bluuebunny/crossref_metadata_2025 huggingface dataset:
The Protective Effect of Aucubin fromEucommia ulmoidesAgainst Status Epilepticus by Inducing Autophagy and Inhibiting Necroptosis
Authors: Wang Jin , Li Ying , Huang Wei-Hua , Zeng Xiang-Chang , Li Xiao-Hui , Li Jian , Zhou Jun , Xiao Jian , Xiao Bo , Ouyang Dong-Sheng , Hu Kai
Published: April 2017

Abstract: Eucommia ulmoides Oliv. is a famous traditional Chinese medicine which exhibits anti-oxidative stress ability and neuro-protective effects. Aucubin is the predominant component of Eucommia ulmoides Oliv. Our present study is intended to investigate aucubin’s potential protective effects on neurons against epilepsy in the hippocampus by establishing the lithium-pilocarpine induced status epilepticus (SE) rat model in vivo. Aucubin (at a low dose and a high dose of 5[Formula: see text]mg/kg and 10[Formula: see text]mg/kg, respectively) was administered through gavage for two weeks before lithium-pilocarpine injection. Rats were sacrificed at 4, 24 and 72[Formula: see text]h after SE induction. Pretreatment with both low-dose and high-dose aucubin significantly reduced the number of death neurons ([Formula: see text]) and increased the number of surviving neurons ([Formula: see text]) in DG, Hilus, CA1 and CA3 hippocampal regions post SE. Meanwhile, it significantly inhibited necroptosis proteins (MLKL and RIP-1) ([Formula: see text] or [Formula: see text]) and enhanced autophagy protein (Beclin-1 and LC3BII/LC3BI) prevalence in the hippocampus ([Formula: see text] or [Formula: see text]). In conclusion, aucubin appeared to ameliorate damages in lithium-pilocarpine induced SE in hippocampus, reduce the number of apoptotic neurons, and increased the number of survival neurons by inducing autophagy and inhibiting necroptosis. These original findings might provide an important basis for the further investigation of the therapeutic role of aucubin in treatment or prevention of epilepsy-related neuronal damages.
Sulfated Galactans from Red Seaweed Gracilaria fisheri Target EGFR and Inhibit Cholangiocarcinoma Cell Proliferation
Authors: Sae-Lao Thannicha , Tohtong Rutaiwan , Bates David O. , Wongprasert Kanokpan
Published: April 2017

Cholangiocarcinoma (CCA) is increasing in incidence worldwide and is resistant to chemotherapeutic agents, making treatment of CCA a major challenge. Previous studies reported that natural sulfated polysaccharides (SPs) disrupted growth factor receptor activation in cancer cells. The present study, therefore, aimed at investigating the antiproliferation effect of sulfated galactans (SG) isolated from the red seaweed Gracilaria fisheri (G. fisheri) on CCA cell lines. Direct binding activity of SG to CCA cells, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) were determined. The effect of SG on proliferation of CCA cells was investigated. Cell cycle analyses and expression of signaling molecules associated with proliferation were also determined. The results demonstrated that SG bound directly to EGFR. SG inhibited proliferation of various CCA cell lines by inhibiting EGFR and extracellular signal-regulated kinases (ERK) phosphorylation, and inhibited EGF-induced increased cell proliferation. Cell cycle analyses showed that SG induced cell cycle arrest at the G0/G1 phase, down-regulated cell cycle genes and proteins (cyclin-D, cyclin-E, cdk-4, cdk-2), and up-regulated the tumor suppressor protein P53 and the cyclin-dependent kinase inhibitor P21. Taken together, these data demonstrate that SG from G. fisheri inhibited proliferation of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on EGFR activation and EGFR/ERK signaling pathway. SG presents a potential EGFR targeted molecule, which may be further clinically developed in a combination therapy for CCA treatment.
DIFFUSIVE THREE SPECIES PLANKTON MODEL IN THE PRESENCE OF TOXIC PREY: APPLICATION TO SUNDARBAN MANGROVE WETLAND
Authors: THAKUR NILESH KUMAR , TIWARI S. K. , DUBEY B. , UPADHYAY RANJIT KUMAR
Published: April 2017

The bloom of toxin producing phytoplankton (TPP) is an environmental issue due to its negative impact on fresh water and marine ecology. In this paper, such a phenomenon is modeled using the reaction–diffusion equations. The spatiotemporal interaction among non-toxin producing phytoplankton (NTP), TPP, and zooplankton has been considered with Holling type II and III functional responses. The stability analysis for non-spatial and spatial model system is carried out and numerical simulations are performed for a fixed set of parameter values, which is realistic to planktonic dynamics. It has been observed that on increasing the reduction rate of zooplankton, the system shows cyclic to stable behavior. The result shows that the predators which avoid to toxic prey promote the bloom. Non-Turing patchy pattern has also been observed on time evolution. In this work, we have taken the case study of Sundarban mangrove wetland which is suffering from algal bloom due to the presence of toxic Dinoflagellates and Cyanophyceae. Through the numerical simulation, it has been shown that the higher value of reduction rate of zooplankton ([Formula: see text]) is responsible for bad health of the wetland system.
Acoustical Green’s Function and Boundary Element Techniques for 3D Half-Space Problems
Authors: Piscoya Rafael , Ochmann Martin
Published: April 2017

