bluuebunny/crossref_metadata_2025 huggingface dataset:
Transverse process anatomy as a guide to vertebral artery exposure during anterior cervical spine approach
Authors: Nourbakhsh Ali , Yang Jinping , Mcmahan Howard , Garges Kim
Published: February 2017

Safe exposure of the vertebral artery (VA) is needed during resection of tumors close to the artery and during repair of lacerations. We defined the anatomy of the anterior root of each transverse process (TP) from C3 to C6 for identification and exposure of the VA during the anterior approach. We examined the anatomy of the TP and assessed two approaches for safe identification of the VA, lateral to medial and medial to lateral dissection of the TP, in 20 cadavers. The safe zone at each level of the cervical spine was defined as an area in which the surgeon can start to dissect at the midline of that level on the TP and safely cross the VA laterally. For the lateral to medial approach the surgical safe zone lies between the mid axis of the TPs and a line 2 mm parallel to and above it. The average TP angle was 11 ± 10.2 degrees. The mean distance of the lateral border of the VA from the TP tip was 3.78–5.28 mm. For the medial to lateral approach, staying at the level of the upper vertebral end plate will lead the surgeon to the tip of the TP. From that point, dissection can be carried out as described above. This study examined the anatomy of the TP and defined the approach to expose the VA safely during anterior cervical spine exposure. Clin. Anat. 30:492–497, 2017. © 2017 Wiley Periodicals, Inc.
Helpful aspects of pluralistic therapy for depression
Authors: Antoniou Pavlina , Cooper Mick , Tempier Adrien , Holliday Courtenay
Published: February 2017

Aim

The purpose of this study was to examine clients’ perspectives regarding the helpful aspects of pluralistic therapy for depression.

Method

Thirty‐nine clients received psychological treatment in a multi‐site study exploring alternative interventions to standardised ‘evidence‐based’ approaches. Eighteen of them consented to a face‐to‐face or telephone change interview at the end of their treatment. Change interviews aim to elicit clients’ perspective regarding changes that they noticed during, and after, therapy and also the possible causes of these changes. Their descriptions were transcribed and analysed thematically using explicit coding of themes which were audited by the research team.

Findings

The data were categorised in three a priori domains consisting of specific themes. The first domain constitutes of client‐originated helpful factors including clients’ positive perspectives of therapy, clients’ overall effort to change and clients’ contribution in the decision‐making process of therapy. Therapists were perceived as helpful when they were accepting and respectful, empathic, responding to clients’ needs, making clients feel comfortable, challenging, empowering, using techniques, flexible and reassuring. Treatment outcomes such as change in perspectives, behaviour and response to problems as well as increased insight were also considered helpful factors of therapy.

Conclusion

These findings suggest that clients in pluralistic therapy are active agents of change and their willingness to engage with treatment is crucial. Helping clients feel comfortable by creating a safe therapeutic environment, challenging dysfunctional patterns associated with depression and empowering them to believe that change is possible through reassurance and non‐intrusive guidance were considered beneficial.
Highly Dispersed Nickel Particles Encapsulated in Multi‐hollow Silicalite‐1 Single Crystal Nanoboxes: Effects of Siliceous Deposits and Phosphorous Species on the Catalytic Performances
Authors: Laprune David , Tuel Alain , Farrusseng David , Meunier Frédéric C.
Published: February 2017

Multi‐hollow silicalite‐1 single crystals (MH) were prepared for the first time by an original synthesis pathway by using tetrabutylphosphonium hydroxide (TBPOH) as a mild desilicating agent. This new generation of hierarchical zeolite allowed the encapsulation of nanoparticles (NPs) featuring an enhanced confinement of the metallic guest and a thin wall thickness. The MH catalyst exhibited a better stability for methane steam reforming at 700 °C than a single‐hollow counterpart (SH). Ni average particle size could be kept lower than 4 nm after 20 h on stream for the MH sample. However, a detailed analysis of kinetic data of the structure‐insensitive CO methanation used as a model reaction revealed that the sample activity was adversely affected by two main factors deriving from the preparation steps. First, a siliceous over‐layer derived from the decomposition of intermediate Ni phyllosilicates, which partly covered the resulting Ni nanoparticles. Second, phosphorus from the templates remained in the samples, probably forming a Ni–P compound upon reduction. The overall catalytic activities observed here were therefore a complex interplay of improved dispersion and poisonous effects.
Select noxious stimuli induce changes on corneal nerve morphology
Authors: Hegarty Deborah M. , Hermes Sam M. , Yang Katherine , Aicher Sue A.
Published: February 2017

