bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomised safety promotion intervention trial among low-income families with toddlers
Authors: Wang Yan , Gielen Andrea C , Magder Laurence S , Hager Erin R , Black Maureen M
Published: April 2017

Background

Toddler-aged children are vulnerable to unintentional injuries, especially those in low-income families.

Objective

To examine the effectiveness of an intervention grounded in social cognitive theory (SCT) on the reduction of home safety problems among low-income families with toddlers.

Methods

277 low-income mother–toddler dyads were randomised into a safety promotion intervention (n=91) or an attention-control group (n=186). Mothers in the safety promotion intervention group received an eight-session, group-delivered safety intervention targeting fire prevention, fall prevention, poison control and car seat use, through health education, goal-setting and social support. Data collectors observed participants' homes and completed a nine-item checklist of home safety problems at study enrolment (baseline), 6 and 12 months after baseline. A total score was summed, with high scores indicating more problems. Linear mixed models compared the changes over time in home safety problems between intervention and control groups.

Results

The intent-to-treat analysis indicated that the safety promotion intervention group significantly reduced safety problems to a greater degree than the attention-control group at the 12-month follow-up (between-group difference in change over time β=−0.54, 95% CI −0.05 to −1.03, p=0.035), with no significant differences at the 6-month follow-up.

Conclusions

A safety promotion intervention built on principles of SCT has the potential to promote toddlers' home safety environment. Future studies should examine additional strategies to determine whether better penetration/compliance can produce more clinically important improvement in home safety practices.

Trial registration number

NCT02615158; post-results.
Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury
Authors: Tatham Kate Colette , O'Dea Kieran Patrick , Romano Rosalba , Donaldson Hannah Elizabeth , Wakabayashi Kenji , Patel Brijesh Vipin , Thakuria Louit , Simon Andre Rudiger , Sarathchandra Padmini ,   Harefield POPSTAR investigators,, Marczin Nandor , Takata Masao
Published: April 2017

Rationale

Primary graft dysfunction in lung transplant recipients derives from the initial, largely leukocyte-dependent, ischaemia-reperfusion injury. Intravascular lung-marginated monocytes have been shown to play key roles in experimental acute lung injury, but their contribution to lung ischaemia-reperfusion injury post transplantation is unknown.

Objective

To define the role of donor intravascular monocytes in lung transplant-related acute lung injury and primary graft dysfunction.

Methods

Isolated perfused C57BL/6 murine lungs were subjected to warm ischaemia (2 hours) and reperfusion (2 hours) under normoxic conditions. Monocyte retention, activation phenotype and the effects of their depletion by intravenous clodronate-liposome treatment on lung inflammation and injury were determined. In human donor lung transplant samples, the presence and activation phenotype of monocytic cells (low side scatter, 27E10+, CD14+, HLA-DR+, CCR2+) were evaluated by flow cytometry and compared with post-implantation lung function.

Results

In mouse lungs following ischaemia-reperfusion, substantial numbers of lung-marginated monocytes remained within the pulmonary microvasculature, with reduced L-selectin and increased CD86 expression indicating their activation. Monocyte depletion resulted in reductions in lung wet:dry ratios, bronchoalveolar lavage fluid protein, and perfusate levels of RAGE, MIP-2 and KC, while monocyte repletion resulted in a partial restoration of the injury. In human lungs, correlations were observed between pre-implantation donor monocyte numbers/their CD86 and TREM-1 expression and post-implantation lung dysfunction at 48 and 72 hours.

Conclusions

These results indicate that lung-marginated intravascular monocytes are retained as a ‘passenger’ leukocyte population during lung transplantation, and play a key role in the development of transplant-associated ischaemia-reperfusion injury.
Analysis of bovine viral diarrhoea virus: Biobank and sequence database to support eradication in Scotland
Authors: Russell G. C. , Grant D. M. , Lycett S. , Bachofen C. , Caldow G. L. , Burr P. D. , Davie K. , Ambrose N. , Gunn G. J. , Zadoks R. N.
Published: April 2017

Samples from bovine viral diarrhoea virus (BVDV)—positive cattle were gathered by Scottish diagnostic laboratories and used to produce a Biobank of samples with associated location and identification data in support of the Scottish BVDV eradication scheme. The samples were subject to direct amplification and sequencing of the 5′‐untranslated region (5′‐UTR) to define the viral types and subtypes present. From 2693 samples collected prior to 2016, approximately 2300 sequences were obtained, representing 8 BVDV type 1 subtypes. No BVDV type 2 samples were detected. The samples came from all regions of the UK but 66 per cent were from Scotland. Analysis of the sequences showed great diversity in the 5′‐UTR, with 1206 different sequences. Many samples carried virus with identical 5′‐UTR sequences; often from single locations, but there were also examples of the same sequence being obtained from samples at several different locations. This work provides a resource that can be used to analyse the movement of BVDV strains both within Scotland and between Scotland and other nations, particularly in the latter stages of the Scottish eradication programme, and so inform the advice available to both livestock keepers and policymakers.
Ellagic acid protects against neuron damage in ischemic stroke through regulating the ratio of Bcl-2/Bax expression
Authors: Liu Qing-shan , Deng Ran , Li Shuran , Li Xu , Li Keqin , Kebaituli Gulibanumu , Li Xueli , Liu Rui
Published: April 2017