This paper presents a review of basic concepts of the boundary element method (BEM) for solving 3D half-space problems in a homogeneous medium and in frequency domain. The usual BEM for exterior problems can be extended easily for half-space problems only if the infinite plane is either rigid or soft, since the necessary tailored Green’s function is available. The difficulties arise when the infinite plane has finite impedance. Numerous expressions for the Green’s function have been found which need to be computed numerically. The practical implementation of some of these formulas shows that their application depends on the type of impedance of the plane. In this work, several formulas in frequency domain are discussed. Some of them have been implemented in a BEM formulation and results of their application in specific numerical examples are summarized. As a complement, two formulas of the Green’s function in time domain are presented. These formulas have been computed numerically and after the application of the Fourier Transformation compared with the frequency domain formulas and with a FEM calculation.
ENERGY FLOWS AND BIODIVERSITY IN A MODEL ECOSYSTEM
Authors: ZENG FANQI , WANG WENXU , ZHANG JIANG
Published: April 2017

Climate change has caught great attention. Ecological systems co-evolve with climate systems, thus, understanding the intrinsic dynamics of ecological systems is of paramount importance for exploring and predicting climate change. Food chains, as a systematic and simplistic model, have been a paradigm for investigating the long-term evolution of ecological systems in virtue of the dynamical analysis on the inter-play between the topology and the dynamical processes occurring in a food chain. We build a food chain model by considering energy exchanges among species, which is characterized by using population dynamical equations. We will compare our model with existing food chain models based on sufficiently empirical data. Our work is expected to be able to quantitatively capture and describe the interactions among species with respect to energy exchange, then deepen the understanding of ecological systems and their coevolution with climate change.
Fast Weather Simulation for Inverse Procedural Design of 3D Urban Models
Authors: Garcia-Dorado Ignacio , Aliaga Daniel G. , Bhalachandran Saiprasanth , Schmid Paul , Niyogi Dev
Published: April 2017

We present the first realistic, physically based, fully coupled, real-time weather design tool for use in urban procedural modeling. We merge designing of a 3D urban model with a controlled long-lasting spatiotemporal interactive simulation of weather. Starting from the fundamental dynamical equations similar to those used in state-of-the-art weather models, we present a novel simplified urban weather model for interactive graphics. Control of physically based weather phenomena is accomplished via an inverse modeling methodology. In our results, we present several scenarios of forward design, inverse design with high-level and detailed-level weather control and optimization, and comparisons of our method against well-known weather simulation results and systems.
Phosphatidylcholine transfer protein/StarD2 promotes microvesicular steatosis and liver injury in murine experimental steatohepatitis
Authors: Nicholls Hayley T. , Hornick Jason L. , Cohen David E.
Published: April 2017

Mice fed a methionine- and choline-deficient (MCD) diet develop steatohepatitis that recapitulates key features of nonalcoholic steatohepatitis (NASH) in humans. Phosphatidylcholine is the most abundant phospholipid in the surfactant monolayer that coats and stabilizes lipid droplets within cells, and choline is required for its major biosynthetic pathway. Phosphatidylcholine-transfer protein (PC-TP), which exchanges phosphatidylcholines among membranes, is enriched in hepatocytes. PC-TP also regulates fatty acid metabolism through interactions with thioesterase superfamily member 2. We investigated the contribution of PC-TP to steatohepatitis induced by the MCD diet. Pctp−/−and wild-type control mice were fed the MCD diet for 5 wk and were then euthanized for histopathologic and biochemical analyses, as well as determinations of mRNA and protein expression. Whereas all mice developed steatohepatitis, plasma alanine aminotransferase and aspartate aminotransferase activities were only elevated in wild-type mice, indicating that Pctp−/−mice were protected from MCD diet-induced hepatocellular injury. Reduced hepatotoxicity due to the MCD diet in the absence of PC-TP expression was further evidenced by decreased activation of c-Jun and reduced plasma concentrations of fibroblast growth factor 21. Despite similar total hepatic concentrations of phosphatidylcholines and other lipids, the relative abundance of microvesicular lipid droplets within hepatocytes was reduced in Pctp−/−mice. Considering that the formation of larger lipid droplets may serve to protect against lipotoxicity in NASH, our findings suggest a pathogenic role for PC-TP that could be targeted in the management of this condition.

NEW & NOTEWORTHY Phosphatidylcholine-transfer protein (PC-TP) is a highly specific phosphatidylcholine-binding protein that we previously showed to regulate hepatocellular nutrient metabolism through its interacting partner thioesterase superfamily member 2 (Them2). This study identifies a pathogenic role for PC-TP, independent of Them2, in the methionine- and choline-deficient diet model of experimental steatohepatitis. Our current observations suggest that PC-TP promotes liver injury by mediating the intermembrane transfer of phosphatidylcholines, thus stabilizing more pathogenic microvesicular lipid droplets.
An Optimal Charging Strategy for PV-Based Battery Swapping Stations in a DC Distribution System
Authors: Wu Shengjun , Xu Qingshan , Li Qun , Yuan Xiaodong , Chen Bing
Published: April 2017

Photovoltaic- (PV-) based battery swapping stations (BSSs) utilize a typical integration of consumable renewable resources to supply power for electric vehicles (EVs). The charging strategy of PV-based BSSs directly influences the availability, cost, and carbon emissions of the swapping service. This paper proposes an optimal charging strategy to improve the self-consumption of PV-generated power and service availability while considering forecast errors. First, we introduce the typical structure and operation model of PV-based BSSs. Second, three indexes are presented to evaluate operational performance. Then, a particle swarm optimization (PSO) algorithm is developed to calculate the optimal charging power and to minimize the charging cost for each time slot. The proposed charging strategy helps decrease the impact of forecast uncertainties on the availability of the battery swapping service. Finally, a day-ahead operation schedule, a real-time decision-making strategy, and the proposed PSO charging strategy for PV-based BSSs are simulated in a case study. The simulation results show that the proposed strategy can effectively improve the self-consumption of PV-generated power and reduce charging cost.
Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells
Authors: Yu Dehai , Du Zhonghua , Pian Lingling , Li Tao , Wen Xue , Li Wei , Kim Su-Jeong , Xiao Jialin , Cohen Pinchas , Cui Jiuwei , Hoffman Andrew R. , Hu Ji-Fan
Published: April 2017