The surface of the cornea contains the highest density of nociceptive nerves of any tissue in the body. These nerves are responsive to a variety of modalities of noxious stimuli and can signal pain even when activated by low threshold stimulation. Injury of corneal nerves can lead to altered nerve morphology, including neuropathic changes which can be associated with chronic pain. Emerging technologies that allow imaging of corneal nerves in vivo are spawning questions regarding the relationship between corneal nerve density, morphology, and function. We tested whether noxious stimulation of the corneal surface can alter nerve morphology and neurochemistry. We used concentrations of menthol, capsaicin, and hypertonic saline that evoked comparable levels of nocifensive eye wipe behaviors when applied to the ocular surface of an awake rat. Animals were sacrificed and corneal nerves were examined using immunocytochemistry and three‐dimensional volumetric analyses. We found that menthol and capsaicin both caused a significant reduction in corneal nerve density as detected with β‐tubulin immunoreactivity 2 hr after stimulation. Hypertonic saline did not reduce nerve density, but did cause qualitative changes in nerves including enlarged varicosities that were also seen following capsaicin and menthol stimulation. All three types of noxious stimuli caused a depletion of CGRP from corneal nerves, indicating that all modalities of noxious stimuli evoked peptide release. Our findings suggest that studies aimed at understanding the relationship between corneal nerve morphology and chronic disease may also need to consider the effects of acute stimulation on corneal nerve morphology.
Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque
Authors: Soares David , Goldrick Isabelle , Lemon Roger N. , Kraskov Alexander , Greensmith Linda , Kalmar Bernadett
Published: February 2017

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration “thin” spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin‐positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32‐postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons.
Credit of ecological interactions: A new conceptual framework to support conservation in a defaunated world
Authors: Genes Luísa , Cid Bruno , Fernandez Fernando A. S. , Pires Alexandra S.
Published: February 2017

As defaunation spreads through the world, there is an urgent need for restoring ecological interactions, thus assuring ecosystem processes. Here, we define the new concept of credit of ecological interactions, as the number of interactions that can be restored in a focal area by species colonization or reintroduction. We also define rewiring time, as the time span until all the links that build the credit of ecological interactions of a focal area have become functional again. We expect that the credit will be gradually cashed following refaunation in rates that are proportional to (1) the abundance of the reintroduced species (that is expected to increase in time since release), (2) the abundance of the local species that interact with them, and (3) the traits of reintroduced species. We illustrated this approach using a theoretical model and an empirical case study where the credit of ecological interactions was estimated. This new conceptual framework is useful for setting reintroduction priorities and for evaluating the success of conservation initiatives that aim to restore ecosystem services.
Pollinator population size and pollination ecosystem service responses to enhancing floral and nesting resources
Authors: Häussler Johanna , Sahlin Ullrika , Baey Charlotte , Smith Henrik G. , Clough Yann
Published: February 2017

Modeling pollination ecosystem services requires a spatially explicit, process‐based approach because they depend on both the behavioral responses of pollinators to the amount and spatial arrangement of habitat and on the within‐ and between‐season dynamics of pollinator populations in response to land use. We describe a novel pollinator model predicting flower visitation rates by wild central‐place foragers (e.g., nesting bees) in spatially explicit landscapes. The model goes beyond existing approaches by: (1) integrating preferential use of more rewarding floral and nesting resources; (2) considering population growth over time; (3) allowing different dispersal distances for workers and reproductives; (4) providing visitation rates for use in crop pollination models. We use the model to estimate the effect of establishing grassy field margins offering nesting resources and a low quantity of flower resources, and/or late‐flowering flower strips offering no nesting resources but abundant flowers, on bumble bee populations and visitation rates to flowers in landscapes that differ in amounts of linear seminatural habitats and early mass‐flowering crops. Flower strips were three times more effective in increasing pollinator populations and visitation rates than field margins, and this effect increased over time. Late‐blooming flower strips increased early‐season visitation rates, but decreased visitation rates in other late‐season flowers. Increases in population size over time in response to flower strips and amounts of linear seminatural habitats reduced this apparent competition for pollinators. Our spatially explicit, process‐based model generates emergent patterns reflecting empirical observations, such that adding flower resources may have contrasting short‐ and long‐term effects due to apparent competition for pollinators and pollinator population size increase. It allows exploring these effects and comparing effect sizes in ways not possible with other existing models. Future applications include species comparisons, analysis of the sensitivity of predictions to life‐history traits, as well as large‐scale management intervention and policy assessment.
Stem cell registry programme for patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting: what benefits does it derive?
Authors: Nesteruk Julia , Voronina Natalia , Kundt Guenther , Donndorf Peter , Klopsch Christian , Kaminski Alexander , Duckers Henrick J. , Steinhoff Gustav
Published: February 2017

Aims

Standardization of stem cell therapy requires application of appropriate methods to evaluate safety and efficacy, including long‐term pharmacovigilance. To accomplish this objective, a long‐term registry programme was installed.

Methods and results

We analysed 150 patients with ischemic cardiomyopathy, who received intramyocardial CD133+ bone marrow mononuclear stem cell treatment combined with coronary artery bypass grafting (CABG) or CABG alone. The mortality rate, major adverse cerebral and cardiac events, and functional outcome parameters were evaluated for the time period up to 14 years follow‐up. As a result, we have stratified the patient population (96 patients) into responders and non‐responders. Furthermore, the analysis of relevant predictors of good response to CD133+ bone marrow mononuclear stem cell treatment was performed. Several positive tendencies related to stem cells transplantation were demonstrated. First, no significant difference in major adverse cardiovascular and cerebral events was observed between stem cell and control group up to 14 years follow‐up. Second, an improvement of left ventricle ejection fraction (LVEF) in stem cell group retained for 5 years in contrast with CABG‐only group, where no significant changes in LVEF after 2 years were observed. In addition, LVEF under 30% and left ventricle end diastolic diameter above 60 mm were independent predictors of functional response to CD133+ cell therapy.

