance of this area of research, the advanced characterization of this coal combustion-derived nanoparticles/nanominerals as well as hazardous elements is likely to be one of the hottest research fields in coming days. In this review, we try to compile the existing knowledge on coal-derived nanoparticles/nanominerals and discuss the advanced level of characterization techniques for future research. This review also provides some of aspects of health risks associated with exposure to ambient nanoparticles. In addition, the presence of some of the hazardous elements in coal and coal combustion activities is also reviewed.

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Building a state space for song learning

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Emily Lambert Mackevicius, Michale Sean Fee
The songbird system has shed light on how the brain produces precisely timed behavioral sequences, and how the brain implements reinforcement learning (RL). RL is a powerful strategy for learning what action to produce in each state, but requires a unique representation of the states involved in the task. Songbird RL circuitry is thought to operate using a representation of each moment within song syllables, consistent with the sparse sequential bursting of neurons in premotor cortical nucleus HVC. However, such sparse sequences are not present in very young birds, which sing highly variable syllables of random lengths. Here, we review and expand upon a model for how the songbird brain could construct latent sequences to support RL, in light of new data elucidating connections between HVC and auditory cortical areas. We hypothesize that learning occurs via four distinct plasticity processes: 1) formation of 'tutor memory' sequences in auditory areas; 2) formation of appropriately-timed latent HVC sequences, seeded by inputs from auditory areas spontaneously replaying the tutor song; 3) strengthening, during spontaneous replay, of connections from HVC to auditory neurons of corresponding timing in the 'tutor memory' sequence, aligning auditory and motor representations for subsequent song evaluation; and 4) strengthening of connections from premotor neurons to motor output neurons that produce the desired sounds, via well-described song RL circuitry.



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Engineered cell and tissue models of pulmonary fibrosis

Publication date: Available online 18 December 2017
Source:Advanced Drug Delivery Reviews
Author(s): Aswin Sundarakrishnan, Ying Chen, Lauren D. Black, Bree B. Aldridge, David L. Kaplan
Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3 years' post diagnosis. Treatments for IPF are limited to two FDA approved treatments, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis.

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Recognized Outstanding Reviewers for Circulation in 2017.

Author: Hill, Joseph A. MD, PhD; de Lemos, James A. MD; McGuire, Darren K. MD, MHSc; on behalf of the Circulation Editors Team

Page: 2399

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Absence of an Ideal Observer II: The Agonizing Search for Experts Without a Conflict of Interest.

Author: Packer, Milton MD

Page: 2400-2402

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Embolic Stroke.

Author: Ntaios, George MD; Hart, Robert G. MD

Page: 2403-2405

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Radiation-Induced DNA Damage in Operators Performing Endovascular Aortic Repair.

Author: El-Sayed, Tamer *,; Patel, Ashish S. PhD *,; Cho, Jun S.; Kelly, James A.; Ludwinski, Francesca E. PhD; Saha, Prakash PhD; Lyons, Oliver T. PhD; Smith, Alberto PhD; Modarai, Bijan PhD; Guy's and St Thomas' Cardiovascular Research Collaborative; Tyrrell, M; Gkoutzios, P; Abisi, S; Black, S; Zayed, H; Bell, RE; Sallam, M; Biasi, L; Patel, SD; Donati, T; Dialynas, M; Sandford, B; Redwood, S; Perera, S; Pavlidis, A; Prendergast, B; Gill, J

Page: 2406-2416

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Health Risks of Ionizing Radiation: Dr Roentgen Today.

Author: Chambers, Charles E. MD

Page: 2417-2419

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Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy.

Author: Rowin, Ethan J. MD; Hausvater, Anais MD; Link, Mark S. MD; Abt, Patrick MD; Gionfriddo, William MD; Wang, Wendy MPH; Rastegar, Hassan MD; Estes, N. A. Mark MD; Maron, Martin S. MD; Maron, Barry J. MD

Page: 2420-2436

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Atrial Fibrillation in Hypertrophic Cardiomyopathy: New Light on an Old Problem.

Author: Spirito, Paolo MD

Page: 2437-2439

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Prevention of Stroke with the Addition of Ezetimibe to Statin Therapy in Patients With Acute Coronary Syndrome in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

Author: Bohula, Erin A. MD, DPhil; Wiviott, Stephen D. MD; Giugliano, Robert P. MD, SM; Blazing, Michael A. MD; Park, Jeong-Gun PhD; Murphy, Sabina A. MPH; White, Jennifer A. MS; Mach, Francois MD; Van de Werf, Frans MD, PhD; Dalby, Anthony J. MD, DPhil, MB, ChB; White, Harvey D. DSc; Tershakovec, Andrew M. MD, MPH; Cannon, Christopher P. MD; Braunwald, Eugene MD

Page: 2440-2450

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Pyruvate Kinase and Warburg Metabolism in Pulmonary Arterial Hypertension: Uncoupled Glycolysis and the Cancer-Like Phenotype of Pulmonary Arterial Hypertension.

Author: Archer, Stephen L. MD

Page: 2486-2490

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Cardiac Imaging in Patients With Ventricular Tachycardia.

Author: Mahida, Saagar MD, PhD; Sacher, Frederic MD, PhD; Dubois, Remi PhD; Sermesant, Maxime PhD; Bogun, Frank MD; Haissaguerre, Michel MD; Jais, Pierre MD; Cochet, Hubert MD, PhD

Page: 2491-2507

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Identification of MicroRNA-124 as a Major Regulator of Enhanced Endothelial Cell Glycolysis in Pulmonary Arterial Hypertension via PTBP1 (Polypyrimidine Tract Binding Protein) and Pyruvate Kinase M2.

Author: Caruso, Paola PhD; Dunmore, Benjamin J. PhD; Schlosser, Kenny PhD; Schoors, Sandra MSc, PhD; Dos Santos, Claudia PhD; Perez-Iratxeta, Carol PhD; Lavoie, Jessie R. PhD; Zhang, Hui MD, PhD; Long, Lu PhD; Flockton, Amanda R. BS; Frid, Maria G. PhD; Upton, Paul D. PhD; D'Alessandro, Angelo PhD; Hadinnapola, Charaka MA, MB BChir; Kiskin, Fedir N. MRes; Taha, Mohamad BSc; Hurst, Liam A. PhD; Ormiston, Mark L. PhD; Hata, Akiko PhD; Stenmark, Kurt R. MD; Carmeliet, Peter MD, PhD; Stewart, Duncan J. MD *,; Morrell, Nicholas W. MD *,

Page: 2451-2467

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Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis.

