bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Susceptibilities of
Chlamydia pneumoniae
Isolates from German Patients and Synergistic Activity of Antibiotic Combinations
Authors: Freidank Heike M. , Losch Philipp , Vögele Heike , Wiedmann-Al-Ahmad Margit
Published: October 2018

The susceptibilities of six
Chlamydia pneumoniae
type strains and of six German patient isolates to erythromycin, azithromycin, roxithromycin, clarithromycin, doxycycline, ofloxacin, and rifampin were investigated. MICs and minimal chlamydicidal concentrations were all within the ranges reported previously. Combinations of azithromycin with either ofloxacin, doxycycline, or rifampin, as well as combinations of three antibiotics (rifampin, azithromycin, and ofloxacin or doxycycline), showed synergistic activity against
C. pneumoniae
.
Analysis of Vancomycin Population Susceptibility Profiles, Killing Activity, and Postantibiotic Effect against Vancomycin-Intermediate
Staphylococcus aureus
Authors: Aeschlimann Jeffrey R. , Hershberger Ellie , Rybak Michael J.
Published: October 2018

Methicillin-resistant
Staphylococcus aureus
strains with decreased vancomycin susceptibility have been isolated from patients in the United States and Japan. The impact of decreased vancomycin susceptibility on the drug’s pharmacodynamic parameters has not been addressed. We studied the activity of vancomycin against three clinical strains of vancomycin intermediate-susceptible
Staphylococcus aureus
(VISA) under high- and low-inoculum conditions, with stationary- and logarithmic-growth-phase kill curves, and in postantibiotic effect (PAE) experiments. We also investigated the stability of the decreased vancomycin susceptibility by using population susceptibility profiles. The respective vancomycin microdilution MICs and MBCs for VISA strains HIP5836, 14379, and Mu50 were 8 and 8, 8 and 8, and 8 and 16 μg/ml. HIP5836 had the most homogeneous elevation of vancomycin MICs, because the MIC for nearly all bacteria in the inoculum was 8 μg/ml. The population MICs (defined as the lowest vancomycin concentration inhibiting 99.9% of growth) for the first serial passages of HIP5836, Mu50, and 14379 were 8, 4, and 2 μg/ml, respectively. After 10 passages, they decreased to 4, 2, and 1 μg/ml, respectively. The Mu50 population MIC increased to 12 μg/ml after five serial passages on vancomycin agar. In the low- and high-inoculum kill curves, time to 99.9% killing was significantly (
P
< 0.05) longer for both Mu50 and HIP5836 than that for 14379 and a control strain. However, colony counts at 24 h were similar to those of the vancomycin-sensitive strain for all VISA strains. The PAE (at 4× MIC) ranged from 1.3 h for 14379 to 2.0 h for HIP5836 and was similar to or greater than the PAE against the vancomycin-sensitive strain. In conclusion, we found that the decreased vancomycin susceptibility increased during persistent exposures to the drug and decreased upon removal of the selective pressure. The decreased vancomycin susceptibility decreased the rate of vancomycin killing, but did not affect the extent of killing or the PAE.
Phenotypes and Genotypes of Erythromycin-Resistant
Streptococcus pyogenes
Strains in Italy and Heterogeneity of Inducibly Resistant Strains
Authors: Giovanetti Eleonora , Montanari Maria Pia , Mingoia Marina , Varaldo Pietro Emanuele
Published: October 2018

A total of 387 clinical strains of erythromycin-resistant (MIC, ≥1 μg/ml)
Streptococcus pyogenes
, all isolated in Italian laboratories from 1995 to 1998, were examined. By the erythromycin-clindamycin double-disk test, 203 (52.5%) strains were assigned to the recently described M phenotype, 120 (31.0%) were assigned to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLS) phenotype, and 64 (16.5%) were assigned to the constitutive MLS resistance (cMLS) phenotype. The inducible character of the resistance of the iMLS strains was confirmed by comparing the clindamycin MICs determined under normal testing conditions and those determined after induction by pregrowth in 0.05 μg of erythromycin per ml. The MICs of erythromycin, clarithromycin, azithromycin, josamycin, spiramycin, and the ketolide HMR3004 were then determined and compared. Homogeneous susceptibility patterns were observed for the isolates of the cMLS phenotype (for all but one of the strains, HMR3004 MICs were 0.5 to 8 μg/ml and the MICs of the other drugs were >128 μg/ml) and those of the M phenotype (resistance only to the 14- and 15-membered macrolides was recorded, with MICs of 2 to 32 μg/ml). Conversely, heterogeneous susceptibility patterns were observed in the isolates of the iMLS phenotype, which were subdivided into three distinct subtypes designated iMLS-A, iMLS-B, and iMLS-C. The iMLS-A strains (
n
= 84) were highly resistant to the 14-, 15-, and 16-membered macrolides and demonstrated reduced susceptibility to low-level resistance to HMR3004. The iMLS-B strains (
n
= 12) were highly resistant to the 14- and 15-membered macrolides, susceptible to the 16-membered macrolides (but highly resistant to josamycin after induction), and susceptible to HMR3004 (but intermediate or resistant after induction). The iMLS-C strains (
n
= 24) had lower levels of resistance to the 14- and 15-membered macrolides (with erythromycin MICs increasing two to four times after induction), were susceptible to the 16-membered macrolides (but resistant to josamycin after induction), and remained susceptible to HMR3004, also after induction. The erythromycin resistance genes in 100 isolates of the different groups were investigated by PCR. All cMLS and iMLS-A isolates tested had the
ermAM
(
ermB
) gene, whereas all iMLS-B and iMLS-C isolates had the
ermTR
gene (neither methylase gene was found in isolates of other groups). The M isolates had only the macrolide efflux (
mefA
) gene, which was also found in variable proportions of cMLS, iMLS-A, iMLS-B, and iMLS-C isolates. The three iMLS subtypes were easily differentiated by a triple-disk test set up by adding a josamycin disk to the erythromycin and clindamycin disks of the conventional double-disk test. Tetracycline resistance was not detected in any isolate of the iMLS-A subtype, whereas it was observed in over 90% of both iMLS-B and iMLS-C isolates.
A Novel Injectable Water-Soluble Amphotericin B-Arabinogalactan Conjugate
Authors: Falk Rama , Domb Abraham J. , Polacheck Itzhack
Published: October 2018