An oxygen-glucose deprivation and reoxygenation model in primary cultured rat cortical neurons was developed for this study to investigate the effects of ellagic acid (EA), a low-molecular-weight polyphenol, on neuron cells and their function, and to evaluate whether EA can be safely utilized by humans as a functional food or therapeutic agent. Administration of EA significantly decreased the volume of cerebrum infarction and the neurological deficit scores of the rats; EA treatment also increased the number of Bcl-2-positive cells and the ratio of Bcl-2-positive to Bax-positive neurons in the semidarkness zone near the brain ischemic focus in the photothrombotic cerebral ischemia model. Treatment of EA resulted in increased neuron viability, cell nuclear integrity, and the ratio of Bcl-2/Bax expression in the primary cultured neuron model; EA treatment also lead to a decrease in the number of apoptotic cells. Our results therefore suggest a specific mechanism for the beneficial effects of EA, providing new insights into how it provides neuroprotection. To the best of our knowledge, these results represent new insights on the mechanisms of the brain cell protective activity of EA. Thus, EA may be used in functional foods or medicines to help treat nerve dysfunction, neurodegenerative disease, and aging.
Paris polyphyllaSuppresses Proliferation and Vasculogenic Mimicry of Human Osteosarcoma Cells and Inhibits Tumor GrowthIn Vivo
Authors: Yao Nan , Ren Ke , Wang Yimin , Jin Qiaomei , Lu Xiao , Lu Yan , Jiang Cuihua , Zhang Dongjian , Lu Jun , Wang Chen , Huo Jiege , Chen Yong , Zhang Jian
Published: April 2017

Paris polyphylla, a traditional antipyretic-detoxicate chinese medicinal herb, has been applied extensively in cancer treatments for nearly 2000 years. The purpose of the present study is to evaluate the potential anti-osteosarcoma effects of Paris polyphylla ethanol extract (PPEE) and to investigate its underlying mechanisms. The antiproliferation activity of PPEE was tested on 143B, MG-63, U-2 OS and hFOB1.19 cells using MTT assay. The pro-apoptotic and cell cycle arrest effects of PPEE were confirmed by Hoechst 33342 staining and flow cytometry. The antimigratory, anti-invasive and antivasculogenic mimicry (VM) effects of PPEE were investigated by wound healing, Transwell and 3D culture assays. Mouse xenograft model was used to examine its anti-osteosarcoma efficacy in vivo. Hematologic profiles and hepatorenal functions were evaluated to assess the toxicity of PPEE. PPEE evidently suppressed cell proliferation of 143B, MG-63 and U-2 OS with IC50 values of 10–60[Formula: see text][Formula: see text]g/mL, but showed little cytotoxicity against normal osteoblastic cell. PPEE promoted apoptosis in 143B cell via caspase activation, increased Bax/Bcl-2 ratio and PARP cleavage. It also induced G2/M phase arrest associated with elevated phosphorylation of CDK1, Cdc25C, Chk2 and down-regulation of cyclin B1, CDK1, Cdc25C expression. Additionally, PPEE inhibited 143B cell migration, invasion and VM formation at noncytotoxic concentrations through decreasing the expression of FAK, Mig-7, MMP2 and MMP9. Finally, daily oral administration of PPEE for four weeks exhibits potent antitumor and anti-VM activity in 143B xenograft model with low toxicity. Taken together, these findings demonstrated PPEE possesses anti-osteosarcoma and anti-VM activity in vitro and in vivo, and therefore is a potential candidate for osteosarcoma treatment.
Proteomic Analysis and Functional Studies of Baicalin on Proteins Associated with Skin Cancer
Authors: Li Dan , Lin Bingjiang , Yusuf Nabiha , Burns Erin M. , Yu Xiuqin , Luo Dan , Min Wei
Published: April 2017

Abundant evidence supports the key role of ultraviolet radiation (UVR) in skin cancer development. The human skin, especially the epidermal layer, is the main defense against UV radiation. Baicalin is a major bioactive component of Scutellaria baicalensis Georgi, a plant which has been found to exhibit antitumor activity. The anticarcinogenic mechanism of baicalin is not completely understood. We have reported that baicalin inhibited UVB-induced photo-damage and apoptosis in HaCaT cells (human skin keratinocytes). The aim of the present study is to investigate the cellular gene targets responsible for baicalin’s antitumor activity by performing two-dimensional electrophoresis liquid chromatography-mass spectrometry/mass spectrometry (2-DE LC-MS/MS) with HaCaT cells following UVB and baicalin exposure. Two-DE for protein separation was performed, followed by matrix-assisted laser desorption/ionization mass spectrometry and database searches. Nucleophosmin (NPM)-specific siRNA was designed and synthesized, and the small interfering RNA was transfected into skin squamous cancer A431 cells to knockdown the NPM expression. Proliferation and cell cycle status were assessed by CCK8 and flow cytometric analyses, respectively. We have identified 38 protein spots that are differentially expressed in HaCaT cells exposed to baicalin and/or UVB irradiation These proteins are involved in detoxification, proliferation, metabolism, cytoskeleton and motility. In particular, we found several proteins that have been linked to tumor progression and resistance, such as NPM. Baicalin treatment reduced the cellular proliferation rate and induced arrest during the S-phase of the cell cycle in A431 cells. NPM1 silencing significantly enhanced the effect of baicalin. Our data indicated that baicalin results in the significant inhibition of tumor growth in the A431 cell line, which may be associated with the regulation of the NPM gene expression.
Research of bubble flow characteristics in microfluidic chip
Authors: Qiu Chao , Cheng Han , Chen Shuxian
Published: April 2017

