bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Activity Enjoyment, Perceived Barriers, and Beliefs Among Adolescents With and Without Intellectual Disabilities
Authors: Stanish Heidi I. , Curtin Carol , Must Aviva , Phillips Sarah , Maslin Melissa , Bandini Linda G. 
Published: April 2015

Background:Youths with intellectual disabilities (ID) exhibit low levels of physical activity, but the underlying contributors to behavior are unclear. We compared physical activity enjoyment, perceived barriers, beliefs, and self-efficacy among adolescents with ID and typically developing (TD) adolescents.Methods:A questionnaire was administered to 38 adolescents with ID (mean age, 16.8 years) and 60 TD adolescents (mean age, 15.3 years). Of the original 33 questionnaire items, 23 met the test-retest reliability criteria and were included in the group comparisons.Results:Fewer adolescents with ID reported that they have someone with whom to do physical activity (64% vs 93%: P < .001), and a greater percentage of adolescents with ID perceived that physical activities were too hard to learn (41% vs 0%; P < .001). Fewer adolescents with ID believed that physical activity would be good for their health (92% vs 100%; P = .05). More adolescents with ID reported a dislike of individual physical activities (P = .02). A large percentage of adolescents with ID (84%) responded that they were good at doing physical activities, but the difference between groups was only of borderline significance (95% of TD adolescents, P = .06).Conclusions:Adolescents shared many of the same perceptions about physical activity, but some important differences between groups were identified.
In Vitro
Activities of Amphotericin B, Terbinafine, and Azole Drugs against Clinical and Environmental Isolates of Aspergillus terreus Sensu Stricto
Authors: Fernández Mariana S. , Rojas Florencia D. , Cattana María E. , Sosa María de los Ángeles , Iovannitti Cristina A. , Lass-Flörl Cornelia , Giusiano Gustavo E. 
Published: April 2015

ABSTRACT

The antifungal susceptibilities of 40 clinical and environmental isolates of
A. terreus sensu stricto
to amphotericin B, terbinafine, itraconazole, and voriconazole were determined in accordance with CLSI document M38-A2. All isolates had itraconazole and voriconazole MICs lower than epidemiologic cutoff values, and 5% of the isolates had amphotericin B MICs higher than epidemiologic cutoff values. Terbinafine showed the lowest MICs. No significant differences were found when MICs of clinical and environmental isolates were compared.
High Prevalence of Mupirocin Resistance in Staphylococcus aureus Isolates from a Pediatric Population
Authors: Antonov Nina K. , Garzon Maria C. , Morel Kimberly D. , Whittier Susan , Planet Paul J. , Lauren Christine T. 
Published: April 2015

ABSTRACT

Topical mupirocin is used widely to treat skin and soft tissue infections and to eradicate nasal carriage of methicillin-resistant
Staphylococcus aureus
(MRSA). Few studies to date have characterized the rates of
S. aureus
mupirocin resistance in pediatric populations. We retrospectively studied 358 unique
S. aureus
isolates obtained from 249 children seen in a predominantly outpatient setting by the Division of Pediatric Dermatology at a major academic center in New York City between 1 May 2012 and 17 September 2013. Mupirocin resistance rates and the associated risk factors were determined using a logistic regression analysis. In our patient population, 19.3% of patients had mupirocin-resistant
S. aureus
isolates at the time of their first culture, and 22.1% of patients with
S. aureus
infection had a mupirocin-resistant isolate at some time during the study period. Overall, 31.3% of all
S. aureus
isolates collected during the study period were resistant to mupirocin. Prior mupirocin use was strongly correlated (odds ratio [OR] = 26.5;
P
= <0.001) with mupirocin resistance. Additional risk factors for mupirocin resistance included methicillin resistance, atopic dermatitis (AD), epidermolysis bullosa (EB), immunosuppression, and residence in northern Manhattan and the Bronx. Resistance to mupirocin is widespread in children with dermatologic complaints in the New York City area, and given the strong association with mupirocin exposure, it is likely that mupirocin use contributes to the increased resistance. Routine mupirocin testing may be important for MRSA decolonization strategies or the treatment of minor skin infections in children.
Population Pharmacokinetic Analysis for a Single 1,200-Milligram Dose of Oritavancin Using Data from Two Pivotal Phase 3 Clinical Trials
Authors: Rubino C. M. , Bhavnani S. M. , Moeck G. , Bellibas S. E. , Ambrose P. G. 
Published: April 2015

