bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home‐Based Tactile Discrimination Training Reduces Phantom Limb Pain
Authors: Wakolbinger Robert , Diers Martin , Hruby Laura A. , Sturma Agnes , Aszmann Oskar C. 
Published: November 2017

AbstractBackgroundPhantom limb pain (PLP) affects a high percentage of amputees. Since treatment options are limited, low quality of life and addiction to pain medication frequently occur. New treatments, such as mirror therapy or electrical sensory discrimination training, make use of the brain's plasticity to alleviate this centrally derived pain.AimThis pilot study assessed the question of whether home‐based tactile discrimination training (TDT) leads to a stronger decrease in PLP levels compared to standard massage treatment.DesignControlled study.SettingOutpatient.PopulationAmputees (upper/lower extremity) with a PLP score of 4 or higher out of a possible 10 points on the visual analog scale.MethodsEight patients participated in the study. The treatment phase comprised 2 weeks (15 minutes daily). Subjects were examined at baseline, after treatment, 2 weeks after completing treatment, and 4 weeks after completing treatment. Pain was assessed using the West Haven–Yale Multidimensional Pain Inventory.ResultsThere was a significantly stronger reduction in PLP in the treatment group receiving TDT. PLP intensity ratings were significantly reduced at the end of therapy, and at 2 and 4 weeks after completing treatment compared to pretreatment.ConclusionsTDT seems to be an easy, cheap, time‐effective, and safe method to achieve sustained alleviation of PLP and also brings about a positive change in body image.Rehabilitation ImpactHome‐based TDT could achieve a sustained reduction in PLP and should be considered as a possible alternative to established treatment methods.
Influence of rare alleles of β‐carotene hydroxylase and lycopene epsilon cyclase genes on accumulation of provitamin A carotenoids in maize kernels
Authors: Zunjare Rajkumar U. , Hossain Firoz , Muthusamy Vignesh , Baveja Aanchal , Chauhan Hema S. , Thirunavukkarasu Nepolean , Saha Supradip , Gupta Hari S. 
Published: November 2017

AbstractVitamin A deficiency is one of the major health problems worldwide. Traditional yellow maize possesses very low provitamin A (proA) concentration in endosperm. The influence of rare alleles of β‐carotene hydroxylase (crtRB1) and lycopene epsilon cyclase (lcyE) genes capable of enhancing proA concentration was studied in four BC2F2 populations generated using subtropical inbreds and CIMMYT‐HarvestPlus lines. The occurrence of severe segregation distortion for crtRB1 gene was observed, while lcyE gene was segregated as per Mendelian ratio. Genotype with favourable allele of crtRB1 (CC) had a significant effect on β‐carotene (BC) (7.9‐fold), β‐cryptoxanthin (BCX) (twofold) and proA (5.5‐fold) accumulation, compared to unfavourable genotype (C+C+). Genotype with favourable allele of lcyE (LL) showed 2.1‐fold, 1.6‐fold and twofold significant enhancement in BC, BCX and proA, respectively, over unfavourable genotype (L+L+) in pooled analysis. Of the nine genotypes, double homozygote (CC/LL) had the highest mean BC (12.60 μg/g), BCX (4.44 μg/g) and proA (14.82 μg/g), and combined effect was significantly better than individual gene effects or any other combinations. The information generated here would be useful in designing strategy for proA enrichment in subtropical maize.
Wound culture isolated antibiograms and caregiver‐reported skin care practices in children with epidermolysis bullosa
Authors: Singer Hannah M. , Levin Laura E. , Garzon Maria C. , Lauren Christine T. , Planet Paul J. , Kittler Nicole W. , Whittier Susan , Morel Kimberly D. 
Published: November 2017