Bubble is the heart of the microfluidic chip, which takes a significant role in drug release, biological detection and so on. In this case, bubble flow characteristics in microfluidic chip are the key to realize its function. In this paper, bubble flow characteristics in the microfluidic chip have been studied with high speed photography system by controlling the wettability and the heat flux of the microelectrode surface. The result shows that bubble flows faster on the electrode with hydrophobic surface. In addition, loading current to the electrode with hydrophilic surface could also speed up the movement of bubble, and the flow rate of bubble increases with the increasing heat flux of the electrode.
A short proof of the McCoy conjecture in higher-dimensional classical continuous models of Kac types
Authors: Lo Assane
Published: April 2017

We consider the pressure and correlation functions of d-dimensional classical continuous models of Kac type. We prove that if the kth moments of the potential exist, then the system cannot have phase transitions of order lower than k. We also obtain a better formula for the higher derivatives of the pressure that leads to more precise estimates of the truncated correlations.
Precharged Phase Detector with Zero Dead-Zone and Minimal Blind-Zone
Authors: Nikolić Goran , Jovanović Goran , Stojčev Mile , Nikolić Tatjana
Published: April 2017

A precharged CMOS high-performance phase frequency detector (PFD) circuit is presented in this paper. The PFD consists of two identical building blocks. Each PFD block generates UP or DOWN signal and consists of [Formula: see text]- and [Formula: see text]-precharge stages connected in cascade. The proposed PFD circuit has no feedback path and has zero dead-zone in the phase characteristic, what is important in low jitter applications. It also has minimal blind-zone (extended input detection range) close to the limit imposed by the used CMOS technology. The PFD is designed in 0.13[Formula: see text][Formula: see text]m BiCMOS technology and has 1.8[Formula: see text]V supply voltage. The simulation results of blind-zone values are within the range from [Formula: see text] for 1[Formula: see text]GHz up to [Formula: see text] for 8[Formula: see text]GHz. This circuit can be used in applications for high-frequency and low-power delay locked loop and phase locked loop circuits, effectively.
Acoustic Imaging with Compressed Sensing and Microphone Arrays
Authors: Ning Fangli , Liu Yong , Zhang Chao , Wei Jingang , Shi Xudong , Wei Juan
Published: April 2017

This work studies the acoustic imaging problem with compressed sensing (CS) and microphone arrays. The CS algorithm with Basis Pursuit (BP) algorithm has shown satisfying results in acoustic imaging, the maps of which are characterized by super-resolution. However, the performance of the CS algorithm with the BP algorithm is limited to Restricted Isometry Property (RIP), and the algorithm has a long CPU-time. We propose a new CS algorithm with Orthogonal Matching Pursuit (OMP) algorithm for acoustic imaging. The performance of the OMP algorithm with regard to RIP is examined through numerical simulation in this work. The simulation results and CPU-time for OMP algorithm are compared with those of the BP algorithm and the conventional beamformer (CBF). When the RIP does not hold, satisfying results can still be obtained by the OMP algorithm, and the CPU-time for OMP algorithm is far less than BP algorithm. In order to validate the feasibility of the OMP algorithm in acoustic imaging, an experiment is also conducted in a semi-anechoic room. Two mobile phones are served as sound sources. We investigate the mobile phones sources and compare the experimental results with those of BP algorithm and CBF method. The OMP algorithm can locate the main sources at low frequencies, while the CBF method can just give a rough indication and fails for low frequencies due to the width of its main lobe. Due to many reconstructed sources outside of the expected source positions existing on the map, the BP algorithm fails to locate the main sources at low frequencies.
Development of viscometric methods for studying the interaction of various porphyrins with DNA. Part III: Meso-tetra-(3N-alylpyridyl)porphyrin and its Cu-, Co- and Zn-containing derivatives
Authors: Barkhudaryan Vigen G. , Ananyan Gayane V.
Published: April 2017

Present research continues the development of viscometry method for studying porphyrin–DNA interactions.Water soluble cationic meso-tetra-(3[Formula: see text]-alylpyridyl) porphyrin (H2TAlPyP3) and its Cu-, Co- and Zn-containing derivatives were studied using UV-vis absorption spectroscopy and viscometry in order to clarify the effect of chemical structure (presence of double bond in structure of a side radical) of porphyrins and ability to affect the DNA structure. Their binding constant ([Formula: see text] and stoichiometry ([Formula: see text] were determined based on the absorbance spectra for each DNA–porphyrin complex. The results were compared with results of previously conducted similar studies with meso-tetra-(3[Formula: see text]-hydroxyethylpyridyl) porphyrins. It was shown, that the planar porphyrins H2TAlPyP3 and CuTAlPyP3 interact with DNA predominantly by intercalation at low relative concentrations of [Formula: see text](([Formula: see text] [Formula: see text] [Porphyrin]/[DNA])) and by external binding mode at high values of [Formula: see text], whereas the change of chemical structure of peripheral radicals of porphyrins does not absolutely affect on the mechanism of interaction of outside binders CoTAlPyP3 and ZnTAlPyP3 with DNA.
Novel self-assembly with zinc porphyrin via axial coordination for dye-sensitized solar cells
Authors: Wu Yu , Zhang Qian , Liu Jia-Cheng , Li Ren-Zhi , Jin Neng-Zhi
Published: April 2017

