Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative Stress Induction of the MexXY Multidrug Efflux Genes and Promotion of Aminoglycoside Resistance Development in Pseudomonas aeruginosa

ABSTRACT Exposure to reactive oxygen species (ROS) (e.g., peroxide) was shown to induce expression of the PA5471 gene, which was previously shown to be required for antimicrobial induction of the MexXY components of the MexXY-OprM multidrug efflux system and aminoglycoside resistance determinant in Pseudomonas aeruginosa. mexXY was also induced by peroxide exposure, and this too was PA5471 dependent. The prospect of ROS promoting mexXY expression and aminoglycoside resistance recalls P. aeruginosa infection of the chronically inflamed lungs of cystic fibrosis (CF) patients, where the organism is exposed to ROS and where MexXY-OprM predominates as the mechanism of aminoglycoside resistance. While ROS did not enhance aminoglycoside resistance in vitro, long-term (8-day) exposure of P. aeruginosa to peroxide (mimicking chronic in vivo ROS exposure) increased aminoglycoside resistance frequency, dependent upon PA5471 and mexXY. This enhanced resistance frequency was also seen in a mutant strain overexpressing PA5471, in the absence of peroxide, suggesting that induction of PA5471 by peroxide was key to peroxide enhancement of aminoglycoside resistance frequency. Resistant mutants selected following peroxide exposure were typically pan-aminoglycoside-resistant, with mexXY generally required for this resistance. Moreover, PA5471 was required for mexXY expression and aminoglycoside resistance in these as well as several CF isolates examined.
Concordance of mental health impairment and service utilization among children in care

This paper describes caregiver-reported patterns of mental health service use for 347 pre-adolescent children in foster and kinship care in New South Wales (NSW), Australia. Children’s mean time in care and mean time with their present caregivers were 4.3 and 3.3 years respectively. Forty-four percent of children received individual therapy or counselling, 45% received interventions in the form of clinical guidance for their caregivers, and 31% received both forms of service. Among children scoring in the clinical range on any CBCL sub-scale (N = 191), equivalent rates of mental health service use were 60%, 55% and 41% respectively. Although not directly comparable, these findings describe a higher rate of service use than that reported for children in care elsewhere. While children with more complex and severe difficulties had higher rates of service use, there was no evidence of variable access for treatment of different types of disorder. Predictors of service use are reported and contrasted with previous findings. The paper considers several features of the NSW child welfare, health and education systems that may account for the relatively high rate of service use.
Interlaboratory Variability of Caspofungin MICs for Candida spp. Using CLSI and EUCAST Methods: Should the Clinical Laboratory Be Testing This Agent?

ABSTRACT Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) are available for interpreting echinocandin MICs for Candida spp. , epidemiologic cutoff values (ECVs) based on collective MIC data from multiple laboratories have not been defined. While collating CLSI caspofungin MICs for 145 to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico, Peru, and the United States), we observed an extraordinary amount of modal variability (wide ranges) among laboratories as well as truncated and bimodal MIC distributions. The species-specific modes across different laboratories ranged from 0.016 to 0.5 μg/ml for C. albicans and C. tropicalis, 0.031 to 0.5 μg/ml for C. glabrata, and 0.063 to 1 μg/ml for C. krusei. Variability was also similar among MIC distributions for C. dubliniensis and C. lusitaniae. The exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where most modes were within one 2-fold dilution of each other. These findings were consistent with available data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for C. albicans, C. glabrata, C. krusei, and C. tropicalis. Although many factors (caspofungin powder source, stock solution solvent, powder storage time length and temperature, and MIC determination testing parameters) were examined as a potential cause of such unprecedented variability, a single specific cause was not identified. Therefore, it seems highly likely that the use of the CLSI species-specific caspofungin CBPs could lead to reporting an excessive number of wild-type (WT) isolates (e.g., C. glabrata and C. krusei) as either non-WT or resistant isolates. Until this problem is resolved, routine testing or reporting of CLSI caspofungin MICs for Candida is not recommended; micafungin or anidulafungin data could be used instead.
Azole Susceptibility and Transcriptome Profiling in Candida albicans Mitochondrial Electron Transport Chain Complex I Mutants