ABSTRACT

Oritavancin is a lipoglycopeptide antibiotic with activity against Gram-positive bacteria. Here we describe oritavancin population pharmacokinetics and the impact of patient-specific covariates on drug exposure variability. Concentration-time data were analyzed from two phase 3 clinical trials, SOLO I and SOLO II, in which oritavancin was administered as a single 1,200-mg dose to patients with acute bacterial skin and skin structure infections. A total of 1,337 drug concentrations from 297 patients (90% of whom had 4 or 5 pharmacokinetic samples) were available for analysis. A previously derived population model based on data from 12 phase 1, 2, and 3 oritavancin studies was applied to the SOLO data set. Alterations to the structural model were made, as necessary, based on model fit. Analyses utilized Monte Carlo parametric expectation maximization (S-ADAPT 1.5.6). The previous population pharmacokinetic model fit the data well (
r
2
= 0.972), and population pharmacokinetic parameters were estimated with acceptable precision and lack of bias. Covariate evaluations revealed statistically significant relationships between central compartment volume and age and between clearance and height; however, these relationships did not indicate a clinically relevant impact on oritavancin exposure over the range of age and height observed in the SOLO studies. The mean (coefficient of variation [CV]) area under the plasma concentration-time curve from time zero to 72 h (AUC
0–72
) and maximum plasma concentration (
C
max
) were 1,530 (36.9%) μg · h/ml and 138 (23%) μg/ml, respectively. The mean (CV) half-life at alpha phase (
t
1/2α
),
t
1/2β
, and
t
1/2γ
were 2.29 (49.8%), 13.4 (10.5%), and 245 (14.9%) hours, respectively. These analyses are the first to describe oritavancin pharmacokinetics following a single 1,200-mg dose. Covariate analyses suggested that no dose adjustments are required for renal impairment (creatinine clearance, >29 ml/min), mild or moderate hepatic impairment, age, weight, gender, or diabetes status.
Sphingolipids Mediate Differential Echinocandin Susceptibility in Candida albicans and Aspergillus nidulans
Authors: Healey Kelley R. , Challa Krishna K. , Edlind Thomas D. , Katiyar Santosh K. 
Published: April 2015

ABSTRACT

The cell wall synthesis-inhibiting echinocandins, including caspofungin and micafungin, play important roles in the treatment of candidiasis and aspergillosis. Previous studies revealed that, in the haploid yeast
Candida glabrata
, sphingolipid biosynthesis pathway mutations confer caspofungin reduced susceptibility (CRS) but micafungin increased susceptibility (MIS). Here, we describe one
Candida albicans
strain (of 10 tested) that similarly yields CRS-MIS mutants at relatively high frequency. Mutants demonstrated increased levels of long-chain bases (sphingolipid pathway intermediates) and, unique to this strain, loss of His104/Pro104 heterozygosity in the
TSC13
-encoded enoyl reductase. CRS-MIS was similarly observed in a
C. albicans
homozygous
fen1
Δ
fen12
Δ laboratory strain and in diverse wild-type strains following exogenous long-chain-base treatment. Analogous to these results, CRS-MIS was demonstrated in an
Aspergillus nidulans
basA
mutant encoding defective sphingolipid C
4
-hydroxylase and in its wild-type parent exposed to long-chain bases. Sphingolipids likely modulate echinocandin interaction with their Fks membrane target in all susceptible fungi, with potential implications for optimizing therapy with existing antifungals and the development of novel agents.
Efflux as a Glutaraldehyde Resistance Mechanism in Pseudomonas fluorescens and Pseudomonas aeruginosa Biofilms
Authors: Vikram Amit , Bomberger Jennifer M. , Bibby Kyle J. 
Published: April 2015