Author: Zhang, Hui MD, PhD; Wang, Daren PhD; Li, Min PhD; Plecita-Hlavata, Lydie PhD; D'Alessandro, Angelo PhD; Tauber, Jan PhD; Riddle, Suzette PhD; Kumar, Sushil PhD; Flockton, Amanda BS; McKeon, B. Alexandre MS; Frid, Maria G. PhD; Reisz, Julie A. PhD; Caruso, Paola PhD; El Kasmi, Karim C. MD, PhD; Jezek, Petr PhD; Morrell, Nicholas W. MD; Hu, Cheng-Jun PhD; Stenmark, Kurt R. MD

Page: 2468-2485

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Efforts Aim to Promote Safer Anticoagulant Prescribing.

Author: Kuehn, Bridget M.

Page: 2508-2509

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Highlights From the Circulation Family of Journals.

Author:

Page: 2510-2515

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Low-Dose Exposure to Ionizing Radiation Deregulates the Brain-Specific MicroRNA-134 in Interventional Cardiologists.

Author: Borghini, Andrea MSc, PhD; Vecoli, Cecilia MSc, PhD; Mercuri, Antonella MSc; Carpeggiani, Clara MD; Piccaluga, Emanuela MD; Guagliumi, Giulio MD; Picano, Eugenio MD, PhD; Andreassi, Maria Grazia MSc, PhD

Page: 2516-2518

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Left Ventricular Hypertrophy Revisited: Cell and Matrix Expansion Have Disease-Specific Relationships.

Author: Treibel, Thomas A. PhD *,,; Kozor, Rebecca PhD *,; Menacho, Katia MD; Castelletti, Silvia MD; Bulluck, Heerajnarain PhD; Rosmini, Stefania MD; Nordin, Sabrina MD; Maestrini, Viviana MD; Fontana, Marianna PhD; Moon, James C. MD

Page: 2519-2521

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Letter by Farina Regarding Article, "A Structured Review of Antithrombotic Therapy in Peripheral Artery Disease With a Focus on Revascularization: A TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) Initiative".

Author: Farina, Alberto PharmD

Page: 2522-2523

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Response by Hess and Hiatt to Letter Regarding Article, "A Structured Review of Antithrombotic Therapy in Peripheral Artery Disease With a Focus on Revascularization: A TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) Initiative".

Author: Hess, Connie N. MD, MHS; Hiatt, William R. MD

Page: 2524-2525

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Letter by Jin-Shan and Xue-Bin Regarding Article, "Out-of-Hospital Cardiac Arrest: An Underlying Reversible Cause".

Author: Jin-Shan, He MD; Xue-Bin, Li MD

Page: 2526

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Response by Derkenne et al Regarding Article, "Out-of-Hospital Cardiac Arrest: An Underlying Reversible Cause".

Author: Derkenne, Clement MD; Jost, Daniel MD; Robert, Jimmy MD; Tourtier, Jean-Pierre PhD; On behalf of the Paris Fire Brigade Cardiac Task Force

Page: 2527-2528

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The dynamic engram: fear memories and the basolateral amygdala

Publication date: Available online 18 December 2017
Source:Brain Research Bulletin
Author(s): Patrick Davis, Leon G. Reijmers
Great progress is being made in our understanding of how the brain stores and retrieves memories, which is exemplified by continuous discoveries of novel spatial and temporal components of so-called memory engrams. These discoveries have led to the realization that engrams are controlled by complex spatiotemporal dynamics across scales that span from molecules to brain regions, and from milliseconds to years. Moreover, it is now clear that across the lifetime of an engram, many of its spatial and temporal properties are not fixed, but instead change in complex ways. The dynamic nature of engrams is especially relevant in the case of fear memories, whose contributions to an animal's fitness depend on a delicate balance of stability and flexibility. Though most fear memories last a lifetime for an obvious reason, their expression also needs to be highly regulated to prevent the maladaptive behavior caused by anxiety disorders. To achieve the right balance of stability and flexibility, fear engrams are subjected to complex spatiotemporal dynamics, making them informative examples of the "dynamic engram". This review will focus on the contributions of the basolateral amygdala (BLA) to the dynamic properties of fear engrams.



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Monitoring biocalcification potential of Lysinibacillus sp. isolated from alluvial soils for improved compressive strength of concrete

Publication date: Available online 18 December 2017
Source:Microbiological Research
Author(s): Rajneesh Vashisht, Sampan Attri, Deepak Sharma, Abhilash Shukla, Gunjan Goel
The present study reports the potential of newly isolated calcite precipitating bacteria isolated from alluvial soil to improve the strength and durability of concrete. A total of sixteen samples of alluvial soil and sewage were collected from the different locations of province Solan (India). For isolation, enrichment culture technique was used to enrich calcite precipitating strains in Urea broth. After enrichment, fourteen distinct bacterial strains were obtained on Urea agar. Based on qualitative and quantitative screening for urease activity, five isolates were obtained possessing higher calcite formation and urease activities (38–77 μmhos/cm) as compared with standard strain of Bacillus megaterium MTCC 1684 (77 μmhos/cm). An isolate I13 identified as Lysinibacillus sp. was selected for self healing property in the concrete mix of M20. An improved compressive strength of 1.5 fold was observed in concrete samples amended with Lysinibacillus sp. over the concrete amended with B. megaterium MTCC 1684 after 28 days of curing. The higher calcite precipitation activity was indicated in Lysinibacillus sp. by FE-SEM micrographs and EDX analysis.



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Regeneration of cortical tissue from brain injury by implantation of defined molecular gradient of semaphorin 3A

Publication date: March 2018
Source:Biomaterials, Volume 157
Author(s): Zhen Xu, Wei Wang, Yutian Ren, Wenchong Zhang, Peilin Fang, Linfeng Huang, Xin Wang, Peng Shi
Despite great efforts in the exploration of therapeutic strategies for treating brain injuries, it is still challenging to regenerate neural tissues and to restore the lost function within an injured brain. In this report, we employed a tissue engineering approach to regenerate cortical tissue from brain injury by implantation of defined semaphorin 3A (Sema3A) gradient packaged in a hydrogel based device. Over a thirty-day recovery period, the implanted Sema3A gradient was sufficient to induce substantial migration of neural progenitor cells to the hydrogel and to promote differentiation of these cells for neuroregeneration at the injury site. As revealed by molecular characterization and RNA transcriptome analysis, the regenerated tissues induced by Sema3A gradient exhibited significant similarity to normal cortical tissues. Many genes associated with neuronal migration and stem cell differentiation were significantly up-regulated. In addition, our result suggested a crosstalk between Sema3A and Wnt/β-catenin pathways in course of induced brain regeneration. This study demonstrated an innovative strategy to regenerate brain tissue after traumatic injury by controlling the in vivo chemotactic environment with unprecedented sophistication, and also resolved new insights about Sema3A's role in adult neurogenesis.