AbstractBackground/ObjectivesMany patients with epidermolysis bullosa (EB) require intensive daily wound care and individualized treatment plans. Understanding patient's home skin care routines and emerging antibiotic resistance patterns in EB wounds is necessary to optimize treatment recommendations. The objective was to identify patterns of antimicrobial resistance in EB wounds and characterize patient's home practices of skin care and bathing.MethodsThis was an observational study of 23 children with EB at an outpatient pediatric dermatology practice in New York City from 2012 to 2014. Information on individual bathing and skin care practices and wound cultures was collected as part of routine examinations and an institutional review board–approved antibiogram protocol.ResultsSixty wound cultures were collected from 23 patients. Eleven organisms were isolated, most commonly methicillin‐susceptible Staphylococcus aureus, methicillin‐resistant S. aureus, Streptococcus species, and Pseudomonas aeruginosa. Six patients (26%) were colonized with methicillin‐resistant S. aureus. Over the course of the study, 13 patients (56%) were found to have mupirocin‐resistant S. aureus. More than half of participants reported mupirocin or bacitracin use. Fewer than half indicated that they regularly used dilute bleach or dilute vinegar as part of their bathing routine.ConclusionNumerous organisms, including resistant bacteria, are known to colonize the wounds of individuals with EB. Mupirocin resistance was prevalent and more than half of the participants reported its use. Testing for mupirocin resistance may be considered for certain patients. These observations may help guide questions for future longitudinal multicenter studies with the goal of optimizing EB wound care recommendations.
Synthesis, Photophysical and Computational Study of Novel Coumarin‐based Organic Dyes
Authors: Kumbar Mahadev N. , Sannaikar Madivalagouda S. , Shaikh Saba Kauser J. , Kamble Atulkumar A. , Wari Manjunath N. , Inamdar Sanjeev R. , Qiao Qiquan , Revanna Bhavya N. , Madegowda Mahendra , Dasappa Jagadeesh P. , Kamble Ravindra R. 
Published: November 2017

AbstractA series of novel coumarin pyrazoline moieties combined with tetrazoles, 3‐(1‐phenyl‐4‐(1H‐tetrazol‐5‐yl)‐1H‐pyrazol‐3‐yl)‐2H‐chromen‐2‐one, 6‐chloro‐3‐(1‐phenyl‐4‐(1H‐tetrazol‐5‐yl)‐1H‐pyrazol‐3‐yl)‐2H‐chromen‐2‐one, 6‐bromo‐3‐(1‐phenyl‐4‐(1H‐tetrazol‐5‐yl)‐1H‐pyrazol‐3‐yl)‐2H‐chromen‐2‐one and 6‐bromo‐3‐(1‐(4‐bromophenyl)‐4‐(1H‐tetrazol‐5‐yl)‐1H pyrazol‐3‐yl)‐2H‐chromen‐2‐one7(a‐d), were designed and synthesized. Single crystal X‐ray diffraction and their interactions were studied by Hirshfeld surface analysis. Thermal stabilities and electrochemical properties of these compounds were examined from differential scanning calorimetry (DSC), thermogravimetric (TGA) and cyclic voltammetric (CV) studies. Their spectroscopic properties were analyzed in various alcohols and general solvents by UV–Vis absorption, fluorescence and time‐resolved spectroscopy. In addition, the ground and excited state electronic properties were investigated using density functional theory (DFT). The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and energy band gap (Eg) values have revealed the effect of substitution of halogens. The substitution has equally affected the ground and excited states of 7(a‐d) compounds. The solvatochromism on absorption, fluorescence spectra and fluorescence lifetimes of these compounds was investigated. All these results showed the chromen‐2‐one of pyrazoline tetrazole derivatives could play an important role in photonic and electronic devices.
An integrative insight on dormancy alleviation in diaspores of Urochloa humidicola (Rendle) Morrone & Zuloaga, a tropical grass with great economic and ecological impact
Authors: Ajala‐Luccas D. , Ribeiro‐Oliveira J. P. , Duarte Silveira L. E. , da Silva E. A. A. 
Published: November 2017

Abstract

Even though exhaustively studied, dormancy alleviation in diaspores of Urochloa humidicola (Rendle) Morrone & Zuloaga remains a mystery. To clarify this, we asked the following question: could dormancy alleviation in diaspores of this species be associated with ageing, GA/ABA balance and remaining structures of the panicoid spikelet?

We answer this question using diaspores of U. humidicola cv. BRS Tupi as a biological model, a cultivar with a wide edaphoclimatic range in Neotropical areas and whose diaspores possess ‘deep dormancy’ when dispersed. We analysed both germination and early plant development using a split‐plot model.

Our findings demonstrate that dormancy alleviation in diaspores of U. humidicola is a synergic phenomenon driven by crosstalk between age, GA/ABA balance and remaining structures of the panicoid spikelet covering caryopses, since this interaction acts on the dynamics of germination and early plant development.