Conclusions

Participants with overt heart failure benefit most from CABG combined with intramyocardial injection of CD133+ bone marrow mononuclear cell within the group. An improvement LVEF in stem cell group remained for 5 years in contrast with the CABG‐only group. The patients, in whom the improvement of both LVEF and LVED was observed, have benefited by increased life expectancy.
Reduced Graphene Oxide@Mesoporous Silica–Doxorubicin/Hydroxyapatite Inorganic Nanocomposites: Preparation and pH–Light Dual‐Triggered Synergistic Chemo‐Photothermal Therapy
Authors: Yang Ying , Wang Yunlong , Xu Wanghua , Zhang Xiuzhen , Shang Yong , Xie Anjian , Shen Yuhua
Published: February 2017

A new nanocomposite, reduced graphene oxide@mesoporous silica–doxorubicin/hydroxyapatite (rGO@mSiO2‐DOX/HA), was prepared by a simple method under mild conditions. Owing to the relatively high loading capacity of the anticancer drug DOX, the biomimetic capping of nontoxic and pH‐dependent biodegradable HA on the surface of rGO@mSiO2‐DOX, and the efficient photothermal conversion effect of rGO under near‐infrared (NIR) irradiation, the rGO@mSiO2‐DOX/HA nanocomposite provides a lasting and pH–light dual‐triggered drug release. Therefore, the excellent biocompatibility and drug‐permeation ability of the nanocomposite are realized, and synergistic chemo‐photothermal therapy is also achieved. The in vitro experimental results indicate that the chemotherapy of DOX and hyperthermia of rGO under NIR light irradiation killed HeLa cells effectively. Therefore, the new nanocomposite has promising prospects as a nano‐drug‐delivery system and in other biomedical applications because of the pH–light dual‐factor sensitivity and chemo‐photothermal synergistic therapy.
Including root reinforcement variability in a probabilistic 3D stability model
Authors: Cislaghi Alessio , Chiaradia Enrico Antonio , Bischetti Gian Battista
Published: February 2017

Forests play a significant role in protecting people, settlements in mountainous terrains from hydrogeomorphic hazards, including shallow landslides. Although several studies have investigated the interactions between forests and slope instabilities, a full understanding of them has not yet been obtained. Additionally, models that incorporate forest stand properties into slope failure probability analyses have not been developed. In principle, physical‐based models, which are powerful tools for landslide hazard analyses, represent an appropriate approach to linking stand properties and slope stability. However, the reliability of these models depends on numerous parameters that describe highly complex geotechnical and hydrological processes (e.g. potential failure depth, saturation ratio, root reinforcement, etc.) that are difficult to measure and model. In particular, the spatial heterogeneity of root reinforcement remains a problem, and the use of physically based models from a forest management perspective has been limited.

This paper presents a procedure for assessing slope stability in terms of the Factor of Safety that accounts for forest stand characteristics such as tree density, average diameter at breast height and minimum distance between trees. The procedure combines a three‐dimensional (3D) slope stability model with an evaluation of the variability of root reinforcement in terms of a probability distribution, according to forest characteristics. Monte Carlo simulation is used to account for the residual uncertainties in both stand characteristics and 3D stability model parameters.

The proposed method was applied in a subalpine catchment in the Italian Alps, mainly covered by coniferous forest and characterized by steep slopes and high landslide risk. The results suggest that the procedure is highly reliable, according to landslide inventory maps [area under the ROC curve (AUC) is 0.82 and modified success rate (MSR) is 0.70]. Thus, it represents a promising tool for studying the role of root reinforcement in landslide hazard mapping and guiding forest management from a slope stability perspective. Copyright © 2017 John Wiley & Sons, Ltd.
Improved exposure estimation in soil screening and cleanup criteria for volatile organic chemicals
Authors: DeVaull George E
Published: February 2017

Soil cleanup criteria define acceptable concentrations of organic chemical constituents for exposed humans. These criteria sum the estimated soil exposure over multiple pathways. Assumptions for ingestion, dermal contact, and dust exposure generally presume a chemical persists in surface soils at a constant concentration level for the entire exposure duration. For volatile chemicals, this is an unrealistic assumption. A calculation method is presented for surficial soil criteria that include volatile depletion of chemical for these uptake pathways. The depletion estimates compare favorably with measured concentration profiles and with field measurements of soil concentration. Corresponding volatilization estimates compare favorably with measured data for a wide range of volatile and semivolatile chemicals, including instances with and without the presence of a mixed-chemical residual phase. Selected examples show application of the revised factors in estimating screening levels for benzene in surficial soils. Integr Environ Assess Manag 2017;13:861–869. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Key Points

Models for depletion of volatile chemicals from surface soil are developed, compared favorably with measured data, and applied in example estimates of soil screening criteria. Models for volatilization rate from surface soils are developed and compared with a range of measured data including pure chemicals and petroleum mixtures, with and without the presence of a residual organic phase.
Accounting for Private Company Interest Rate Swaps: An Overview With Planning Strategies
Authors: Hollingsworth Danny P. , Trussel John M.
Published: February 2017