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Tumor acidity activating multifunctional nanoplatform for NIR-mediated multiple enhanced photodynamic and photothermal tumor therapy

Publication date: March 2018
Source:Biomaterials, Volume 157
Author(s): Junjie Liu, Huining Liang, Menghuan Li, Zhong Luo, Jixi Zhang, Xingming Guo, Kaiyong Cai
The study reports a multifunctional nanoplatform based on mesoporous silica coated gold nanorod (AuNR@MSN) to overcome biological barriers associating with nanocarrier for multiple enhanced photodynamic therapy (PDT) and photothermal therapy (PPT). Indocyanine green (ICG) was loaded into AuNR@MSN and end-capped with β-cyclodextrin (β-CD). Then, a peptide RLA ([RLARLAR]2) with plasma membrane permeability and mitochondria-targeting capacity was anchored to AuNR@MSN via host-gust interaction. Subsequently, a charge-reversible polymer was introduced to endow stealth property. When the nanoplatform extravasates to tumor tissue, the weak acidity in tumor microenvironment could induce the dissociation of charge-reversible polymer and re-exposure of RLA peptide. Such a pH-mediated transition could facilitate the targeted accumulation of the nanoplatform in mitochondria. Upon singular 808 nm laser irradiation, the nanoplatform displayed enhanced PDT effect through the generation of reactive oxygen species (ROS) mediated by the local electric field of AuNR, plasmonic photothermal effect, and leakage of endogenous ROS by mitochondrion-targeted PDT. Meanwhile, local hyperthermia was generated by both ICG and AuNR for PPT. The in vitro and in vivo experiments demonstrated that the composite nanoplatform had good antitumor effect with minimal side effect. This work provides new insight into the development of new phototherapeutics for oncotherapy.



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Multifunctional hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release for enhanced tumor suppression

Publication date: March 2018
Source:Biomaterials, Volume 157
Author(s): Xuhan Liu, Yinghuan Li, Xi Tan, Rong Rao, Yuanyuan Ren, Lingyan Liu, Xiangliang Yang, Wei Liu
Therapeutic efficacy of conventional single PEGylated polymeric micelles is significantly reduced by limited endocytosis and intracellular drug release. To improve drug delivery efficiency, poly (ethylene glycol)-block-poly (l-lactic acid)/(Arg-Gly-Asp-Phe)-poly (aminoethyl ethylene phosphate)-block-poly (l-lactic acid) (PEG-PLLA/RGDF-PAEEP-PLLA) hybrid micelles with tunable active targeting and acid/phosphatase-stimulated drug release are developed. The optimized hybrid micelles with 6 wt % of RGDF have favorable in vitro and in vivo activities. The hybrid micelles could temporarily shield the targeting efficacy of RGDF at pH 7.4 due to the steric effect exerted by concealment of RGDF peptides in the PEG corona, which strongly decreases the clearance by mononuclear phagocyte system and consequently improves the tumor accumulation. Inside the solid tumor with a lower acidic pH, the hybrid micelles restore the active tumor targeting property with exposed RGDF on the surface of the micelles because of the increased protonation and stretching degree of PAEEP blocks. RGDF-mediated endocytosis improves the tumor cell uptake. The hybrid micelles would also enhance intracellular drug release because of the hydrolysis of the acid/phosphatase-sensitivity of PAEEP blocks in endo/lysosome. Systemic administration of the hybrid micelles significantly inhibits tumor growth by 96% due to the integration of enhanced circulation time, tumor accumulation, cell uptake and intracellular drug release.



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Long-term follow up of an adult with alternating hemiplegia of childhood and a p.Gly755Ser mutation in the ATP1A3 gene

Publication date: Available online 18 December 2017
Source:Brain and Development
Author(s): Tomoshiro Ito, Masashi Narugami, Kiyoshi Egawa, Hiroyuki Yamamoto, Naoko Asahina, Shinobu Kohsaka, Atsushi Ishii, Shinichi Hirose, Hideaki Shiraishi
Alternating hemiplegia of childhood (AHC) is a rare neurological disease mainly caused by mutations in the ATP1A3 gene and showing varied clinical severity according to genotype. Patients with a p.Gly755Ser (p.G755S) mutation, one of minor genotypes for AHC, were recently described as having a mild phenotype, although their long-term outcomes are still unclear due to the lack of long-term follow up. Here, we demonstrate the full clinical course of a 43-year-old female AHC patient with p.G755S mutation. Although her motor dysfunction had been relatively mild into her 30 s, she showed a subsequent severe aggravation of symptoms that left her bedridden, concomitant with a recent recurrence of seizure status. The seizures were refractory to anti-epileptic drugs, but administration of flunarizine improved seizures and the paralysis.Our case suggests that the phenotype of AHC with p.G755S mutation is not necessarily mild, despite such a presentation during the patient's younger years.



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Differential effects of a visuospatial attention task on measures of postural control in young and older adults

Publication date: Available online 18 December 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Jeffrey J. Peterson, Kevin G. Keenan
The purpose of this study was to examine the influence of a visuospatial attention task on three measures of postural control in young and older adults. 20 young (19 – 36 years) and 20 older (67 – 91 years) adults performed a choice stepping response time (CSRT) task, a submaximal dorsiflexion force steadiness task, and quiet standing in 3 bilateral stances. All tasks were performed with and without a visuospatial (VS) attention task that involved visualizing a star moving within a 2×2 grid. CSRT increased with the addition of the VS task in both groups (p < .001), with a larger increase for older adults than young adults (p < .001). Older adults were less steady while performing the dorsiflexion task with the VS task (p < .001), while the VS task did not influence steadiness in young adults (p = .235). Performance during quiet standing was not influenced by the VS task in any stance (p > .084). The findings suggest that visuospatial attention differentially affects postural control in young and older adults and the effect is task-specific. These findings suggest the need to include stepping and force control tasks to further determine what role visuospatial attention plays in postural control.