We demonstrate that: (i) spreading germination time is a maternal survival mechanism of this species, which has repercussions for occupational aggressiveness of the species; (ii) remaining structures of the panicoid spikelet covering caryopses are the main modulator of embryo development. These structures control the after‐ripening process, which is modulated by some molecular factor. We also highlight that it is necessary to review concepts about dormancy of dispersal units in this grass species.
A Comparison of the Bow‐Tie and STAMP Approaches to Reduce the Risk of Surgical Instrument Retention
Authors: Chatzimichailidou Maria Mikela , Ward James , Horberry Tim , Clarkson P. John 
Published: November 2017

AbstractAlthough relatively rare, surgical instrument retention inside a patient following central venous catheterization still presents a significant risk. The research presented here compared two approaches to help reduce retention risk: Bow‐Tie Analysis and Systems‐Theoretic Accident Model and Processes. Each method was undertaken separately and then the results of the two approaches were compared and combined. Both approaches produced beneficial results that added to existing domain knowledge, and a combination of the two methods was found to be beneficial. For example, the Bow‐Tie Analysis gave an overview of which activities keep controls working and who is responsible for each control, and the Systems‐Theoretic Accident Model and Processes revealed the safety constraints that were not enforced by the supervisor of the controlled process. Such two‐way feedback between both methods is potentially helpful for improving patient safety. Further methodology ideas to minimize surgical instrument retention risks are also described.
Estimating Dynamic Macroeconomic Models: How Informative are the Data?
Authors: Beltran Daniel O. , Draper David 
Published: November 2017

SummaryCentral banks have long used dynamic stochastic general equilibrium models, which are typically estimated by using Bayesian techniques, to inform key policy decisions. This paper offers an empirical strategy that quantifies the information content of the data relative to that of the prior distribution. Using an off-the-shelf dynamic stochastic general equilibrium model applied to quarterly euro area data from 1970, quarter 3, to 2009, quarter 4, we show how Monte Carlo simulations can reveal parameters for which the model's structure obscures identification. By integrating out components of the likelihood function and conducting a Bayesian sensitivity analysis, we uncover parameters that are weakly informed by the data. The weak identification of some key structural parameters in our comparatively simple model should raise a red flag to researchers trying to draw valid inferences from, and to base policy on, complex large-scale models featuring many parameters.
Validation of Putative Apicoplast-Targeting Drugs Using a Chemical Supplementation Assay in Cultured Human Malaria Parasites
Authors: Uddin Taher , McFadden Geoffrey Ian , Goodman Christopher Dean 
Published: November 2017

ABSTRACTMalaria parasites contain a relict plastid, the apicoplast, which is considered an excellent drug target due to its bacterial-like ancestry. Numerous parasiticidals have been proposed to target the apicoplast, but few have had their actual targets substantiated. Isopentenyl pyrophosphate (IPP) production is the sole required function of the apicoplast in the blood stage of the parasite life cycle, and IPP supplementation rescues parasites from apicoplast-perturbing drugs. Hence, any drug that kills parasites when IPP is supplied in culture must have a nonapicoplast target. Here, we use IPP supplementation to discriminate whether 23 purported apicoplast-targeting drugs are on- or off-target. We demonstrate that a prokaryotic DNA replication inhibitor (ciprofloxacin), several prokaryotic translation inhibitors (chloramphenicol, doxycycline, tetracycline, clindamycin, azithromycin, erythromycin, and clarithromycin), a tRNA synthase inhibitor (mupirocin), and two IPP synthesis pathway inhibitors (fosmidomycin and FR900098) have apicoplast targets. Intriguingly, fosmidomycin and FR900098 leave the apicoplast intact, whereas the others eventually result in apicoplast loss. Actinonin, an inhibitor of bacterial posttranslational modification, does not produce a typical delayed-death response but is rescued with IPP, thereby confirming its apicoplast target. Parasites treated with putative apicoplast fatty acid pathway inhibitors could not be rescued, demonstrating that these drugs have their primary targets outside the apicoplast, which agrees with the dispensability of the apicoplast fatty acid synthesis pathways in the blood stage of malaria parasites. IPP supplementation provides a simple test of whether a compound has a target in the apicoplast and can be used to screen novel compounds for mode of action.
Overtreatment of Asymptomatic Candiduria among Hospitalized Patients: a Multi-institutional Study
Authors: Jacobs David M. , Dilworth Thomas J. , Beyda Nicholas D. , Casapao Anthony M. , Bowers Dana R. 
Published: November 2017