Background. Fetal heart can regenerate to restore its normal anatomy and function in response to injury, but this regenerative capacity is lost within the first week of postnatal life. Although the specific molecular mechanisms remain to be defined, it is presumed that aging of cardiac stem or progenitor cells may contribute to the loss of regenerative potential. Methods. To study this aging-related dysfunction, we cultured mesenchymal stem cells (MSCs) from human fetal heart tissues. Senescence was induced by exposing cells to chronic oxidative stress/low serum. Mitochondrial DNA methylation was examined during the period of senescence. Results. Senescent MSCs exhibited flattened and enlarged morphology and were positive for the senescence-associated beta-galactosidase (SA-β-Gal). By scanning the entire mitochondrial genome, we found that four CpG islands were hypomethylated in close association with senescence in MSCs. The mitochondrial COX1 gene, which encodes the main subunit of the cytochrome c oxidase complex and contains the differentially methylated CpG island 4, was upregulated in MSCs in parallel with the onset of senescence. Knockdown of DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B) also upregulated COX1 expression and induced cellular senescence in MSCs. Conclusions. This study demonstrates that mitochondrial CpG hypomethylation may serve as a critical biomarker associated with cellular senescence induced by chronic oxidative stress.
Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin in Pig against Korean Local Isolates ofActinobacillus pleuropneumoniae
Authors: Hossain Md. Akil , Park Hae-chul , Jeong Kyunghun , Jang Yang ho , Kim Dae Gyun , Kang JeongWoo , Lee Kwang-jick
Published: April 2017

The pharmacokinetics of marbofloxacin in pigs after intravenous (i.v.), intramuscular (i.m.), and peroral (p.o.) administration and pharmacokinetic/pharmacodynamic indices of this drug against Korean local isolates ofActinobacillus pleuropneumoniaewere determined in this study. Marbofloxacin (2.50 mg/kg of body weight) was administered, and blood samples were collected with designated time intervals. Plasma-extracted marbofloxacin was injected into the LC-MS/MS system. The in vitro and ex vivo antibacterial activities of marbofloxacin were evaluated against 20 isolates ofA. pleuropneumoniae. The mean peak plasma concentrations (Cmax) after i.v., i.m., and p.o administration were2.60±0.10,2.59±0.12, and2.34±0.12 µg/mL at0.25±0.00,0.44±0.10, and1.58±0.40 h, respectively. The area under the plasma concentration-time curves (AUC0–24) and elimination half-lives were24.80±0.90,25.80±1.40, and23.40±5.00 h·μg/mL and8.60±0.30,12.80±1.10, and8.60±0.00 h, for i.v., i.m., and p.o. administration, correspondingly. The AUC0–24/MICs of marbofloxacin after i.v., i.m., and p.o. administration were253.86±179.91,264.1±187.16, and239.53±169.75 h, respectively. TheCmax/MIC values were26.58±18.84,26.48±18.77, and23.94±16.97, and T>MICs were42.80±1.01,36.40±1.24, and38.60±1.18 h, after i.v., i.m., and p.o. administration, respectively. Thus, marbofloxacin dosage of 2.50 mg/kg of body weight by i.v., i.m., and p.o. administration with 24 h dosing interval will provide effective treatment for the infection of pig byA. pleuropneumonia.
Advanced Age as a Predictor of Survival and Weaning in Venoarterial Extracorporeal Oxygenation: A Retrospective Observational Study
Authors: Lee WooSurng , Kim YoHan , Choi HyunHee , Kim HyoungSoo , Lee SunHee , Lee HeeSung , Chee HyunKeun , Kim JunSeok , Hwang JaeJoon , Lee SongAm , Kim YongHun , Cho SeongJoon , Ryu SeMin , Park SungMin
Published: April 2017

Background. In most reports on ECMO treatment, advanced age is classified as a contraindication to VA ECMO. We attempted to investigate whether advanced age would be a main risk factor deciding VA ECMO application and performing VA ECMO support. We determined whether advanced age should be regarded as an absolute or relative contraindication to VA ECMO and could affect weaning and survival rates of VA ECMO patients.Methods.VA ECMO was performed on 135 adult patients with primary cardiogenic shock between January 2010 and December 2014. Successful weaning was defined as weaning from ECMO followed by survival for more than 48 hours.Results. Among the 135 patients, 35 survived and were discharged uneventfully, and the remaining 100 did not survive. There were significant differences in survival between age groups, and older age showed a lower survival rate with statistical significance (P= .01). By multivariate logistic regression analysis, age was not significantly associated with in-hospital mortality (P= .83) and was not significantly associated with VA ECMO weaning (P= .11).Conclusions.Advanced age is an undeniable risk factor for VA ECMO; however, patients of advanced age should not be excluded from the chance of recovery after VA ECMO treatment.
Interleukin-7 and Immunosenescence
Authors: Nguyen Vanloan , Mendelsohn Andrew , Larrick James W.
Published: April 2017