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Porous chitosan microspheres containing zinc ion for enhanced thrombosis and hemostasis

Publication date: 1 April 2018
Source:Materials Science and Engineering: C, Volume 85
Author(s): Meng Pan, Zonghao Tang, Jianbing Tu, Zhengchao Wang, Qinhui Chen, Rongdong Xiao, Haiqing Liu
Quick hemostats for non-lethal massive traumatic bleeding in battlefield and civilian accidents are important for reducing mortality and medical costs. Chitosan (CS) has been widely used as a clinic hemostat. To enhance its hemostatic efficiency, Zn²⁺ in the form of zinc alginate (ZnAlg) was introduced to CS to make porous CS@ZnAlg microspheres with ZnAlg component on the surface. Such microspheres were prepared by successive steps of micro-emulsion, polyelectrolyte adhesion, and thermally induced phase separation. Their structure and hemostatic performance were analyzed by SEM, FT-IR, XPS and a series of in vitro hemostatic experiments including thromboelastography analysis. The composite microspheres had an outer and internal interconnected porous structure. Their size, surface area, and water absorption ratio were ca. 70μm, 48m²/g, and 1850%, respectively. Compared to the neat chitosan microspheres, the CS@ZnAlg microspheres showed shorter onset of clot formation, much faster in vitro and in vivo whole blood clotting, bigger clot, less blood loss, and shorter hemostatic time in the rat liver laceration and tail amputation models. The synergetic hemostatic effects from (1) the electrostatic attraction between chitosan component and red blood cells, (2) the activation of coagulation factor XII by Zn²⁺ of zinc alginate component, and (3) physical blocking by microsphere matrix, contributed to the enhanced hemostatic performance of CS@ZnAlg microspheres.



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Effects of bamboo biochar on soybean root nodulation in multi-elements contaminated soils

Publication date: 15 April 2018
Source:Ecotoxicology and Environmental Safety, Volume 150
Author(s): Chunyan Wang, Darioush Alidoust, Xueling Yang, Akihiro Isoda
Improvements in plant physiological performance by means of biochar application in soils contaminated by multi-elements are determinants of agroecosystem functioning. This study analyzed the effects of bamboo-derived biochar on root nodulation and plant growth in a moderately acidic Andosol (pH = 5.56) contaminated with multi-elements during a 70-day investigation of soybean growth.Bamboo biochar that had been pyrolyzed at a temperature below 500°C was applied to soils at three different and moderately high rates (5%, 10%, and 15%, w/w). Biochar amendment beyond 5% stimulated root nodulation as well as soybean growth. The nodule weight per root system was significantly enhanced by 186% and 243% over the control at the 10% and 15% addition rates, respectively. The primary explanation for these stimulatory effects was attributed to an increase in the K and Mo supplies for plant uptake that was induced by the biochar application, whereas the increased availability of P contributed to a lesser extent. Leaf CO2 assimilation rate was slightly enhanced at the highest application rate, but this enhancement was not associated with an increase in biomass. The incorporation of biochar into the soil reduced extractable-NH4NO3 Cd, Cu, Mn, Ni, and Zn, but not Pb, regardless of the application dose. This change was accompanied by a significant (P < 0.05) suppression of the uptake od trace elements in soybean shoots at the optimum application rate (10%); the degree of reduction followed this order: Pb>Mn>Cd>Zn>Cu>Ni. The increase in soil pH and the diffusion/adsorption of trace elements onto the biochar may have contributed to the lowering of the concentration of trace elements in the soil as well as in soybean shoots.



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Induced mutation analysis with biochemical and molecular characterization of high yielding lentil mutant lines

Publication date: 1 April 2018
Source:International Journal of Biological Macromolecules, Volume 109
Author(s): Rafiul Amin Laskar, Amaj Ahmed Laskar, Aamir Raina, Samiullah Khan, Hina Younus
Induced mutagenesis generates macromolecular variations which ultimately alters the bio-physiological and morphological nature of the crop genotypes. In the present study, molecular characterization of six high yielding lentil mutant lines, developed from hydrazine hydrates (HZ) and gamma rays mutagenesis, was carried out with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and random amplified polymorphic DNA (RAPD) markers. Activity of nitrate reductase (NR) and content of chlorophyll and carotenoid were found to be significantly high in the mutant lines. Protein and mineral (Fe, Zn & Cu) contents were also increased considerably in the mutant lines compared to their respective parent genotypes. SDS-PAGE profile of seed storage proteins showed 35 unique bands with 97.14% polymorphism. Genetic divergence analysis generated total 41 reproducible RAPD bands with average calculated polymorphic percentage of 63.06%. Among the primers, OPA-10 showed the highest polymorphism with significant PIC value. Genetic divergent analysis revealed that genome of cultivar DPL 62 mutated relatively more than the cultivar Pant L 406 due to the mutagen treatments, while DPL 62-B and Pant L406-A were the most divergent mutants induced in the present study. Biochemical and molecular profile of the induced mutant lines facilitates a basis for future conservation and utilization strategies to widen the genetic base of the current lentil breeding population.



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Assessing Liver Stiffness by 2-D Shear Wave Elastography in a Healthy Cohort

Publication date: Available online 18 December 2017
Source:Ultrasound in Medicine & Biology
Author(s): Felix Bende, Anesa Mulabecirovic, Ioan Sporea, Alina Popescu, Roxana Sirli, Odd Helge Gilja, Mette Vesterhus, Roald Flesland Havre
The aim of this study was to assess the normal ranges of liver stiffness measurements (LSMs) in participants with healthy livers, using General Electric 2-D shear wave elastography (2-D-SWE-GE) compared with transient elastography (TE). We included 80 participants with healthy livers and without known liver disease, in whom liver stiffness was evaluated in the same session using two elastographic methods, TE and 2-D-SWE-GE. Reliable LSMs were defined for TE as the median of 10 measurements with a success rate of ≥60% and an interquartile range (IQR) < 30%, and for 2-D-SWE-GE, as the median of 10 measurements acquired in a homogenous area and an IQR < 30%. Participants with LSMs > 6.5 kPa by TE were excluded. Reliable LSMs were obtained in 79 participants (98.7%) by means of 2-D-SWE-GE and in 80 participants (100%) by means of TE (p = 0.9). The mean LSM obtained by 2-D-SWE-GE in our cohort of participants with healthy livers was 5.1 ± 1.3 kPa, which was significantly higher than the LSM assessed by TE (4.3 ± 0.9 kPa, p < 0.0001). In 2-D SWE-GE, mean LSMs were significantly higher for men than for women, 5.9 ± 1.2 kPa versus 4.7 ± 1.2 kPa (p = 0.0005). In conclusion, 2-D-SWE-GE has very good feasibility (98.7%) in healthy persons. The mean LSM determined by 2-D-SWE-GE in healthy participants was 5.1 ± 1.3 kPa. LSMs obtained by means of 2-D-SWE-GE were higher than those obtained by TE in participants with healthy livers.