ABSTRACT Mitochondrial dysfunction in pathogenic fungi or model yeast causes altered susceptibilities to antifungal drugs. Here we have characterized the role of mitochondrial complex I (CI) of Candida albicans in antifungal susceptibility. Inhibitors of CI to CV, except for CII, increased the susceptibility of both patient and lab isolates, even those with a resistance phenotype. In addition, in a C. albicans library of 12 CI null mutants, 10 displayed hypersusceptibility to fluconazole and were severely growth inhibited on glycerol, implying a role for each gene in cell respiration. We chose two other hypersusceptible null mutants of C. albicans, the goa1Δ and ndh51Δ mutants, for transcriptional profiling by RNA-Seq. Goa1p is required for CI activity, while Ndh51p is a CI subunit. RNA-Seq revealed that both the ndh51Δ mutant and especially the goa1Δ mutant had significant downregulation of transporter genes, including CDR1 and CDR2, which encode efflux proteins. In the goa1Δ mutant, we noted the downregulation of genes required for the biogenesis and replication of peroxisomes, as well as metabolic pathways assigned to peroxisomes such as β-oxidation of fatty acids, glyoxylate bypass, and acetyl coenzyme A (acetyl-CoA) transferases that are known to shuttle acetyl-CoA between peroxisomes and mitochondria. The transcriptome profile of the ndh51Δ mutant did not include downregulation of peroxisome genes but had, instead, extensive downregulation of the ergosterol synthesis gene family. Our data establish that cell energy is required for azole susceptibility and that downregulation of efflux genes may be an outcome of that dysfunction. However, there are mutant-specific changes that may also increase the susceptibility of both of these C. albicans mutants to azoles.
Comparative Study of Small Electrical Machines With Soft Magnetic Composite Cores

In this paper, various kinds of electrical machines with soft magnetic composite (SMC) cores are compared, based on the qualitative and quantitative comparison methods. In the first part, the performances of five typical electrical machines with SMC cores are qualitatively compared. Simplified power equations for transverse flux, axial flux, and radial flux electrical machines are deduced to show the main difference among them and key design points of each machine. In the second part, the outer rotor claw pole machine (CPM) and outer rotor transverse flux machine (TFM) are comprehensively compared in a quantitative way, based on the three-dimensional finite-element method. It shows that the power capability of the outer rotor CPM is much higher than that of the TFM. On the other hand, the outer rotor CPM has higher cogging torque and no-load losses than the TFM. Furthermore, the four outer rotor radial flux machines are optimized and compared with the outer rotor CPM. The calculated results of the outer rotor TFM are compared with the experiment results, showing that the analysis results match well with the experiment ones. Several useful and interesting conclusions have been obtained for the electrical machines with SMC cores.
Automating Discovery of Dominance in Synchronous Computer-Mediated Communication

With the advent of electronic interaction, dominance (or the assertion of control over others) has acquired new dimensions. This study investigates the dynamics and characteristics of dominance in virtual interaction by analyzing electronic chat transcripts of groups solving a hidden profile task. We investigate computer-mediated communication behavior patterns that demonstrate dominance and identify a number of relevant variables. These indicators are calculated with automatic and manual coding of text transcripts. A comparison of both sets of variables indicates that automatic text analysis methods yield similar conclusions than manual coding. These findings are encouraging to advance research in text analysis methods in general, and in the study of virtual team dominance in particular.
Interventions in foster and kinship care: A systematic review

Foster care is a complex setting in which to provide therapeutic interventions due to the high rates of difficulty, poor outcomes and high numbers of professionals and carers involved. This systematic review aims to examine interventions that have been empirically assessed in foster care. Thirty papers describing 20 interventions were included. It was found that there was good support for wraparound services and relational interventions, but little support for widely used carer training programmes. A need was identified to further research and implement wraparound services within the UK, and to empirically test interventions which may be efficacious with a foster care population.
Managing eating and drinking difficulties (dysphagia) with children who have learning disabilities: What is effective?