The age of an individual is an important, independent risk factor for many of the most common diseases afflicting modern societies. Interleukin-7 (IL-7) plays a central, critical role in the homeostasis of the immune system. Recent studies support a critical role for IL-7 in the maintenance of a vigorous healthspan. We describe the role of IL-7 and its receptor in immunosenescence, the aging of the immune system. An understanding of the role that IL-7 plays in aging may permit parsimonious preventative or therapeutic solutions for diverse conditions. Perhaps IL-7 might be used to “tune” the immune system to optimize human healthspan and longevity.
Rapid Identification and Isolation of Inhibitors of Rat Lens Aldose Reductase and Antioxidant inMaackia amurensis
Authors: Kim Set Byeol , Hwang Seung Hwan , Wang Zhiqiang , Yu Jae Myung , Lim Soon Sung
Published: April 2017

Oxidative stress and aldose reductase activity have been implicated in the development of diabetic complications. In this study, the antioxidant and aldose reductase (AR) inhibitory effects ofMaackia amurensis(MA) were investigated. The ethyl acetate fraction of the MA extract showed the highest inhibitory activity in antioxidant and rat lens AR (RLAR). To identify and isolate the active components in the ethyl acetate fraction of the MA extract, high-speed countercurrent chromatography and Sephadex LH-20 column chromatography were performed and guided by an offline HPLC-ABTS assay and HPLC microfractionation AR assay. Four antioxidants, namely, piceatannol (IC50= 6.73 μM), resveratrol (IC50= 11.05 μM),trans-ferulic acid (IC50= 13.51 μM), and chlorogenic acid (IC50= 27.23 μM), and six AR inhibitors, namely, chlorogenic acid (IC50= 4.2 μM), tectoridin (IC50= 50.4 μM), genistein (IC50= 57.1 μM), formononetin (IC50= 69.2 μM), resveratrol (IC50= 117.6 μM), and daidzein (IC50= 151.9 μM), were isolated and identified. The screening results of the offline HPLC-ABTS assay and HPLC microfractionation AR assay matched the activity of isolated compounds. Thus, MA is potentially valuable for antioxidant and AR inhibitor discovery and efficient drug design for the prevention and treatment of diabetic complications.
Multinuclear NMR and MRI Reveal an Early Metabolic Response to mTOR Inhibition in Sarcoma
Authors: Di Gialleonardo Valentina , Aldeborgh Hannah N. , Miloushev Vesselin , Folkers Kelly M. , Granlund Kristin , Tap William D. , Lewis Jason S. , Weber Wolfgang A. , Keshari Kayvan R.
Published: April 2017

Biomarkers predicting rapalog responses in sarcomas where PI3K and mTOR are often hyperactivated could improve the suitable recruitment of responsive patients to clinical trials. PI3K/mTOR pathway activation drives energy production by regulating anaerobic glycolysis in cancer cells, suggesting a route toward a monitoring strategy. In this study, we took a multimodality approach to evaluate the phenotypic effects and metabolic changes that occur with inhibition of the PI3K/mTOR pathway. Its central role in regulating glycolysis in human sarcomas was evaluated by short- and long-term rapamycin treatment in sarcoma cell lines. We observed an overall decrease in lactate production in vitro, followed by cell growth inhibition. In vivo, we observed a similar quantitative reduction in lactate production as monitored by hyperpolarized MRI, also followed by tumor size changes. This noninvasive imaging method could distinguish reduced cell proliferation from induction of cell death. Our results illustrate the use of hyperpolarized MRI as a sensitive technique to monitor drug-induced perturbation of the PI3K/mTOR pathway in sarcomas. Cancer Res; 77(11); 3113–20. ©2017 AACR.
Concomitant B Hairy Cell Leukemia and Mycosis Fungoides in an Elderly Man
Authors: Wong Eric , Mahmood Muhammad N. , Salopek Thomas G.
Published: April 2017

The development of both a T- and B-cell lymphoproliferative disorder in one patient is an unlikely coincidence due to the low prevalence of each malignancy. We report a 65-year-old man with a previously documented history of B hairy cell leukemia, who presented with a new-onset acneiform eruption of his scalp, face, trunk, back, and extremities. Routine pathology of the skin lesions with immunohistochemical stains and molecular studies were consistent with a folliculotropic mycosis fungoides. B hairy cell leukemia and mycosis fungoides occurring in the same patient seems to be a rare phenomenon with only 5 cases reported in the literature.
Inception and Development of the Papanicolaou Stain Method
Authors: Chantziantoniou Nikolaos , Donnelly Amber D. , Mukherjee Maheswari , Boon Mathilde E. , Austin R. Marshall
Published: April 2017