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Improved detectability of sex steroids from frozen sections of breast cancer tissue using GC-triple quadrupole-MS

Publication date: Available online 18 December 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Ju-Yeon Moon, Keely May McNamara, Jung-Jin Lee, Bong Chul Chung, Hironobu Sasano, Man Ho Choi
Sex steroids in clinical endocrinology have been mainly investigated with peripheral blood and urine samples, while there is limited information regarding the local levels within tissues. To improve analytical properties of sex steroids from trace amounts of tissue samples, two-phase extractive ethoxycarbonlyation and subsequent pentafluoropropionyl derivatization coupled to gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed. The optimized analytical conditions led to excellent chromatographic separation of 15 estrogens, 6 androgens, and 2 progestins. The quantitative results were calculated based on in-house control samples as the steroid-free tissues, and the precision and accuracy were 4.2% − 26.8% and 90.8% − 116.4%, respectively. The on-column limit of quantification was from 180 fg to 0.5 pg for androgens and estrogens, and 1.25 pg for progestins, which were found to be linear (r²> 0 .990). The validated method was then applied to quantify 7 sex steroids from three 100-μm-thick frozen breast tissue slices from postmenopausal patients with breast cancer. This is the first report on the improved GC-MS/MS method for the detection of androgens and pregnenolone from breast cancer tissues, and it can be a useful technique to measure the local levels of sex steroids, thus, enhancing our understanding of the pathophysiological significances of steroidogenesis.

Graphical abstract

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Crescendo Skin Sympathetic Nerve Activity and Ventricular Arrhythmia

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Diagnostic Accuracy of Angiography-Based Quantitative Flow Ratio Measurements for Online Assessment of Coronary Stenosis

AbstractBackground

Quantitative flow ratio (QFR) is a novel angiography-based method for deriving fractional flow reserve (FFR) without pressure wire or induction of hyperemia. The accuracy of QFR when assessed online in the catheterization laboratory has not been adequately examined to date.

Objectives

The goal of this study was to assess the diagnostic performance of QFR for the diagnosis of hemodynamically significant coronary stenosis defined by FFR ≤0.80.

Methods

This prospective, multicenter trial enrolled patients who had at least 1 lesion with a diameter stenosis of 30% to 90% and a reference diameter ≥2 mm according to visual estimation. QFR, quantitative coronary angiography (QCA), and wire-based FFR were assessed online in blinded fashion during coronary angiography and re-analyzed offline at an independent core laboratory. The primary endpoint was that QFR would improve the diagnostic accuracy of coronary angiography such that the lower boundary of the 2-sided 95% confidence interval (CI) of this estimate exceeded 75%.

Results

Between June and July 2017, a total of 308 patients were consecutively enrolled at 5 centers. Online QFR and FFR results were both obtained in 328 of 332 interrogated vessels. Patient- and vessel-level diagnostic accuracy of QFR was 92.4% (95% CI: 88.9% to 95.1%) and 92.7% (95% CI: 89.3% to 95.3%), respectively, both of which were significantly higher than the pre-specified target value (p < 0.001). Sensitivity and specificity in identifying hemodynamically significant stenosis were significantly higher for QFR than for QCA (sensitivity: 94.6% vs. 62.5%; difference: 32.0% [p < 0.001]; specificity: 91.7% vs. 58.1%; difference: 36.1% [p < 0.001]). Positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for QFR were 85.5%, 97.1%, 11.4, and 0.06. Offline analysis also revealed that vessel-level QFR had a high diagnostic accuracy of 93.3% (95% CI: 90.0% to 95.7%).

Conclusions

The study met its prespecified primary performance goal for the level of diagnostic accuracy of QFR in identifying hemodynamically significant coronary stenosis. (The FAVOR [Functional Diagnostic Accuracy of Quantitative Flow Ratio in Online Assessment of Coronary Stenosis] II China study]; NCT03191708)

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Structure and Function of the Left Atrium and Left Atrial Appendage: AF and Stroke Implications

Abstract

Atrial fibrillation (AF) and stroke are important major health problems that share common risk factors and frequently coexist. Left atrial (LA) remodeling is an important underlying substrate for AF and stroke. LA dilation and dysfunction form a prothrombotic milieu characterized by blood stasis and endothelial dysfunction. In addition, alterations of the atrial cardiomyocytes, increase of noncollagen deposits in the interstitial space and fibrosis, favor the occurrence of re-entry that predisposes to AF. Eventually, AF further impairs LA function and promotes LA remodeling, closing a self-perpetuating vicious circle. Multimodality imaging provides a comprehensive evaluation of several aspects of LA remodeling and offers several parameters to identify patients at risk of AF and stroke. How multimodality imaging can be integrated in clinical management of patients at risk of AF and stroke is the focus of the present review paper.

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Comparison of Different Diastolic Resting Indexes to iFR: Are They All Equal?

AbstractBackground

Pressure measurement for the duration of the wave-free period (WFP) is considered essential for resting-state physiological assessment of coronary stenosis severity using the instantaneous wave-free ratio (iFR).

Objectives

The aim of this study was to compare other diastolic resting indexes to iFR.

Methods

In the population of the VERIFY2 (Pd/Pa vs iFR in an Unselected Population Referred for Invasive Angiography) study, iFR calculated by proprietary software (Volcano Harvest, Volcano Corporation, Rancho Cordova, California) was compared with the ratio of resting distal coronary pressure and aortic pressure during the complete duration of diastole (dPR), 25% to 75% of diastole (dPR_25–75), and midpoint of diastole (dPR_mid), along with Matlab calculated iFR (iFR_matlab) and iFR-like indexes shortening the length of the WFP by 50 and 100 ms (iFR_–50ms and iFR_–100ms), respectively. Mutual differences, Spearman correlations, area under the curve values from receiver-operating characteristic analyses, and diagnostic performance with respect to iFR and fractional flow reserve (FFR) were calculated for all indexes.