The Financial Accounting Standard Board's (FASB) Private Company Council (PCC) was created in 2012 to improve the accounting standard‐setting process for private companies. Due to influence from PCC, the FASB issued Accounting Standards Update No. 2014‐03 in January 2014 to address accounting for interest rate swaps for certain private companies. The issue addressed was the complexity of complying with ASC 815 rules that are highly detailed and difficult to implement. The FASB Update provides an alternative, simplified hedge accounting, for receive‐variable, pay‐fixed interest rate swaps if certain criteria are met. This accounting method allows private companies to more easily classify these interest rate swaps as cash flow hedges, which will reduce income volatility and aid in compliance. This article provides an overview of the provisions of this update and offers planning strategies for maximizing the benefits and minimizing the costs of receive‐variable, pay‐fixed interest rate swaps. © 2017 Wiley Periodicals, Inc.
The Role of c‐SKI in Regulation of TGFβ‐Induced Human Cardiac Fibroblast Proliferation and ECM Protein Expression
Authors: Wang Juan , Guo Liping , Shen Difei , Xu Xiao , Wang Jiaping , Han Suxia , He Wen
Published: February 2017

Cardiac fibrosis is characterized by over‐deposition of extracellular matrix (ECM) proteins and over‐proliferation of cardiac fibroblast, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. Transforming growth factor β 1 (TGFβ1) is as an essential inducing factor of cardiac fibrosis. C‐Ski protein has been identified as an inhibitory regulator of TGFβ signaling. In the present study, we revealed the repressive effect of c‐Ski on TGFβ1‐induced human cardiac fibroblast (HCFB) proliferation and ECM protein increase (Collagen I and α‐SMA). Moreover, miR‐155 and miR‐17 could inhibit SKI mRNA expression by direct binding to the 3′UTR of SKI, so as to reduce c‐Ski protein level. Either miR‐155 inhibition or miR‐17 inhibition could reverse TGFβ1‐induced HCFB proliferation and ECM protein increase. Taken together, we provided a potential therapy to treat cardiac fibrosis by inhibiting miR‐155/miR‐17 so as to restore the repressive effect of c‐Ski on TGFβ1 signaling. J. Cell. Biochem. 118: 1911–1920, 2017. © 2017 Wiley Periodicals, Inc.
Maternal IGF1 and IGF1R polymorphisms and the risk of spontaneous preterm birth
Authors: He Jian‐Rong , Lai Yu‐Mian , Liu Hui‐Hui , Liu Guang‐Jian , li Wei‐Dong , Fan Xue‐Jiao , Wei Xue‐Ling , Xia Xiao‐Yan , Kuang Ya‐Shu , Liu Xiao‐Dan , Chen Nian‐Nian , Lu Jin‐Hua , Chen Qiao‐Zhu , Mai Wei‐Bi , Xia Hui‐Min , Qiu Xiu
Published: February 2017

Background

The insulin‐like growth factor (IGF) pathway was involved in the occurrence of spontaneous preterm birth (SPTB), but little is known regarding the relationship between genetic variations in IGF pathway and the risk of SPTB. We aimed to investigate the associations of IGF1 rs972936 and IGF1 receptor (IGF1R) rs2229765 polymorphisms with SPTB risk in a Chinese population.

Method

A total of 114 cases of SPTB and 250 controls of term delivery were included from Guangzhou Women and Children's Medical Center, China. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated using multivariate logistic regression.

Results

We found that the GA and GA/AA genotypes of IGF1 rs972936 were associated with an increased risk of SPTB, and the adjusted ORs (95% CI) were 1.74 (1.01‐3.02) and 1.75 (1.04‐2.93) respectively. Women carrying GA and GA/AA genotypes of IGF1R rs2229765 had a reduced risk compared to those with the GG genotype (0.60 [0.37‐0.98] and 0.64 [0.40‐1.00] respectively). There were significant interactions between IGF1 rs972936 and GDM status (P for interaction=.02), as well as between IGF1R rs2229765 and pre‐pregnancy BMI (P for interaction <.001) on the risk of SPTB.

Conclusion

Our findings suggest that polymorphisms of IGF1 rs972936 and IGF1R rs2229765 were associated with the risk of SPTB in Chinese pregnant women and these effects depend on the maternal metabolic status.
Application of CRS‐PCR‐RFLP to identify CYP1A1 gene polymorphism
Authors: Ding Mingcui , Duan Xiaoran , Feng Xiaolei , Wang Pengpeng , Wang Wei
Published: February 2017

Background

Cytochrome P4501A1 (CYP1A1) is a member of the cytochrome P450 gene family and plays an important role in the metabolism of exogenous and endogenous material. In recent research, it has been shown that its genetic polymorphisms are associated with many diseases. But the isoschizomers such as the BsrDI enzyme required for the detection of this polymorphism are expensive.

Methods

The study used an improved PCR‐RFLP method with mismatched base for detection of the single‐nucleotide polymorphism rs1048943. A new restriction enzyme cutting site was created by created restriction site PCR (CRS‐PCR), and the restriction enzyme StyI for RFLP was cheaper than other enzymes. A total of 320 samples from Han Chinese were tested to evaluate this novel method. The PCR results were confirmed by DNA sequencing.