Objective: Cytodiagnoses of specific malignancies are enabled through analyses of abnormal nuclear chromatin and cytoplasmic features in stained cells. Aim: The objective of this work was to explore the inception, development, and chemistry of the Pap stain method introduced in 1942 by Dr. G.N. Papanicolaou. Study Design: To achieve this, we carried out a review of the English literature. Results: Between 1914 and 1933, Papanicolaou first analyzed vaginal squamous cells in guinea pigs and later in human vaginal fluid samples using hematoxylin and eosin with limited color reactions, correlating the cell-type morphology with endocrinology and histology. The 5-dye Pap stain method evolved through 2 salient phases. The first, between 1933 and 1942, saw the introduction of alcohol-ether fixation and aqueous waterblue staining to enhance cellular transparency, aiding the distinction of cervical cancer cells from benign cells, with quantitative and qualitative assessment of squamous cell maturity. The second phase, between 1942 and 1960, saw the introduction and refinement of various alcoholic cytoplasmic counterstaining schemes with orange G and EA (light green, Bismarck brown, eosin) and phosphotungstic acid, allowing wider ranges of polychromasia and further enhancing cellular visualization, facilitating the distinction of cell types and improving diagnostic confidence. Conclusions: Development of the Pap stain method followed specific historical and scientific events. The staining method evolved following incremental improvements in cellular transparency achieved through tailored cellular fixation and cytoplasmic staining using variable dye and pH combinations.
Dexmedetomidine Combined with Therapeutic Hypothermia Is Associated with Cardiovascular Instability and Neurotoxicity in a Piglet Model of Perinatal Asphyxia
Authors: Ezzati Mojgan , Kawano Go , Rocha-Ferreira Eridan , Alonso-Alconada Daniel , Hassell Jane K. , Broad Kevin D. , Fierens Igor , Fleiss Bobbi , Bainbridge Alan , Price David L. , Kaynezhad Pardis , Anderson Brian , Hristova Mariya , Tachtsidis Ilias , Golay Xavier , Gressens Pierre , Sanders Robert D. , Robertson Nicola J.
Published: April 2017

The selective α2-adrenoreceptor agonist dexmedetomidine has shown neuroprotective, analgesic, anti-inflammatory, and sympatholytic properties that may be beneficial in neonatal encephalopathy (NE). As therapeutic hypothermia is only partially effective, adjunct therapies are needed to optimize outcomes. The aim was to assess whether hypothermia + dexmedetomidine treatment augments neuroprotection compared to routine treatment (hypothermia + fentanyl sedation) in a piglet model of NE using magnetic resonance spectroscopy (MRS) biomarkers, which predict outcomes in babies with NE, and immunohistochemistry. After hypoxia-ischaemia (HI), 20 large White male piglets were randomized to: (i) hypothermia + fentanyl with cooling to 33.5°C from 2 to 26 h, or (ii) hypothermia + dexmedetomidine (a loading dose of 2 μg/kg at 10 min followed by 0.028 μg/kg/h for 48 h). Whole-brain phosphorus-31 and regional proton MRS biomarkers were assessed at baseline, 24, and 48 h after HI. At 48 h, cell death was evaluated over 7 brain regions by means of transferase-mediated d-UTP nick end labeling (TUNEL). Dexmedetomidine plasma levels were mainly within the target sedative range of 1 μg/L. In the hypothermia + dexmedetomidine group, there were 6 cardiac arrests (3 fatal) versus 2 (non-fatal) in the hypothermia + fentanyl group. The hypothermia + dexmedetomidine group required more saline (p = 0.005) to maintain blood pressure. Thalamic and white-matter lactate/N-acetylaspartate did not differ between groups (p = 0.66 and p = 0.21, respectively); the whole-brain nucleotide triphosphate/exchangeable phosphate pool was similar (p = 0.73) over 48 h. Cell death (TUNEL-positive cells/mm2) was higher in the hypothermia + dexmedetomidine group than in the hypothermia + fentanyl group (mean 5.1 vs. 2.3, difference 2.8 [95% CI 0.6-4.9], p = 0.036). Hypothermia + dexmedetomidine treatment was associated with adverse cardiovascular events, even within the recommended clinical sedative plasma level; these may have been exacerbated by an interaction with either isoflurane or low body temperature. Hypothermia + dexmedetomidine treatment was neurotoxic following HI in our piglet NE model, suggesting that caution is vital if dexmedetomidine is combined with cooling following NE.
Fetal Aortic Valvuloplasty: Experience and Results of Two Tertiary Centers in Spain
Authors: Galindo Alberto , Gómez-Montes Enery , Gómez Olga , Bennasar Mar , Crispi Fàtima , Herraiz Ignacio , Mendoza Alberto , Escribano David , García-Torres Enrique , Carretero Juan Manuel , Gratacós Eduard , Martínez Josep María
Published: April 2017

Objective: Fetal aortic valvuloplasty (FAV) may avoid progression of critical aortic stenosis (CAS) to hypoplastic left ventricle, improving the options for biventricular circulation (BVC). We describe the results of FAV in 2 referral centers in Spain. Methods: We analyzed all FAVs performed in the period 2007-2015. The selection of candidates, the technique, and postnatal management were made following an agreed protocol. A descriptive analysis of survival, type of circulation after birth, and complications was made, considering all deaths in the first 48 h after FAV as FAV-related. Results: FAV was performed in 28 fetuses at a median gestational age (GA) of 23 weeks (range, 20-32). FAV was technically successful in 22 (78.6%), of whom 11 were born alive and with intention to treat. Eight (72.7%) resulted in BVC and 3 (27.3%) in univentricular circulation. The rate of FAV-related deaths was 32%. These patients underwent FAV earlier than live-born fetuses (median GA at FAV 22 weeks [range, 20.0-25.0] vs. 24.5 weeks [range, 21.0-32.0], respectively, p = 0.031). Conclusions: A significant proportion of fetuses with CAS who undergo technically successful FAV have BVC postnatally. However, FAV implies a high risk of fetal death, which highly depends on the GA at which this intervention is required.
Various Indices of Arterial Stiffness: Are They Closely Related or Distinctly Different?
Authors: Tanaka Hirofumi
Published: April 2017

