bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Review and Meta-analyses of the Effect of Chemotherapy on Pulmonary Mycobacterium abscessus Outcomes and Disease Recurrence
Authors: Pasipanodya Jotam G. , Ogbonna Deborah , Ferro Beatriz E. , Magombedze Gesham , Srivastava Shashikant , Deshpande Devyani , Gumbo Tawanda
Published: August 2017

In pharmacokinetic/pharmacodynamic models of pulmonary
Mycobacterium abscessus
complex, the recommended macrolide-containing combination therapy has poor kill rates. However, clinical outcomes are unknown. We searched the literature for studies published between 1990 and 2017 that reported microbial outcomes in patients treated for pulmonary
M. abscessus
disease. A good outcome was defined as sustained sputum culture conversion (SSCC) without relapse. Random effects models were used to pool studies and estimate proportions of patients with good outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Sensitivity analyses and metaregression were used to assess the robustness of findings. In 19 studies of 1,533 patients, combination therapy was administered to 508 patients with
M. abscessus
subsp.
abscessus
, 204 with
M. abscessus
subsp.
massiliense
, and 301 with
M. abscessus
with no subspecies specified. Macrolide-containing regimens achieved SSCC in only 77/233 (34%) new
M. abscessus
subsp.
abscessus
patients versus 117/141 (54%)
M. abscessus
subsp.
massiliense
patients (OR, 0.108 [95% CI, 0.066 to 0.181]). In refractory disease, SSCC was achieved in 20% (95% CI, 7 to 36%) of patients, which was not significantly different across subspecies. The estimated recurrent rates per month were 1.835% (range, 1.667 to 3.196%) for
M. abscessus
subsp.
abscessus
versus 0.683% (range, 0.229 to 1.136%) for
M. abscessus
subsp.
massiliense
(OR, 6.189 [95% CI, 2.896 to 13.650]). The proportion of patients with good outcomes was 52/223 (23%) with
M. abscessus
subsp.
abscessus
versus 118/141 (84%) with
M. abscessus
subsp.
massiliense
disease (OR, 0.059 [95% CI, 0.034 to 0.101]).
M. abscessus
subsp.
abscessus
pulmonary disease outcomes with the currently recommended regimens are atrocious, with outcomes similar to those for extensively drug-resistant tuberculosis. Therapeutically, the concept of nontuberculous mycobacteria is misguided. There is an urgent need to craft entirely new treatment regimens.
Chronic Brucella Infection Induces Selective and Persistent Interferon Gamma-Dependent Alterations of Marginal Zone Macrophages in the Spleen
Authors: Machelart Arnaud , Khadrawi Abir , Demars Aurore , Willemart Kevin , De Trez Carl , Letesson Jean-Jacques , Muraille Eric
Published: August 2017

The spleen is known as an important filter for blood-borne pathogens that are trapped by specialized macrophages in the marginal zone (MZ): the CD209+MZ macrophages (MZMs) and the CD169+marginal metallophilic macrophages (MMMs). Acute systemic infection strongly impacts MZ populations and the location of T and B lymphocytes. This phenomenon has been linked to reduced chemokine secretion by stromal cells.Brucellaspp. are the causative agent of brucellosis, a widespread zoonotic disease. Here, we usedBrucella melitensisinfection as a model to investigate the impact of chronic stealth infection on splenic MZ macrophage populations. During the late phase ofBrucellainfection, we observed a loss of both MZMs and MMMs, with a durable disappearance of MZMs, leading to a reduction of the ability of the spleen to take up soluble antigens, beads, and unrelated bacteria. This effect appears to be selective as every other lymphoid and myeloid population analyzed increased during infection, which was also observed followingBrucella abortusandBrucella suisinfection. Comparison of wild-type and deficient mice suggested that MZ macrophage population loss is dependent on interferon gamma (IFN-γ) receptor but independent of T cells or tumor necrosis factor alpha receptor 1 (TNF-αR1) signaling pathways and is not correlated to an alteration of CCL19, CCL21, and CXCL13 chemokine mRNA expression. Our results suggest that MZ macrophage populations are particularly sensitive to persistent low-level IFN-γ-mediated inflammation and thatBrucellainfection could reduce the ability of the spleen to perform certain MZM- and MMM-dependent tasks, such as antigen delivery to lymphocytes and control of systemic infection.
Identification of Staphylococcus aureus Factors Required for Pathogenicity and Growth in Human Blood
Authors: Connolly John , Boldock Emma , Prince Lynne R. , Renshaw Stephen A. , Whyte Moira K. , Foster Simon J.
Published: August 2017

Staphylococcus aureus
is a human commensal but also has devastating potential as an opportunistic pathogen.
S. aureus
bacteremia is often associated with an adverse outcome. To identify potential targets for novel control approaches, we have identified
S. aureus
components that are required for growth in human blood. An ordered transposon mutant library was screened, and 9 genes involved specifically in hemolysis or growth on human blood agar were identified by comparing the mutants to the parental strain. Three genes (
purA
,
purB
, and
pabA
) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model. The
pabA
growth defect was specific to the red blood cell component of human blood, showing no difference from the parental strain in growth in human serum, human plasma, or sheep or horse blood. PabA is required in the tetrahydrofolate (THF) biosynthesis pathway. The
pabA
growth defect was found to be due to a combination of loss of THF-dependent dTMP production by the ThyA enzyme and increased demand for pyrimidines in human blood. Our work highlights
pabA
and the pyrimidine salvage pathway as potential targets for novel therapeutics and suggests a previously undefined role for a human blood factor in the activity of sulfonamide antibiotics.
Influence of the Gut Microbiota Composition on Campylobacter jejuni Colonization in Chickens
Authors: Han Zifeng , Willer Thomas , Li Li , Pielsticker Colin , Rychlik Ivan , Velge Philippe , Kaspers Bernd , Rautenschlein Silke
Published: August 2017