Results

After detecting 320 Chinese Han individuals, the genotype frequencies were 63.74% for AA, 31.54% for AG, and 4.72% for GG. The allelic frequencies were 75.48% for A and 24.52% for G. The x2 test showed the genotype and allele frequencies of CYP1A1 do not deviate from Hardy‐Weinberg equilibrium, and the sequences of amplified products were consistent with the one published in GenBank with the exception of mismatched base.

Conclusions

Based on PCR with mismatched primers we designed, the CYP1A1 polymorphism could be identified effectively with low cost.
The relation between international normalized ratio and mortality in acute pulmonary embolism: A retrospective study
Authors: Kırış Tuncay , Yazıcı Selcuk , Durmuş Gündüz , Çanga Yiğit , Karaca Mustafa , Nazlı Cem , Dogan Abdullah
Published: February 2017

Background

Acute pulmonary embolism (PE) is a serious clinical disease characterized by a high mortality rate. The aim of this study was to assess the prognostic value of international normalized ratio (INR) in acute PE patients not on anticoagulant therapy.

Methods

The study included 244 hospitalized acute PE patients who were not receiving previous anticoagulant therapy. Based on their 30‐day mortality, patients were categorized as survivors or non‐survivors. INR was measured during the patients’ admission, on the same day as the diagnosis of PE but before anticoagulation started.

Results

Thirty‐day mortality occurred in 39 patients (16%). INR was higher in non‐survivors than in survivors (1.3±0.4 vs 1.1±0.3, P=.003). In multivariate analysis, INR (HR: 3.303, 95% CI: 1.210–9.016, P=.020) was independently associated with 30‐day mortality from PE. Inclusion of INR in a model with simplified pulmonary embolism severity index (sPESI) score improved the area under the receiver operating characteristics (ROC) curve from 0.736 (95% CI: 0.659‐0.814) to 0.775 (95% CI: 0.701‐0.849) (P=.028). Also, the addition of INR to sPESI score enhanced the net reclassification improvement (NRI=8.8%, P<.001) and integrated discrimination improvement (IDI=0.043, P=.027).

Conclusion

Elevated INR may have prognostic value for 30‐day mortality in acute PE patients not on anticoagulation. Combining INR with sPESI score improved the predictive value for all‐cause mortality. However, further large‐scale studies are needed to confirm it's prognostic role.
Specifics of fetuin‐A levels in distinct types of chronic heart failure
Authors: Lichtenauer Michael , Wernly Bernhard , Paar Vera , Rohm Ilonka , Jung Christian , Yilmaz Atilla , Hoppe Uta C. , Schulze Paul Christian , Kretzschmar Daniel , Pistulli Rudin
Published: February 2017

Introduction

Fetuin‐A has been described to correlate inversely with vascular calcification both in animal models but also in patients with heart and renal disease. In this current study, we sought to investigate whether fetuin‐A might be a useful marker for the discrimination of ischemic (ICM) from dilated cardiomyopathy (DCM).

Methods

A total of 124 non‐consecutive patients were included in this study, 59 patients suffered from ICM and 65 patients from DCM. Serum samples were obtained during out‐patient visits and analyzed for fetuin‐A by ELISA.

Results

Median fetuin‐A concentration in the overall cohort was significantly lower in ICM patients compared to DCM patients (62.2±16.4 μg/mL vs. 129.6±56.6 μg/mL; P<.001). A positive correlation of fetuin‐A levels was found with BMI, cholesterol, LDL/HDL ratio and triglycerides and an inverse correlation with age (r=−.36; P<.001). Moreover, patients suffering from (stable) angina pectoris evidenced lower fetuin‐A levels compared to non‐symptomatic patients (73.1±22.7 μg/mL vs. 83.7±26.2 μg/mL; P=.047)

Conclusions

Fetuin‐A was shown to be a potential discriminator and biomarker for the differential diagnosis between ICM and DCM. Fetuin‐A levels might also be helpful in the process of diagnostic decision‐making in regards to invasive management or medical therapy.
Chrysin induces death of prostate cancer cells by inducing ROS and ER stress
Authors: Ryu Soomin , Lim Whasun , Bazer Fuller W. , Song Gwonhwa
Published: February 2017

Chrysin is a natural flavone found in numerous plant extracts, honey, and propolis that has multiple biological activities including anti‐cancer effects. Understanding of biological mechanisms mediated in response to chrysin in cancerous cells may provide novel insight into chemotherapeutic approaches with reduced side effects in cancers. In the present study, we investigated functional roles of chrysin in progression of prostate cancer cells using DU145 and PC‐3 cell lines. The results showed that chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC‐3 cells in the sub‐G1 phase of the cell cycle. In addition, chrysin reduced expression of proliferating cell nuclear antigen in the prostate cancer cell lines compared to untreated prostate cancer cells. Moreover, chrysin induced loss of mitochondria membrane potential (MMP), while increasing production of reactive oxygen species (ROS) and lipid peroxidation in a dose‐dependent manner. Also, it induced endoplasmic reticulum (ER) stress through activation of unfolded protein response (UPR) proteins including PRKR‐like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α), and 78 kDa glucose‐regulated protein (GRP78) in DU145 and PC‐3 cells. The chrysin‐mediated intracellular signaling pathways suppressed phosphoinositide 3‐kinase (PI3K) and the abundance of AKT, P70S6K, S6, and P90RSK proteins, but stimulated mitogen‐activated protein kinases (MAPK) and activation of ERK1/2 and P38 proteins in the prostate cancer cells. Collectively, these results indicate that chrysin initiates cell death through induction of mitochondrial‐mediated apoptosis and ER stress, and regulation of signaling pathways responsible for proliferation of prostate cancer cells.
Estrogens and androgens inhibit association of RANKL with the pre‐osteoblast membrane through post‐translational mechanisms
Authors: Martin Anthony , Yu Jiali , Xiong Jian , Khalid Aysha B. , Katzenellenbogen Benita , Kim Sung Hoon , Katzenellenbogen John A. , Malaivijitnond Suchinda , Gabet Yankel , Krum Susan A. , Frenkel Baruch
Published: February 2017