Two zinc porphyrins substituted at the meso-positions with different donor units (denoted as ZnP1 and ZnP2) have been designed and synthesized to construct new self-assemblies (denoted as ZnPx-ZnPA) with anchor porphyrin (ZnPA) dyads formed by the coordination bonds of Zn-to-ligand approach. Then these assemblies were absorbed on the semiconducting TiO2 electrode surfaces by the carboxylic groups of anchor porphyrin (ZnPA) to build dye sensitized solar cells. Their spectral properties, electrochemical, theoretical calculations and photovoltaic properties were systematically investigated. Interestingly, these self-assemblies devices compared to monomer anchoring porphyrin device showed higher [Formula: see text] and [Formula: see text]. Especially, the dyad of ester-based zinc porphyrin (ZnP2) assembly device has the highest photoelectric conversion efficiency. The assembled modes of the assemblies immobilized on TiO2 electrode surfaces were also verified by transmission electron microscopy (TEM).
Anterior cerebral blood velocity and end-tidal CO2 responses to exercise differ in children and adults
Authors: Ellis Lindsay A. , Ainslie Philip N. , Armstrong Victoria A. , Morris Laura E. , Simair Ryan G. , Sletten Nathan R. , Tallon Christine M. , McManus Ali M.
Published: April 2017

Little is known about the response of the cerebrovasculature to acute exercise in children and how these responses might differ with adults. Therefore, we compared changes in middle cerebral artery blood velocity (MCAVmean), end-tidal Pco2 ([Formula: see text]), blood pressure, and minute ventilation (V̇e) in response to incremental exercise between children and adults. Thirteen children [age: 9 ± 1 (SD) yr] and thirteen sex-matched adults (age: 25 ± 4 yr) completed a maximal exercise test, during which MCAVmean, [Formula: see text], and V̇e were measured continuously. These variables were measured at rest, at exercise intensities specific to individual ventilatory thresholds, and at maximum. Although MCAVmean was higher at rest in children compared with adults, there were smaller increases in children (1–12%) compared with adults (12–25%) at all exercise intensities. There were alterations in [Formula: see text] with exercise intensity in an age-dependent manner [ F(2.5,54.5) = 7.983, P < 0.001; η2 = 0.266], remaining stable in children with increasing exercise intensity (37–39 mmHg; P > 0.05) until hyperventilation-induced reductions following the respiratory compensation point. In adults, [Formula: see text] increased with exercise intensity (36–45 mmHg, P < 0.05) until the ventilatory threshold. From the ventilatory threshold to maximum, adults showed a greater hyperventilation-induced hypocapnia than children. These findings show that the relative increase in MCAVmean during exercise was attenuated in children compared with adults. There was also a weaker relationship between MCAVmean and [Formula: see text] during exercise in children, suggesting that cerebral perfusion may be regulated by different mechanisms during exercise in the child.

NEW & NOTEWORTHY These findings provide the first direct evidence that exercise increases cerebral blood flow in children to a lesser extent than in adults. Changes in end-tidal CO2 parallel changes in cerebral perfusion in adults but not in children, suggesting age-dependent regulatory mechanisms of cerebral blood flow during exercise.
Pyk2 phosphorylation of VE-PTP downstream of STIM1-induced Ca2+entry regulates disassembly of adherens junctions
Authors: Soni Dheeraj , Regmi Sushil C. , Wang Dong-Mei , DebRoy Auditi , Zhao You-Yang , Vogel Stephen M. , Malik Asrar B. , Tiruppathi Chinnaswamy
Published: April 2017

Vascular endothelial protein tyrosine phosphatase (VE-PTP) stabilizes endothelial adherens junctions (AJs) through constitutive dephosphorylation of VE-cadherin. Here we investigated the role of stromal interaction molecule 1 (STIM1) activation of store-operated Ca2+entry (SOCE) in regulating AJ assembly. We observed that SOCE induced by STIM1 activated Pyk2 in human lung microvascular endothelial cells (ECs) and induced tyrosine phosphorylation of VE-PTP at Y1981. Pyk2-induced tyrosine phosphorylation of VE-PTP promoted Src binding to VE-PTP, Src activation, and subsequent VE-cadherin phosphorylation and thereby increased the endothelial permeability response. The increase in permeability was secondary to disassembly of AJs. Pyk2-mediated responses were blocked in EC-restricted Stim1 knockout mice, indicating the requirement for STIM1 in initiating the signaling cascade. A peptide derived from the Pyk2 phosphorylation site on VE-PTP abolished the STIM1/SOCE-activated permeability response. Thus Pyk2 activation secondary to STIM1-induced SOCE causes tyrosine phosphorylation of VE-PTP, and VE-PTP, in turn, binds to and activates Src, thereby phosphorylating VE-cadherin to increase endothelial permeability through disassembly of AJs. Our results thus identify a novel signaling mechanism by which STIM1-induced Ca2+signaling activates Pyk2 to inhibit the interaction of VE-PTP and VE-cadherin and hence increase endothelial permeability. Therefore, targeting the Pyk2 activation pathway may be a potentially important anti-inflammatory strategy.
Does lack ofglutathione peroxidase 1gene expression exacerbate lung injury induced by neonatal hyperoxia in mice?
Authors: Bouch Sheena , O’Reilly Megan , de Haan Judy B. , Harding Richard , Sozo Foula
Published: April 2017