People who work with children who have neurological and learning disabilities frequently need to manage the health and emotional risks associated with eating, drinking and swallowing (dysphagia). Some approaches can support children to develop oral feeding competence or to maximise their ability to maintain some oral intake supplemented with tube feeding. However, some clinicians feel that oral-motor exercises can support eating and drinking skills as well as speech and language development, whereas there is little evidence to support this. The implied “beneficial” association between oral-motor exercises, speech and swallowing skills gives a false impression in terms of future outcomes for parents and carers of children with learning disabilities. This paper considers oral-motor approaches in the remediation of dysphagia and the need for a cultural shift away from this view. Realistic and useful outcomes for people with learning disabilities need to be an essential part of therapeutic intervention.
A Taxonomy of Industrial Service Systems Enabled by Digital Product Innovation

Against the backdrop of pervasive digitization, industrial equipment in the manufacturing industry is increasingly augmented with digital technology. Since the industrial service business plays a growing role for original equipment manufacturers (OEMs), the physical and digital materiality of industrial equipment particularly has gained importance for service innovation. Despite these new opportunities, OEMs, industrial equipment operators, and service organizations struggle to (1) identify and build up adequate technological capabilities and (2) fully harness the potential of digital product innovation for their service business. Within this paper, we propose an evaluated taxonomy to classify and better understand industrial service systems enabled by digital product innovation. As an anchor in theory, we draw on the service-dominant logic and the theory of affordances. The taxonomy helps practitioners to better understand the impact of digital product innovation on the service business in respective industry contexts.
Larger Vancomycin Doses (at Least Four Grams per Day) Are Associated with an Increased Incidence of Nephrotoxicity

ABSTRACT Recent guidelines recommend vancomycin trough concentrations between 15 and 20 mg/liter. In response, some clinicians increased vancomycin dosing to ≥4 g/day. Scant data are available regarding toxicities associated with higher vancomycin doses. The purpose of this study was to examine vancomycin-associated nephrotoxicity at ≥4 g/day. To accomplish the study objective, a cohort study among a random selection of patients receiving vancomycin or linezolid between 2005 and 2006 was performed. Patients were included if they (i) were ≥18 years of age, (ii) were nonneutropenic, (iii) were on therapy for >48 h, (iv) had baseline serum creatinine levels of <2.0 mg/dl, (v) did not suffer from cystic fibrosis, and (vi) had no intravenous contrast dye within the previous 7 days. For drug exposure, three treatment strata were created: standard vancomycin dose (<4 g/day), high vancomycin dose (≥4 g/day), and linezolid. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/dl or 50%, whichever was greater, after therapy initiation. Stratified Kaplan-Meier analysis and Cox modeling were used to compare times to nephrotoxicity across groups. During the study, 246 patients on vancomycin (26 patients taking ≥4 g/day and 220 patients taking <4 g/day) and 45 patients on linezolid met the criteria. A significant difference in nephrotoxicity between patients receiving ≥4 g vancomycin/day, those receiving <4 g vancomycin/day, and those receiving linezolid was noted (34.6%, 10.9%, and 6.7%, respectively; P = 0.001), and Kaplan-Meier analysis identified significant differences in time to nephrotoxicity for the high-vancomycin-dose cohort compared to those for groups taking the standard dose and linezolid. In the Cox model, patients taking ≥4 g vancomycin/day, a total body weight of ≥101.4 kg, estimated creatinine clearance of ≤86.6 ml/min, and intensive care unit residence were independently associated with time to nephrotoxicity. The data suggest that higher-dose vancomycin regimens are associated with a higher likelihood of vancomycin-related nephrotoxicity.
Parametric Resonance in Electrostatically Actuated Micromirrors

We consider an electrostatically actuated torsional micromirror, a key element of recent optical microdevices. The mechanical response is analyzed with specific emphasis on its nonlinear features. We show that the mirror motion is an example of parametric resonance, activated when the drive frequency is twice the natural frequency of the system. The numerical model, solved with a continuation approach, is validated with very good accuracy through an extensive experimental campaign.
Chlorhexidine and Mupirocin Susceptibilities of Methicillin-Resistant Staphylococcus aureus from Colonized Nursing Home Residents