We have recently demonstrated that RUNX2 promoted, and 17β‐Estradiol (E2) diminished, association of RANKL with the cell membrane in pre‐osteoblast cultures. Here we show that, similar to E2, dihydrotestosterone (DHT) diminishes association of RANKL, and transiently transfected GFP‐RANKL with the pre‐osteoblast membrane without decreasing total RANKL mRNA or protein levels. Diminution of membrane‐associated RANKL was accompanied with marked suppression of osteoclast differentiation from co‐cultured pre‐osteoclasts, even though DHT increased, not decreased, RANKL concentrations in pre‐osteoblast conditioned media. A marked decrease in membrane‐associated RANKL was observed after 30 min of either E2 or DHT treatment, and near‐complete inhibition was observed by 1 hr, suggesting that the diminution of RANKL membrane association was mediated through non‐genomic mechanisms. Further indicating dispensability of nuclear action of estrogen receptor, E2‐mediated inhibition of RANKL membrane association was mimicked by an estrogen dendrimer conjugate (EDC) that cannot enter the cell nucleus. Finally, the inhibitory effect of E2 and DHT on RANKL membrane association was counteracted by the MMP inhibitor NNGH, and the effect of E2 (and not DHT) was antagonized by the Src inhibitor SU6656. Taken together, these results suggest that estrogens and androgens inhibit osteoblast‐driven osteoclastogenesis through non‐genomic mechanism(s) that entail, MMP‐mediated RANKL dissociation from the cell membrane.
Transforming growth factor β induces bone marrow mesenchymal stem cell migration via noncanonical signals and N‐cadherin
Authors: Dubon Maria Jose , Yu Jinyeong , Choi Sanghyuk , Park Ki‐Sook
Published: February 2017

Transforming growth factor‐beta (TGF‐β) induces the migration and mobilization of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF‐β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration, and mobilization of BM‐MSCs mediated by TGF‐β are unclear. In this study, we showed that TGF‐β activated noncanonical signaling molecules, such as Akt, extracellular signal‐regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF‐β type I receptor in human BM‐MSCs and murine BM‐MSC‐like ST2 cells. Inhibition of Rac1 by NSC23766 and Src by PP2 resulted in impaired TGF‐β‐mediated migration. These results suggested that the Smad‐independent, noncanonical signals activated by TGF‐β were necessary for migration. We also showed that N‐cadherin‐dependent intercellular interactions were required for TGF‐β‐mediated migration using functional inhibition of N‐cadherin with EDTA treatment and a neutralizing antibody (GC‐4 antibody) or siRNA‐mediated knockdown of N‐cadherin. However, N‐cadherin knockdown did not affect the global activation of noncanonical signals in response to TGF‐β. Therefore, these results suggested that the migration of BM‐MSCs in response to TGF‐β was mediated through N‐cadherin and noncanonical TGF‐β signals.
Promotion of cell growth and adhesion of a peptide hydrogel scaffold via mTOR/cadherin signaling
Authors: Wei Guojun , Wang Liping , Dong Daming , Teng Zhaowei , Shi Zuowei , Wang Kaifu , An Gang , Guan Ying , Han Bo , Yao Meng , Xian Cory J.
Published: February 2017

Understanding neurite outgrowth, orientation, and migration is important for the design of biomaterials that interface with the neural tissue. However, the molecular signaling alternations have not been well elucidated to explain the impact of hydrogels on cell morphology. In our previous studies, a silk fibroin peptide (SF16) hydrogel was found to be an effective matrix for the viability, morphology, and proliferation of PC12 rat pheocrhomocytoma cells. We found that PC12 cells in the peptide hydrogel exhibited adhesive morphology compared to those cultured in agarose or collagen. Moreover, we identified that cell adhesion molecules (E‐ and N‐cadherin) controlled by mTOR signaling were highly induced in PC12 cells cultured in the SF16 peptide hydrogel. Our findings suggest that the SF16 peptide might be suitable to be a cell‐adhesion material in cell culture or tissue engineering, and mTOR/cadherin signaling is required for the cell adhesion in the SF16‐peptide hydrogel.
Mitochondria‐targeted esculetin inhibits PAI‐1 levels by modulating STAT3 activation and miR‐19b via SIRT3: Role in acute coronary artery syndrome
Authors: Katta Sujana , Karnewar Santosh , Panuganti Devayani , Jerald Mahesh Kumar , Sastry B. K. S. , Kotamraju Srigiridhar
Published: February 2017