The
Campylobacter jejuni
-host interaction may be affected by the host's gut microbiota through competitive exclusion, metabolites, or modification of the immune response. To understand this interaction,
C. jejuni
colonization and local immune responses were compared in chickens with different gut microbiota compositions. Birds were treated with an antibiotic cocktail (AT) (experiments 1 and 2) or raised under germfree (GF) conditions (experiment 3). At 18 days posthatch (dph), they were orally inoculated either with 10
4
CFU of
C. jejuni
or with diluent. Cecal as well as systemic
C. jejuni
colonization, T- and B-cell numbers in the gut, and gut-associated tissue were compared between the different groups. Significantly higher numbers of CFU of
C. jejuni
were detected in the cecal contents of AT and GF birds, with higher colonization rates in spleen, liver, and ileum, than in birds with a conventional gut microbiota (
P
< 0.05). Significant upregulation of T and B lymphocyte numbers was detected in cecum, cecal tonsils, and bursa of Fabricius of AT or GF birds after
C. jejuni
inoculation compared to the respective controls (
P
< 0.05). This difference was less clear in birds with a conventional gut microbiota. Histopathological gut lesions were observed only in
C. jejuni
-inoculated AT and GF birds but not in microbiota-colonized
C. jejuni
-inoculated hatchmates. These results demonstrate that the gut microbiota may contribute to the control of
C. jejuni
colonization and prevent lesion development. Further studies are needed to identify key players of the gut microbiota and the mechanisms behind their protective role.
Role for FimH in Extraintestinal Pathogenic Escherichia coli Invasion and Translocation through the Intestinal Epithelium
Authors: Poole Nina M. , Green Sabrina I. , Rajan Anubama , Vela Luz E. , Zeng Xi-Lei , Estes Mary K. , Maresso Anthony W.
Published: August 2017

The translocation of bacteria across the intestinal epithelium of immunocompromised patients can lead to bacteremia and life-threatening sepsis. Extraintestinal pathogenic
Escherichia coli
(ExPEC), so named because this pathotype infects tissues distal to the intestinal tract, is a frequent cause of such infections, is often multidrug resistant, and chronically colonizes a sizable portion of the healthy population. Although several virulence factors and their roles in pathogenesis are well described for ExPEC strains that cause urinary tract infections and meningitis, they have not been linked to translocation through intestinal barriers, a fundamentally distant yet important clinical phenomenon. Using untransformed
ex situ
human intestinal enteroids and transformed Caco-2 cells, we report that ExPEC strain CP9 binds to and invades the intestinal epithelium. ExPEC harboring a deletion of the gene encoding the mannose-binding type 1 pilus tip protein FimH demonstrated reduced binding and invasion compared to strains lacking known
E. coli
virulence factors. Furthermore, in a murine model of chemotherapy-induced translocation, ExPEC lacking
fimH
colonized at levels comparable to that of the wild type but demonstrated a statistically significant reduction in translocation to the kidneys, spleen, and lungs. Collectively, this study indicates that FimH is important for ExPEC translocation, suggesting that the type 1 pilus is a therapeutic target for the prevention of this process. Our study also highlights the use of human intestinal enteroids in the study of enteric diseases.
Gene Duplication in Pseudomonas aeruginosa Improves Growth on Adenosine
Authors: Toussaint Jean-Paul , Farrell-Sherman Anna , Feldman Tamar Perla , Smalley Nicole E. , Schaefer Amy L. , Greenberg E. Peter , Dandekar Ajai A.
Published: August 2017

The laboratory strain of
Pseudomonas aeruginosa
, PAO1, activates genes for catabolism of adenosine using quorum sensing (QS). However, this strain is not well-adapted for growth on adenosine, with doubling times greater than 40 h. We previously showed that when PAO1 is grown on adenosine and casein, variants emerge that grow rapidly on adenosine. To understand the mechanism by which this adaptation occurs, we performed whole-genome sequencing of five isolates evolved for rapid growth on adenosine. All five genomes had a gene duplication-amplification (GDA) event covering several genes, including the quorum-regulated nucleoside hydrolase gene,
nuh
, and PA0148, encoding an adenine deaminase. In addition, two of the growth variants also exhibited a
nuh
promoter mutation. We recapitulated the rapid growth phenotype with a plasmid containing six genes common to all the GDA events. We also showed that
nuh
and PA0148, the two genes at either end of the common GDA, were sufficient to confer rapid growth on adenosine. Additionally, we demonstrated that the variant
nuh
promoter increased basal expression of
nuh
but maintained its QS regulation. Therefore, GDA in
P. aeruginosa
confers the ability to grow efficiently on adenosine while maintaining QS regulation of nucleoside catabolism.