ABSTRACT

A major challenge in microbial biofilm control is biocide resistance. Phenotypic adaptations and physical protective effects have been historically thought to be the primary mechanisms for glutaraldehyde resistance in bacterial biofilms. Recent studies indicate the presence of genetic mechanisms for glutaraldehyde resistance, but very little is known about the contributory genetic factors. Here, we demonstrate that efflux pumps contribute to glutaraldehyde resistance in
Pseudomonas fluorescens
and
Pseudomonas aeruginosa
biofilms. The RNA-seq data show that efflux pumps and phosphonate degradation, lipid biosynthesis, and polyamine biosynthesis metabolic pathways were induced upon glutaraldehyde exposure. Furthermore, chemical inhibition of efflux pumps potentiates glutaraldehyde activity, suggesting that efflux activity contributes to glutaraldehyde resistance. Additionally, induction of known modulators of biofilm formation, including phosphonate degradation, lipid biosynthesis, and polyamine biosynthesis, may contribute to biofilm resistance and resilience. Fundamental understanding of the genetic mechanism of biocide resistance is critical for the optimization of biocide use and development of novel disinfection strategies. Our results reveal genetic components involved in glutaraldehyde resistance and a potential strategy for improved control of biofilms.
Oral Tolerance Failure upon Neonatal Gut Colonization with Escherichia coli Producing the Genotoxin Colibactin
Authors: Secher Thomas , Payros Delphine , Brehin Camille , Boury Michele , Watrin Claude , Gillet Marion , Bernard-Cadenat Isabelle , Menard Sandrine , Theodorou Vassilia , Saoudi Abdelhadi , Olier Maiwenn , Oswald Eric 
Published: April 2015

ABSTRACT

The intestinal barrier controls the balance between tolerance and immunity to luminal antigens. When this finely tuned equilibrium is deregulated, inflammatory disorders can occur. There is a concomitant increase, in urban populations of developed countries, of immune-mediated diseases along with a shift in
Escherichia coli
population from the declining phylogenetic group A to the newly dominant group B2, including commensal strains producing a genotoxin called colibactin that massively colonized the gut of neonates. Here, we showed that mother-to-offspring early gut colonization by colibactin-producing
E. coli
impairs intestinal permeability and enhances the transepithelial passage of luminal antigen, leading to an increased immune activation. Functionally, this was accompanied by a dramatic increase in local and systemic immune responses against a fed antigen, decreased regulatory T cell population, tolerogenic dendritic cells, and enhanced mucosal delayed-type hypersensitivity response. Conversely, the abolition of colibactin expression by mutagenesis abrogates the alteration of oral tolerance induced by neonatal colonization by
E. coli
. In conclusion, the vertical colonization by
E. coli
producing the genotoxin colibactin enhances intestinal translocation and subsequently alters oral tolerance. Thus, early colonization by
E. coli
from the newly dominant phylogenetic group B2, which produces colibactin, may represent a risk factor for the development of immune-mediated diseases.
Cytotoxic and Apoptotic Effects of Recombinant Subtilase Cytotoxin Variants of Shiga Toxin-Producing Escherichia coli
Authors: Funk J. , Biber N. , Schneider M. , Hauser E. , Enzenmüller S. , Förtsch C. , Barth H. , Schmidt H. 
Published: April 2015

ABSTRACT

In this study, the cytotoxicity of the recently described subtilase variant SubAB
2-2
of Shiga toxin-producing
Escherichia coli
was determined and compared to the plasmid-encoded SubAB
1
and the chromosome-encoded SubAB
2-1
variant. The genes for the respective enzymatic active (A) subunits and binding (B) subunits of the subtilase toxins were amplified and cloned. The recombinant toxin subunits were expressed and purified. Their cytotoxicity on Vero cells was measured for the single A and B subunits, as well as for mixtures of both, to analyze whether hybrids with toxic activity can be identified. The results demonstrated that all three SubAB variants are toxic for Vero cells. However, the values for the 50% cytotoxic dose (CD
50
) differ for the individual variants. Highest cytotoxicity was shown for SubAB
1
. Moreover, hybrids of subunits from different subtilase toxins can be obtained which cause substantial cytotoxicity to Vero cells after mixing the A and B subunits prior to application to the cells, which is characteristic for binary toxins. Furthermore, higher concentrations of the enzymatic subunit SubA
1
exhibited cytotoxic effects in the absence of the respective B
1
subunit. A more detailed investigation in the human HeLa cell line revealed that SubA
1
alone induced apoptosis, while the B
1
subunit alone did not induce cell death.
Inhibition of Cell Differentiation in Bacillus subtilis by Pseudomonas protegens
Authors: Powers Matthew J. , Sanabria-Valentín Edgardo , Bowers Albert A. , Shank Elizabeth A. 
Published: April 2015

