bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue Distribution and Visualization of Internalized Human Norovirus in Leafy Greens
Authors: Esseili Malak A. , Meulia Tea , Saif Linda J. , Wang Qiuhong
Published: April 2018

Lettuce has been implicated in human norovirus (HuNoV) outbreaks. The virus is stable on the leaf surface for at least 2 weeks; however, the dynamics of virus internalization have not been fully investigated. The purpose of this study was to assess the internalization and distribution of HuNoV and two surrogate viruses, porcine sapovirus (SaV) and Tulane virus (TV), in lettuce and spinach. Viral inoculations through the roots of seedlings and the petiole of leaves from mature plants were performed, and the viruses were tracked on days 1 and 6 post-root inoculation and at 16 h and 72 h post-petiole inoculation. Confocal microscopy was used to visualize root-internalized HuNoV. In both lettuce and spinach, (i) HuNoV was internalized into the roots and leaves at similar RNA titers, whereas surrogate viruses were more restricted to the roots, (ii) all three viruses were stable inside the roots and leaves for at least 6 days, and (iii) HuNoV disseminated similarly inside the central veins and leaf lamina, whereas surrogate viruses were more restricted to the central veins. Infectious TV, but not SaV, was detectable in all tissues, suggesting that TV has greater stability than SaV. HuNoV was visualized inside the roots' vascular bundle and the leaf mesophyll of both plants. In conclusion, using surrogate viruses may underestimate the level of HuNoV internalization into edible leaves. The internalization of HuNoV through roots and cut leaves and the dissemination into various spinach and lettuce tissues raise concerns of internal contamination through irrigation and/or wash water.

IMPORTANCEHuman noroviruses are the leading cause of foodborne outbreaks, with lettuce being implicated in the majority of outbreaks. The virus causes acute gastroenteritis in all age groups, with more severe symptoms in children, the elderly, and immunocompromised patients, contributing to over 200,000 deaths worldwide annually. The majority of deaths due to HuNoV occur in the developing world, where limited sanitation exists along with poor wastewater treatment facilities, resulting in the contamination of water resources that are often used for irrigation. Our study confirms the ability of lettuce and spinach to internalize HuNoV from contaminated water through the roots into the edible leaves. Since these leafy greens are consumed with minimal processing that targets only surface pathogens, the internalized HuNoV presents an added risk to consumers. Thus, preventive measures should be in place to limit the contamination of irrigation water. In addition, better processing technologies are needed to inactivate internalized viral pathogens.
Heightened Systemic Levels of Neutrophil and Eosinophil Granular Proteins in Pulmonary Tuberculosis and Reversal following Treatment
Authors: Moideen Kadar , Kumar Nathella Pavan , Nair Dina , Banurekha Vaithilingam V. , Bethunaickan Ramalingam , Babu Subash
Published: April 2018

Granulocytes are activated during
Mycobacterium tuberculosis
infection and act as immune effector cells, and granulocyte responses are implicated in tuberculosis (TB) pathogenesis. Plasma levels of neutrophil and eosinophil granular proteins provide an indirect measure of degranulation. In this study, we wanted to examine the levels of neutrophil and eosinophil granular proteins in individuals with pulmonary tuberculosis (PTB) and to compare them with the levels in individuals with latent TB (LTB). Hence, we measured the plasma levels of myeloperoxidase (MPO), neutrophil elastase, proteinase 3, major basic protein (MBP), eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPX) in these individuals. Finally, we also measured the levels of all of these proteins in PTB individuals following antituberculosis treatment (ATT). Our data reveal that PTB individuals are characterized by significantly higher plasma levels of MPO, elastase, proteinase 3, as well as MBP and EDN in comparison to those in LTB individuals. Our data also reveal that ATT resulted in the reversal of all of these changes, indicating an association with TB disease. Finally, our data show that the systemic levels of MPO and proteinase 3 can significantly discriminate PTB from LTB individuals. Thus, our data suggest that neutrophil and eosinophil granular proteins could play a potential role in the innate immune response and, therefore, the pathogenesis of pulmonary TB.
cAMP and Vfr Control Exolysin Expression and Cytotoxicity of Pseudomonas aeruginosa Taxonomic Outliers
Authors: Berry Alice , Han Kook , Trouillon Julian , Robert-Genthon Mylène , Ragno Michel , Lory Stephen , Attrée Ina , Elsen Sylvie
Published: April 2018

The two-partner secretion system ExlBA, expressed by strains of
Pseudomonas aeruginosa
belonging to the PA7 group, induces hemorrhage in lungs due to disruption of host cellular membranes. Here we demonstrate that the
exlBA
genes are controlled by a pathway consisting of cAMP and the virulence factor regulator (Vfr). Upon interaction with cAMP, Vfr binds directly to the
exlBA
promoter with high affinity (equilibrium binding constant [
K
eq
] of ≈2.5 nM). The
exlB
and
exlA
expression was diminished in the Vfr-negative mutant and upregulated with increased intracellular cAMP levels. The Vfr binding sequence in the
exlBA
promoter was mutated
in situ
, resulting in reduced cytotoxicity of the mutant, showing that Vfr is required for the
exlBA
expression during intoxication of epithelial cells. Vfr also regulates function of type 4 pili previously shown to facilitate ExlA activity on epithelial cells, which indicates that the cAMP/Vfr pathway coordinates these two factors needed for full cytotoxicity. As in most
P. aeruginosa
strains, the adenylate cyclase CyaB is the main provider of cAMP for Vfr regulation during both
in vitro
growth and eukaryotic cell infection. We discovered that the absence of functional Vfr in the reference strain PA7 is caused by a frameshift in the gene and accounts for its reduced cytotoxicity, revealing the conservation of ExlBA control by the CyaB-cAMP/Vfr pathway in
P. aeruginosa
taxonomic outliers.