New, stable, highly water-soluble, nontoxic polysaccharide conjugates of amphotericin B (AmB) are described. AmB was conjugated by a Schiff-base reaction with oxidized arabinogalactan (AG). AG is a highly branched natural polysaccharide with unusual water solubility (70% in water). A high yield of active AmB was obtained with the conjugates which were similarly highly water soluble and which could be appropriately formulated for injection. They showed comparable MICs forCandida albicansandCryptococcus neoformans(MICs, 0.1 to 0.2 μg/ml). The reduced AmB conjugate, which was synthesized at pH 11 for 48 h at 37°C, was nonhemolytic and was much safer than conventional micellar AmB-deoxycholate. It was the least toxic AmB-AG conjugate among those tested with mice (maximal tolerated dose, 50 mg/kg of body weight), and histopathology indicated no damage to the liver or kidneys. This conjugate, similarly to the liposomal formulation (AmBisome), was more effective than AmB-deoxycholate in prolonging survival. It was more effective than both the liposomal and the deoxycholate formulations in eradicating yeast cells from target organs. The overall results suggest that after further development of the AmB-AG conjugate, it may be a potent agent in the treatment of fungal infections.
Contribution of Topoisomerase IV and DNA Gyrase Mutations in
Streptococcus pneumoniae
to Resistance to Novel Fluoroquinolones
Authors: Pestova Ekaterina , Beyer Rebecca , Cianciotto Nicholas P. , Noskin Gary A. , Peterson Lance R.
Published: October 2018

In this study, we assessed the activity of ciprofloxacin, levofloxacin, sparfloxacin, and trovafloxacin against clinical isolates of
Streptococcus pneumoniae
that were resistant to the less-recently developed fluoroquinolones by using defined amino acid substitutions in DNA gyrase and topoisomerase IV. The molecular basis for resistance was assessed by using mutants selected with trovafloxacin, ciprofloxacin, and levofloxacin in vitro. This demonstrated that the primary target of trovafloxacin in
S. pneumoniae
is the ParC subunit of DNA topoisomerase IV, similar to most other fluoroquinolones. However, first-step mutants bearing the Ser79→Phe/Tyr substitution in topoisomerase IV subunit ParC were susceptible to trovafloxacin with a minimum inhibitory concentration of 0.25 μg/ml, and mutations in the structural genes for both topoisomerase IV subunit ParC (
parC
) and the DNA gyrase subunit (
gyrA
) were required to achieve levels of resistance above the breakpoint. The data also suggest that enhanced activity of trovafloxacin against pneumococci is due to a combination of factors that may include reduced efflux of this agent and an enhanced activity against both DNA gyrase and topoisomerase IV.
Effects of the Human Immunodeficiency Virus (HIV) Proteinase Inhibitors Saquinavir and Indinavir on In Vitro Activities of Secreted Aspartyl Proteinases of
Candida albicans
Isolates from HIV-Infected Patients
Authors: Korting Hans C. , Schaller Martin , Eder Gabriele , Hamm Gerald , Böhmer Ursula , Hube Bernhard
Published: October 2018

The effects of therapeutically relevant concentrations of the human immunodeficiency virus (HIV) proteinase inhibitors saquinavir and indinavir on the in vitro proteinase activity of
Candida albicans
were investigated with isolates from HIV-infected and uninfected patients with oral candidiasis. After exposure to the HIV proteinase inhibitors, proteinase activity was significantly reduced in a dose-dependent manner. These inhibitory effects, which were similar to that of pepstatin A, and the reduced virulence phenotype in experimental candidiasis after application of saquinavir indicate the usefulness of these HIV proteinase inhibitors as potential anticandidal agents.
Histatin 3-Mediated Killing of
Candida albicans
: Effect of Extracellular Salt Concentration on Binding and Internalization
Authors: Xu Yanying , Ambudkar Indu , Yamagishi Hisako , Swaim William , Walsh Thomas J. , O’Connell Brian C.
Published: October 2018

Human saliva contains histidine-rich proteins, histatins, which have antifungal activity in vitro. The mechanism by which histatins are able to kill
Candida albicans
may have clinical significance but is currently unknown. Using radiolabeled histatin 3, we show that the protein binds to
C. albicans
spheroplasts in a manner that is dependent on time and concentration. Binding to the spheroplasts was saturable and could be competed with unlabeled histatin 3. A single histatin 3 binding site with a