ABSTRACT

Candiduria is common in hospitalized patients, and asymptomatic candiduria contributes to antifungal overuse. The guidelines for management of asymptomatic candiduria do not recommend antifungal use, but rather the elimination of predisposing factors. It is unknown whether these recommendations are being followed. The primary objective of this study was to characterize candiduria management among hospitalized patients. This was a retrospective cohort study of a random sample of 305 hospitalized patients with candiduria at four U.S. medical centers from January 2010 to December 2013. Patients were classified as asymptomatic or symptomatic based on established criteria, and data were collected by chart review. Infectious Diseases Society of America (IDSA) treatment guideline adherence and its association with clinical outcomes, including candiduria recurrence (short- and long-term) and 30-day readmission, were assessed. Eighty percent of patients were classified as having asymptomatic candiduria. Overall, 143 (47%) patients were not managed according to recommended guidelines, including 105/243 (43%) in the asymptomatic candiduria group and 38/62 (61%) in the symptomatic group (
P
= 0.01). Discordance among asymptomatic patients was driven by overtreatment with an antifungal (98/105 [93%]). Thirty-three percent of patients with asymptomatic candiduria not managed according to the guidelines were treated for over 7 days, and 5% received over 14 days of therapy. Fluconazole was the most commonly used empirical antifungal among asymptomatic candiduria patients (96%), followed by micafungin (4%). Asymptomatic candiduria patients not managed according to the guidelines had a trend toward higher 30-day readmission (35% versus 26%,
P
= 0.27). Inappropriate management of candiduria among hospitalized patients was high, leading to overtreatment with antifungal therapy.
Metabolic Mitigation of Staphylococcus aureus Vancomycin Intermediate-Level Susceptibility
Authors: Gardner Stewart G. , Marshall Darrell D. , Daum Robert S. , Powers Robert , Somerville Greg A. 
Published: November 2017

ABSTRACT

Staphylococcus aureus
is a major human pathogen whose infections are increasingly difficult to treat due to increased antibiotic resistance, including resistance to vancomycin. Vancomycin-intermediate
S. aureus
(VISA) strains develop resistance to vancomycin through adaptive changes that are incompletely understood. Central to this adaptation are metabolic changes that permit growth in the presence of vancomycin. To define the metabolic changes associated with adaptive resistance to vancomycin in
S. aureus
, the metabolomes of a vancomycin-sensitive and VISA strain pair isolated from the same patient shortly after vancomycin therapy began and following vancomycin treatment failure were analyzed. The metabolic adaptations included increases in acetogenesis, carbon flow through the pentose phosphate pathway, wall teichoic acid and peptidoglycan precursor biosynthesis, purine biosynthesis, and decreased tricarboxylic acid (TCA) cycle activity. The significance of these metabolic pathways for vancomycin-intermediate susceptibility was determined by assessing the synergistic potential of human-use-approved inhibitors of these pathways in combination with vancomycin against VISA strains. Importantly, inhibitors of amino sugar and purine biosynthesis acted synergistically with vancomycin to kill a diverse set of VISA strains, suggesting that combinatorial therapy could augment the efficacy of vancomycin even in patients infected with VISA strains.
The Streptococcus agalactiae Stringent Response Enhances Virulence and Persistence in Human Blood
Authors: Hooven Thomas A. , Catomeris Andrew J. , Bonakdar Maryam , Tallon Luke J. , Santana-Cruz Ivette , Ott Sandra , Daugherty Sean C. , Tettelin Hervé , Ratner Adam J. 
Published: November 2017

ABSTRACT

Streptococcus agalactiae
(group B
Streptococcus
[GBS]) causes serious infections in neonates. We previously reported a transposon sequencing (Tn-seq) system for performing genomewide assessment of gene fitness in GBS. In order to identify molecular mechanisms required for GBS to transition from a mucosal commensal lifestyle to bloodstream invasion, we performed Tn-seq on GBS strain A909 with human whole blood. Our analysis identified 16 genes conditionally essential for GBS survival in blood, of which 75% were members of the capsular polysaccharide (
cps
) operon. Among the non-
cps
genes identified as conditionally essential was
relA
, which encodes an enzyme whose activity is central to the bacterial stringent response—a conserved adaptation to environmental stress. We used blood coincubation studies of targeted knockout strains to confirm the expected growth defects of GBS deficient in capsule or stringent response activation. Unexpectedly, we found that the
relA
knockout strains demonstrated decreased expression of β-hemolysin/cytolysin, an important cytotoxin implicated in facilitating GBS invasion. Furthermore, chemical activation of the stringent response with serine hydroxamate increased β-hemolysin/cytolysin expression. To establish a mechanism by which the stringent response leads to increased cytotoxicity, we performed transcriptome sequencing (RNA-seq) on two GBS strains grown under stringent response or control conditions. This revealed a conserved decrease in the expression of genes in the arginine deiminase pathway during stringent response activation. Through coincubation with supplemental arginine and the arginine antagonist canavanine, we show that arginine availability is a determinant of GBS cytotoxicity and that the pathway between stringent response activation and increased virulence is arginine dependent.
Characterization of an Aldolase Involved in Cholesterol Side Chain Degradation in Mycobacterium tuberculosis
Authors: Gilbert Stephanie , Hood LaChae , Seah Stephen Y. K. 
Published: November 2017