IMPORTANCE
The human opportunistic pathogen
Pseudomonas aeruginosa
provokes severe acute and chronic human infections associated with defined sets of virulence factors. The main virulence determinant of
P. aeruginosa
taxonomic outliers is exolysin, a membrane-disrupting pore-forming toxin belonging to the two-partner secretion system ExlBA. In this work, we demonstrate that the conserved CyaB-cAMP/Vfr pathway controls cytotoxicity of outlier clinical strains through direct transcriptional activation of the
exlBA
operon. Therefore, despite the fact that the type III secretion system and exolysin are mutually exclusive in classical and outlier strains, respectively, these two major virulence determinants share similarities in their mechanisms of regulation.
RNA Thermometers in Bacterial Pathogens
Authors: Loh Edmund , Righetti Francesco , Eichner Hannes , Twittenhoff Christian , Narberhaus Franz
Published: April 2018

Temperature variation is one of the multiple parameters a microbial pathogen encounters when it invades a warm-blooded host. To survive and thrive at host body temperature, human pathogens have developed various strategies to sense and respond to their ambient temperature. An instantaneous response is mounted by RNA thermometers (RNATs), which are integral sensory structures in mRNAs that modulate translation efficiency. At low temperatures outside the host, the folded RNA blocks access of the ribosome to the translation initiation region. The temperature shift upon entering the host destabilizes the RNA structure and thus permits ribosome binding. This reversible zipper-like mechanism of RNATs is ideally suited to fine-tune virulence gene expression when the pathogen enters or exits the body of its host. This review summarizes our present knowledge on virulence-related RNATs and discusses recent developments in the field.
Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials
Authors: Houston Brett L , Hurrie Daryl , Graham Jeff , Perija Brittany , Rimmer Emily , Rabbani Rasheda , Bernstein Charles N , Turgeon Alexis F , Fergusson Dean A , Houston Donald S , Abou-Setta Ahmed M , Zarychanski Ryan
Published: April 2018

Objective

Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults.

Design

Systematic review and meta-analysis of randomised controlled trials (RCTs).

Setting

Primary care.

Participants

Adults (≥18 years) who were iron deficient but non-anaemic.

Interventions

Oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included.

Comparators

Placebo or active therapy.

Results

We identified RCTs in Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health, SportDiscus and CAB Abstracts from inception to 31 October 2016. We searched the WHO’s International Clinical Trials Registry Platform for relevant ongoing trials and performed forward searches of included trials and relevant reviews in Web of Science. We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment, Development and Evaluation methodology. From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients. Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) −0.38; 95% CI −0.52 to −0.23; I20%; 4 trials; 714 participants) but was not associated with differences in objective measures of physical capacity, including maximal oxygen consumption (SMD 0.11; 95% CI −0.15 to 0.37; I20%; 9 trials; 235 participants) and timed methods of exercise testing. Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I248%; 12 trials; 298 participants) and serum ferritin (MD 9.23 µmol/L; 95% CI 6.48 to 11.97; I258%; 14 trials; 616 participants).

Conclusion

In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia.

PROSPERO registration number

CRD42014007085.
Impact of workplace incivility against new nurses on job burn-out: a cross-sectional study in China
Authors: Shi Yu , Guo Hui , Zhang Shue , Xie Fengzhe , Wang Jinghui , Sun Zhinan , Dong Xinpeng , Sun Tao , Fan Lihua
Published: April 2018

This study had three objectives: (1) to investigate the impact of workplace incivility on job burn-out of new nursing staff, (2) to verify the partial mediating role of anxiety in the relationship between workplace incivility and job burn-out, (3) to examine the resilience moderating the relations between workplace incivility and job burn-out.

Design

A cross-sectional online survey was conducted in May 2016 in China.

Setting

The survey was conducted in 54 cities across 29 provinces of China.

Participants

A total of 903 participants were invited. Ultimately, 696 new nurses (<3 service years) completed valid questionnaires. The effective response rate was 77.1%. Entry criteria: voluntary participation, having less than three service years and being a registered nurse. Exclusion criteria: being an irregular nurse, having more than three service years and refusing to participate in this work.

Outcome measures

An anonymous questionnaire was distributed among new nurses. The relationships and mechanism among the variables were explored using descriptive statistical analysis, Pearson’s correlation coefficient and multiple linear regression analysis.

Results

The findings showed that workplace incivility was positively correlated with anxiety (r=0.371, p<0.01) and job burn-out (r=0.238, p<0.01) of new nurses. The positive relation between anxiety (β=0.364, p<0.01) and job burn-out (β=0.240, p<0.01) was also significant. Moreover, anxiety partially mediated (z=7.807, p<0.01) and resilience moderated (β=−0.564, p<0.01) the association between workplace incivility and job burn-out.

