bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occurrence of Acquired 16S rRNA Methyltransferase-Mediated Aminoglycoside Resistance in Clinical Isolates of Enterobacteriaceae within a Tertiary Referral Hospital of Northeast India
Authors: Wangkheimayum Jayalaxmi , Paul Deepjyoti , Dhar Debadatta , Nepram Rajlakshmi , Chetri Shiela , Bhowmik Deepshikha , Chakravarty Atanu , Bhattacharjee Amitabha 
Published: March 2017

ABSTRACT

The methylation of a ribosomal target leads to a high level of resistance to all clinically relevant aminoglycoside antibiotics, so early detection of these resistance determinants will help to reduce the incidence of treatment failures as well as lessen the dissemination rate. Here, we characterized different 16S rRNA methyltransferases responsible for aminoglycoside resistance and their epidemiological background in clinical isolates of
Enterobacteriaceae
in a tertiary referral hospital in India. All aminoglycoside-resistant isolates were screened for different 16S rRNA methyltransferases by PCR assay, and incompatibility typing of the conjugable plasmid harboring resistance genes was performed by PCR-based replicon typing. An assay for the stability and elimination of these resistance plasmids was performed. The coexistence of extended-spectrum β-lactamases and metallo-β-lactamases was also detected, and the heterogeneity of these isolates was determined by enterobacterial repetitive intergenic consensus PCR. The PCR assay revealed the presence of
armA
,
rmtA
,
rmtB
,
rmtC
, and
rmtD
in single and multiple combinations, and these were carried by a diverse group of Inc plasmids. Plasmids harboring these resistance determinants were highly stable and maintained until the 55th serial passage, but SDS treatment could easily eliminate the plasmids harboring the resistance determinants. The coexistence of
bla
TEM
,
bla
PER
,
bla
GES
, and
bla
SHV
, as well as
bla
VIM
and
bla
NDM
, within these isolates was also detected. Strains with different clonal patterns of aminoglycoside resistance were found to spread in this hospital setting. We observed that the 16S rRNA methyltransferase genes were encoded within different Inc plasmid types, suggesting diverse origins and sources of acquisition. Therefore, the present study is of epidemiological importance and can have a role in infection control policy in hospital settings.
In Vitro
Activity of Imipenem-Relebactam against Gram-Negative ESKAPE Pathogens Isolated by Clinical Laboratories in the United States in 2015 (Results from the SMART Global Surveillance Program)
Authors: Lob Sibylle H. , Hackel Meredith A. , Kazmierczak Krystyna M. , Young Katherine , Motyl Mary R. , Karlowsky James A. , Sahm Daniel F. 
Published: March 2017

ABSTRACT

Relebactam (formerly MK-7655) is an inhibitor of class A and C β-lactamases, including
Klebsiella pneumoniae
carbapenemase (KPC), and is currently in clinical development in combination with imipenem-cilastatin. Using Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution methodology, we evaluated the
in vitro
activities of imipenem-relebactam, imipenem, and seven routinely tested parenteral antimicrobial agents against Gram-negative ESKAPE pathogens (including
Klebsiella pneumoniae
,
n
= 689;
Acinetobacter baumannii
,
n
= 72;
Pseudomonas aeruginosa
,
n
= 845; and
Enterobacter
spp.,
n
= 399) submitted by 21 clinical laboratories in the United States in 2015 as part of the SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Relebactam was tested at a fixed concentration of 4 μg/ml in combination with doubling dilutions of imipenem. Imipenem-relebactam MICs were interpreted using CLSI imipenem breakpoints. The respective rates of susceptibility to imipenem-relebactam and imipenem were 94.2% (796/845) and 70.3% (594/845) for
P. aeruginosa
, 99.0% (682/689) and 96.1% (662/689) for
K. pneumoniae
, and 100% (399/399) and 98.0% (391/399) for
Enterobacter
spp. Relebactam restored imipenem susceptibility to 80.5% (202/251), 74.1% (20/27), and 100% (8/8) of isolates of imipenem-nonsusceptible
P. aeruginosa
,
K. pneumoniae
, and
Enterobacter
spp. Relebactam did not increase the number of isolates of
Acinetobacter
spp. susceptible to imipenem, and the rates of resistance to all of the agents tested against this pathogen were >30%. Further development of imipenem-relebactam is warranted given the demonstrated ability of relebactam to restore the activity of imipenem against current clinical isolates of
Enterobacteriaceae
and
P. aeruginosa
that are nonsusceptible to carbapenems and its potential as a therapy for treating patients with antimicrobial-resistant Gram-negative infections.
Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum
Authors: Moreira Vanessa Ribeiro , de Jesus Luís Cláudio Lima , Soares Rossy-Eric Pereira , Silva Luis Douglas Miranda , Pinto Bruno Araújo Serra , Melo Maria Norma , Paes Antonio Marcus de Andrade , Pereira Silma Regina Ferreira 
Published: March 2017