K
d

= 5.1 μM was detected. Histatin 3 binding resulted in potassium and magnesium efflux, predominantly within the first 30 min of incubation. Studies with fluorescent histatin 3 demonstrate that the protein is internalized by
C. albicans
and that translocation of histatin inside the cell is closely associated with cell death. Histatin binding, internalization, and cell death are accelerated in low-ionic-strength conditions. Indeed, a low extracellular salt concentration was essential for cell death to occur, even when histatin 3 was already bound to the cell. The interaction of histatin 3 with
C. albicans
, and subsequent cell death, is inhibited at low temperature. These results demonstrate that the candidacidal activity of histatin 3 is not due exclusively to binding at the cell surface but also involves subsequent interactions with the cell.
Bactericidal/Permeability-Increasing Protein Inhibits Growth of a Strain of
Acholeplasma laidlawii
and L Forms of the Gram-Positive Bacteria
Staphylococcus aureus
and
Streptococcus pyogenes
Authors: Horwitz Arnold H. , Williams Robert E. , Liu Pei-Syan , Nadell Rossana
Published: October 2018

Bactericidal/permeability-increasing protein (BPI) inhibited growth of cell wall-deficient
Acholeplasma laidlawii
and L forms of certain strains of
Staphylococcus aureus
and
Streptococcus pyogenes
. However, the same strains of
S. aureus
and
S. pyogenes
with intact cell walls were not susceptible to the growth-inhibitory effects of BPI.
In Vitro Activities of
Strychnos
Alkaloids and Extracts against
Plasmodium falciparum
Authors: Frederich Michel , Hayette Marie-Pierre , Tits Monique , De Mol Patrick , Angenot Luc
Published: October 2018

The in vitro antimalarial activities of 46 alkaloids and extracts from
Strychnos
species were evaluated. Two types of quasidimeric alkaloids exhibit high and selective activities against
Plasmodium
. Strychnopentamine and isostrychnopentamine were active against chloroquine-sensitive and -resistant strains (50% inhibitory concentration [IC
50
] ≈ 0.15 μM), while dihydrousambarensine exhibited a 30-fold higher activity against the chloroquine-resistant strain (IC
50
= 0.03 μM) than it did against the chloroquine-sensitive strain.
Improving quality of care during childbirth in primary health centres: a stepped-wedge cluster-randomised trial in India
Authors: Agarwal Ramesh , Chawla Deepak , Sharma Minakshi , Nagaranjan Shyama , Dalpath Suresh K , Gupta Rakesh , Kumar Saket , Chaudhuri Saumyadripta , Mohanty Premananda , Sankar Mari Jeeva , Agarwal Krishna , Rani Shikha , Thukral Anu , Jain Suksham , Yadav Chandra Prakash , Gathwala Geeta , Kumar Praveen , Sarin Jyoti , Sreenivas Vishnubhatla , Aggarwal Kailash C , Kumar Yogesh , Kharya Pradip , Bisht Surender Singh , Shridhar Gopal , Arora Raksha , Joshi Kapil , Bhalla Kapil , Soni Aarti , Singh Sube , Devakirubai Prischillal , Samuel Ritu , Yadav Reena , Bahl Rajiv , Kumar Vijay , Paul Vinod Kumar
Published: October 2018

Background

Low/middle-income countries need a large-scale improvement in the quality of care (QoC) around the time of childbirth in order to reduce high maternal, fetal and neonatal mortality. However, there is a paucity of scalable models.

Methods

We conducted a stepped-wedge cluster-randomised trial in 15 primary health centres (PHC) of the state of Haryana in India to test the effectiveness of a multipronged quality management strategy comprising capacity building of providers, periodic assessments of the PHCs to identify quality gaps and undertaking improvement activities for closure of the gaps. The 21-month duration of the study was divided into seven periods (steps) of 3  months each. Starting from the second period, a set of randomly selected three PHCs (cluster) crossed over to the intervention arm for rest of the period of the study. The primary outcomes included the number of women approaching the PHCs for childbirth and 12 directly observed essential practices related to the childbirth. Outcomes were adjusted with random effect for cluster (PHC) and fixed effect for ‘months of intervention’.

Results

The intervention strategy led to increase in the number of women approaching PHCs for childbirth (26 vs 21 women per PHC-month, adjusted incidence rate ratio: 1.22; 95% CI 1.17 to 1.28). Of the 12 practices, 6 improved modestly, 2 remained near universal during both intervention and control periods, 3 did not change and 1 worsened. There was no evidence of change in mortality with a majority of deaths occurring either during referral transport or at the referral facilities.

Conclusion

A multipronged quality management strategy enhanced utilisation of services and modestly improved key practices around the time of childbirth in PHCs in India.

Trial registration number

CTRI/2016/05/006963.
Bridging clinic: The initial medical management of patients with newly diagnosed pancreatic cancer
Authors: Sreedharan Loveena , Kumar Bhaskar , Jewell Anna , Banim Paul , Koulouris Andreas , Hart Andrew R
Published: October 2018

Pancreatic cancer is the 11th most common cancer in the UK and has the worst prognosis of any tumour with minimal improvements in survival over recent decades. As most patients are either ineligible for surgery or may decline chemotherapy, the emphasis is on control of symptoms and management of complications such as poor nutritional status. The time period between informing the patient of their diagnosis and commencing cancer treatments presents a valuable opportunity to proactively identify and treat symptoms to optimise patients’ overall well-being. The ‘bridging clinic’, delivered by a range of healthcare professionals from gastroenterologists to nurse practitioners, can provide this interface where patients are first informed of their diagnosis and second supportive therapies offered. In this article, we provide a structure for instituting such supportive therapies at the bridging clinic. The components of the clinic are summarised using the mnemonic INDASH (Information/Nutrition/Diabetes and Depression/Analgesia/Stenting/Hereditary) and each is discussed in detail below.
Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver
Authors: Habib Aida , Chokr Dina , Wan JingHong , Hegde Pushpa , Mabire Morgane , Siebert Matthieu , Ribeiro-Parenti Lara , Le Gall Maude , Lettéron Philippe , Pilard Nathalie , Mansouri Abdellah , Brouillet Arthur , Tardelli Matteo , Weiss Emmanuel , Le Faouder Pauline , Guillou Hervé , Cravatt Benjamin F , Moreau Richard , Trauner Michael , Lotersztajn Sophie
Published: October 2018