Conclusion

Experience of workplace incivility by new nurses would likely generate anxiety in the victims. Further, the increased anxiety state could elevate their level of job burn-out. New nurses with high levels of resilience could buffer the negative influence of workplace incivility by using a positive coping style.
Safest light in a combat area while performing intravenous access in the dark
Authors: Aydin Attila , Bilge S , Eryilmaz M
Published: April 2018

Introduction

Cannulation for the administration of intravenous fluids is integral to the prehospital management of injured military patients. However, this may be technically challenging to undertake during night-time conditions where the use of light to aid cannulation may give the tactical situation away to opponents. The aim of this study was to investigate the success and tactical safety of venepuncture under battlefield conditions with different colour light sources.

Method

The procedure was carried out with naked eye in a bright room in the absence of a separate light source, with a naked eye in a dark room under red, white, blue and green light sources and under an infrared light source while wearing night vision goggles (NVGs). The success, safety, degree of difficulty and completion time for each procedure were then explored.

Results

All interventions made in daylight and in a dark room were found to be 100% successful. Interventions performed under infrared light while wearing NVGs took longer than under other light sources or in daylight. Interventions performed under blue light were tactically safer when compared with interventions performed under different light sources.

Conclusion

Blue light offered the best tactical safety during intravenous cannulation under night-time conditions and is recommended for future use in tactical casualty care. The use of NVGs using infrared light cannot be recommended if there is the possibility of opponents having access to the technology.
How a major incident plan can be used in an acute healthcare setting
Authors: Makin Seth , Smith L , McDevitt K
Published: April 2018

All NHS Trusts face a diverse range of potential threats and disruptions that can overwhelm the delivery of their routine healthcare services. Major incidents range from significant infrastructure failure to responding to significant casualty numbers from natural disasters and malicious incidents. Major incident plans are one of the body of documents that support trusts and in this instance acute NHS trusts in emergency preparedness. Major incident plans can be used as a reference point for staff of all disciplines, that is, clinical and non-clinical. Major incident plans incorporate the requirements of the Civil Contingencies Act 2004 for NHS-funded providers to ensure trusts conduct risk assessments, emergency planning, cooperating with other organisations, and internal and external communication. This paper summarises some of the key aspects in the construction and the use of major incident plans in acute care trusts.
A SAT-Based Methodology for Effective Clock Gating for Power Minimization
Authors: Chandrakar Khushbu , Roy Suchismita
Published: April 2018

A possible solution to handle the rising complexity of modern Systems-on-Chip (SoCs) is to raise the level of abstraction for the design and optimization. A better optimization of performance and power can be achieved at higher abstraction levels by applying suitable optimization techniques. Insertion of clock gating logic into the generated Register-Transfer Level (RTL) would facilitate lowering dynamic power consumption by switching off the clock signal to portions of the circuit not currently in use and thereby reducing unnecessary toggling. In this work, we have tried to minimize the power consumption of synchronous circuits by reducing the number of activity string patterns. Activity-driven clock trees have been used wherein sections of the clock tree are turned off by gating the clock signals. Since gating the clock signal implies additional control signals and gates, there is always a trade-off existing between the logic circuit area overhead and the total power consumption of the clock tree. A pseudo-Boolean satisfiability (PB-SAT)-based approach is proposed in this work which focuses on the reduction of power consumption by reducing the activity pattern of the clock tree which will reduce the power consumption with appropriate module-binding solutions.
On-axis scalar absorption cross section of Kerr–Newman black holes: Geodesic analysis, sinc and low-frequency approximations
Authors: Benone Carolina L. , Leite Luiz C. S. , Crispino Luís C. B. , Dolan Sam R.
Published: April 2018

We investigate null geodesics impinging parallel to the rotation axis of a Kerr–Newman black hole, and show that the absorption cross section for a massless scalar field in the eikonal limit can be described in terms of the photon orbit parameters. We compare our sinc and low-frequency approximations with numerical results, showing that they are in excellent agreement.
Isothermal perfect fluid as a hydrodynamic vortex: Quasinormal mode investigation
Authors: Oliveira Leandro A. , Crispino Luís C. B.
Published: April 2018

We compute the quasinormal frequencies of a purely rotating isothermal perfect fluid. We show that this system is unstable under linear perturbations, when the boundary condition is imposed inside the ergoregion.
Video Caption Extraction Using Spatio-Temporal Slices
Authors: Chen Liang-Hua , Su Chih-Wen
Published: April 2018

Captions in videos play an important role for video indexing and retrieval. In this paper, we propose a novel algorithm to extract multilingual captions from video. Our approach is based on the analysis of spatio-temporal slices of video. If the horizontal (or vertical) scan line contains some pixels of caption region then the corresponding spatio-temporal slice will have bar-code like patterns. By integrating the structure information of bar-code like patterns in horizontal and vertical slices, the spatial and temporal positions of video captions can be located accurately. Experimental results show that the proposed algorithm is effective and outperforms some existing techniques.
Linear list r-hued coloring of sparse graphs
Authors: Ma Hongping , Hu Xiaoxue , Kong Jiangxu , Xu Murong
Published: April 2018