Supplemental oxygen (O2) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasing glutathione peroxidase 1 ( GPx1) gene expression increases the injurious effects of hyperoxia (Hyp). GPx1+/+and GPx1−/−C57Bl/6J mice were exposed to 21% O2(Air) or 40% O2(Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pulmonary oxidative stress (P7d, P56d), macrophages in lung tissue (P7d), immune cells in bronchoalveolar lavage fluid (BALF; P56d), and GPx1-4 and catalase gene expression in lung tissue (P7d, P56d). On P7d, macrophages were decreased by lack of GPx1 expression and further decreased by hyperoxia. GPx1 expression was increased in GPx1+/+Hyp mice and decreased in both GPx1−/−groups. On P56d, heme oxygenase-1 was increased by hyperoxia when GPx1 was absent. There were significantly more immune cells from Hyp groups than from the GPx1+/+Air group and a greater proportion of lymphocytes in GPx1−/−Hyp mice. GPx1 expression was significantly decreased in GPx1−/−mice; GPx2-4 and catalase expression was increased in GPx1−/−Hyp mice compared with other groups. Tissue fraction was decreased in GPx1−/−Air mice; bronchiolar smooth muscle was decreased in GPx1−/−mice. GPx1 does not clearly exacerbate hyperoxia-induced increases in oxidative stress or lung injury but may alter pulmonary immune function. Increased expression of GPx2-4 and catalase in GPx1−/−Hyp mice suggests gene redundancy within the model.
Sirtuin 7 is decreased in pulmonary fibrosis and regulates the fibrotic phenotype of lung fibroblasts
Authors: Wyman Anne E. , Noor Zahid , Fishelevich Rita , Lockatell Virginia , Shah Nirav G. , Todd Nevins W. , Atamas Sergei P.
Published: April 2017

Pulmonary fibrosis is a severe condition with no cure and limited therapeutic options. A better understanding of its pathophysiology is needed. Recent studies have suggested that pulmonary fibrosis may be driven by accelerated aging-related mechanisms. Sirtuins (SIRTs), particularly SIRT1, SIRT3, and SIRT6, are well-known mediators of aging; however, limited data exist on the contribution of sirtuins to lung fibrosis. We assessed the mRNA and protein levels of all seven known sirtuins in primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in comparison with lung fibroblasts from healthy controls. These unbiased tests revealed a tendency for all sirtuins to be expressed at lower levels in fibroblasts from patients compared with controls, but the greatest decrease was observed with SIRT7. Similarly, SIRT7 was decreased in lung tissues of bleomycin-challenged mice. Inhibition of SIRT7 with siRNA in cultured lung fibroblasts resulted in an increase in collagen and α-smooth muscle actin (α-SMA). Reciprocally, overexpression of SIRT7 resulted in lower basal and TGF-β-induced levels of COL1A1, COL1A2, COL3A1, and α-SMA mRNAs, as well as collagen and α-SMA proteins. Induced changes in SIRT7 had no effect on endogenous TGF-β mRNA levels or latent TGF-β activation, but overexpression of SIRT7 reduced the levels of Smad3 mRNA and protein. In conclusion, the decline in SIRT7 in lung fibroblasts has a profibrotic effect, which is mediated by changes in Smad3 levels.
Acidosis increases the susceptibility of respiratory epithelial cells toPseudomonas aeruginosa-induced cytotoxicity
Authors: Torres Iviana M. , Demirdjian Sally , Vargas Jennifer , Goodale Britton C. , Berwin Brent
Published: April 2017

Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Pseudomonas aeruginosa. Our findings support the idea that acidosis in the context of P. aeruginosa infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during P. aeruginosa infection demonstrates that cytotoxicity is dependent on the acidosis. Investigation of the underlying mechanisms revealed that host cell cytotoxicity correlated with increased bacterial survival during an acidic infection that was due to reduced bactericidal activity of host-derived antimicrobial peptides. These findings extend previous reports that the activities of antimicrobial peptides are pH-dependent and provide novel insights into the consequences of acidosis on infection-derived pathology. Therefore, this report provides the first evidence that physiological levels of acidosis increase the susceptibility of epithelial cells to acute Pseudomonas infection and demonstrates the benefit of maintaining pH homeostasis during a bacterial infection.
Robust Nonnegative Matrix Factorization via Joint Graph Laplacian and Discriminative Information for Identifying Differentially Expressed Genes
Authors: Dai Ling-Yun , Feng Chun-Mei , Liu Jin-Xing , Zheng Chun-Hou , Yu Jiguo , Hou Mi-Xiao
Published: April 2017

Differential expression plays an important role in cancer diagnosis and classification. In recent years, many methods have been used to identify differentially expressed genes. However, the recognition rate and reliability of gene selection still need to be improved. In this paper, a novel constrained method named robust nonnegative matrix factorization via joint graph Laplacian and discriminative information (GLD-RNMF) is proposed for identifying differentially expressed genes, in which manifold learning and the discriminative label information are incorporated into the traditional nonnegative matrix factorization model to train the objective matrix. Specifically,L2,1-norm minimization is enforced on both the error function and the regularization term which is robust to outliers and noise in gene data. Furthermore, the multiplicative update rules and the details of convergence proof are shown for the new model. The experimental results on two publicly available cancer datasets demonstrate that GLD-RNMF is an effective method for identifying differentially expressed genes.
Effect of Taichi Softball on Function‐Related Outcomes in Older Adults: A Randomized Control Trial
Authors: Lou Lin , Zou Liye , Fang Qun , Wang Huiru , Liu Yang , Tian Zuguo , Han Yunpeng
Published: April 2017