In this study we explored the microRNAs responsible for the regulation of PAI‐1 during LPS‐stimulated inflammation in human aortic endothelial cells and subsequently studied the effect of a newly synthesized mitochondria‐targeted esculetin (Mito‐Esc) that was shown for its anti‐atherosclerotic potential, in modulating PAI‐1 levels and its targeted miRs during angiotensin‐II‐induced atherosclerosis in ApoE−/− mice. LPS‐stimulated PAI‐1 was accompanied with an upregulation of miR‐19b and down‐regulation of miR‐30c. These effects of LPS on PAI‐1 were reversed in the presence of both parent esculetin and Mito‐Esc. However, the effect of Mito‐Esc was more pronounced in the regulation of PAI‐1. In addition, LPS‐stimulated PAI‐1 expression was significantly decreased in cells treated with Anti‐miR‐19b, thereby suggesting that miR‐19b co‐expression plays a key role in PAI‐1 regulation. The results also show that incubation of cells with Stattic, an inhibitor of STAT‐3, inhibited LPS‐stimulated PAI‐1 expression. Interestingly, knockdown of SIRT3, a mitochondrial biogenetic marker, enhanced PAI‐1 levels via modulation of miR‐19b and ‐30c. Mito‐Esc treatment significantly inhibited Ang‐II‐induced PAI‐1, possibly via altering miR‐19b and 30c in ApoE−/− mice. The association between PAI‐1, miR‐19b and ‐30c were further confirmed in plasma and microparticles isolated from patients suffering from acute coronary syndrome of various degrees. Taken together, LPS‐induced PAI‐1 involves co‐expression of miR‐19b and down regulation of miR‐30c, and Mito‐Esc treatment by modulating miR‐19b and miR‐30c through SIRT3 activation, inhibits PAI‐1 levels that, in part, contribute to its anti‐atherosclerotic effects. Moreover, there exists a strong positive correlation between miR‐19b and PAI‐1 in patients suffering from ST‐elevated myocardial infarction.
Palmitate induces mitochondrial superoxide generation and activates AMPK in podocytes
Authors: Lee Eugene , Choi Jin , Lee Hyun Soon
Published: February 2017

Studies have shown that high levels of serum free fatty acids (FFAs) are associated with lipotoxicity and type 2 diabetes. Palmitic acid (PA) is the predominant circulating saturated FFA, yet its role in the pathogenesis of diabetic nephropathy (DN) is not clear. Recently, one study suggested that mitochondrial superoxide production is related to AMP‐activated protein kinase (AMPK) activity in diabetic mice kidneys. To elucidate the link between PA and oxidative stress and AMPK activity in DN, we compared the cultured murine podocytes exposed to PA and oleic acid (OA). Incubation of cells with 250 μM PA or OA induced a translocation of CD36, a fatty acid transport protein, with intracellular lipid accumulation. PA, but not OA, induced mitochondrial superoxide and hydrogen peroxide (H2O2) generation in podocytes, as shown by enhanced fluorescence of MitoSOX Red and dichlorofluorescein (DCF), respectively. Costimulation of PA‐treated cells with the H2O2 scavenger catalase abolished the PA‐induced DCF fluorescence. Only PA induced mitochondrial damage as shown by electron microscopy. The AMPK activity was determined by immunoblotting, measuring the ratio of phosphorylated AMPK (p‐AMPK) to total AMPK. Only PA significantly increased the p‐AMPK levels compared with controls. Addition of catalase to PA‐treated cells did not affect the PA‐stimulated p‐AMPK levels. Collectively, our results indicate that PA induces mitochondrial superoxide and H2O2 generation in cultured podocytes, which may not be directly linked to AMPK activation. Given that, PA seems to play an important role in the pathogenesis of DN through lipotoxicity initiated by mitochondrial superoxide overproduction.
Comparison of culture, single and multiplex real‐time PCR for detection of Sabin poliovirus shedding in recently vaccinated Indian children
Authors: Giri Sidhartha , Rajan Anand K. , Kumar Nirmal , Dhanapal Pavithra , Venkatesan Jayalakshmi , Iturriza‐Gomara Miren , Taniuchi Mami , John Jacob , Abraham Asha Mary , Kang Gagandeep
Published: February 2017

Although, culture is considered the gold standard for poliovirus detection from stool samples, real‐time PCR has emerged as a faster and more sensitive alternative. Detection of poliovirus from the stool of recently vaccinated children by culture, single and multiplex real‐time PCR was compared. Of the 80 samples tested, 55 (68.75%) were positive by culture compared to 61 (76.25%) and 60 (75%) samples by the single and one step multiplex real‐time PCR assays respectively. Real‐time PCR (singleplex and multiplex) is more sensitive than culture for poliovirus detection in stool, although the difference was not statistically significant.
Association of rhinovirus with exacerbations in young children affected by cystic fibrosis: Preliminary data
Authors: Stelzer‐Braid Sacha , Liu Nancy , Doumit Michael , D'Cunha Russell , Belessis Yvonne , Jaffe Adam , Rawlinson William D.
Published: February 2017