An [Formula: see text]-hued coloring is a proper coloring such that the number of colors used by the neighbors of [Formula: see text] is at least [Formula: see text]. A linear [Formula: see text]-hued coloring is an [Formula: see text]-hued coloring such that each pair of color classes induces a union of disjoint paths. We study the linear list [Formula: see text]-hued chromatic number, denoted by [Formula: see text], of sparse graphs. It is clear that any graph [Formula: see text] with maximum degree [Formula: see text] satisfies [Formula: see text]. Let [Formula: see text] be the maximum average degree of a graph [Formula: see text]. In this paper, we obtain the following results:

(1) If [Formula: see text], then [Formula: see text] (2) If [Formula: see text], then [Formula: see text]. (3) If [Formula: see text], then [Formula: see text].
Sugar sensor genes in the murine gastrointestinal tract display a cephalocaudal axis of expression and a diurnal rhythm
Authors: O’Brien Patrick , Hewett Rhys , Corpe Christopher
Published: April 2018

Distributed along the length of the gastrointestinal (GI) tract are nutrient sensing cells that release numerous signaling peptides influencing GI function, nutrient homeostasis and energy balance. Recent studies have shown a diurnal rhythm in GI nutrient sensing, but the mechanisms responsible for rhythmicity are poorly understood. In this report we studied murine GI sugar sensor gene and protein expression levels in the morning (7 AM) and evening (7 PM). Sweet taste receptor ( tas1r2/tas1r3/gnat3/gnat1) sugar transporter ( slc5a1, slc2a2, slc2a5) and putative sugar sensor ( slc5a4a and slc5a4b) gene expression levels were highest in tongue and proximal and distal small intestine, respectively. Clock gene ( cry2/arntl) activity was detected in all regions studied. Slc5a4a and slc5a4b gene expression showed clear diurnal rhythmicity in the small intestine and stomach, respectively, although no rhythmicity was detected in SGLT3 protein expression. Tas1r2, tas1r3, gnat1, and gcg displayed a limited rhythm in gene expression in proximal small intestine. Microarray analysis revealed a diurnal rhythm in gut peptide gene expression in tongue (7 AM vs. 7 PM) and in silico promoter analysis indicated intestinal sugar sensors and transporters possessed the canonical E box elements necessary for clock gene control over gene transcription. In this report we present evidence of a diurnal rhythm in genes that are responsible for intestinal nutrient sensing that is most likely controlled by clock gene activity. Disturbances in clock gene/nutrient sensing interactions may be important in the development of diet-related diseases, such as obesity and diabetes.
Rosai-Dorfman Disease: Rare Pulmonary Involvement Mimicking Pulmonary Langerhans Cell Histiocytosis and Review of the Literature
Authors: AL Umairi Rashid , Blunt Danielle , Hana Wedad , Cheung Matthew , Oikonomou Anastasia
Published: April 2018

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare nonmalignant lymphohistiocytic proliferative disorder. We report a patient with RDD who presented with multiple skin lesions, pulmonary involvement, and CT manifestations mimicking Langerhans cell histiocytosis, which improved after initiation of corticosteroid treatment.
Young and Especially Senescent Endothelial Microvesicles Produce NADPH: The Fuel for Their Antioxidant Machinery
Authors: Bodega Guillermo , Alique Matilde , Bohórquez Lourdes , Morán Miriam , Magro Luis , Puebla Lilian , Ciordia Sergio , Mena María C. , Arza Elvira , Ramírez Manuel R.
Published: April 2018

In a previous study, we demonstrated that endothelial microvesicles (eMVs) have a well‐developed enzymatic team involved in reactive oxygen species detoxification. In the present paper, we demonstrate that eMVs can synthesize the reducing power (NAD(P)H) that nourishes this enzymatic team, especially those eMVs derived from senescent human umbilical vein endothelial cells. Moreover, we have demonstrated that the molecules that nourish the enzymatic machinery involved in NAD(P)H synthesis are blood plasma metabolites: lactate, pyruvate, glucose, glycerol, and branched‐chain amino acids. Drastic biochemical changes are observed in senescent eMVs to optimize the synthesis of reducing power. Mitochondrial activity is diminished and the glycolytic pathway is modified to increase the activity of the pentose phosphate pathway. Different dehydrogenases involved in NADPH synthesis are also increased. Functional experiments have demonstrated that eMVs can synthesize NADPH. In addition, the existence of NADPH in eMVs was confirmed by mass spectrometry. Multiphoton confocal microscopy images corroborate the synthesis of reducing power in eMVs. In conclusion, our present and previous results demonstrate that eMVs can act as autonomous reactive oxygen species scavengers: they use blood metabolites to synthesize the NADPH that fuels their antioxidant machinery. Moreover, senescent eMVs have a stronger reactive oxygen species scavenging capacity than young eMVs.
A Validation of the Ultrasound Wave Velocity Method to Predict Porosity of Dry and Saturated Cement Paste
Authors: Zou Zhenting , Meegoda Jay N.
Published: April 2018