IMPORTANCE
Pseudomonas aeruginosa
thrives in many habitats and is an opportunistic pathogen of humans. In these diverse environments,
P. aeruginosa
must adapt to use myriad potential carbon sources.
P. aeruginosa
PAO1 cannot grow efficiently on nucleosides, including adenosine; however, it can acquire this ability through genetic adaptation. We show that the mechanism of adaptation is by amplification of a specific region of the genome and that the amplification preserves the regulation of the adenosine catabolic pathway by quorum sensing. These results demonstrate an underexplored mechanism of adaptation by
P. aeruginosa
, with implications for phenotypes such as development of antibiotic resistance.
Growth- and Stress-Induced PASTA Kinase Phosphorylation in Enterococcus faecalis
Authors: Labbe Benjamin D. , Kristich Christopher J.
Published: August 2017

Transmembrane Ser/Thr kinases containing extracellular PASTA domains are ubiquitous amongActinobacteriaandFirmicutes. Such PASTA kinases regulate critical processes, including antibiotic resistance, cell division, toxin production, and virulence, and are essential for viability in certain organisms. Based onin vitrostudies with purified extracellular and intracellular fragments of PASTA kinases, a model for signaling has been proposed, in which the extracellular PASTA domains bind currently undefined ligands (typically thought to be peptidoglycan, or fragments thereof) to drive kinase dimerization, which leads to enhanced kinase autophosphorylation and enhanced phosphorylation of substrates. However, this model has not been rigorously testedin vivo.Enterococcus faecalisis a Gram-positive intestinal commensal and major antibiotic-resistant opportunistic pathogen. InE. faecalis, the PASTA kinase IreK drives intrinsic resistance to cell wall-active antimicrobials, suggesting that such antimicrobials may trigger IreK signaling. Here we show that IreK responds to cell wall stressin vivoby enhancing its phosphorylation and that of a downstream substrate. This response requires both the extracellular PASTA domains and specific phosphorylatable residues in the kinase domain. Thus, our results providein vivoevidence, with an intact full-length PASTA kinase in its native physiological environment, that supports the prevailing model of PASTA kinase signaling. In addition, we show that IreK responds to a signal associated with growth and/or cell division, in the absence of cell wall-active antimicrobials. Surprisingly, the ability of IreK to respond to growth and/or division does not require the extracellular PASTA domains, suggesting that IreK monitors multiple parameters for sensory inputin vivo.

IMPORTANCETransmembrane Ser/Thr kinases containing extracellular PASTA domains are ubiquitous amongActinobacteriaandFirmicutesand regulate critical processes. The prevailing model for signaling by PASTA kinases proposes that the extracellular PASTA domains bind ligands to drive kinase dimerization, enhanced autophosphorylation, and enhanced phosphorylation of substrates. However, this model has not been rigorously testedin vivo. We show that the PASTA kinase IreK ofEnterococcus faecalisresponds to cell wall stressin vivoby enhancing its phosphorylation and that of a downstream substrate. This response requires the PASTA domains and phosphorylatable residues in the kinase domain. Thus, our results providein vivoevidence, with an intact full-length PASTA kinase in its native physiological environment, that supports the prevailing model of PASTA kinase signaling.
The Components of the Unique Zur Regulon of Cupriavidus metallidurans Mediate Cytoplasmic Zinc Handling
Authors: Bütof Lucy , Schmidt-Vogler Christopher , Herzberg Martin , Große Cornelia , Nies Dietrich H.
Published: August 2017

Zinc is an essential trace element, yet it is toxic at high concentrations. In the betaproteobacterium
Cupriavidus metallidurans
, the highly efficient removal of surplus zinc from the periplasm is responsible for the outstanding metal resistance of the organism. Rather than having a typical Zur-dependent, high-affinity ATP-binding cassette transporter of the ABC protein superfamily for zinc uptake at low concentrations,
C. metallidurans
has the secondary zinc importer ZupT of the zinc-regulated transporter, iron-regulated transporter (ZRT/IRT)-like protein (ZIP) family. It is important to understand, therefore, how this zinc-resistant bacterium copes with exposure to low zinc concentrations. Members of the Zur regulon in
C. metallidurans
were identified by comparing the transcriptomes of a Δ
zur
mutant and its parent strain. The consensus sequence of the Zur-binding box was derived for the
zupTp
promoter-regulatory region by use of a truncation assay. The motif was used to predict possible Zur boxes upstream of Zur regulon members. The binding of Zur to these boxes was confirmed. Two Zur boxes upstream of the
cobW
1
gene, encoding a putative zinc chaperone, proved to be required for complete repression of
cobW
1
and its downstream genes in cells cultivated in mineral salts medium. A Zur box upstream of each of
zur-cobW
2
,
cobW
3
, and
zupT
permitted both low expression levels of these genes and their upregulation under conditions of zinc starvation. This demonstrates a compartmentalization of zinc homeostasis in
C. metallidurans
, where the periplasm is responsible for the removal of surplus zinc, cytoplasmic components are responsible for the management of zinc as an essential cofactor, and the two compartments are connected by ZupT.