ABSTRACTInterspecies interactions have been described for numerous bacterial systems, leading to the identification of chemical compounds that impact bacterial physiology and differentiation for processes such as biofilm formation. Here, we identified soil microbes that inhibit biofilm formation and sporulation in the common soil bacteriumBacillus subtilis. We did so by creating a reporter strain that fluoresces when the transcription of a biofilm-specific gene is repressed. Using this reporter in a coculture screen, we identifiedPseudomonas putidaandPseudomonas protegensas bacteria that secrete compounds that inhibit biofilm gene expression inB. subtilis. The active compound produced byP. protegenswas identified as the antibiotic and antifungal molecule 2,4-diacetylphloroglucinol (DAPG). Colonies ofB. subtilisgrown adjacent to a DAPG-producingP. protegensstrain had altered colony morphologies relative toB. subtiliscolonies grown next to a DAPG-nullP. protegensstrain (phlDstrain). Using a subinhibitory concentration of purified DAPG in a pellicle assay, we saw that biofilm-specific gene transcription was delayed relative to transcription in untreated samples. These transcriptional changes also corresponded to phenotypic alterations: both biofilm biomass and spore formation were reduced inB. subtilisliquid cultures treated with subinhibitory concentrations of DAPG. Our results add DAPG to the growing list of antibiotics that impact bacterial development and physiology at subinhibitory concentrations. These findings also demonstrate the utility of using coculture as a means to uncover chemically mediated interspecies interactions between bacteria.IMPORTANCEBiofilms are communities of bacteria adhered to surfaces by an extracellular matrix; such biofilms can have important effects in both clinical and agricultural settings. To identify chemical compounds that inhibited biofilm formation, we used a fluorescent reporter to screen for bacteria that inhibited biofilm gene expression inBacillus subtilis. We identifiedPseudomonas protegensas one such bacterium and found that the biofilm-inhibiting compound it produces was the antibiotic 2,4-diacetylphloroglucinol (DAPG). We showed that even at subinhibitory concentrations, DAPG inhibits biofilm formation and sporulation inB. subtilis. These findings have potential implications for understanding the interactions between these two microbes in the natural world and support the idea that many compounds considered antibiotics can impact bacterial development at subinhibitory concentrations.
Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis through Modulation of Bacterial Virulence and Host Immunity
Authors: Goneau Lee W. , Hannan Thomas J. , MacPhee Roderick A. , Schwartz Drew J. , Macklaim Jean M. , Gloor Gregory B. , Razvi Hassan , Reid Gregor , Hultgren Scott J. , Burton Jeremy P. 
Published: April 2015

ABSTRACTThe capacity of subinhibitory levels of antibiotics to modulate bacterial virulencein vitrohas recently been brought to light, raising concerns over the appropriateness of low-dose therapies, including antibiotic prophylaxis for recurrent urinary tract infection management. However, the mechanisms involved and their relevance in influencing pathogenesis have not been investigated. We characterized the ability of antibiotics to modulate virulence in the uropathogensStaphylococcus saprophyticusandEscherichia coli. Several antibiotics were able to induce the expression of adhesins critical to urothelial colonization, resulting in increased biofilm formation, colonization of murine bladders and kidneys, and promotion of intracellular niche formation. Mice receiving subinhibitory ciprofloxacin treatment were also more susceptible to severe infections and frequent recurrences. A ciprofloxacin prophylaxis model revealed this strategy to be ineffective in reducing recurrences and worsened infection by creating larger intracellular reservoirs at higher frequencies. Our study indicates that certain agents used for antibiotic prophylaxis have the potential to complicate infections.IMPORTANCEAntibiotics are the mainstay treatment for bacterial infections; however, evidence is emerging that argues these agents may have off-target effects if sublethal concentrations are present. Most studies have focused on changes occurringin vitro, leaving questions regarding the clinical relevancein vivo. We utilized a murine urinary tract infection model to explore the potential impact of low-dose antibiotics on pathogenesis. Using this model, we showed that subinhibitory antibiotics prime uropathogens for adherence and invasion of murine urothelial tissues. These changes in initial colonization promoted the establishment of chronic infection. Furthermore, treatment of chronically infected mice with subtherapeutic ciprofloxacin served to exacerbate infection. A part of these changes was thought to be due to suppression of mucosal immunity, as demonstrated through reductions in cytokine secretion and migration of leukocytes into the urinary tract. This work identifies novel risk factors associated with antibiotic therapy when dosing strategies fall below subtherapeutic levels.
Structural and Mechanistic Roles of Novel Chemical Ligands on the SdiA Quorum-Sensing Transcription Regulator
Authors: Nguyen Y , Nguyen Nam X. , Rogers Jamie L. , Liao Jun , MacMillan John B. , Jiang Youxing , Sperandio Vanessa 
Published: April 2015