An approximate theoretical validation of the measured variation of ultrasound velocity with porosity of dry and saturated cement paste is proposed using finite element analysis of cement paste assuming as a multiphase composite. Cement paste is a multiphase composite consisting of solid cement and microscopic voids filled either with air or water. The void content in cement paste is directly related to strength and durability. Experimental tests showed that ultrasound wave velocity is decreased with the increase in porosity of cement paste, where pore sizes are similar in dimension to the wavelength of the sound enabling ultrasound to be used as a potential condition assessment technique. However, the variation of ultrasound wave velocity also depends on the fluid in the voids. Several finite element simulations using two commercially available software packages were performed for both fully saturated and dry blocks of cement paste with different porosities. Then back‐calculated elastic moduli values from finite element simulations were used to compute the wave velocities of both fully saturated and dry cement paste with different porosities. The predicted ultrasound velocities with porosity for both dry and saturated cement paste are compared well with the laboratory measurements.
IL-1β-Induced Matrix Metalloprotease-1 Promotes Mesenchymal Stem Cell Migration via PAR1 and G-Protein-Coupled Signaling Pathway
Authors: Chen Ming-Siou , Lin Cheng-Yu , Chiu Yun-Hsuan , Chen Chie-Pein , Tsai Pei-Jiun , Wang Hwai-Shi
Published: April 2018

Mesenchymal stem cells (MSCs) are known for homing to sites of injury in response to signals of cellular damage. However, the mechanisms of how cytokines recruit stem cells to target tissue are still unclear. In this study, we found that the proinflammation cytokine interleukin-1β(IL-1β) promotes mesenchymal stem cell migration. The cDNA microarray data show that IL-1βinduces matrix metalloproteinase-1 (MMP-1) expression. We then used quantitative real-time PCR and MMP-1 ELISA to verify the results. MMP-1 siRNA transfected MSCs, and MSC pretreatment with IL-1βinhibitor interleukin-1 receptor antagonist (IL-1RA), MMP tissue inhibitor of metalloproteinase 1 (TIMP1), tissue inhibitor of metalloproteinase 2 (TIMP2), MMP-1 inhibitor GM6001, and protease-activated receptor 1 (PAR1) inhibitor SCH79797 confirms that PAR1 protein signaling pathway leads to IL-1β-induced cell migration. In conclusion, IL-1βpromotes the secretion of MMP-1, which then activates the PAR1 and G-protein-coupled signal pathways to promote mesenchymal stem cell migration.
The Efficacy of Gait Training Using a Body Weight Support Treadmill and Visual Biofeedback in Patients with Subacute Stroke: A Randomized Controlled Trial
Authors: Drużbicki Mariusz , Przysada Grzegorz , Guzik Agnieszka , Brzozowska-Magoń Agnieszka , Kołodziej Krzysztof , Wolan-Nieroda Andzelina , Majewska Joanna , Kwolek Andrzej
Published: April 2018

Background.This study was designed to determine whether or not gait training based on the use of treadmill with visual biofeedback and body weight support (BWS) would produce better effects in patients with subacute stroke compared to BWS treadmill training with no visual biofeedback.Materials and Methods.30 patients with subacute stroke were randomly assigned to do body weight supported treadmill training with visual biofeedback (BB group) or BWS treadmill training without visual biofeedback. Their gait was assessed with a 3D system (spatiotemporal gait parameters and symmetry index) and by means of 2-minute walk test (2 MWT), 10-metre walk test (10 MWT), and Timed Up & Go test. Subjects in both groups participated in 15 treadmill training sessions (30 minutes each).Results.The participants from both groups achieved a statistically significant improvement in spatiotemporal gait parameters, walking speed, endurance, and mobility. The average change in the BB group after the end of the programme did not differ significantly compared to the change in the control group. The change in the symmetry index value of stance phase in the BB group was 0.03 (0.02) and in the control group was 0.02 (0.02). The difference was not statistically significant (p=0.902). The statistically significantly higher improvement in the BB group was found in the range of walking speed (p=0.003) and endurance (p=0.012), but the difference between groups was of low clinical significance.Conclusions.The findings do not confirm that BWS treadmill training with the function of visual biofeedback leads to significantly greater improvement in gait compared to BWS treadmill training with no visual biofeedback at an early stage after stroke. This study was registered at ClinicalTrials.gov, ID:ACTRN12616001283460.
Drosophila melanogasterModels of Friedreich’s Ataxia
Authors: Calap-Quintana P. , Navarro J. A. , González-Fernández J. , Martínez-Sebastián M. J. , Moltó M. D. , Llorens J. V.
Published: April 2018

Friedreich’s ataxia (FRDA) is a rare inherited recessive disorder affecting the central and peripheral nervous systems and other extraneural organs such as the heart and pancreas. This incapacitating condition usually manifests in childhood or adolescence, exhibits an irreversible progression that confines the patient to a wheelchair, and leads to early death. FRDA is caused by a reduced level of the nuclear-encoded mitochondrial protein frataxin due to an abnormal GAA triplet repeat expansion in the first intron of the humanFXNgene.FXNis evolutionarily conserved, with orthologs in essentially all eukaryotes and some prokaryotes, leading to the development of experimental models of this disease in different organisms. These FRDA models have contributed substantially to our current knowledge of frataxin function and the pathogenesis of the disease, as well as to explorations of suitable treatments. Drosophila melanogaster, an organism that is easy to manipulate genetically, has also become important in FRDA research. This review describes the substantial contribution ofDrosophilato FRDA research since the characterization of the fly frataxin ortholog more than 15 years ago. Fly models have provided a comprehensive characterization of the defects associated with frataxin deficiency and have revealed genetic modifiers of disease phenotypes. In addition, these models are now being used in the search for potential therapeutic compounds for the treatment of this severe and still incurable disease.
Numerical and Experimental Identification of Seven‐Wire Strand Tensions Using Scale Energy Entropy Spectra of Ultrasonic Guided Waves
Authors: Qian Ji , Chen Xin , Sun Limin , Yao Guowen , Wang Xu
Published: April 2018