IMPORTANCE
Elucidating zinc homeostasis is necessary for understanding both host-pathogen interactions and the performance of free-living bacteria in their natural environments.
Escherichia coli
acquires zinc under conditions of low zinc concentrations via the Zur-controlled ZnuABC importer of the ABC superfamily, and this was also the paradigm for other bacteria. In contrast, the heavy-metal-resistant bacterium
C. metallidurans
achieves high tolerance to zinc through sophisticated zinc handling and efflux systems operating on periplasmic zinc ions, so that removal of surplus zinc is a periplasmic feature in this bacterium. It is shown here that this process is augmented by the management of zinc by cytoplasmic zinc chaperones, whose synthesis is controlled by the Zur regulator. This demonstrates a new mechanism, involving compartmentalization, for organizing zinc homeostasis.
Conjugative Plasmid Transfer in Xylella fastidiosa Is Dependent on
tra
and
trb
Operon Functions
Authors: Burbank Lindsey P. , Van Horn Christopher R.
Published: August 2017

The insect-transmitted plant pathogen
Xylella fastidiosa
is capable of efficient horizontal gene transfer (HGT) and recombination. Natural transformation occurs at high rates in
X. fastidiosa
, but there also is evidence that certain strains of
X. fastidiosa
carry native plasmids equipped with transfer and mobilization genes, suggesting conjugation as an additional mechanism of HGT in some instances. Two operons,
tra
and
trb
, putatively encoding a conjugative type IV secretion system, are found in some but not all
X. fastidiosa
isolates, often on native plasmids.
X. fastidiosa
strains that carry the conjugative transfer genes can belong to different subspecies and frequently differ in host ranges. Using
X. fastidiosa
strain M23 (
X. fastidiosa
subsp.
fastidiosa
) or Dixon (
X. fastidiosa
subsp.
multiplex
) as the donor strain and Temecula (
X. fastidiosa
subsp.
fastidiosa
) as the recipient strain, plasmid transfer was characterized using the mobilizable broad-host-range vector pBBR5pemIK. Transfer of plasmid pBBR5pemIK was observed under
in vitro
conditions with both donor strains and was dependent on both
tra
and
trb
operon functions. A conjugative mechanism likely contributes to gene transfer between diverse strains of
X. fastidiosa
, possibly facilitating adaptation to new environments or different hosts.

IMPORTANCE
Xylella fastidiosa
is an important plant pathogen worldwide, infecting a wide range of different plant species. The emergence of new diseases caused by
X. fastidiosa
, or host switching of existing strains, is thought to be primarily due to the high frequency of HGT and recombination in this pathogen. Transfer of plasmids by a conjugative mechanism enables movement of larger amounts of genetic material at one time, compared with other routes of gene transfer such as natural transformation. Establishing the prevalence and functionality of this mechanism in
X. fastidiosa
contributes to a better understanding of HGT, adaptation, and disease emergence in this diverse pathogen.
Intercellular Communication via the
comX
-Inducing Peptide (XIP) of Streptococcus mutans
Authors: Kaspar Justin , Underhill Simon A. M. , Shields Robert C. , Reyes Adrian , Rosenzweig Suzanne , Hagen Stephen J. , Burne Robert A.
Published: August 2017

Gram-positive bacteria utilize exported peptides to coordinate genetic and physiological processes required for biofilm formation, stress responses, and ecological competitiveness. One example is activation of natural genetic competence by ComR and the
com

X

-
i
nducing
p
eptide (XIP) in
Streptococcus mutans
. Although the competence pathway can be activated by the addition of synthetic XIP in defined medium, the hypothesis that XIP is able to function as an intercellular signaling molecule has not been rigorously tested. Coculture model systems were developed that included a “sender” strain that overexpressed the XIP precursor (ComS) and a “responder” strain harboring a green fluorescent protein (GFP) reporter fused to a ComR-activated gene (
comX
) promoter. The ability of the sender strain to provide a signal to activate GFP expression was monitored at the individual cell and population levels using (i) planktonic culture systems, (ii) cells suspended in an agarose matrix, or (iii) cells growing in biofilms. XIP was shown to be freely diffusible, and XIP signaling between the
S. mutans
sender and responder strains did not require cell-to-cell contact. The presence of a sucrose-derived exopolysaccharide matrix diminished the efficiency of XIP signaling in biofilms, possibly by affecting the spatial distribution of XIP senders and potential responders. Intercellular signaling was greatly impaired in a strain lacking the primary autolysin, AtlA, and was substantially greater when the sender strain underwent lysis. Collectively, these data provide evidence that
S. mutans
XIP can indeed function as a peptide signal between cells and highlight the importance of studying signaling with an endogenously produced peptide(s) in populations in various environments and physiologic states.