Results

Median iFR in 197 patients with 257 vessels was 0.91 with an interquartile range of 0.87 to 0.95. The mutual differences (± SD) with iFR were 0.006 ± 0.011 (dPR), 0.001 ± 0.007 (dPR_25–75), 0.001 ± 0.008 (dPR_mid), 0.005 ± 0.009 (iFR_matlab), 0.003 ± 0.008 (iFR_–50ms), and 0.001 ± 0.009 (iFR_–100ms). Correlations for all indexes with iFR were >0.99 (p < 0.001 for all). Area under the curve values for predicting iFR were >0.99 for all indexes as well. Diagnostic accuracy compared with FFR was 76% to 77% for all indexes including iFR.

Conclusions

All diastolic resting indexes tested were identical to iFR, both numerically and with respect to their agreement with FFR. A numerically equal value to iFR can be determined without restriction to the WFP. Cutoff values, guidelines, and clinical recommendations for iFR can therefore be extended to these other indexes. (Pd/Pa vs iFR in an Unselected Population Referred for Invasive Angiography [VERIFY2]; NCT02377310)

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New Valves May Overcome Weaknesses of Transcatheter Aortic Valve Replacement

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Approximate Truth

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Madame President

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Association of Elevated NT-proBNP With Myocardial Fibrosis in the Multi-Ethnic Study of Atherosclerosis (MESA)

AbstractBackground

Serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) is considered a marker that is expressed in response to myocardial strain and possibly fibrosis. However, the relationship to myocardial fibrosis in a community-based population is unknown.

Objectives

The authors evaluated the relationship between cardiac magnetic resonance (CMR) measures of fibrosis and NT-proBNP levels in the MESA (Multi-Ethnic Study of Atherosclerosis) study.

Methods

A total of 1,334 participants (52% white, 23% black, 11% Chinese, 14% Hispanic, and 52% men with a mean age of 67.6 years) at 6 sites had both serum NT-proBNP measurements and CMR with T1 mapping of indices of fibrosis at 1.5 T. Univariate and multivariable regression analyses adjusting for demographics, cardiovascular risk factors, and left ventricular (LV) mass were performed to examine the association of log NT-proBNP with CMR T1 mapping indices.

Results

In the fully adjusted model, each 1-SD increment (0.44 pg/ml) of log NT-proBNP was associated with a 0.62% increment in extracellular volume fraction (p < 0.001), 0.011 increment in partition coefficient (p < 0.001), and 4.7-ms increment in native T1 (p = 0.001). Results remained unchanged after excluding individuals with clinical cardiovascular disease or late gadolinium enhancement (n = 167), and after replacing LV mass by LV end-diastolic volume in the regression models.

Conclusions

Elevated NT-proBNP is related to subclinical fibrosis in a community-based setting. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487)

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JACC Instructions for Authors

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NT-proBNP and Myocardial Fibrosis: The Invisible Link Between Health and Disease

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The Future Role of the United States in Global Health: Emphasis on Cardiovascular Disease

Abstract

U.S. global health investment has focused on detection, treatment, and eradication of infectious diseases such as tuberculosis, malaria, and human immunodeficiency virus/acquired immunodeficiency syndrome, with significant results. Although efforts should be maintained and expanded to provide ongoing therapy for chronic infectious disease, there is a pressing need to meet the challenge of noncommunicable diseases, which constitute the highest burden of diseases globally. A Committee of the National Academies of Sciences, Engineering, and Medicine has made 14 recommendations that require ongoing commitments to eradication of infectious disease and increase the emphasis on chronic diseases such as cardiovascular disease. These include improving early detection and treatment, mitigating disease risk factors, shifting global health infrastructure to include management of cardiovascular disease, developing global partners and private-public ventures to meet infrastructure and funding challenges, streamlining medical product development and supply, increasing research and development capacity, and addressing gaps in global political and institutional leadership to meet the shifting challenge.

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Quality-of-Life After Everolimus-Eluting Stents or Bypass Surgery for Left-Main Disease: Results From the EXCEL Trial

AbstractBackground

The EXCEL (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial compared outcomes in patients with unprotected left main coronary artery disease (LMCAD) treated with coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) using everolimus-eluting stents. Whereas rates of death, stroke, and myocardial infarction were similar at 36 months, event timing and repeat revascularization rates differed by treatment group.

Objectives

To understand the effects of revascularization strategy from the patient's perspective, a prospective quality of life (QoL) substudy was performed alongside the EXCEL trial.

Methods

Between September 2010 and March 2014, 1,905 patients with LMCAD were randomized to undergo CABG or PCI, of whom 1,788 participated in the QoL substudy. QoL was assessed at baseline and 1, 12, and 36 months using the Seattle Angina Questionnaire, the 12-Item Short Form Health Survey, the Rose Dyspnea Scale, the Patient Health Questionnaire-8, and the EQ-5D. Differences between PCI and CABG were assessed using longitudinal random-effect growth curve models.

Results

Over 36 months, both PCI and CABG were associated with significant improvements in QoL compared with baseline. At 1 month, PCI was associated with better QoL than CABG. By 12 months though, these differences were largely attenuated, and by 36 months, there were no significant QoL differences between PCI and CABG.

Conclusions

Among selected patients with LMCAD, both PCI and CABG result in similar QoL improvement through 36 months, although a greater early benefit is seen with PCI. Taken together with the 3-year clinical results of EXCEL, these findings suggest that PCI and CABG provide similar intermediate-term outcomes for patients with LMCAD. (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776)

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Fontan-Associated Liver Disease: Proceedings from the American College of Cardiology Stakeholders Meeting, October 1 to 2, 2015, Washington DC

Abstract

Over the past decade, as the majority of patients with single ventricle anatomy who have undergone the Fontan operation reach adulthood, a newly recognized disease process, Fontan-associated liver disease (FALD), has emerged. FALD is an extracardiac complication that may lead to substantial comorbid disease and premature mortality. The risk factors, pathophysiology, longitudinal consequences, and therapeutic options related to FALD remain poorly defined. Although we recognize that Fontan circulatory properties are associated with extracardiac organ dysfunction, numerous gaps in our understanding of the nature of this relationship exist. Such extracardiac manifestations, in addition to other late complications of the circulation, can significantly affect quality of life and healthcare use. Therefore, to initiate a formal evaluation of FALD, the American College of Cardiology (ACC) sponsored a stakeholders meeting on October 1 to 2, 2015, in Washington, DC. The goal of the meeting was to bring together subspecialty experts in the fields of adult and pediatric hepatology, congenital cardiology (adult congenital and pediatric cardiology), heart failure/transplant, epidemiology, and cardiothoracic surgery, as well as patient advocates, patients, parents of children and young adults who have had the Fontan procedure, and research organizations and societies to discuss the current state of FALD. Topics included gaps in knowledge, optimal care, research opportunities and barriers, and sound practices to guide providers, patients, and families. This report summarizes findings from the stakeholders meeting and seeks to establish a platform for understanding and addressing FALD.