Accurate identification of tension in multiwire strands is a key issue to ensure structural safety and durability of prestressed concrete structures, cable‐stayed bridges, and hoist elevators. This paper proposes a method to identify strand tensions based on scale energy entropy spectra of ultrasonic guided waves (UGWs). A numerical method was first developed to simulate UGW propagation in a seven‐wire strand, employing the wavelet transform to extract UGW time‐frequency energy distributions for different loadings. Mode separation and frequency band loss of L(0,1) were then found for increasing tension, and UGW scale energy entropy spectra were extracted to establish a tension identification index. A good linear relationship was found between the proposed identification index and tensile force, and effects of propagation distance and propagation path were analyzed. Finally, UGWs propagation was examined experimentally for a long seven‐wire strand to investigate attenuation and long distance propagation. Numerical and experimental results verified that the proposed method not only can effectively identify strand tensions but can also adapt to long distance tests for practical engineering.
Efficacy and Safety of Botulinum Toxin Type A in Treating Patients of Advanced Age with Idiopathic Trigeminal Neuralgia
Authors: Liu Jing , Xu Ying-Ying , Zhang Qi-Lin , Luo Wei-Feng
Published: April 2018

Objective. To assess the therapeutic efficacy and safety of botulinum toxin type A (BTX-A) for treating idiopathic trigeminal neuralgia (ITN) in patients ≥80 years old. Methods. Selected patients n=43 with ITN, recruited from the neurology clinic and inpatient department of the Second Affiliated Hospital of Soochow University between August 2008 and February 2014, were grouped by age, one subset n=14 ≥80 years old and another n=29 <60 years old. Each group scored similarly in degrees of pain registered by the visual analogue scale (VAS). Dosing, efficacy, and safety of BTX-A injections were compared by group. Results. Mean dosages of BTX-A were 91.3 ± 25.6 U and 71.8 ± 33.1 U in older and younger patients, respectively t=1.930, p=0.061. The median of the VAS score in older patients at baseline (8.5) declined significantly at 1 month after treatment (4.5) p=0.007, as did that of younger patients (8.0 and 5.0, resp.) p=0.001. The median of the D values of the VAS scores did not differ significantly by group (older, 2.5; younger, 0; Z=−1.073, p=0.283). Two patients in each group developed minor transient side effects p=0.825. Adverse reactions in both groups were mild, resolving spontaneously within 3 weeks. Conclusions. BTX-A is effective and safe in treating patients of advanced age (≥80 years old) with ITN, at dosages comparable to those used in much younger counterparts (<60 years old).
Modulation of Glucose Takeup by Glucose Transport on the Isolated OHCs
Authors: Cheng Xiao-ting , Yang Feng-bo , Jiang Qing-qing , Zhang Rong , Yang Shi-ming , Yu Ning
Published: April 2018

Glucose is a fundamental source of energy for mammalian cells; however, whether glucose is taken up through the lateral walls of cochlear outer hair cells (OHCs) is unknown. The OHC lateral wall is complex, composed of a plasma membrane, cortical lattice, and subsurface cisternae. This study assessed the uptake of glucose by OHCs using live-cell microscopy and examined the distribution of glucose transporter isoforms by immunohistochemistry. We found that glucose transporter-4 was mostly expressed on the lateral wall of OHCs. Glucose crossed the lateral walls of OHCs via glucose transporters-4 mainly, and this process could be modulated. These results suggest that the lateral walls are involved in modulating energy transport into OHCs.
The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions
Authors: Li Longman , Yang Xiaobo
Published: April 2018

Manganese (Mn) is an essential element that is involved in the synthesis and activation of many enzymes and in the regulation of the metabolism of glucose and lipids in humans. In addition, Mn is one of the required components for Mn superoxide dismutase (MnSOD) that is mainly responsible for scavenging reactive oxygen species (ROS) in mitochondrial oxidative stress. Both Mn deficiency and intoxication are associated with adverse metabolic and neuropsychiatric effects. Over the past few decades, the prevalence of metabolic diseases, including type 2 diabetes mellitus (T2MD), obesity, insulin resistance, atherosclerosis, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and hepatic steatosis, has increased dramatically. Previous studies have found that ROS generation, oxidative stress, and inflammation are critical for the pathogenesis of metabolic diseases. In addition, deficiency in dietary Mn as well as excessive Mn exposure could increase ROS generation and result in further oxidative stress. However, the relationship between Mn and metabolic diseases is not clear. In this review, we provide insights into the role Mn plays in the prevention and development of metabolic diseases.
Utilization of Local Ingredients for the Production of High‐Early‐Strength Engineered Cementitious Composites
Authors: Deng Hanwen
Published: April 2018