ABSTRACT

Bacteria engage in chemical signaling, termed quorum sensing (QS), to mediate intercellular communication, mimicking multicellular organisms. The LuxR family of QS transcription factors regulates gene expression, coordinating population behavior by sensing endogenous acyl homoserine lactones (AHLs). However, some bacteria (such as
Escherichia coli
) do not produce AHLs. These LuxR orphans sense exogenous AHLs but also regulate transcription in the absence of AHLs. Importantly, this AHL-independent regulatory mechanism is still largely unknown. Here we present several structures of one such orphan LuxR-type protein, SdiA, from enterohemorrhagic
E. coli
(EHEC), in the presence and absence of AHL. SdiA is actually not in an apo state without AHL but is regulated by a previously unknown endogenous ligand, 1-octanoyl-
rac
-glycerol (OCL), which is ubiquitously found throughout the tree of life and serves as an energy source, signaling molecule, and substrate for membrane biogenesis. While exogenous AHL renders to SdiA higher stability and DNA binding affinity, OCL may function as a chemical chaperone placeholder that stabilizes SdiA, allowing for basal activity. Structural comparison between SdiA-AHL and SdiA-OCL complexes provides crucial mechanistic insights into the ligand regulation of AHL-dependent and -independent function of LuxR-type proteins. Importantly, in addition to its contribution to basic science, this work has implications for public health, inasmuch as the SdiA signaling system aids the deadly human pathogen EHEC to adapt to a commensal lifestyle in the gastrointestinal (GI) tract of cattle, its main reservoir. These studies open exciting and novel avenues to control shedding of this human pathogen in the environment.

IMPORTANCE
Quorum sensing refers to bacterial chemical signaling. The QS acyl homoserine lactone (AHL) signals are recognized by LuxR-type receptors that regulate gene transcription. However, some bacteria have orphan LuxR-type receptors and do not produce AHLs, sensing them from other bacteria. We solved three structures of the
E. coli
SdiA orphan, in the presence and absence of AHL. SdiA with no AHL is not in an apo state but is regulated by a previously unknown endogenous ligand, 1-octanoyl-
rac
-glycerol (OCL). OCL is ubiquitously found in prokaryotes and eukaryotes and is a phospholipid precursor for membrane biogenesis and a signaling molecule. While AHL renders to SdiA higher stability and DNA-binding affinity, OCL functions as a chemical chaperone placeholder, stabilizing SdiA and allowing for basal activity. Our studies provide crucial mechanistic insights into the ligand regulation of SdiA activity.
Virus-Induced Dormancy in the Archaeon Sulfolobus islandicus
Authors: Bautista Maria A. , Zhang Changyi , Whitaker Rachel J. 
Published: April 2015

ABSTRACT

We investigated the interaction between Sulfolobus spindle-shaped virus (SSV9) and its native archaeal host
Sulfolobus islandicus
. We show that upon exposure to SSV9, S. islandicus strain RJW002 has a significant growth delay where the majority of cells are dormant (viable but not growing) for 24 to 48 hours postinfection (hpi) compared to the growth of controls without virus. We demonstrate that in this system, dormancy (i) is induced by both active and inactive virus particles at a low multiplicity of infection (MOI), (ii) is reversible in strains with active CRISPR-Cas immunity that prevents the establishment of productive infections, and (iii) results in dramatic and rapid host death if virus persists in the culture even at low levels. Our results add a new dimension to evolutionary models of virus-host interactions, showing that the mere presence of a virus induces host cell stasis and death independent of infection. This novel, highly sensitive, and risky bet-hedging antiviral response must be integrated into models of virus-host interactions in this system so that the true ecological impact of viruses can be predicted and understood.

IMPORTANCE
Viruses of microbes play key roles in microbial ecology; however, our understanding of viral impact on host physiology is based on a few model bacteria that represent a small fraction of the life history strategies employed by hosts or viruses across the three domains that encompass the microbial world. We have demonstrated that rare and even inactive viruses induce dormancy in the model archaeon S. islandicus. Similar virus-induced dormancy strategies in other microbial systems may help to explain several confounding observations in other systems, including the surprising abundance of dormant cell types found in many microbial environments, the difficulty of culturing microorganisms in the laboratory, and the paradoxical virus-to-host abundances that do not match model predictions. A more accurate grasp of virus-host interactions will expand our understanding of the impact of viruses in microbial ecology.