The purpose of this present study was to examine the effect of Taichi softball (TCSB) on physical function in Chinese older adults. Eighty Chinese older adults were randomly assigned into either an experimental group experiencing four 90‐minute TCSB sessions weekly for seven consecutive weeks or a control group. At baseline and 7 weeks later, all participants were asked to perform physical functional tests for both lower and upper limbs. Multiple separate Analyses of Variance (ANOVA) with repeated measures were applied to evaluate the effects of TCSB on function‐related outcomes between baseline and postintervention in the two groups. The findings indicate that a short‐term and intensive TCSB training program does not only improve low limb‐related physical function such as dynamic balance and leg strength, but also strengthen upper limb‐related physical function (e.g., arm and forearm strength, shoulder mobility, fine motor control, handgrip strength, and fine motor function). Health professionals could take into account TCSB exercise as an alternative method to help maintain or alleviate the inevitable age‐related physical function degeneration in healthy older adults. In addition, researchers could investigate the effect of TCSB exercise on physical function in special populations such as patients with different chronic diseases or neurological disorder (e.g., Parkinson’s disease).
Contrast of Backscattered Electron SEM Images of Nanoparticles on Substrates with Complex Structure
Authors: Kowoll Thomas , Müller Erich , Fritsch-Decker Susanne , Hettler Simon , Störmer Heike , Weiss Carsten , Gerthsen Dagmar
Published: April 2017

This study is concerned with backscattered electron scanning electron microscopy (BSE SEM) contrast of complex nanoscaled samples which consist of SiO2 nanoparticles (NPs) deposited on indium-tin-oxide covered bulk SiO2 and glassy carbon substrates. BSE SEM contrast of NPs is studied as function of the primary electron energy and working distance. Contrast inversions are observed which prevent intuitive interpretation of NP contrast in terms of material contrast. Experimental data is quantitatively compared with Monte-Carlo- (MC-) simulations. Quantitative agreement between experimental data and MC-simulations is obtained if the transmission characteristics of the annular semiconductor detector are taken into account. MC-simulations facilitate the understanding of NP contrast inversions and are helpful to derive conditions for optimum material and topography contrast.
Gastrointestinal Stromal Tumor Induced Hypercalcemia
Authors: Barbaryan Aram , Bailuc Stefania , Poddutoori Padma , Richardson Aida , Mirrakhimov Aibek E.
Published: April 2017

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D3mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D3. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor described in literature resulting in hypercalcemia. In our case, the mechanism of hypercalcemia was thought to be related to overproduction of 1,25-dihydroxyvitamin by tumor cells. The patient had a favorable response to imatinib with normalization of serum calcium level. Unfortunately, she developed fluid retention due to imatinib which was discontinued resulting in relapse of hypercalcemia that was resistant to all other treatment options.
HIF1A(rs11549465) andAKNA(rs10817595) Gene Polymorphisms Are Associated with Primary Sjögren’s Syndrome
Authors: Hernández-Molina Gabriela , Rodríguez-Pérez José Manuel , Fernández-Torres Javier , Lima Guadalupe , Pérez-Hernández Nonanzit , López-Reyes Alberto , Martínez-Nava Gabriela Angélica
Published: April 2017

Objective. To evaluate the allele and genotype frequencies of polymorphic sites ofHIF1AandANKAgenes in primary Sjögren’s syndrome (pSS).Methods. We included 110 patients with pSS and 141 ethnically matched healthy controls. ThreeHIF1Agene polymorphisms(Pro582Ser,Ala588Thr, andC191T)and twoAKNA genepolymorphisms(−1372C>AandPro624Leu)were genotyped using TaqMan probes in a Real-Time PCR instrument. Associations between pSS and genotypes, alleles, and inheritance models of the SNPs of interest were evaluated by logistic regression adjusted by age and gender.Results. TheC/Tgenotype and theTallele of theHIF1A Pro582Serpolymorphism protected against pSS (OR = 0.22; 95% CI = 0.09–0.52;P<0.01; OR = 0.26; 95% CI = 0.12–0.58;P<0.01, resp.), whereas under a recessive model adjusted by age and gender, theAKNA −1372C>Apolymorphism A/A genotype was associated with an increased risk of pSS (OR = 2.60; 95% CI = 1.11–6.12;P=0.03).Conclusions. We identifiedHIF1A Pro582SerTallele andC/Tgenotype as well asAKNA −1372C>Apolymorphism A/A genotype as genetic factors associated with pSS. Further studies in other populations are needed to validate our findings and research is warranted in order to shed some light on their functional implications across biological pathways in this disease.
Plasma Circulating Tumor DNA Levels for the Monitoring of Melanoma Patients: Landscape of Available Technologies and Clinical Applications
Authors: Busser Benoit , Lupo Julien , Sancey Lucie , Mouret Stéphane , Faure Patrice , Plumas Joel , Chaperot Laurence , Leccia Marie Thérèse , Coll Jean Luc , Hurbin Amandine , Hainaut Pierre , Charles Julie
Published: April 2017

Melanoma is a cutaneous cancer with an increasing worldwide prevalence and high mortality due to unresectable or metastatic stages. Mutations inBRAF,NRAS, orKITare present in more than 60% of melanoma cases, but a useful blood-based biomarker for the clinical monitoring of melanoma patients is still lacking. Thus, the analysis of circulating tumor cells (CTCs) and/or cell-free circulating tumor DNA (ctDNA) analysis from blood (liquid biopsies) appears to be a promising noninvasive, repeatable, and systemic sampling tool for detecting and monitoring melanoma. Here, we review the molecular biology-based strategies used for ctDNA quantification in melanoma patients, as well as their main clinical applications. Droplet digital PCR (ddPCR) and next generation sequencing (NGS) technologies appear to be two versatile and complementary strategies to study rare variant mutations for the detection and monitoring of melanoma progression. Among the different clinical uses of ctDNA, we highlight the assessment of molecular heterogeneity and the identification of genetic determinants for targeted therapy as well as the analysis of acquired resistance. Importantly, ctDNA quantification might also be a novel biomarker with a prognostic value for melanoma patients.
A Study on Vehicle Connectivity for VANETs Adopting Beamforming Antenna Array
Authors: Yang Liu , Xiang Weidong , Zheng Guoxin
Published: April 2017