The rapid repair and retrofitting of existing transportation infrastructure requires dimensional stability and ductile repair material that can obtain sufficiently high strength in a few hours to accommodate the large loading and deformation at an early age. Engineering cementitious composites (ECCs) is a class representative of the new generation of high‐performance fiber‐reinforced cement‐based composites (HPFRCC) with medium fiber content. The unique properties of tremendous ductility and tight multiple crack behavior indicate that ECC can be used as an effective retrofit material. The wide application of this material in China will require the use of all local ingredients. In this study, based on Chinese domestic ingredients, including matrix materials and all fibers, high‐early‐strength ECC (HES‐ECC) was designed under the guidance of strain‐hardening criterion of ECC. The matrix properties and fiber/matrix interfacial micromechanics properties were obtained from three‐point‐bending test and single‐fiber pullout test. The mechanical properties of HES‐ECC were achieved by direct tensile test. The experimental results show that HES‐ECC was successfully developed by using all Chinese materials. When using the domestic PVA fiber at 2%, the strength requirement can be achieved but only a low ductility. When using the domestic PE fiber at 0.8%, the strength and deformation requirement both can be obtained. The HES‐ECC developed in this study exhibited compressive strength of more than 25 MPa within 6 hours, and an ultimate tensile strength of 5‐6 MPa and tensile strain capacity of 3‐4% after 60 days. Moreover, the cost of using domestic fiber can be largely reduced compared with using imported fiber, up to 70%; it is beneficial to the promotion of these high‐early‐strength ECCs in the Chinese market.
Parameters of Somatosensory Evoked Potentials in Patients with Primary Sjӧgren’s Syndrome: Preliminary Results
Authors: Dziadkowiak Edyta , Sebastian Agata , Wieczorek Małgorzata , Kusińska Elżbieta , Waliszewska-Prosół Marta , Wiland Piotr , Ejma Maria
Published: April 2018

Primary Sjogren’s syndrome (pSS) is a chronic autoimmune disease. The aim of the study was to establish whether in patients with pSS without central nervous system (CNS) involvement, the function of the central portion of the sensory pathway can be challenged. In 33 patients with pSS without clinical features of CNS damage and normal head computed tomography scan, somatosensory evoked potentials (SEP) were studied. The results were compared to other clinical parameters of the disease, particularly to immunological status. The control group consisted of 20 healthy volunteers. Mean latency of all components of SEP was considerably prolonged in patients compared to the control group. Mean interpeak latency N20-N13 (duration of central conduction TT) did not differ significantly between the groups. However, in the study group, mean amplitude of N20P22 and N13P16 was significantly higher compared to healthy individuals. In patients with pSS, significant differences in SEP parameters depending on the duration of the disease and presence of SSA and SSB antibodies were noted. The authors confirmed CNS involvement often observed in patients with pSS. They also showed dysfunction of the central sensory neuron as a difference in the amplitude of cortical response, which indicates subclinical damage to the CNS.
Inhibition of Acetylcholinesterase and Butyrylcholinesterase by a Plant Secondary Metabolite Boldine
Authors: Kostelnik Adam , Pohanka Miroslav
Published: April 2018

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two enzymes sensitive to various chemical compounds having ability to bind to crucial parts of these enzymes. Boldine is a natural alkaloid and it was mentioned in some older works that it can inhibit some kinds of AChE. We reinvestigated this effect on AChE and also on BChE using acetyl (butyryl) thiocholine and Ellman’s reagents as standard substances for spectrophotometric assay. We found out IC50 of AChE equal to 372 μmol/l and a similar level to BChE, 321 μmol/l. We conclude our experiment by a finding that boldine is cholinesterase inhibitor; however we report significantly weaker inhibition than that suggested in literature. Likewise, we tried to investigate the mechanism of inhibition and completed it with in silico study. Potential toxic effect on cholinesterases in real conditions is also discussed.
APTO-253 Stabilizes G-quadruplex DNA, Inhibits MYC Expression, and Induces DNA Damage in Acute Myeloid Leukemia Cells
Authors: Local Andrea , Zhang Hongying , Benbatoul Khalid D. , Folger Peter , Sheng Xia , Tsai Cheng-Yu , Howell Stephen B. , Rice William G.
Published: April 2018

APTO-253 is a phase I clinical stage small molecule that selectively induces CDKN1A (p21), promotes G0–G1 cell-cycle arrest, and triggers apoptosis in acute myeloid leukemia (AML) cells without producing myelosuppression in various animal species and humans. Differential gene expression analysis identified a pharmacodynamic effect on MYC expression, as well as induction of DNA repair and stress response pathways. APTO-253 was found to elicit a concentration- and time-dependent reduction in MYC mRNA expression and protein levels. Gene ontogeny and structural informatic analyses suggested a mechanism involving G-quadruplex (G4) stabilization. Intracellular pharmacokinetic studies in AML cells revealed that APTO-253 is converted intracellularly from a monomer to a ferrous complex [Fe(253)3]. FRET assays demonstrated that both monomeric APTO-253 and Fe(253)3 stabilize G4 structures from telomeres, MYC, and KIT promoters but do not bind to non-G4 double-stranded DNA. Although APTO-253 exerts a host of mechanistic sequelae, the effect of APTO-253 on MYC expression and its downstream target genes, on cell-cycle arrest, DNA damage, and stress responses can be explained by the action of Fe(253)3 and APTO-253 on G-quadruplex DNA motifs. Mol Cancer Ther; 17(6); 1177–86. ©2018 AACR.
Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome
Authors: Sullivan David A. , Dana Reza , Sullivan Rose M. , Krenzer Kathleen L. , Sahin Afsun , Arica Beril , Liu Yang , Kam Wendy R. , Papas Athena S. , Cermak Jennifer M.
Published: April 2018