Rhinovirus (RV) is a common respiratory viral infection linked to worsening of chronic respiratory diseases including cystic fibrosis (CF) and asthma. RV was tested by RT‐PCR in samples (n = 465) collected from the upper (nasal swab, oropharyngeal suction, and sputum) and lower (bronchoalveolar washings) respiratory tract of 110 children with CF. Air samples (n = 52) collected from the operating theatres and outpatient clinics were tested for RV. RV was found in 43% of children <5 years suffering an exacerbation, and 12% of older children (5‐17 years). RV particles were detected in the air of clinic rooms. Detection of RV is important in better understanding viral infections in patients with CF.
Molecular characterization and clinical epidemiology of human respiratory syncytial virus (HRSV) A and B in hospitalized children, Southern Brazil
Authors: Moreira Francielli B. , Rosario Cristine S. , Santos Jucelia S. , Avanzi Valéria M. , Nogueira Meri Bordignon , Vidal Luine R. , Raboni Sonia Mara
Published: February 2017

Human respiratory syncytial virus (HRSV) is a major etiologic agent of pediatric respiratory infections. Genetic variability of its glycoprotein G enables HRSV to evade the immune response and determines its seasonal dissemination. This study reports genetic variability and clinical profiles of HRSV‐infected patients from Southern Brazil. Seventy positive samples, 78% type A and 22% type B, were analyzed. Of the patients (median age, 6 months; interquartile range, 2‐11 years), 16% had co‐morbidities and 17% developed severe disease. The ON1 HRSV genotype first appeared in 2012, and patients infected with this genotype showed an increased tendency to develop severe disease.
Lab‐in‐a‐tube: Real‐time molecular point‐of‐care diagnostics for influenza A and B using the cobas® Liat® system
Authors: Melchers Willem J.G. , Kuijpers Judith , Sickler Joanna Jackson , Rahamat‐Langendoen Janette
Published: February 2017

Rapid diagnosis of influenza A and B is important for direct treatment decisions in patient care and for the reduction of in‐hospital transmissions. The new real‐time PCR based molecular point‐of‐care (POC) assay, the cobas® Influenza A/B test on the cobas® Liat® System (cobas® Liat® Influenza A/B assay), generated a PCR result in less than 20 min, was evaluated for the detection of influenza A and B. One hundred twenty‐one retrospectively collected respiratory specimens, previously analyzed with a routine influenza A/B test (Diagenode) were tested using the cobas® Liat® Influenza A/B assay. The cobas® Liat® Influenza A/B assay allows influenza A and B testing by RT‐PCR within 20 min. This assay detected influenza A in 51 of 56 samples positive by the Diagenode test. The five discrepant results were retested with the Cepheid Influenza A/B test, confirming two positive cases. All 30 influenza B Diagenode positive samples were found positive by the cobas® Liat® Influenza A/B assay. Control samples (viral negative and non‐influenza pathogens) were all negative by the cobas® Liat® Influenza A/B assay. The cobas® Liat® Influenza A/B assay showed a sensitivity for influenza A/B of 96% and 100%, respectively, and 100% specificity for both targets. The cobas® Liat® Influenza A/B assay is a useful tool for accurate, rapid, and sensitive detection of influenza A and B, offering timely and personalized patient management and infection control when implemented at the point‐of‐care.
Exploration of the Brn4‐regulated genes enhancing adult hippocampal neurogenesis by RNA sequencing
Authors: Guo Jingjing , Cheng Xiang , Zhang Lei , Wang Linmei , Mao Yongxin , Tian Guixiang , Xu Wenhao , Wu Yuhao , Ma Zhi , Qin Jianbing , Tian Meiling , Jin Guohua , Shi Wei , Zhang Xinhua
Published: February 2017

Adult hippocampal neurogenesis is essential for learning and memory, and its dysfunction is involved in neurodegenerative diseases. However, the molecular mechanisms underlying adult hippocampal neurogenesis are still largely unknown. Our previous studies indicated that the transcription factor Brn4 was upregulated and promoted neuronal differentiation of neural stem cells (NSCs) in the surgically denervated hippocampus in rats. In this study, we use high‐throughput RNA sequencing to explore the molecular mechanisms underlying the enhancement of adult hippocampal neurogenesis induced by lentivirus‐mediated Brn4 overexpression in vivo. After 10 days of the lentivirus injection, we found that the expression levels of genes related to neuronal development and maturation were significantly increased and the expression levels of genes related to NSC maintenance were significantly decreased, indicating enhanced neurogenesis in the hippocampus after Brn4 overexpression. Through RNA sequencing, we found that 658 genes were differentially expressed in the Brn4‐overexpressed hippocampi compared with GFP‐overexpressed controls. Many of these differentially expressed genes are involved in NSC division and differentiation. By using quantitative real‐time PCR, we validated the expression changes of three genes, including Ctbp2, Notch2, and Gli1, all of which are reported to play key roles in neuronal differentiation of NSCs. Importantly, the expression levels of Ctbp2 and Notch2 were also significantly changed in the hippocampus of Brn4 KO mice, which indicates that the expression levels of Ctbp2 and Notch2 may be directly regulated by Brn4. Our current study provides a solid foundation for further investigation and identifies Ctbp2 and Notch2 as possible downstream targets of Brn4. © 2017 Wiley Periodicals, Inc.