IMPORTANCE
The
comX
-inducing peptide (XIP) of
Streptococcus mutans
is a key regulatory element in the activation of genetic competence, which allows cells to take up extracellular DNA. XIP has been found in cell culture fluids, and the addition of synthetic XIP to physiologically receptive cells can robustly induce competence gene expression. However, there is a lack of consensus as to whether XIP can function as an intercellular communication signal. Here, we show that XIP indeed signals between cells in
S. mutans
, but that cell lysis may be a critical factor, as opposed to a dedicated secretion/processing system, in allowing for release of XIP into the environment. The results have important implications in the context of the ecology, virulence, and evolution of a ubiquitous human pathogen and related organisms.
One-dimensional large-strain thaw consolidation using nonlinear effective stress – void ratio – hydraulic conductivity relationships
Authors: Dumais Simon , Konrad Jean-Marie
Published: August 2017

A one-dimensional model for the consolidation of thawing soils is formulated in terms of large-strain consolidation and heat-transfer equations. The model integrates heat transfer due to conduction, phase change, and advection. The hydromechanical behaviour is modelled by large-strain consolidation theory. The equations are coupled in a moving boundary scheme developed in Lagrangian coordinates. Finite strains are allowed and nonlinear effective stress – void ratio – hydraulic conductivity relationships are proposed to characterize the thawing soil properties. Initial conditions and boundary conditions are presented with special consideration for the moving boundary condition at the thaw front developed in terms of large-strain consolidation. The proposed model is applied and compared with small-strain thaw consolidation theory in a theoretical working example of a thawing fine-grained soil sample. The modelling results are presented in terms of temperature, thaw penetration, settlements, void ratio, and excess pore-water pressures.
Modeling browse impacts on sapling and tree recruitment across forests in the northern United States
Authors: Russell Matthew B. , Westfall James A. , Woodall Christopher W.
Published: August 2017

Understanding the patterns of tree recruitment is essential to quantifying the future health and productivity of forest ecosystems. Using national forest inventory information, we incorporated browse impact measurements into models of sapling (2.5–12.7 cm diameter at breast height (DBH)) and overstory tree (≥12.7 cm DBH) ingrowth across the northern United States. Ingrowth was modeled with standard and zero-inflated techniques using discrete Poisson and negative binomial distributions. Zero-inflated models using stand attributes and browse impacts provided the best fit statistics for modeling the occurrence and frequency of ingrowth over a 5-year time period. Results indicate that stands with very high browse impact would contain 50.0% fewer ingrowth saplings compared with stands with no browse impact. Greater browse impacts similarly yielded a negative effect on overstory tree ingrowth, but to a lesser degree than saplings. Despite the stochastic nature of ingrowth observations, incorporating browse impacts may be essential in determining accurate levels of ingrowth in forests where herbivory constrains forest regeneration objectives.
Exploring the Interaction of Ethidium Bromide and HOECHST 33258 with DNA by Means of Electrochemical Approach
Authors: Tavadyan Levon A. , Minasyan Seyran H. , Kocharyan Gaspar H. , Antonyan Ara P. , Sahakyan Viktoria G. , Parsadanyan Marine A. , Vardevanyan Poghos O.
Published: August 2017

The binding of both ethidium bromide (EtBr) and Hoechst 33258 (H33258) to calf thymus DNA differing by the mechanism at different ionic strengths of NaCl water solutions (2, 20 and 150[Formula: see text]mM) has been quantitatively studied by square wave voltammetry (SWV). It was revealed that EtBr binds to DNA by more than one mode: at the solution ionic strengths 2 and 150[Formula: see text]mM, two modes were revealed, at 20[Formula: see text]mM — three modes. Values of EtBr binding constant ([Formula: see text]) to DNA and the number of nucleotides per one binding site ([Formula: see text]) for respective binding modes were determined. For H33258 under the same conditions, two binding modes were found and for both these modes values of [Formula: see text] and [Formula: see text] were determined. Dependence of the binding types and parameters on the solution ionic strength by SWV method was revealed, which differs by the binding type of EtBr and H33258. The obtained data are in good accordance with the ones determined by spectroscopic (absorption and fluorescence) and differential pulse voltammetry (DPV) methods. The obtained data indicate the sensibility and high precision of SWV method which may be applied to studies on interaction of different ligands with DNA, which reveal some peculiarities of their binding to DNA that are hidden and are not found by other methods.
Circulating soluble RAGE isoforms are attenuated in obese, impaired-glucose-tolerant individuals and are associated with the development of type 2 diabetes
Authors: Miranda Edwin R. , Somal Vikram S. , Mey Jacob T. , Blackburn Brian K. , Wang Edward , Farabi Sarah , Karstoft Kristian , Fealy Ciaran E. , Kashyap Sangeeta , Kirwan John P. , Quinn Laurie , Solomon Thomas P. J. , Haus Jacob M.
Published: August 2017

The soluble receptor for advanced glycation end products (sRAGE) may be protective against inflammation associated with obesity and type 2 diabetes (T2DM). The aim of this study was to determine the distribution of sRAGE isoforms and whether sRAGE isoforms are associated with risk of T2DM development in subjects spanning the glucose tolerance continuum. In this retrospective analysis, circulating total sRAGE and endogenous secretory RAGE (esRAGE) were quantified via ELISA, and cleaved RAGE (cRAGE) was calculated in 274 individuals stratified by glucose tolerance status (GTS) and obesity. Group differences were probed by ANOVA, and multivariate ordinal logistic regression was used to test the association between sRAGE isoform concentrations and the proportional odds of developing diabetes, vs. normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). When stratified by GTS, total sRAGE, cRAGE, and esRAGE were all lower with IGT and T2DM, while the ratio of cRAGE to esRAGE (cRAGE:esRAGE) was only lower ( P < 0.01) with T2DM compared with NGT. When stratified by GTS and obesity, cRAGE:esRAGE was higher with obesity and lower with IGT ( P < 0.0001) compared with lean, NGT. In ordinal logistic regression models, greater total sRAGE (odds ratio, 0.91; P < 0.01) and cRAGE (odds ratio, 0.84; P < 0.01) were associated with lower proportional odds of developing T2DM. Reduced values of sRAGE isoforms observed with both obesity and IGT are independently associated with greater proportional odds of developing T2DM. The mechanisms by which each respective isoform contributes to obesity and insulin resistance may reveal novel treatment strategies for diabetes.
Percutaneous Emergency Needle Caecostomy for Prevention of Caecal Perforation
Authors: Limmer Alexandra M. , Clement Zackariah
Published: August 2017