Arterial stiffness is an independent risk factor for cardiovascular disease. There are a number of techniques and devices that have been developed and utilized to capture the information pertaining to the elasticity of the blood vessel. Almost all the available indices of arterial stiffness are known to increase with advancing age and are elevated in the presence of hypertension and coronary heart disease. It is not known how closely these different measures of arterial stiffness are related to each other. Available evidence indicates that arterial stiffness indices that share a homogeneous methodology appear to demonstrate good correlations. However, there are no significant associations between some measures. These overall results may be surprising considering that all the indices are supposed to reflect the same property of the arterial wall (i.e., arterial elasticity). Interestingly, no or weak correlations between indices of vascular function are not confined only to arterial stiffness and can be extended to endothelial function and vascular reactivity measures.
Simultaneous versus Sequential Intratympanic Steroid Treatment for Severe-to-Profound Sudden Sensorineural Hearing Loss
Authors: Yoo Myung Hoon , Lim Won Sub , Park Joo Hyun , Kwon Joong Keun , Lee Tae-Hoon , An Yong-Hwi , Kim Young-Jin , Kim Jong Yang , Lim Hyun Woo , Park Hong Ju
Published: April 2017

Objectives: Severe-to-profound sudden sensorineural hearing loss (SSNHL) has a poor prognosis. We aimed to compare the efficacy of simultaneous and sequential oral and intratympanic steroids for this condition. Methods: Fifty patients with severe-to-profound SSNHL (>70 dB HL) were included from 7 centers. The simultaneous group (27 patients) received oral and intratympanic steroid injections for 2 weeks. The sequential group (23 patients) was treated with oral steroids for 2 weeks and intratympanic steroids for the subsequent 2 weeks. Pure-tone averages (PTA) and word discrimination scores (WDS) were compared before treatment and 2 weeks and 1 and 2 months after treatment. Treatment outcomes according to the modified American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria were also analyzed. Results: The improvement in PTA and WDS at the 2-week follow-up was 23 ± 21 dB HL and 20 ± 39% in the simultaneous group and 31 ± 29 dB HL and 37 ± 42% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-week follow-up was observed in 26% of the simultaneous group and 30% of the sequential group; this was also not significant. The improvement in PTA and WDS at the 2-month follow-up was 40 ± 20 dB HL and 37 ± 35% in the simultaneous group and 41 ± 25 dB HL and 48 ± 41% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-month follow-up was observed in 33% of the simultaneous group and 35% of the sequential group; this was also not significant. Seven patients in the sequential group did not need intratympanic steroid injections for sufficient improvement after oral steroids alone. Conclusions: Simultaneous oral/intratympanic steroid treatment yielded a recovery similar to that produced by sequential treatment. Because the addition of intratympanic steroids can be decided upon based on the improvement after an oral steroid, the sequential regimen can be recommended to avoid unnecessary intratympanic injections.
Liver in the Chinese and Western Medicine
Authors: Liu Zhan-Wen , Shu Jin , Tu Jia-Ying , Zhang Cui-Hong , Hong Jue
Published: April 2017

Background: The traditional Chinese medicine (TCM) is based on the 5-element theory, which emphasizes the importance of the dynamic balance among the liver, heart, spleen, lung, and kidney. It is quite confusing that the 5 viscera in TCM share the same names with the organs in Western medicine. Spleen is the only viscus that differs most from the modern concept, while the remaining 4 viscera can all find similarities with the corresponding organs in Western medicine; however, the viscus in TCM is always a broader concept. Key Messages: The 5 major functions of the liver in TCM correspond to the nerve-endocrine-immune network in Western medicine, and all of the functions are associated with emotion.
A Modified Tracheal Transaction Approach for the Repair of Nonmalignant Tracheoesophageal Fistulas: A Report of 5 Cases
Authors: Liu Jie , Wu Wei , Liu Shaoyan , Xu Zhengang , Wang Jian , Li Baowei
Published: April 2017

Background: A postintubation tracheoesophageal fistula is a rare complication of a tracheotomy. Surgical repair is the only viable option for these patients, but the repair techniques presented in the literature vary. Methods: We used a modified tracheal transaction approach to repair 5 cases of nonmalignant tracheoesophageal fistulas. The procedure was performed with a low cervical collar incision, and the trachea was transected directly. All the procedures were only carried out in the surgical field created by tracheostomy and paratracheal and esophageal dissection was no longer necessary. The esophageal and tracheal walls were separated. Then, a 2-layer longitudinal suture was used for esophageal reconstruction, and end-to-end anastomosis with excessive cartilage resection was used for tracheal reconstruction. Results: A successful 1-stage repair of both the esophagus and the trachea was achieved in 4 cases. The remaining case had a tracheostomy fistula and required a second-stage reconstruction for a long (5.5 cm) defect of the tracheal membrane. No perioperative complications occurred, and all gastric tubes and tracheostomies were removed within 3 months of surgery. Conclusion: Based on our primary experience, this modified tracheal transection approach can be considered an appropriate choice for the reconstruction of nonmalignant tracheal fistulas.
Gleason Score within Prostate Abnormal Areas Defined by Multiparametric Magnetic Resonance Imaging Did Not Vary According to the PIRADS Score
Authors: Slaoui Hakim , Neuzillet Yann , Ghoneim Tarek , Rouanne Mathieu , Abdou Abdelali , Lugagne-Delpon Pierre Marie , Scherrer Antoine , Radulescu Camelia , Delancourt Christian , Molinié Vincent , Lebret Thierry
Published: April 2017