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Patient-Reported Outcomes in Revascularization Decisions for Left-Main Disease: Sharing the EXCELlence

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Who Truly Benefits From Pre-Publishing and Rushing Publishing?: Not Patients, Nor Clinicians

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Self-Expanding Transcatheter Aortic Valve System for Symptomatic High-Risk Patients With Severe Aortic Stenosis

AbstractBackground

The CENTERA transcatheter heart valve (THV) is a low-profile, self-expanding nitinol valve made from bovine pericardial tissue that is 14-F compatible with a motorized delivery system allowing for repositionability.

Objectives

The pivotal study evaluated safety and efficacy of this THV in high–surgical-risk study patients with severe symptomatic aortic stenosis.

Methods

Implantations were completed in 23 centers. Clinical and echocardiographic outcomes were assessed at baseline, discharge, and 30 days. Major events were adjudicated by an independent clinical events committee. Echocardiograms and computed tomography scans were reviewed by core laboratories. The primary endpoint was all-cause mortality at 30 days.

Results

Between March 25, 2015 and July 5, 2016, 203 patients with severe symptomatic aortic stenosis and increased surgical risk, as determined by the heart team, were treated by transfemoral THV implantation (age 82.7 ± 5.5 years, 67.5% female, 68.0% New York Heart Association functional class III/IV). At 30 days, mortality was 1%, disabling stroke occurred in 2.5% of patients, and New York Heart Association functional class I/II was observed in 93.0% of patients. Effective orifice area increased from 0.71 ± 0.20 cm² to 1.88 ± 0.43 cm² (p < 0.001). Mean aortic transvalvular gradient decreased from 40.5 ± 13.2 mm Hg to 7.2 ± 2.8 mm Hg at 30 days post-procedure (p < 0.001). Paravalvular aortic regurgitation at 30 days was moderate or higher in 0.6% of patients. A new permanent pacemaker was implanted in 4.5% of patients receiving the THV (4.9% for patients at risk).

Conclusions

The herein described THV is safe and effective at 30 days with low mortality, significant improvements in hemodynamic outcomes, and low incidence of adverse events. Of particular interest is the low incidence of permanent pacemaker implantations. (Safety and Performance Study of the Edwards CENTERA-EU Self-Expanding Transcatheter Heart Valve [CENTERA-2]; NCT02458560)

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Trimethylamine-N-oxide and Heart Failure With Reduced Versus Preserved Ejection Fraction

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Patient-reported health-related quality of life for men treated with low-dose-rate prostate brachytherapy as monotherapy with 125-iodine, 103-palladium, or 131-cesium: Results of a prospective phase II study

Publication date: Available online 18 December 2017
Source:Brachytherapy
Author(s): Pierre Blanchard, Thomas J. Pugh, David A. Swanson, Usama Mahmood, Hsiang-Chun Chen, Xuemei Wang, William J. Graber, Rajat J. Kudchadker, Teresa Bruno, Thomas Feeley, Steven J. Frank
PurposeTo compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes.Methods and MaterialsPatients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs.ResultsFrom 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively.ConclusionsThe three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance.



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On a Cold Table, How Will They Put Me In?, Rabies

Publication date: Available online 18 December 2017
Source:The Journal of Emergency Medicine
Author(s): Stewart Manley




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Incidental Bony Changes on Infant Chest Radiograph

Publication date: Available online 18 December 2017
Source:The Journal of Emergency Medicine
Author(s): Claire T. Wang, Simon J. Lucio, Michael T. Long




http://ift.tt/2zkGreF

ESTRO ACROP: Technology for precision small animal radiotherapy research: Optimal use and challenges

Publication date: Available online 18 December 2017
Source:Radiotherapy and Oncology
Author(s): Frank Verhaegen, Ludwig Dubois, Stefano Gianolini, Mark A. Hill, Christian P. Karger, Kirsten Lauber, Kevin M. Prise, David Sarrut, Daniela Thorwarth, Christian Vanhove, Boris Vojnovic, Robert Weersink, Jan J. Wilkens, Dietmar Georg
Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more closely than older technology. To facilitate the optimal use of these novel integrated precision irradiators and various small animal imaging devices, and to maximize the impact of the associated research, the ESTRO committee on coordinating guidelines ACROP (Advisory Committee in Radiation Oncology Practice) has commissioned a report to review the state of the art of the technology used in this new field of research, and to issue recommendations. This report discusses the combination of precision irradiation systems, small animal imaging (CT, MRI, PET, SPECT, bioluminescence) systems, image registration, treatment planning, and data processing. It also provides guidelines for reporting on studies.



http://ift.tt/2CWOWMI

Miniaturised electrically actuated high pressure injection valve for portable capillary liquid chromatography

Publication date: 1 April 2018
Source:Talanta, Volume 180
Author(s): Yan Li, Kirsten Pace, Pavel N. Nesterenko, Brett Paull, Roger Stanley, Mirek Macka
A miniaturised high pressure 6-port injection valve has been designed and evaluated for its performance in order to facilitate the development of portable capillary high performance liquid chromatography (HPLC). The electrically actuated valve features a very small size (65 × 19 × 19mm) and light weight (33g), and therefore can be easily integrated in a miniaturised modular capillary LC system suited for portable field analysis. The internal volume of the injection valve was determined as 98 nL. The novel conical shape of the stator and rotor and the spring-loaded rotor performed well up to 32MPa (4641psi), the maximum operating pressure investigated. Suitability for application was demonstrated using a miniaturised capillary LC system applied to the chromatographic separation of a mixture of biogenic amines and common cations. The RSD (relative standard deviation) values of retention times and peak areas of 6 successive runs were 0.5–0.7% and 1.8–2.8% for the separation of biogenic amines, respectively, and 0.1–0.2% and 2.1–3.0% for the separation of cations, respectively. This performance was comparable with bench-top HPLC systems thus demonstrating the applicability of the valve for use in portable and miniaturised capillary HPLC systems.