Purpose: We hypothesized that women with primary (pSS) and secondary Sjögren syndrome (sSS; with systemic lupus erythematosus [SLE] or rheumatoid arthritis [RA]) have meibomian gland dysfunction (MGD). We sought to test our hypothesis. Methods: Subjects with pSS, sSS + SLE, sSS + RA, and non-SS-related MGD were recruited from the Sjögren’s Syndrome Foundation or outpatient clinics at Tufts University School of Dental Medicine or Brigham and Women’s Hospital. The control population was recruited from the Greater Boston area. After providing written informed consent, the subjects underwent an eye examination and/or completed two questionnaires that assess symptoms of dry eye disease (DED). Results: Our results demonstrate that pSS and sSS patients have MGD. These subjects had meibomian gland orifice metaplasia, an increased number of occluded meibomian gland orifices, and a reduced quality of meibomian gland secretions. Further, patients with pSS, sSS + SLE, sSS + RA, and MGD had significant alterations in their tear film, lid margin, cornea, and conjunctiva. Symptoms of DED were increased ∼10-fold in all pSS, sSS, and MGD groups relative to controls. Conclusions: Our findings support our hypothesis and show that individuals with pSS, sSS + SLE, and sSS + RA have MGD. In addition, our study indicates that patients with pSS and sSS have both aqueous-deficient and evaporative DED.
No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma
Authors: Saeki Issei , Yamasaki Takahiro , Maeda Masaki , Kawano Reo , Hisanaga Takuro , Iwamoto Takuya , Matsumoto Toshihiko , Hidaka Isao , Ishikawa Tsuyoshi , Takami Taro , Sakaida Isao
Published: April 2018

Background: Sorafenib is a standard therapy for patients with advanced hepatocellular carcinoma (HCC). However, no predictive biomarkers of sorafenib efficacy have been discovered. Herein, we investigated the impact of body composition, such as skeletal muscle and visceral fat, on the prognosis of advanced HCC patients treated with sorafenib. Methods: We enrolled 100 patients with advanced HCC treated with sorafenib. Prior to receiving sorafenib therapy, skeletal muscle index (SMI) and visceral fat area (VFA) were measured using computed tomography at the third lumbar vertebra and umbilical level, respectively. Muscle depletion was defined as an SMI value < 42 cm2/m2 in men and < 38 cm2/m2 in women. High VFA (H-VFA) was defined as a value ≥100 cm2. In addition to SMI and VFA, we also analyzed various clinical parameters as potential prognostic factors. Results: Multivariate analysis showed that having a tumor number < 7 (hazard ratio [HR] = 0.409, p < 0.001), absence of extrahepatic spread (EHS) (HR = 0.562, p < 0.001), absence of muscle depletion (HR = 0.498, p = 0.006), and H-VFA (HR = 0.556, p = 0.031) were significant factors for long-term survival. Therefore, we evaluated the prognosis of those with no muscle depletion with H-VFA. The no muscle depletion with H-VFA group showed significantly longer survival than the other group (median survival time 15.6 vs. 11.0 months, p = 0.003). Multivariate analysis showed that having a tumor number < 7 (HR = 0.454, p = 0.001), absence of EHS (HR = 0.511, p = 0.008), and no muscle depletion with H-VFA (HR = 0.454, p = 0.002) were significant predictors of survival. Conclusions: We identified no muscle depletion with H-VFA as a novel biomarker for advanced HCC patients treated with sorafenib.
Somatically Acquired Isodicentric Y and Mosaic Loss of Chromosome Y in a Boy with Hypospadias
Authors: Miyado Mami , Muroya Koji , Katsumi Momori , Saito Kazuki , Kon Masafumi , Fukami Maki
Published: April 2018

Isodicentric Y chromosome [idic(Y)] represents a relatively common subtype of Y chromosomal rearrangements in the germline; however, limited evidence supports the postzygotic occurrence of idic(Y). Here, we report a boy with hypospadias and somatically acquired idic(Y). The 3.5-year-old boy has been identified in our previous study for patients with hypospadias. In the present study, cytogenetic analysis including FISH revealed a 45,X[5]/46,X,idic(Y)[7]/46,XY[8] karyotype. MLPA showed a mosaic deletion involving PPP1R12BP1 and RBMY2DP. The idic(Y) was likely to have been formed through aberrant recombination between P1 palindromes and subsequently underwent mosaic loss. The patient's phenotype was attributable to deletion of some Y chromosomal genes and/or mosaic loss of chromosome Y (mLOY). The results suggest that idic(Y) can originate in postzygotic cells via palindrome-mediated crossovers. Moreover, our data indicate that somatically acquired idic(Y) can trigger mLOY, which usually appears as an aging-related phenomenon in elderly men.