Caecal perforation is a life-threatening complication of large bowel obstruction with a reported mortality of 34% to 72%. This case describes the novel use of percutaneous needle caecostomy as a life-saving measure to prevent imminent caecal perforation in a 68-year-old lady with large bowel obstruction secondary to an incarcerated incisional hernia. After careful review of computed tomography images and measurement of distances from the abdominal wall to the caecum, the patient’s caecum was decompressed in the emergency department using a needle under local anaesthetic. The patient subsequently underwent laparoscopic hernia repair and had an uncomplicated recovery. When conducted safely and with precision in an appropriate patient, percutaneous needle caecostomy can provide immediate symptom relief, reduce risk of caecal perforation, and allow a laparoscopic surgical approach.
A Review of Elliptic Flow of Light Nuclei in Heavy-Ion Collisions at RHIC and LHC Energies
Authors: Haque Md. Rihan , Jena Chitrasen , Mohanty Bedangadas
Published: August 2017

We present a review of the measurements of elliptic flow (v2) of light nuclei (d, d¯, t, He3, and He¯3) from the RHIC and LHC experiments. Light (anti)nuclei v2 have been compared with that of (anti)proton. We observed a similar trend in light nuclei v2 to that in identified hadron v2 with respect to the general observations such as pT dependence, low pT mass ordering, and centrality dependence. We also compared the difference of nuclei and antinuclei v2 with the corresponding difference of v2 of proton and antiproton at various collision energies. Qualitatively they depict similar behavior. We also compare the data on light nuclei v2 to various theoretical models such as blast-wave and coalescence. We then present a prediction of v2 for He3 and He4 using coalescence and blast-wave models.
New Antihyperglycemic Drugs and Heart Failure: Synopsis of Basic and Clinical Data
Authors: von Lewinski Dirk , Kolesnik Ewald , Wallner Markus , Resl Michael , Sourij Harald
Published: August 2017

The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors. LEADER, SUSTAIN-6, EMPA-REG OUTCOME, and CANVAS showed potential beneficial results, while the SAVOR-TIMI trial had an increased rate of hospitalization for heart failure. Meanwhile, the same drugs are investigated in preclinical experiments mainly using various animal models, which aim to find interactions and elucidate the underlying downstream mechanisms between the antihyperglycemic drugs and the cardiovascular system. Yet the direct link for observed effects, especially for DPP-4 and SGLT-2 inhibitors, is still unknown. Further inquiry into these mechanisms is crucial for the interpretation of the clinical trials’ outcome and, vice versa, the clinical trials provide hints for an involvement of the cardiovascular system. The synopsis of preclinical and clinical data is essential for a detailed understanding of benefits and risks of new antihyperglycemic drugs.
Poisson Summation Formulae Associated with the Special Affine Fourier Transform and Offset Hilbert Transform
Authors: Zhuo Zhi-Hai
Published: August 2017

This paper investigates the generalized pattern of Poisson summation formulae from the special affine Fourier transform (SAFT) and offset Hilbert transform (OHT) points of view. Several novel summation formulae are derived accordingly. Firstly, the relationship between SAFT (or OHT) and Fourier transform (FT) is obtained. Then, the generalized Poisson sum formulae are obtained based on above relationships. The novel results can be regarded as the generalizations of the classical results in several transform domains such as FT, fractional Fourier transform, and the linear canonical transform.
A Case of Immediate Hypersensitivity Reaction to Maltitol
Authors: Rodríguez Trabado Ana , Cámara Hijón Carmen , García-Trujillo José Antonio , Magriz Trascón Irene , Fernández Pereira Luis Miguel
Published: August 2017

Background. Maltitol is a sugar alcohol that is frequently used as a noncaloric sweetener, although it is also used as an excipient, a plasticizer in gelatin capsules, and an emollient. It has not been previously described as an agent involved in immediate hypersensitivity reactions. Methods. We report on an anaphylactoid reaction with pharyngeal occlusion suffered by a 60-year-old man after ingestion of a candy containing maltitol syrup. A prick-to-prick test was performed with the candy and maltitol powder. Other allergens were excluded as causative agents of the adverse reaction, although the patient refused to undergo an oral challenge test with the candy. A basophil activation test (BAT) was performed with maltitol powder, and a dose-response curve was generated. The test was also performed in 3 healthy controls. Results. Both prick-to-prick tests were negative. The result of the BAT was positive at all the concentrations tested in the patient’s blood and negative in all the controls. Conclusions. The BAT can help to clarify the agents implicated in an adverse reaction and can reduce the risk involved in diagnosis. The BAT can also prove useful in the study of reactions caused by low-molecular-weight antigens, for which routine diagnostic tests are not feasible.
MPPT Control Strategy of PV Based on Improved Shuffled Frog Leaping Algorithm under Complex Environments
Authors: Nie Xiaohua , Nie Haoyao
Published: August 2017