Background: We aim to correlate multiparametric magnetic resonance imaging (mpMRI) of the prostate reporting (Prostate Imaging Reporting and Data System [PI-RADS] version 2) with the Gleason score into both radical prostatectomy (RP) specimen and MRI fusion-targeted biopsies (FTB). Methods: mpMRI of 74 patients who underwent an RP after FTB were retrospectively reviewed. The Gleason score distribution was compared according to the PI-RADS score using the Kruskal-Wallis test. Results were compared to those of the mpMRI-guided biopsy of the same anatomical zone. For comparison, 903 RP specimen and their corresponding classical biopsies were also reviewed. Cohen's kappa concordance test was used to compare biopsies and prostatectomy specimen analyses. Results: An exact match between Gleason grade in RP specimen and FTB was found in 62% of the cases. There was no significant difference in Gleason score ≤7 (3 + 4) vs. ≥7 (4 + 3) distribution according to the PI-RADS scores (p = 0.096). Overall, Kappa coefficients were similar with MRI-targeted biopsies compared to classical biopsies (κ = 0.378, 95% CI [0.194-0.563], and κ = 0.316, 95% CI [0.259-0.374], respectively). Conclusions: PI-RADS score was not associated with significant differences regarding Gleason score distribution within target. Moreover, concordance of Gleason score in both MRI-targeted and classical biopsies with those within target in RP specimen was weak.
Unusual Case of Laryngeal Squamous Cell Carcinoma with Cervical Metastasis of a Prostatic Adenocarcinoma: A Case Report
Authors: Lauffer David Cédric , Lang Florian Johann Werner , Kueng Marc , Allal Abdelkarim Said
Published: April 2017

Brain and Head and neck metastases are rare in prostatic carcinoma patients. In this report we present a very uncommon case of the concomitant occurrence of a prostatic adenocarcinoma with neck metastases and an advanced laryngeal squamous cell carcinoma without neck metastases. The presence of cervical lymph node prostate adenocarcinoma metastasis concomitantly with a laryngeal squamous cell carcinoma is at least intriguing and may remind us of a rare event called “collision tumors”. In this case we had the metastatization of 1 carcinoma to the site of the drainage of another carcinoma, but we never found the 2 histological types as close as requested to reach the definition of a collision tumor. This emphasizes the need of histological verification of different sites of recurrence when 2 or more primary cancers are known in a patient, particularly when the treatments of those primary cancers vary widely.
Notch Signaling Augments BMP9-Induced Bone Formation by Promoting the Osteogenesis-Angiogenesis Coupling Process in Mesenchymal Stem Cells (MSCs)
Authors: Liao Junyi , Wei Qiang , Zou Yulong , Fan Jiaming , Song Dongzhe , Cui Jing , Zhang Wenwen , Zhu Yunxiao , Ma Chao , Hu Xue , Qu Xiangyang , Chen Liqun , Yu Xinyi , Zhang Zhicai , Wang Claire , Zhao Chen , Zeng Zongyue , Zhang Ruyi , Yan Shujuan , Wu Tingting , Wu Xingye , Shu Yi , Lei Jiayan , Li Yasha , Luu Hue H. , Lee Michael J. , Reid Russell R. , Ameer Guillermo A. , Wolf Jennifer Moriatis , He Tong-Chuan , Huang Wei
Published: April 2017

Background/Aims: Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into several lineages including bone. Successful bone formation requires osteogenesis and angiogenesis coupling of MSCs. Here, we investigate if simultaneous activation of BMP9 and Notch signaling yields effective osteogenesis-angiogenesis coupling in MSCs. Methods: Recently-characterized immortalized mouse adipose-derived progenitors (iMADs) were used as MSC source. Transgenes BMP9, NICD and dnNotch1 were expressed by adenoviral vectors. Gene expression was determined by qPCR and immunohistochem¡stry. Osteogenic activity was assessed by in vitro assays and in vivo ectopic bone formation model. Results: BMP9 upregulated expression of Notch receptors and ligands in iMADs. Constitutively-active form of Notch1 NICD1 enhanced BMP9-induced osteogenic differentiation both in vitro and in vivo, which was effectively inhibited by dominant-negative form of Notch1 dnNotch1. BMP9- and NICD1-transduced MSCs implanted with a biocompatible scaffold yielded highly mature bone with extensive vascularization. NICD1 enhanced BMP9-induced expression of key angiogenic regulators in iMADs and Vegfa in ectopic bone, which was blunted by dnNotch1. Conclusion: Notch signaling may play an important role in BMP9-induced osteogenesis and angiogenesis. It’s conceivable that simultaneous activation of the BMP9 and Notch pathways should efficiently couple osteogenesis and angiogenesis of MSCs for successful bone tissue engineering.
Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma
Authors: Wu Xinchao , Liu Dong , Gao Xuemei , Xie Fei , Tao Dan , Xiao Xingyuan , Wang Liang , Jiang Guosong , Zeng Fuqing
Published: April 2017

Background/Aims: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. Methods: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. Results: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. Conclusions: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.
Mesenteric Fibrosis in Midgut Neuroendocrine Tumors: Functionality and Radiological Features
Authors: Rodríguez Laval Víctor , Pavel Marianne , Steffen Ingo G. , Baur Alexander D. , Dilz Lisa M. , Fischer Christian , Detjen Katharina , Prasad Vikas , Pascher Andreas , Geisel Dominik , Denecke Timm
Published: April 2017