ABSTRACT Chlorhexidine and mupirocin are used in health care facilities to eradicate methicillin-resistant Staphylococcus aureus (MRSA) carriage. The objective of this study was to assess the frequency of chlorhexidine and mupirocin resistance in isolates from nares carriers in multiple nursing homes and to examine characteristics associated with resistance. Nasal swab samples were collected from approximately 100 new admissions and 100 current residents in 26 nursing homes in Orange County, CA, from October 2008 to May 2011. MRSA isolates were tested for susceptibility by using broth microdilution, disk diffusion, and Etest; for genetic relatedness using pulsed-field gel electrophoresis; and for qac gene carriage by PCR. Characteristics of the nursing homes and their residents were collected from the Medicare Minimum Data Set and Long-Term Care Focus. A total of 829 MRSA isolates were obtained from swabbing 3,806 residents in 26 nursing homes. All isolates had a chlorhexidine MIC of ≤4 μg/ml. Five (0.6%) isolates harbored the qacA and/or qacB gene loci. Mupirocin resistance was identified in 101 (12%) isolates, with 78 (9%) isolates exhibiting high-level mupirocin resistance (HLMR). HLMR rates per facility ranged from 0 to 31%. None of the isolates with HLMR displayed qacA or qacB, while two isolates carried qacA and exhibited low-level mupirocin resistance. Detection of HLMR was associated with having a multidrug-resistant MRSA isolate (odds ratio [OR], 2.69; P = 0.004), a history of MRSA (OR, 2.34; P < 0.001), and dependency in activities of daily living (OR, 1.25; P = 0.004). In some facilities, HLMR was found in nearly one-third of MRSA isolates. These findings may have implications for the increasingly widespread practice of MRSA decolonization using intranasal mupirocin.
Cationic Antimicrobial Peptide LL-37 Is Effective against both Extra- and Intracellular Staphylococcus aureus

ABSTRACT The increasing resistance of bacteria to conventional antibiotics and the challenges posed by intracellular bacteria, which may be responsible for chronic and recurrent infections, have driven the need for advanced antimicrobial drugs for effective elimination of both extra- and intracellular pathogens. The purpose of this study was to determine the killing efficacy of cationic antimicrobial peptide LL-37 compared to conventional antibiotics against extra- and intracellular Staphylococcus aureus. Bacterial killing assays and an infection model of osteoblasts and S. aureus were studied to determine the bacterial killing efficacy of LL-37 and conventional antibiotics against extra- and intracellular S. aureus. We found that LL-37 was effective in killing extracellular S. aureus at nanomolar concentrations, while lactoferricin B was effective at micromolar concentrations and doxycycline and cefazolin at millimolar concentrations. LL-37 was surprisingly more effective in killing the clinical strain than in killing an ATCC strain of S. aureus. Moreover, LL-37 was superior to conventional antibiotics in eliminating intracellular S. aureus. The kinetic studies further revealed that LL-37 was fast in eliminating both extra- and intracellular S. aureus. Therefore, LL-37 was shown to be very potent and prompt in eliminating both extra- and intracellular S. aureus and was more effective in killing extra- and intracellular S. aureus than commonly used conventional antibiotics. LL-37 could potentially be used to treat chronic and recurrent infections due to its effectiveness in eliminating not only extracellular but also intracellular pathogens.
Antimicrobial Susceptibility of Mycoplasma pneumoniae Isolates and Molecular Analysis of Macrolide-Resistant Strains from Shanghai, China

ABSTRACT Fifty-three Mycoplasma pneumoniae strains were isolated from pediatric patients in Shanghai, China, from October 2005 to February 2008. Of 53 clinical isolates, 44 (83%) were resistant to erythromycin (MICs of >128 μg/ml for all 44 strains), azithromycin, and clarithromycin. All macrolide-resistant M. pneumoniae strains harbored an A-to-G transition mutation at position 2063 in 23S rRNA genes. Forty-five (85%) clinical isolates were classified into the P1 gene restriction fragment length polymorphism type I, and six (11%) were type II.
The Fluoroquinolone Levofloxacin Triggers the Transcriptional Activation of Iron Transport Genes That Contribute to Cell Death in Streptococcus pneumoniae