This work presents a maximum power point tracking (MPPT) based on the particle swarm optimization (PSO) improved shuffled frog leaping algorithm (PSFLA). The swarm intelligence algorithm (SIA) has vast computing ability. The MPPT control strategies of PV array based on SIA are attracting considerable interests. Firstly, the PSFLA was proposed by adding the inertia weight factor w of PSO in standard SFLA to overcome the defect of falling into the partial optimal solutions and slow convergence speed. The proposed PSFLA algorithm increased calculation speed and excellent global search capability of MPPT. Then, the PSFLA was applied to MPPT to solve the multiple extreme point problems of nonlinear optimization. Secondly, for the problems of MPPT under complex environments, a new MPPT strategy of the PSFLA combined with recursive least square filtering was proposed to overcome the measurement noise effects on MPPT accuracy. Finally, the simulation comparisons between PSFLA and SFLA algorithm were developed. The experiment and comparison between PSLFA and PSO algorithm under complex environment were executed. The simulation and experiment results indicate that the proposed MPPT control strategy based on PSFLA can suppress the measurement noise effects effectively and improve the PV array efficiency.
Simulation of Wellbore Stability during Underbalanced Drilling Operation
Authors: Abdel Azim Reda
Published: August 2017

The wellbore stability analysis during underbalance drilling operation leads to avoiding risky problems. These problems include (1) rock failure due to stresses changes (concentration) as a result of losing the original support of removed rocks and (2) wellbore collapse due to lack of support of hydrostatic fluid column. Therefore, this paper presents an approach to simulate the wellbore stability by incorporating finite element modelling and thermoporoelastic environment to predict the instability conditions. Analytical solutions for stress distribution for isotropic and anisotropic rocks are presented to validate the presented model. Moreover, distribution of time dependent shear stresses around the wellbore is presented to be compared with rock shear strength to select appropriate weight of mud for safe underbalance drilling.
An Extract from the Plant Deschampsia antarctica Protects Fibroblasts from Senescence Induced by Hydrogen Peroxide
Authors: Ortiz-Espín Ana , Morel Esther , Juarranz Ángeles , Guerrero Antonio , González Salvador , Jiménez Ana , Sevilla Francisca
Published: August 2017

The Antarctic plant Deschampsia antarctica (DA) is able to survive in extreme conditions thanks to its special mechanism of protection against environmental aggressions. In this work, we investigated whether an aqueous extract of the plant (EDA) retains some of its defensive properties and is able to protect our skin against common external oxidants. We evaluated EDA over young human fibroblasts and exposed to H2O2, and we measured cell proliferation, viability, and senescence‐associated β‐galactosidase (SA‐β‐Gal). We also tested the expression of several senescence‐associated proteins including sirtuin1, lamin A/C, the replicative protein PCNA, and the redox protein thioredoxin 2. We found that EDA promoted per se cell proliferation and viability and increased the expression of anti‐senescence‐related markers. Then, we selected a dose of H2O2 as an inductor of senescence in human fibroblasts, and we found that an EDA treatment 24 h prior H2O2 exposure increased fibroblast proliferation. EDA significantly inhibited the increase in SA‐β‐Gal levels induced by H2O2 and promoted the expression of sirtuin 1 and lamin A/C proteins. Altogether, these results suggest that EDA protects human fibroblasts from cellular senescence induced by H2O2, pointing to this compound as a potential therapeutic agent to treat or prevent skin senescence.
An Online Platform to Support the Network of Caregivers of People with Dementia
Authors: Boessen April B. C. G. , Verwey Renée , Duymelinck Saskia , van Rossum Erik
Published: August 2017

Increasing numbers of persons with dementia (PWD) augment the pressure on dementia care, especially informal care. Care technology can support the network of PWD. We tested the usability and perceived value of an online platform that aims to support the communication and collaboration between family and professional caregivers of PWD. A mixed methods design was used for this pilot study, including semistructured interviews, a postal questionnaire, and monitoring of log data. Seven family and thirty-two professional caregivers involved with four PWD participated during a 10-week period. Overall, the results indicate that the platform is easy to use and valuable for both family and professional caregivers. They felt better informed and prepared regarding the situation of the PWD and felt supported by the more direct lines of communication within the network. Also, a broadening and deepening of the relationship between family and professional caregivers was experienced. Although connecting care organizations’ record systems with the platform and an active contribution of all care professionals involved (e.g., general practitioners and those working at day care units) were suggested for optimal use of the platform, family and professional caregivers positively valued the platform for improving the efficiency and ease of communication and collaboration.
A Cystine‐Rich Whey Supplement (Immunocal®) Provides Neuroprotection from Diverse Oxidative Stress‐Inducing Agents In Vitro by Preserving Cellular Glutathione
Authors: Winter Aimee N. , Ross Erika K. , Daliparthi Vamsi , Sumner Whitney A. , Kirchhof Danielle M. , Manning Evan , Wilkins Heather M. , Linseman Daniel A.
Published: August 2017