Objective

Sustained inflammation originating from macrophages is a driving force of fibrosis progression and resolution. Monoacylglycerol lipase (MAGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. It is a proinflammatory enzyme that metabolises 2-arachidonoylglycerol, an endocannabinoid receptor ligand, into arachidonic acid. Here, we investigated the impact of MAGL on inflammation and fibrosis during chronic liver injury.

Design

C57BL/6J mice and mice with global invalidation of MAGL (MAGL-/-), or myeloid-specific deletion of either MAGL (MAGLMye-/-), ATG5 (ATGMye-/-) or CB2 (CB2Mye-/-), were used. Fibrosis was induced by repeated carbon tetrachloride (CCl4) injections or bile duct ligation (BDL). Studies were performed on peritoneal or bone marrow-derived macrophages and Kupffer cells.

Results

MAGL-/- or MAGLMye-/- mice exposed to CCl4 or subjected to BDL were more resistant to inflammation and fibrosis than wild-type counterparts. Therapeutic intervention with MJN110, an MAGL inhibitor, reduced hepatic macrophage number and inflammatory gene expression and slowed down fibrosis progression. MAGL inhibitors also accelerated fibrosis regression and increased Ly-6Clow macrophage number. Antifibrogenic effects exclusively relied on MAGL inhibition in macrophages, since MJN110 treatment of MAGLMye-/- BDL mice did not further decrease liver fibrosis. Cultured macrophages exposed to MJN110 or from MAGLMye-/- mice displayed reduced cytokine secretion. These effects were independent of the cannabinoid receptor 2, as they were preserved in CB2Mye-/- mice. They relied on macrophage autophagy, since anti-inflammatory and antifibrogenic effects of MJN110 were lost in ATG5Mye-/- BDL mice, and were associated with increased autophagic flux and autophagosome biosynthesis in macrophages when MAGL was pharmacologically or genetically inhibited.

Conclusion

MAGL is an immunometabolic target in the liver. MAGL inhibitors may show promising antifibrogenic effects during chronic liver injury.
Incidence of primary graft dysfunction after lung transplantation is altered by timing of allograft implantation
Authors: Cunningham Peter S , Maidstone Robert , Durrington Hannah J , Venkateswaran Rajamayier V , Cypel Marcelo , Keshavjee Shaf , Gibbs Julie E , Loudon Andrew S , Chow Chung-Wai , Ray David W , Blaikley John F
Published: October 2018

The importance of circadian factors in managing patients is poorly understood. We present two retrospective cohort studies showing that lungs reperfused between 4 and 8 AM have a higher incidence (OR 1.12; 95% CI 1.03 to 1.21; p=0.01) of primary graft dysfunction (PGD) in the first 72 hours after transplantation. Cooling of the donor lung, occurring during organ preservation, shifts the donor circadian clock causing desynchrony with the recipient. The clock protein REV-ERBα directly regulates PGD biomarkers explaining this circadian regulation while also allowing them to be manipulated with synthetic REV-ERB ligands.
Axial and radial thermal responses of energy pile under six storey residential building
Authors: Faizal Mohammed , Bouazza Abdelmalek , McCartney John S. , Haberfield Chris
Published: October 2018

The axial and radial thermal responses of a cast-in-place energy pile, 10 m long and 0.6 m in diameter, installed in unsaturated sand under a six storey building are examined during a heating–cooling cycle. The instrumentation in the pile was configured to compare radial and axial thermal responses at the same elevations and to evaluate the temperature and axial thermal stress distribution across the cross-sectional area of the pile. The magnitudes of the axial thermal strains were more constrained than the radial thermal strains at all depths, leading to the development of axial and radial thermal stresses of up to –4.5 and –0.015 MPa, respectively, for a change in average pile temperature of 24.1 °C. The magnitudes of the radial thermal stresses with changes in pile temperature were significantly lower than the axial thermal stresses at all depths of the pile, indicating that the radial thermal expansion had negligible effects on the development of axial thermal strains and stresses. The temperature distribution over the cross section of the pile showed low variations at all depths, indicating that it would be justified to consider a uniform temperature distribution at least in piles of similar dimensions and with even heat exchanger layouts.
Fluctuation Dissipation Theorem and Electrical Noise Revisited
Authors: Reggiani Lino , Alfinito Eleonora
Published: October 2018