ABSTRACT

The heteromeric acyl coenzyme A (acyl-CoA) dehydrogenase FadE28-FadE29 and the enoyl-CoA hydratase ChsH1-ChsH2, encoded by genes within the intracellular growth (
igr
) operon of
Mycobacterium tuberculosis
, catalyze the dehydrogenation of the cholesterol metabolite 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA), with a 3-carbon side chain, and subsequent hydration of the product 3-oxo-4,17-pregnadiene-20-carboxyl-CoA (3-OPDC-CoA) to form 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA (17-HOPC-CoA). The gene downstream of
chsH2
, i.e.,
ltp2
, was expressed in recombinant
Rhodococcus jostii
RHA1 in combination with other genes within the
igr
operon. His-tagged Ltp2 copurified with untagged ChsH1-ChsH2, ChsH2, or the C-terminal domain of ChsH2, which contains a domain of unknown function (DUF35). Ltp2 in association with ChsH1-ChsH2 or just the DUF35 domain of ChsH2 was shown to catalyze the retroaldol cleavage of 17-HOPC-CoA to form androst-4-ene-3,17-dione and propionyl-CoA. Steady-state kinetic analysis using the Ltp2-DUF35 complex showed that the aldolase had optimal activity at pH 7.5, with a

K
m

of 6.54 ± 0.90 μM and a
k
cat
of 159 ± 8.50 s
−1
. ChsH1-ChsH2 could hydrate only about 30% of 3-OPDC-CoA, but this unfavorable equilibrium could be overcome when the aldolase was present to remove the hydrated product, providing a rationale for the close association of the aldolase with the hydratase. Homologs of ChsH1, ChsH2, and Ltp2 are found in steroid-degrading Gram-positive and Gram-negative bacteria, suggesting that side chains of diverse steroids may be cleaved by aldolases in the bacteria.

IMPORTANCE
The C-C bond cleavage of the D-ring side chain of cholesterol was shown to be catalyzed by an aldolase. The aldolase associates with the hydratase that catalyzes the preceding reaction in the cholesterol side chain degradation pathway. These enzymes are encoded by genes within the intracellular growth (
igr
) operon of
M. tuberculosis
, and the operon was demonstrated previously to be linked to the pathogenicity and persistence of the bacteria in macrophages and in mice.
Homologous VapC Toxins Inhibit Translation and Cell Growth by Sequence-Specific Cleavage of tRNA
fMet
Authors: Walling Lauren R. , Butler J. Scott 
Published: November 2017

ABSTRACT

Type II toxin-antitoxin (TA) systems play a critical role in the establishment and maintenance of bacterial dormancy. They are composed of a protein toxin and its cognate protein antitoxin. They function to regulate growth under conditions of stress, such as starvation or antibiotic treatment. As cellular proteases degrade the antitoxin, which normally binds and neutralizes the toxin, this frees the toxin to act on its cellular targets and arrest bacterial growth. TA systems are of particular concern in regard to pathogenic organisms, such as nontypeable
Haemophilus influenzae
(NTHi), as dormancy may lead to chronic infections and failure of antibiotic treatment. Many targets of VapC toxins have not been identified, to date, and this knowledge is crucial to understanding how toxins control the establishment and maintenance of bacterial dormancy. Accordingly, we characterized the target specificity of the VapC toxins from the two paralogous NTHi
vapBC
TA systems. RNA sequencing and Northern blot analysis revealed that VapC1 and VapC2 cleave tRNA
fMet
in the anticodon loop. Overexpression of tRNA
fMet
suppresses VapC toxicity, suggesting that translation inhibition results from the depletion of tRNA
fMet
. These experiments also identified base pairs in the tRNA
fMet
anticodon stem that play a key role in VapC-specific cleavage of the tRNA. Together these findings suggest the potential for NTHi VapC1 and VapC2 to induce dormancy by sequence-specific cleavage of tRNA
fMet
.

IMPORTANCE
Bacterial persistence is a significant concern in regard to pathogenic organisms, such as nontypeable
Haemophilus influenzae
, as it can result in recurrent and chronic infections. Toxin-antitoxin systems can lead to persistence by causing bacteria to enter a slow-growing state that renders them antibiotic tolerant. Type II toxin components affect a wide variety of bacterial targets in order to elicit dormancy, and for many toxin-antitoxin systems, these mechanisms are not well understood. Thus, in order to understand how
vapBC
toxin-antitoxin systems cause dormancy, it is crucial to investigate the substrate specificity of VapC toxins. This study identifies the target of the VapC1 and VapC2 toxins from NTHi and takes important steps toward understanding the specificity of these toxins for their tRNA target.