An analytical mobility model based on Erlang distribution is introduced to portray sparse and dense traffic scenarios in the distributions of time headway. Upon the mobility model, the connectivity probability is then derived in two‐way highway when adopting store‐forward strategy. Moreover, path losses with and without beamforming antenna array are compared to further study the connectivity under different traffic density scenarios. Meanwhile, the effectiveness of beamforming technology in Vehicular Ad hoc Networks (VANETs) is investigated and concluded through analytical study and simulations.
Recent Progress in Research on the Pathogenesis of Pulmonary Thromboembolism: An Old Story with New Perspectives
Authors: Yan Chao , Wang Xiaohua , Su Hua , Ying Kejing
Published: April 2017

Pulmonary thromboembolism (PTE) is part of a larger clinicopathological entity, venous thromboembolism. It is also a complex, multifactorial disorder divided into four major disease processes including venous thrombosis, thrombus in transit, acute pulmonary embolism, and pulmonary circulation reconstruction. Even when treated, some patients develop chronic thromboembolic pulmonary hypertension. PTE is also a common fatal type of pulmonary vascular disease worldwide, but earlier studies primarily focused on the pathological changes in the blood component of the disease. With contemporary advances in molecular and cellular biology, people are becoming increasingly aware of coagulation pathways, the function of vascular smooth muscle cells, microparticles, and the inflammatory pathways that play key roles in PTE. Combined hypoxia and immune research has revealed that PTE should be regarded as a class of complex diseases caused by multiple factors involving the vascular microenvironment and vascular cell dysfunction.
Gene Expression Profiling of the Optic Nerve Head of Patients with Primary Open-Angle Glaucoma
Authors: Wang Xinrong , Gong Ke , Li Haiyan , Wang Congyi , Qu Chaoyi , Li Hui
Published: April 2017

Background. The pressure-induced axonal injury of the vulnerable ONH has led many researchers to view glaucoma from the perspective of the genetic basis of the angle of the ONH. However, genetic studies on POAG from this perspective are limited.Methods. Microarray dataset GSE45570 of the ONH of healthy individuals and POAG patients were downloaded from the Gene Expression Omnibus. After screening for the DEGs using the limma package, enrichment analysis was performed using DAVID. The DEG interaction network was constructed using cancer spider at BioProfiling.de. Thereafter, DEG-related TFs were predicted using TRANSFAC, and TF-DEG regulatory networks were visualized using Cytoscape.Results. Thirty-one DEGs were identified including 11 upregulated and 20 downregulated DEGs. Thereafter, gene ontology terms of nucleosome assembly, sensory perception and cognition, and pathway of signaling by GPCR were found to be enriched among the DEGs. Furthermore, DEG interaction and TF-DEG networks were constructed. NEUROD1 was present in both the DEG network and the TF-DEG network as the node with the highest degree and was predicted as a marker gene in the ONH of patients with POAG.Conclusion. NEUROD1 may contribute greatly to the ONH of patients with POAG and was found to be involved in eye development and diseases.
Maximum Lateness Scheduling on Two-Person Cooperative Games with Variable Processing Times and Common Due Date
Authors: Liu Peng , Wang Xiaoli
Published: April 2017

A new maximum lateness scheduling model in which both cooperative games and variable processing times exist simultaneously is considered in this paper. The job variable processing time is described by an increasing or a decreasing function dependent on the position of a job in the sequence. Two persons have to cooperate in order to process a set of jobs. Each of them has a single machine and their processing cost is defined as the minimum value of maximum lateness. All jobs have a common due date. The objective is to maximize the multiplication of their rational positive cooperative profits. A division of those jobs should be negotiated to yield a reasonable cooperative profit allocation scheme acceptable to them. We propose the sufficient and necessary conditions for the problems to have positive integer solution.
Sulphurous Mineral Waters: New Applications for Health
Authors: Carbajo Jose Manuel , Maraver Francisco
Published: April 2017

Sulphurous mineral waters have been traditionally used in medical hydrology as treatment for skin, respiratory, and musculoskeletal disorders. However, driven by recent intense research efforts, topical treatments are starting to show benefits for pulmonary hypertension, arterial hypertension, atherosclerosis, ischemia‐reperfusion injury, heart failure, peptic ulcer, and acute and chronic inflammatory diseases. The beneficial effects of sulphurous mineral waters, sulphurous mud, or peloids made from sulphurous mineral water have been attributed to the presence of sulphur mainly in the form of hydrogen sulphide. This form is largely available in conditions of low pH when oxygen concentrations are also low. In the organism, small amounts of hydrogen sulphide are produced by some cells where they have numerous biological signalling functions. While high levels of hydrogen sulphide are extremely toxic, enzymes in the body are capable of detoxifying it by oxidation to harmless sulphate. Hence, low levels of hydrogen sulphide may be tolerated indefinitely. In this paper, we review the chemistry and actions of hydrogen sulphide in sulphurous mineral waters and its natural role in body physiology. This is followed by an update of available data on the impacts of exogenous hydrogen sulphide on the skin and internal cells and organs including new therapeutic possibilities of sulphurous mineral waters and their peloids.
Evaluating the Trends of Bloodstream Infections among Pediatric and Adult Patients at a Teaching Hospital of Kathmandu, Nepal: Role of Drug Resistant Pathogens
Authors: Parajuli Narayan Prasad , Parajuli Hridaya , Pandit Roshan , Shakya Jyotsna , Khanal Puspa Raj
Published: April 2017