The fluctuation dissipation theorem (FDT) is the basis for a microscopic description of the interaction between electromagnetic radiation and matter. By assuming the electromagnetic radiation in thermal equilibrium and the interaction in the linear-response regime, the theorem interrelates the macroscopic spontaneous fluctuations of an observable with the kinetic coefficients that are responsible for energy dissipation in the linear response to an applied perturbation. In the quantum form provided by Callen and Welton in their pioneering paper of 1951 for the case of conductors [H. B. Callen and T. A. Welton, Irreversibility and generalized noise, Phys. Rev. 83 (1951) 34], electrical noise in terms of the spectral density of voltage fluctuations, [Formula: see text], detected at the terminals of a conductor was related to the real part of its impedance, [Formula: see text], by the simple relation [Formula: see text] where [Formula: see text] is the Boltzmann constant, [Formula: see text] is the absolute temperature, [Formula: see text] is the reduced Planck constant and [Formula: see text] is the angular frequency. The drawbacks of this relation concern with: (i) the appearance of a zero-point contribution which implies a divergence of the spectrum at increasing frequencies; (ii) the lack of detailing the appropriate equivalent-circuit of the impedance, (iii) the neglect of the Casimir effect associated with the quantum interaction between zero-point energy and boundaries of the considered physical system; (iv) the lack of identification of the microscopic noise sources beyond the temperature model. These drawbacks do not allow to validate the relation with experiments, apart from the limiting conditions when [Formula: see text]. By revisiting the FDT within a brief historical survey of its formulation, since the announcement of Stefan–Boltzmann law dated in the period 1879–1884, we shed new light on the existing drawbacks by providing further properties of the theorem with particular attention to problems related with the electrical noise of a two-terminals sample under equilibrium conditions. Accordingly, among others, we will discuss the duality and reciprocity properties of the theorem, the role played by different statistical ensembles, its applications to the ballistic transport-regime, to the case of vacuum and to the case of a photon gas.
Domain Knowledge-Based Link Prediction in Customer-Product Bipartite Graph for Product Recommendation
Authors: Zhang Lingling , Li Jing , Zhang Qiuliu , Meng Fan , Teng Weili
Published: October 2018

In this paper, we propose domain knowledge-based link prediction algorithm in customer-product bipartite network to improve effectiveness of product recommendation in retail. The domain knowledge is classified into product domain knowledge and time context knowledge, which play an important part in link prediction. We take both of them into consideration in recommendation and form a unified domain knowledge-based link prediction framework. We capture product semantic similarity by ontology-based analysis and time attenuation factor from time context knowledge, then incorporate them into network topological similarity to form a new linkage measure. To evaluate the algorithm, we use a real retail transaction dataset from Food Mart. Experimental results demonstrate that the usage of domain knowledge in link prediction achieved significantly better performance.
Mapping Genes Is Good for You
Authors: Womack James E. (Jim)
Published: October 2018

I abandoned my original career choice of high school teaching to pursue dentistry and soon abandoned that path for genetics. The latter decision was due to a challenge by a professor that led to me reading Nobel speeches by pioneer geneticists before I had formal exposure to the subject. Even then, I was 15 years into my career before my interest in rodent genomes gave way to mapping cattle genes. Events behind these twists and turns in my career path comprise the first part of this review. The remainder is a review of the development of the field of bovine genomics from my personal perspective. I have had the pleasure of working with outstanding graduate students, postdocs, and colleagues to contribute my small part to a discipline that has evolved from a few individuals mapping an orphan genome to a discipline underlying a revolution in animal breeding.
Multiomics approach reveals metabolic changes in the heart at birth
Authors: Walejko Jacquelyn M. , Koelmel Jeremy P. , Garrett Timothy J. , Edison Arthur S. , Keller-Wood Maureen
Published: October 2018

During late gestation, the fetal heart primarily relies on glucose and lactate to support rapid growth and development. Although numerous studies describe changes in heart metabolism to utilize fatty acids preferentially a few weeks after birth, little is known about metabolic changes of the heart within the first day following birth. Therefore, we used the ovine model of pregnancy to investigate metabolic differences between the near-term fetal and the newborn heart. Heart tissue was collected for metabolomic, lipidomic, and transcriptomic approaches from the left and right ventricles and intraventricular septum in 7 fetuses at gestational day 142 and 7 newborn lambs on the day of birth. Significant metabolites and lipids were identified using a Student’s t-test, whereas differentially expressed genes were identified using a moderated t-test with empirical Bayes method [false discovery rate (FDR)-corrected P < 0.10]. Single-sample gene set enrichment analysis (ssGSEA) was used to identify pathways enriched on a transcriptomic level (FDR-corrected P < 0.05), whereas overrepresentation enrichment analysis was used to identify pathways enriched on a metabolomic level ( P < 0.05). We observed greater abundance of metabolites involved in butanoate and propanoate metabolism, and glycolysis in the term fetal heart and differential expression in these pathways were confirmed with ssGSEA. Immediately following birth, newborn hearts displayed enrichment in purine, fatty acid, and glycerophospholipid metabolic pathways as well as oxidative phosphorylation with significant alterations in both lipids and metabolites to support transcriptomic findings. A better understanding of metabolic alterations that occur in the heart following birth may improve treatment of neonates at risk for heart failure.
Duration of Heat Stress Effect on Invasiveness ofL. monocytogenesStrains
Authors: Wałecka-Zacharska Ewa , Gmyrek Renata , Skowron Krzysztof , Kosek-Paszkowska Katarzyna , Bania Jacek
Published: October 2018