Graphical abstract

http://ift.tt/2oJn2kz

Systematic review of empirical studies on cyberbullying in adults: What we know and what we should investigate

Publication date: Available online 17 December 2017
Source:Aggression and Violent Behavior
Author(s): Cristina Jenaro, Noelia Flores, Cinthia Patricia Frías
Cyberbullying is a worldwide phenomenon and most of our knowledge comes from studies with adolescent and younger populations. Adult populations have received scarce attention. The present study is a systematic review of empirical academic papers on cyberbullying in the adult population. An online databases search (CINHAL, PsycInfo, ERIC, Medline, Pubmed, and Web of Science) identified 3986 references that, in successive steps, were reduced to 90 studies published between 2004 and 2016 that met the inclusion criteria. Each study was analyzed regarding topic, methods, ages, and other general characteristics. In addition, the measures used to assess cyberbullying, the impact of cyberbullying, and the different roles of those involved in the studies with adult population were explored. Results showed that there is a need for studies conducted in locations other than university settings and that the variety of measures, as well as the different criteria utilized to identify the cyberbullied, cyberbullies, and bystanders makes it difficult to compare findings. There is a need for longitudinal studies and for evidence-based practices to deal with these violent and aggressive behaviors.



http://ift.tt/2CWLVMw

Scholar : New articles have been published for Journal of Natural History, Volume 52, Issue 1-2

The online platform for Taylor & Francis Online content The following articles have been newly published in the issue Journal of Natural History, Volume 52, Issue 1-2 on Taylor & Francis Online: Original Articles The carcinofauna found in stomach contents of the flying gurnard (Dactylopterus volitans) on the continental shelf of the Campos Basin, Brazil Juliana L. Segadilha, Priscila S. Nascimento, Fábio M. Mauro, Cristiana S. Serejo, Taiara R. Ramos, Irene A. Cardoso, Agnaldo S. Martins, Paulo A. S. Costa Pages: 1-11 | DOI: 10.1080/00222933.2017.1401138 A new deep-sea Psammogammarus species (Crustacea: Amphipoda: Eriopisidae) from the continental slope of the SE Gulf of Mexico Manuel Ortiz, Ignacio Winfield, Pedro-Luis Ardisson Pages: 13-28 | DOI: 10.1080/00222933.2017.1401139 The issue is in progress. To view all articles already published in this issue, please visit: http://ift.tt/2zjrfhN Editors' Choice Collection from two Natural History Museum journals! Enjoy free access to this article collection from Systematics and Biodiversity, and the Journal of Systematic Palaeontology. The Editors' have chosen these articles for free access until the end of 2017. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

The Gleason pattern 4 in radical prostatectomy specimens in current practice - Quantification, morphology and concordance with biopsy

Publication date: Available online 18 December 2017
Source:Annals of Diagnostic Pathology
Author(s): Maiara Ferreira de Souza, André Luis Cardoso de Azevedo Araujo, Mariana Trindade da Silva, Daniel Abensur Athanazio
PurposeThe upgrading of a prostate acinar adenocarcinoma grade group 1 (GG1) between needle biopsy and prostatectomy is common. The extent of high-grade tumor and cribriform morphology are currently suggested as prognostic factors.MethodsWe reviewed 159 prostatectomy specimens from a private laboratory and an academic/public institution in Salvador, Bahia.ResultsTumors signed as GG1 at biopsy were upgraded in 59% of all cases. These tumors showed a low frequency of non-focal extraprostatic extension (one case, 3%), extensive positive surgical margins (two cases, 6%) and seminal vesicle invasion (one case, 3%). Among GG2 and GG3 tumors at prostatectomy, the percentage of Gleason pattern 4 (Gp4) involving the gland at ≤1%, 2–5% and >5% was associated with extensive extraprostatic extension (9%, 8% and 42%, respectively) and seminal vesicle invasion (1%, 10% and 31%, respectively). The volume of Gp4 of ≤1ml, >1 to 2ml and >2ml was associated with extensive extraprostatic extension (8%, 26% and 38%, respectively), seminal vesicle invasion (2%, 21% and 33%, respectively) and non-focal positive surgical margins (12%, 26% and 29%, respectively). Some GG2 tumors (~20%) indeed showed at least one measurement of Gp4 higher than one quarter of GG3 carcinomas. Cribriform morphology showed no significant associations for other adverse pathologic prognostic factors.ConclusionUpgrading from GG1 to GG2 is associated with a very low frequency of morphologic features associated with poor prognosis. Routine quantification of Gp4 is feasible in radical prostatectomy products and seems to better stratify tumors regarding the association with other morphologic parameters of prognostic importance.



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Diagnostic difficulties in cases of papillary urothelial neoplasm of low malignant potential, urothelial proliferation of uncertain malignant potential, urothelial dysplasia and urothelial papilloma: A review of current literature

Publication date: Available online 17 December 2017
Source:Annals of Diagnostic Pathology
Author(s): Damian Jaworski, Łukasz Szylberg, Arkadiusz Gzil, Peter Stawinski, Andrzej Marszałek
Tumours of the urinary tract are the fifth most frequent type of cancer. The most common types are urothelial tumours, among which, non-invasive urothelial neoplasms represent 45% of all cases. The 2016 WHO classification of urinary tract tumours introduced new classifications of non-invasive lesions. Besides urothelial papilloma (UP) and papillary urothelial neoplasm of low malignant potential (PUNLMP), as described in the former classification, the new classification also includes new entities such as urothelial proliferation of uncertain malignant potential (UPUMP) and urothelial dysplasia (UD). Of the aforementioned, UPUMP is the lesion that most commonly progresses, but solely to non-invasive carcinomas. UD is associated with a high risk of progression to invasive carcinoma. Understanding the biological character, and establishing the correct differential diagnosis in cases of non-invasive, non-cancerous lesions of the urinary bladder, will be of importance in establishing outcome predictions for future patients. A systematic review of the current literature allows us to systematize genetic, morphologic and prognostic factors of such lesions. Moreover, the collected data provide the basis for a proposed diagnostic algorithm which facilitates quick and effective differential diagnoses in cases of non-invasive non-cancerous urinary bladder lesions.



http://ift.tt/2kEOk66