Background: Mesenteric fibrosis (MF) surrounding a lymph node metastasis is a known phenomenon in midgut neuroendocrine tumors (NETs) with characteristic radiological appearance. Its etiology is poorly understood as it affects some but not all midgut NET patients with lymphatic involvement. This study assessed a potential relationship of MF with carcinoid syndrome, urinary 5-hydroxyindoleacetic acid (5-HIAA), and carcinoid heart disease (CHD). Methods: A cohort of 81 patients with pathologically proven NETs with the primary site in the midgut and mesenteric lymphatic metastases on imaging were retrospectively included. Imaging characteristics of lymphatic and hepatic metastases at diagnosis (size, number, burden, and morphologic features, including presence of MF), Ki67 grading, 5-HIAA, functionality, and development of CHD were analyzed. Results: Overall, 54% of patients had MF. The presence of MF was more frequently associated with mesenteric vessel encasement (100 vs. 46% without MF; p < 0.001), presence of hepatic metastases (91 vs. 62%; p = 0.002), larger hepatic tumor burden (15 vs. 5%; p = 0.001), and functionality (86 vs. 43%; p < 0.001). Multivariate analysis revealed 5-HIAA ≥395 µmol/day (p = 0.020), age (p = 0.013), and largest lymphatic metastasis ≥24 mm (p = 0.009) as independent predictors of MF, while functionality (p = 0.098) and CHD (p = 0.070) showed a tendency towards significance. MF was associated with decreased time to development of CHD in functional midgut NETs (p = 0.043). Conclusions: We found a significant association of MF with metastatic patterns and with criteria of functionality. The association of MF with elevated 5-HIAA, and consecutively with carcinoid syndrome and potential development of CHD, suggests a linked pathophysiological mechanism, which might be similar to that of endocardial fibrosis.
Reading and writing: a right of all people
Authors: Azevedo Cleomar
Published: April 2017

For many decades, innumerable failures and high dropout rates – especially during the reading and writing learning process – have been pointed to as some of the main problems of elementary education. Even after several educational system changes, the literacy learning process still maintains a high rate of students who fail to learn how to read and write, and thus remains a prominent concern for the educational system. This issue becomes even more critical in light of the fact that despite new legislation, a contingency of students reach the fourth grade without having at the very least begun the process of written language comprehension, which is to reach the alphabetic hypothesis, in which the student is able to read and write graphically what he thinks and speaks. It is the comprehension of the alphabetic basis logic that provides a platform for understanding this process, so that the same can be developed with quality. The objective of this paper is to reflect on how educators act in relation to this population that is already behind in their reading and writing learning, as they are fourth-grade students who need a different educational program in order to continue their learning. The data and analysis are from a broader study and serve to clear up the relationship between professional practice and the efficacy of the transmission of knowledge related to reading and writing: a right of all people.
O pensamento de Emilia Ferreiro sobre alfabetização
Authors: Mello Maria Cristina de Oliveira
Published: April 2017

Com o objetivo de contribuir para a compreensão de um importante momento da história da alfabetização no Brasil, analisam-se aspectos do pensamento da pesquisadora Emilia Ferreiro (1937 – ) sobre alfabetização, com ênfase em suas concepções a respeito do processo de construção do conhecimento da língua escrita, por parte de crianças, que resultam de sua pesquisa sobre a psicogênese da língua escrita fundamentada na Epistemologia Genética de Jean Piaget e na Psicolinguística de Noam Chomsky e que tiveram significativa repercussão em nosso país, a partir de meados dos anos de 1980. O tema é abordado de uma perspectiva histórica, por meio da utilização de procedimentos de localização, reunião e ordenação da bibliografia disponível de e sobre Emilia Ferreiro e da análise da configuração textual do livro Psicogênese da língua escrita.
A presença dos EUA na obra infantil de Monteiro Lobato
Authors: Penteado J. Roberto Whitaker
Published: April 2017

Besides living in a period in which the United States prevailed economically and politically across the planet, Monteiro Lobato (1882-1948) also showed interest and concern about Brazilian identity and the country’s “lagging behind” its powerful neighbor. His view might have been sparked by the time he spent in that country, between 1926 and 1930, as a consular commercial attaché. An analysis focusing specifically on his children’s books shows the author’s undeniable admiration for the material achievements, American productivity, and often the emphasis placed at that time on its film production. There is also criticism and irony. In general, all “Americanist” remarks are balanced − and even overshadowed − by the true universal character of Lobato’s children’s world, in the almost 5,000 pages the author dedicated to them
Um olhar para as cidades: Richard Morse e a história urbana no Brasil
Authors: Castro Ana Claudia Veiga de
Published: April 2017

Richard Morse, a North-American historian best known for his work Prospero’s Mirror, a comparative study of Anglo-America and Iberian-America published in the 1980s, is also the author of a seminal book on the history of São Paulo: From Community to Metropolis: A Biography of São Paulo, Brazil, first published in 1954 and republished in 1970. This book from his early years was a kind of study platform that allowed Morse to tread a path through the history of cities to understand society from a singular viewpoint. As he became a professor of Latin American History in the United States, Morse privileged in his courses the study of cities, an approach that provided him with access to society from a special angle, providing clues to understanding the Western culture. The main goal of this paper is to shed light on the way Morse devised his courses, to discuss the outcomes of his ideas in the urban historical studies today in Brazil
Monteiro Lobato e os Estados Unidos: espectador, leitor, tradutor
Authors: Martins Milena Ribeiro
Published: April 2017

This text presents and analyzes aspects of the North American culture represented in some of Monteiro Lobato’s critical, fictional and personal texts. The Brazilian writer discusses narratives and ideology of movies; translates and incorporates into his work some themes of written culture; helps to increase the circulation of North American books in Brazil; and also writes comments from the point of view of someone who experienced the America of the late 1920s