During food production and food conservation, as well as the passage through the human gastrointestinal (GI) tract,L. monocytogenesis exposed to many adverse conditions which may elicit a stress response. As a result the pathogen may become more resistant to other unpropitious factors and may change its virulence. It has been shown that low and high temperature, salt, low pH, and high pressure affect the invasion capacity ofL. monocytogenes. However, there is a scarcity of data on the duration of the stress effect on bacterial biology, including invasiveness. The aim of this work was to determine the period during whichL. monocytogenesinvasiveness remains altered under optimal conditions following exposure of bacteria to mild heat shock stress. TenL. monocytogenesstrains were exposed to heat shock at 54°C for 20 minutes. Then both heat-treated and nontreated control bacteria were incubated under optimal growth conditions, 37°C, for up to 72 hours and the invasion capacity was tested. Additionally, the expression of virulence and stress response genes was investigated in 2 strains. We found that heat stress exposure significantly decreases the invasiveness of all tested strains. However, during incubation at 37°C the invasion capacity of heat-treated strains recovered to the level of nontreated controls. The observed effect was strain-dependent and lasted from less than 24 hours to 72 hours. The invasiveness of 6 out of the 10 nontreated strains decreased during incubation at 37°C. The expression ofinlABcorrelated with the increase of invasiveness but the decrease of invasiveness did not correlate with changes of the level of these transcripts.Conclusions. The effect of heat stress onL. monocytogenesinvasiveness is strain-dependent and was transient, lasting up to 72 hours.
Optimal Design of Fault‐Tolerant Controller for an Electric Power Steering System with Sensor Failures Using Genetic Algorithm
Authors: Liu Xue , Pang Hui , Shang Yuting , Wu Wen
Published: October 2018

This paper focuses on the fault‐tolerant control (FTC) problem for an electric power steering (EPS) system subjected to stochastic sensor failures, and a novel fault‐tolerant controller is proposed based on the genetic algorithm (GA). A mathematical model of the EPS system with sensor failures is first established, and the state feedback control law is solved by using linear quadratic regulator techniques to stabilize the closed‐loop control system. Then, the dynamic response errors of the EPS system with and without sensor faults are chosen as the optimization objective function. Furthermore, the appropriate weighting matrices are evaluated to obtain the optimal fault control law by using GA. Finally, simulation results are presented to illustrate the effectiveness of the proposed control strategy.
Predefined-Time Consensus of Nonlinear First-Order Systems Using a Time Base Generator
Authors: Colunga J. Armando , Vázquez Carlos R. , Becerra Héctor M. , Gómez-Gutiérrez David
Published: October 2018

This paper proposes a couple of consensus algorithms for multiagent systems in which agents have first-order nonlinear dynamics, reaching the consensus state at a predefined time independently of the initial conditions. The proposed consensus protocols are based on the so-called time base generators (TBGs), which are time-dependent functions used to build time-varying control laws. Predefined-time convergence to the consensus is proved for connected undirected communication topologies and directed topologies having a spanning tree. Furthermore, one of the proposed protocols is based on the super-twisting controller, providing robustness against disturbances while maintaining the predefined-time convergence property. The performance of the proposed methods is illustrated in simulations, and it is compared with finite-time, fixed-time, and predefined-time consensus protocols. It is shown that the proposed TBG protocols represent an advantage not only in the possibility to define a settling time but also in providing smoother and smaller control actions than existing finite-time, fixed-time, and predefined-time consensus.
Metal Availability and Transfer along Food Chains in Siena, a Small Medieval Town in Italy
Authors: Rota Emilia , Bianchi Nicola , Bargagli Roberto
Published: October 2018

Heavy metals originating from vehicular emissions and other anthropogenic sources pose one of the main environmental health risks in urban areas. The assessment of metal bioaccumulation in selected species of synanthropic organisms allows evaluating their bioavailability and the transfer along food chains in urban ecosystems. An overall view of the results achieved in Siena on urban ecosystems shows that the mean Cd, Cu, Pb, and Zn concentrations in biological crusts covering urban walls (0.66, 34, 65, and 184 μg·g−1 d.w.) are higher than the respective concentrations in tree leaf litter (0.19, 9.5, 9.2, and 38 μg·g−1 d.w.) and topsoil (0.40, 44, 34.2, and 102 μg·g−1 d.w.). Furthermore, the epilithic moss Tortula muralis accumulated much higher levels of Cd, Cu, Pb, and Zn (0.34, 65, 17.6, and 106 μg·g−1 d.w.) than epiphytic lichens (0.22, 11.6, 2.1, and 47.3 μg·g−1 d.w.) or the holm oak live foliage (0.15, 14, 1.51, and 26.5 μg·g−1 d.w.), respectively. However, analyses of the soft tissues of Papillifera papillaris, a snail dwelling on stone walls, show that metals deposited on urban walls are scarcely bioavailable. Papillifera accumulates (and transfers to the next trophic level) amounts of Cd, Cu, Pb, and Zn (1.7, 171, 1.1, and 71 μg·g−1 d.w., respectively) that are comparable or inferior to those found in a ground-dwelling snail (3.3, 88, 2.0, and 880 μg·g−1 d.w.) and two earthworm species (2.0–4.4, 18–23, 1.4–2.2, and 356–594 μg·g−1 d.w.) from the same urban green area.
Value of Transvaginal Two-Dimensional Contrast-Enhanced Ultrasonography in Diagnosing Atypical Ovarian Corpus Luteum Hematoma
Authors: Liu Hui , Xiang Hong , Mu Ruixue , Tuoerhan Palida , Zeng Qianqian , Zhou Huili , Hu Rong , Shahai Gulinaer
Published: October 2018