Oxidative stress is a principal mechanism underlying the pathophysiology of neurodegeneration. Therefore, nutritional enhancement of endogenous antioxidant defenses may represent a viable treatment option. We investigated the neuroprotective properties of a unique whey protein supplement (Immunocal®) that provides an essential precursor (cystine) for synthesis of the endogenous antioxidant, glutathione (GSH). Primary cultures of rat cerebellar granule neurons (CGNs), NSC34 motor neuronal cells, or HT22 hippocampal cells were preincubated in medium containing Immunocal and then subsequently treated with agents known to induce oxidative stress. Immunocal protected CGNs against neurotoxicity induced by the Bcl‐2 inhibitor, HA14‐1, the nitric oxide donor, sodium nitroprusside, CuCl2, and AlCl3. Immunocal also significantly reduced NSC34 cell death due to either H2O2 or glutamate and mitigated toxicity in HT22 cells overexpressing β‐amyloid1-42. The neuroprotective effects of Immunocal were blocked by inhibition of γ‐glutamyl‐cysteine ligase, demonstrating dependence on de novo GSH synthesis. These findings indicate that sustaining GSH with Immunocal significantly protects neurons against diverse inducers of oxidative stress. Thus, Immunocal is a nutritional supplement worthy of testing in preclinical animal models of neurodegeneration and in future clinical trials of patients afflicted by these diseases.
Ambient Air Quality Classification by Grey Wolf Optimizer Based Support Vector Machine
Authors: Saxena Akash , Shekhawat Shalini
Published: August 2017

With the development of society along with an escalating population, the concerns regarding public health have cropped up. The quality of air becomes primary concern regarding constant increase in the number of vehicles and industrial development. With this concern, several indices have been proposed to indicate the pollutant concentrations. In this paper, we present a mathematical framework to formulate a Cumulative Index (CI) on the basis of an individual concentration of four major pollutants (SO2, NO2, PM2.5, and PM10). Further, a supervised learning algorithm based classifier is proposed. This classifier employs support vector machine (SVM) to classify air quality into two types, that is, good or harmful. The potential inputs for this classifier are the calculated values of CIs. The efficacy of the classifier is tested on the real data of three locations: Kolkata, Delhi, and Bhopal. It is observed that the classifier performs well to classify the quality of air.
FOXO Transcriptional Factors and Long‐Term Living
Authors: Murtaza Ghulam , Khan Abida Kalsoom , Rashid Rehana , Muneer Saiqa , Hasan Syed Muhammad Farid , Chen Jianxin
Published: August 2017

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin‐like growth factor signaling. Only one FOXO gene (FOXO DAF‐16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity.
Mode II Fracture of GFRP Laminates Bonded Interfaces under 4-ENF Test
Authors: Zhong Zhi-peng , Liu Hong
Published: August 2017

This experiment studies the mode II fracture behavior of an adhesively bonded joint composed of GFRP laminates. A new beam model is presented to calculate the mode II ERR for GFRP bonded 4-ENF specimens. In this model, the deformation of 4-ENF specimens caused by the relative deflection angle between the upper and lower layers and by the bending deformation of the upper and lower layers, respectively, is introduced; the effect of the adhesive layer deformation is presented. The closed-form analytical solutions of compliance and energy release rate based on the crack compliance method are obtained. The high accuracy of present analytical solutions are verified by finite element analysis through bonded GFRP 4-ENF specimens and compared to the rigid joint model and the CBT model. The interfacial crack propagation is numerically simulated using shear fracture toughness determined in this experiment, from which the predicted critical load results are in good agreement with the experimental results. The conclusion indicates that the compliance and ERR can accurately be predicted using the new bonded 4-ENF beam model.
Pneumonia due to a Rare Pathogen: Achromobacter xylosoxidans, Subspecies denitrificans
Authors: Awadh Hesham , Mansour Munthir , Aqtash Obadah , Shweihat Yousef
Published: August 2017

Achromobacter xylosoxidans, subspecies denitrificans, is a gram-negative rod recently implicated as an emerging cause of infection in both immunosuppressed and immunocompetent populations. Few cases are reported in literature involving multiple body systems. Diagnosis depends on cultures of appropriate specimens, and management usually is by administration of appropriate antibiotics (usually agents with antipseudomonal activity). We report a rare case of pneumonia due to infection with this organism, in a patient with preexisting bronchiectasis secondary to chronic aspiration.
Permeability and Tensile Strength of Concrete with Arabic Gum Biopolymer
Authors: Mohamed Abdeliazim Mustafa , Osman Mohd Hanim , Smaoui Hichem , Mohd Ariffin Mohd Azreen
Published: August 2017

The use of materials of vegetal origin is increasingly being promoted in many industries due to their cost effectiveness and the rising sensitivity to environmental protection and sustainability. Arabic Gum Biopolymer (AGB) is a wild plant byproduct that is abundantly found in Sudan and is also produced in other African countries. It has long been used in various industries. However, its utilization is very limited in the construction sector although there appears to be a significant potential for use of AGB in the building industry. As an example, there is evidence that AGB may be an effective additive to concrete mixes that would improve fresh and hardened concrete properties. The aim of the present work is to provide further experimental evidence on the improvement that can be achieved in the physical and mechanical properties of hardened concrete when AGB is added to the mixture. The experimental results show a significant reduction in permeability for an optimum percentage of AGB and an increase in flexural and tensile strength and in the elastic modulus.