Bloodstream infections (BSIs) are among the significant causes of morbidity and mortality for patients of all age groups. However, very little is known about the trends of bacterial bloodstream infections and antimicrobial susceptibilities among pediatric and adult population from Nepal. In this study, we have investigated the different etiological agents responsible for bloodstream infections among pediatric and adult patients and the role of drug resistant organisms in these infections at a tertiary care teaching hospital of Kathmandu, Nepal. A total of 3,088 blood culture specimens obtained from pediatric and adult patients suspected to have bloodstream infections were processed by standard microbiological methods. Significant bacterial pathogens were identified by morphological, biochemical, and serological methods as suggested by American Society for Microbiology. In vitro antimicrobial susceptibility testing was performed by Kirby-Bauer disk diffusion method and interpreted according to the guidelines of Clinical and Laboratory Standards Institute. Overall, incidence of bloodstream infections among the suspected patients was 7.48%. Pediatric patients (n=90, 9.37%) were the significant subgroup of patients affected with bloodstream infections compared to adults (p<0.05, CI-95%). Gram positive (n=49, 54.4%) bacteria in pediatric and gram negative bacteria (n=141, 78.7%) in adult patients were the most common isolates for BSI.Staphylococcus aureus(n=41, 45.6%) in pediatric patients andSalmonella enterica(n=40, 28.3%) in adult patients were the leading pathogens. Trends of antimicrobial resistance among isolated bacterial strains were significantly high in adults compared to pediatric patients. Methicillin resistantStaphylococcus aureus(MRSA) (31.4%), extended spectrum beta-lactamase (ESBL) (12.5%), and metallo-beta-lactamase (MBL) (3.9%) producing gram negatives were major resistant strains. Our study shows higher rates of bloodstream infections in pediatric patients compared to adult patients. Alarming rates of antimicrobial resistance among blood culture isolates is a serious issue. Prompt and accurate diagnosis and rational antimicrobial therapy are extremely needed.
Rapid Analysis Procedures for Triglycerides and Fatty Acids as Pentyl and Phenethyl Esters for the Detection of Butter Adulteration Using Chromatographic Techniques
Authors: Naviglio Daniele , Dellagreca Marina , Ruffo Francesco , Andolfi Anna , Gallo Monica
Published: April 2017

This paper presents the development of three methods for quality control, fraud detection, and authentication of butter fat and other oils/fats using chromatographic techniques, with one method for triglycerides and two methods for fatty acids (FAs). The procedure for the analysis of triglycerides requires only dissolution of the sample inn-hexane and gas chromatography (GC) analysis using a capillary column. The second method is based on the transesterification of triglycerides as pentyl esters in a single-step reaction using sodium pentanoate in pentanol. The reaction proceeds at room temperature and is similar to the potassium hydroxide-catalysed transesterification of triglycerides with methanol and even more similar to the sodium methoxide method and sodium butanoate method. The advantage of using pentyl esters includes reducing the volatility of short-chain FAs, and substantial recoveries were obtained compared with methyl ester analysis. The third method involves the transesterification of triglycerides in fat through reaction with 2-phenylethanol in a single step; 2-phenylethanol possesses a chromophore, and the phenethyl esters formed are analysed by high-performance liquid chromatography (HPLC) with UV detection.
Spermidine Prolongs Lifespan and Prevents Liver Fibrosis and Hepatocellular Carcinoma by Activating MAP1S-Mediated Autophagy
Authors: Yue Fei , Li Wenjiao , Zou Jing , Jiang Xianhan , Xu Guibin , Huang Hai , Liu Leyuan
Published: April 2017

Liver fibrosis and hepatocellular carcinoma (HCC) have worldwide impact but continue to lack safe, low cost, and effective treatments. In this study, we show how the simple polyamine spermidine can relieve cancer cell defects in autophagy, which trigger oxidative stress–induced cell death and promote liver fibrosis and HCC. We found that the autophagic marker protein LC3 interacted with the microtubule-associated protein MAP1S, which positively regulated autophagy flux in cells. MAP1S stability was regulated in turn by its interaction with the histone deacetylase HDAC4. Notably, MAP1S-deficient mice exhibited a 20% reduction in median survival and developed severe liver fibrosis and HCC under stress. Wild-type mice or cells treated with spermidine exhibited a relative increase in MAP1S stability and autophagy signaling via depletion of cytosolic HDAC4. Extending recent evidence that orally administered spermidine can extend lifespan in mice, we determined that life extension of up to 25% can be produced by lifelong administration, which also reduced liver fibrosis and HCC foci as induced by chemical insults. Genetic investigations established that these observed impacts of oral spermidine administration relied upon MAP1S-mediated autophagy. Our findings offer a preclinical proof of concept for the administration of oral spermidine to prevent liver fibrosis and HCC and potentially extend lifespan. Cancer Res; 77(11); 2938–51. ©2017 AACR.