Objective. To evaluate the value of transvaginal two-dimensional contrast-enhanced ultrasonography (2D-CEUS) in the diagnosis of atypical ovarian corpus luteum hematoma (AT-OCLH). Methods. A prospective study was performed on 53 consecutive patients with suspected AT-OCLH, and the diagnostic results by transvaginal 2D-CEUS were statistically compared with the gold standard. The gold standard results were confirmed by surgical pathology or long-term follow-up. Results. The characteristic perfusion patterns of AT-OCLH in 2D-CEUS showed no contrast agent perfusion within the tumor mass, and the capsule wall showed rapid, annular, high enhancement perfusion; perfusion patterns could be classified into type Ia and type IIa. AT-OCLH can be distinguished from ovarian tumors based on perfusion characteristics and perfusion pattern type, which can be diagnosed based on the significantly stronger cystic wall perfusion intensity, earlier arrival time, and thicker cystic wall than nonluteal cystic foci (P<0.05). The sensitivity of 2D-CEUS for diagnosing AT-OCLH was 95.7%, with a specificity of 96.6%. A 2D-CEUS scoring system for AT-OCLH was established. Lesions with scores >17.5 were diagnosed as AT-OCLH. Conclusion. 2D-CEUS is an effective method for diagnosing AT-OCLH.
Complementary Judgment Matrix Method with Imprecise Information for Multicriteria Decision-Making
Authors: Wang Haichao , Lahdelma Risto , Salminen Pekka
Published: October 2018

The complementary judgment matrix (CJM) method is an MCDA (multicriteria decision aiding) method based on pairwise comparisons. As in AHP, the decision-maker (DM) can specify his/her preferences using pairwise comparisons, both between different criteria and between different alternatives with respect to each criterion. The DM specifies his/her preferences by allocating two nonnegative comparison values so that their sum is 1. We measure and pinpoint possible inconsistency byinconsistency errors. We also compare the consistency of CJM and AHP trough simulation. Because preference judgments are always more or less imprecise or uncertain, we introduce a way to represent the uncertainty through stochastic distributions, and a computational method to treat the uncertainty. As in Stochastic Multicriteria Acceptability Analysis (SMAA), we consider different uncertainty levels: precise comparisons, imprecise comparisons with a stochastic distribution, and missing comparisons between criteria. We compute rank acceptability indices for the alternatives, describing the probability of an alternative to obtain a given rank considering the level of uncertainty and study the influence of the uncertainty on the SMAA-CJM results.
Plasma Nucleotide Dynamics during Exercise and Recovery in Highly Trained Athletes and Recreationally Active Individuals
Authors: Zarębska Ewa A. , Kusy Krzysztof , Słomińska Ewa M. , Kruszyna Łukasz , Zieliński Jacek
Published: October 2018

Circulating plasma ATP is able to regulate local skeletal muscle blood flow and 02 delivery causing considerable vasodilatation during exercise. We hypothesized that sport specialization and specific long-term training stimuli have an impact on venous plasma [ATP] and other nucleotides concentration. Four athletic groups consisting of sprinters (n=11; age range 21–30 yr), endurance-trained athletes (n=16; age range 18–31 yr), futsal players (n=14; age range 18–30 yr), and recreationally active individuals (n=12; age range 22–33 yr) were studied. Venous blood samples were collected at rest, during an incremental treadmill test, and during recovery. Baseline [ATP] was 759±80 nmol·l−1 in competitive athletes and 680±73 nmol·l−1 in controls and increased during exercise by ~61% in competitive athletes and by ~31% in recreationally active participants. We demonstrated a rapid increase in plasma [ATP] at exercise intensities of 83–87% of VO2max in competitive athletes and 94% in controls. Concentrations reported after 30 minutes of recovery were distinct from those obtained preexercise in competitive athletes (P<0.001) but not in controls (P=0.61). We found a correlation between total-body skeletal muscle mass and resting and maximal plasma [ATP] in competitive athletes (r=0.81 and r=0.75, respectively). In conclusion, sport specialization is significantly related to plasma [ATP] at rest, during exercise, and during maximal effort. Intensified exercise-induced plasma [ATP] increases may contribute to more effective vessel dilatation during exercise in highly trained athletes than in recreational runners. The most rapid increase in ATP concentration was associated with the respiratory compensation point. No differences between groups of competitive athletes were observed during the recovery period suggesting a similar pattern of response after exercise. Total-body skeletal muscle mass is indirectly related to plasma [ATP] in highly trained athletes.
An Evaluation of Clinical and Histopathological Aspects of Patients with Oral Submucous Fibrosis in the Background of Oral Squamous Cell Carcinoma
Authors: Siriwardena B. S. M. S. , Jayawardena K. L. T. D. , Senarath N. H. , Tilakaratne W. M.
Published: October 2018

Background. The behavior and prognosis of oral squamous cell carcinoma (OSCC) is presumably different in patients with oral submucous fibrosis (OSF). The objective of this study was to assess the effects of demographic features, habits, and histopathological features in the transformation of OSF to OSCC.Methods. Data were extracted from the archives and histopathological evaluation and presence of nodal metastasis were recorded.Results. OSF was detected in 130 (48%) out of 273 OSCC patients. The mean age of presentation among OSF-positive patients was 57.7 years, while patients diagnosed only with OSCC had a comparatively higher age, 59.5 years. In the below 50 years of age group, presence of OSF with OSCC was less (40%). In the OSF-positive group, male to female ratio was 3.2:1. The common primary sites were buccal mucosa and tongue in both groups. Betel quid chewing was present in more than 95% of the sample. Betel chewing, smoking, and alcohol consumption were present in 26.15% of OSF-positive patients. Degree of fibrosis was neither associated with the level of histological differentiation of the tumor (p= 0.195) nor associated with the malignant transformation (p =0.373). Lymph node metastasis was not seen in 76.63% and 68.54% of the patients with and without OSF, respectively.Conclusions. High degree of prevalence of OSF was observed among the OSCC patients. There were also a male predilection and younger age at presentation in these patients. However, a significant association was not observed in the degree of fibrosis with malignant transformation or the level of histopathological differentiation of the tumor. Lymph node metastasis also failed to express a significant relationship with the presence of OSF.
Overexpression of CD44 Variant 9: A Novel Cancer Stem Cell Marker in Human Cholangiocarcinoma in Relation to Inflammation
Authors: Suwannakul Nattawan , Ma Ning , Thanan Raynoo , Pinlaor Somchai , Ungarreevittaya Piti , Midorikawa Kaoru , Hiraku Yusuke , Oikawa Shinji , Kawanishi Shosuke , Murata Mariko
Published: October 2018