ABSTRACT We studied the transcriptomic response of Streptococcus pneumoniae to levofloxacin (LVX) under conditions inhibiting topoisomerase IV but not gyrase. Although a complex transcriptomic response was observed, the most outstanding result was the upregulation of the genes of the fatDCEB operon, involved in iron (Fe2+ and Fe3+) uptake, which were the only genes varying under every condition tested. Although the inhibition of topoisomerase IV by levofloxacin did not have a detectable effect in the level of global supercoiling, increases in general supercoiling and fatD transcription were observed after topoisomerase I inhibition, while the opposite was observed after gyrase inhibition with novobiocin. Since fatDCEB is located in a topological chromosomal domain downregulated by DNA relaxation, we studied the transcription of a copy of the 422-bp (including the Pfat promoter) region located upstream of fatDCEB fused to the cat reporter inserted into the chromosome 106 kb away from its native position: PfatfatD was upregulated in the presence of LVX in its native location, whereas no change was observed in the Pfatcat construction. Results suggest that topological changes are indeed involved in PfatfatDCE transcription. Upregulation of fatDCEB would lead to an increase of intracellular iron and, in turn, to the activation of the Fenton reaction and the increase of reactive oxygen species. In accordance, we observed an attenuation of levofloxacin lethality in iron-deficient media and in a strain lacking the gene coding for SpxB, the main source of hydrogen peroxide. In addition, we observed an increase of reactive oxygen species that contributed to levofloxacin lethality.
vanM, a New Glycopeptide Resistance Gene Cluster Found in Enterococcus faecium

ABSTRACT Since glycopeptide-resistant enterococci (GRE) were reported in 1988, they have appeared in hospitals worldwide. Seven van gene cluster types (vanA, vanB, vanC, vanD, vanE, vanG, and vanL) are currently known. We investigated a clinical strain of Enterococcusfaecium Efm-HS0661 that was isolated in 2006 from an inpatient with intra-abdominal infection in Shanghai. It was resistant to most antimicrobials, including vancomycin (MIC, >256 μg/ml) and teicoplanin (MIC, 96 μg/ml). Glycopeptide resistance could be transferred to E. faecium BM4105RF by conjugation. The donor and its transconjugant were negative by PCR for the known van genes. By cloning and primer walk sequencing, we discovered a novel van gene cluster, designated vanM. The vanM ligase gene was 1,032-bp in length and encoded a 343-amino-acid protein that shared 79.9, 70.8, 66.3, and 78.8% amino acid identity with VanA, VanB, VanD, and VanF, respectively. Although the vanM DNA sequence was closest to vanA, the organization of the vanM gene cluster was most similar to that of vanD. Upstream from the vanM cluster was an IS1216-like element, which may play a role in the dissemination of this resistance determinant. Liquid chromatography-mass spectrometry analysis of peptidoglycan precursors extracted from the VanM-type strain Efm-HS0661 treated with vancomycin or teicoplanin revealed a modified precursor (UDP-N-acetylmuramic acid [MurNAc]-tetrapeptide-d-Lac), indicating that VanM, like VanA, confers glycopeptide resistance by the inducible synthesis of precursor ending in d-Ala-d-Lac.
Understanding the Sharing Economy -- Drivers and Impediments for Participation in Peer-to-Peer Rental

As peer-to-peer coordinated products and services increasingly constitute competition for traditional businesses in many areas, understanding the underlying user motives of provision and consumption is key -- not only for business operators, but also for researchers investigating such markets. In this article, we develop a questionnaire for assessing motives for and against participating in what is casually referred to as the "Sharing Economy. " More specifically, we focus on peer-to-peer rental services and investigate drivers and impediments for user activity in such markets by means of an online survey with over 600 participants.
KPC Presence in Pseudomonas aeruginosa Has Minimal Impact on the In Vivo Efficacy of Carbapenem Therapy

ABSTRACT While reports of Klebsiella pneumoniae carbapenemase (KPC) production among Pseudomonas aeruginosa strains have emerged from a number of countries worldwide, outcome data are lacking. This is the first report evaluating how KPC production in P. aeruginosa impacts the efficacy of carbapenems by using the murine thigh infection model. Our findings suggest that the impact of KPC-2 in vivo is less pronounced than would be anticipated based on the in vitro potency.