Various CD44 isoforms are expressed in several cancer stem cells during tumor progression and metastasis. In particular, CD44 variant 9 (CD44v9) is highly expressed in chronic inflammation-induced cancer. We investigated the expression of CD44v9 and assessed whether CD44v9 is a selective biomarker of human cholangiocarcinoma (CCA). The expression profile of CD44v9 was evaluated in human liver flukeOpisthorchis viverrini-related CCA (OV-CCA) tissues, human CCA (independent of OV infection, non-OV-CCA) tissues, and normal liver tissues. CD44v9 overexpression was detected by immunohistochemistry (IHC) in CCA tissues. There was a higher level of CD44v9 expression and IHC score in OV-CCA tissues than in non-OV-CCA tissues, and there was no CD44v9 staining in the bile duct cells of normal liver tissues. In addition, we observed significantly higher expression of inflammation-related markers, such as S100P and COX-2, in OV-CCA tissues compared to that in non-OV and normal liver tissues. Thus, these findings suggest that CD44v9 may be a novel candidate CCA stem cell marker and may be related to inflammation-associated cancer development.
Excess Hydrocortisone Hampers Placental Nutrient Uptake Disrupting Cellular Metabolism
Authors: Mateos Rosa María , Jiménez Gema , Álvarez-Gil Carmen , Visiedo Francisco , Rivera-Rodríguez Fátima , Santos-Rosendo Celeste , Rodriguez-Pareja Antonia , Perdomo Germán , Lechuga-Sancho Alfonso M.
Published: October 2018

Low birth weight increases neonatal morbidity and mortality, and surviving infants have increased risk of metabolic and cardiovascular disturbances later in life, as well as other neurological, psychiatric, and immune complications. A gestational excess of glucocorticoids (GCs) is a well-known cause for fetal growth retardation, but the biological basis for this association remains elusive. Placental growth is closely related to fetal growth. The placenta is the main regulator of nutrient transport to the fetus, resulting from the difference between placental nutrient uptake and the placenta’s own metabolism. The aim of this study was to analyze how excess hydrocortisone affects placental glucose and lipid metabolism. Human placenta explants from term physiological pregnancies were cultured for 18 hours under different hydrocortisone concentrations (2.75, 5.5, and 55 mM; 1, 2, and 20 mg/ml). Placental glucose and lipid uptake and the metabolic partitioning of fatty acids were quantified by isotopic techniques, and expression of specific glucose transporter GLUT1 was quantified by western blot. Cell viability was assessed by MTT, immunohistochemistry and caspase activity. We found that excess hydrocortisone impairs glucose uptake and lipoprotein lipase (LPL) activity, coincident with a GC-dose dependent inhibition of fatty acid oxidation and esterification. None of the experimental conditions showed an increased cell death. In conclusion, our results show that GC overexposure exerts a dysfunctional effect on lipid transport and metabolism and glucose uptake in human placental explants. These findings could well be directly related to a reduced placental growth and possibly to a reduced supply of nutrients to the fetus and the consequent fetal growth retardation and metabolic programming.
Weaning from Mechanical Ventilation in ARDS: Aspects to Think about for Better Understanding, Evaluation, and Management
Authors: Wawrzeniak Iuri Christmann , Regina Rios Vieira Silvia , Almeida Victorino Josué
Published: October 2018

Acute respiratory distress syndrome (ARDS) is characterized by severe inflammatory response and hypoxemia. The use of mechanical ventilation (MV) for correction of gas exchange can cause worsening of this inflammatory response, called “ventilator-induced lung injury” (VILI). The process of withdrawing mechanical ventilation, referred to as weaning from MV, may cause worsening of lung injury by spontaneous ventilation. Currently, there are few specific studies in patients with ARDS. Herein, we reviewed the main aspects of spontaneous ventilation and also discussed potential methods to predict the failure of weaning in this patient category. We also reviewed new treatments (modes of mechanical ventilation, neuromuscular blocker use, and extracorporeal membrane oxygenation) that could be considered in weaning ARDS patients from MV.
A Constraint-Aware Optimization Method for Concurrency Bug Diagnosis Service in a Distributed Cloud Environment
Authors: Bo Lili , Jiang Shujuan
Published: October 2018

The advent of cloud computation and big data applications has enabled data access concurrency to be prevalent in the distributed cloud environment. In the meantime, security issue becomes a critical problem for researchers to consider. Concurrency bug diagnosis service is to analyze concurrent software and then reason about concurrency bugs in them. However, frequent context switches in concurrent program execution traces will inevitably impact the service performance. To optimize the service performance, this paper presents a static constraint-aware method to simplify concurrent program buggy traces. First, taking the original buggy trace as the operation object, we calculate the maximal sound dependence relations based on the constraint models. Then, we iteratively check the dependent constraints and move forward current event to extend thread execution intervals. Finally, we obtain the simplified trace that is equivalent to the original buggy trace. To evaluate our approach, we conduct a set of experiments on 12 widely used Java projects. Experimental results show that our approach outperforms other state-of-the-art approaches in terms of execution time.