ABSTRACT

Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite
Leishmania
. Meglumine antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which meglumine antimoniate causes DNA damage was investigated for BALB/c mice infected by
Leishmania
(
Leishmania
)
infantum
and treated with meglumine antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that meglumine antimoniate, as well as
L. infantum
infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both meglumine antimoniate treatment and
L. infantum
infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a meglumine antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
Variability in Trough Total and Unbound Teicoplanin Concentrations and Achievement of Therapeutic Drug Monitoring Targets in Adult Patients with Hematological Malignancy
Authors: Byrne Catherine J. , Roberts Jason A. , McWhinney Brett , Fennell Jerome P. , O'Byrne Philomena , Deasy Evelyn , Egan Sean , Desmond Ronan , Enright Helen , Ryder Sheila A. , D'Arcy Deirdre M. , McHugh Johnny 
Published: March 2017

ABSTRACT

The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ≥20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (
P
< 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.)
The Suf Iron-Sulfur Cluster Biosynthetic System Is Essential in Staphylococcus aureus, and Decreased Suf Function Results in Global Metabolic Defects and Reduced Survival in Human Neutrophils
Authors: Roberts Christina A. , Al-Tameemi Hassan M. , Mashruwala Ameya A. , Rosario-Cruz Zuelay , Chauhan Unnati , Sause William E. , Torres Victor J. , Belden William J. , Boyd Jeffrey M. 
Published: March 2017

ABSTRACT

Staphylococcus aureus
remains a causative agent for morbidity and mortality worldwide. This is in part a result of antimicrobial resistance, highlighting the need to uncover novel antibiotic targets and to discover new therapeutic agents. In the present study, we explored the possibility that iron-sulfur (Fe-S) cluster synthesis is a viable antimicrobial target. RNA interference studies established that Suf (
su
l
f
ur mobilization)-dependent Fe-S cluster synthesis is essential in
S. aureus
. We found that
sufCDSUB
were cotranscribed and that
suf
transcription was positively influenced by sigma factor B. We characterized an
S. aureus
strain that contained a transposon inserted in the intergenic space between
sufC
and
sufD
(
sufD
*), resulting in decreased transcription of
sufSUB
. Consistent with the transcriptional data, the
sufD
* strain had multiple phenotypes associated with impaired Fe-S protein maturation. They included decreased activities of Fe-S cluster-dependent enzymes, decreased growth in media lacking metabolites that require Fe-S proteins for synthesis, and decreased flux through the tricarboxylic acid (TCA) cycle. Decreased Fe-S cluster synthesis resulted in sensitivity to reactive oxygen and reactive nitrogen species, as well as increased DNA damage and impaired DNA repair. The
sufD
* strain also exhibited perturbed intracellular nonchelated Fe pools. Importantly, the
sufD*
strain did not exhibit altered exoprotein production or altered biofilm formation, but it was attenuated for survival upon challenge by human polymorphonuclear leukocytes. The results presented are consistent with the hypothesis that Fe-S cluster synthesis is a viable target for antimicrobial development.
Metabolism Shapes the Cell
Authors: Sperber Anthony M. , Herman Jennifer K. 
Published: March 2017

ABSTRACT
More than 5 decades of work support the idea that cell envelope synthesis, including the inward growth of cell division, is tightly coordinated with DNA replication and protein synthesis through central metabolism. Remarkably, no unifying model exists to account for how these fundamentally disparate processes are functionally coupled. Recent studies demonstrate that proteins involved in carbohydrate and nitrogen metabolism can moonlight as direct regulators of cell division, coordinate cell division and DNA replication, and even suppress defects in DNA replication. In this minireview, we focus on studies illustrating the intimate link between metabolism and regulation of peptidoglycan (PG) synthesis during growth and division, and we identify the following three recurring themes. (i) Nutrient availability, not growth rate, is the primary determinant of cell size. (ii) The degree of gluconeogenic flux is likely to have a profound impact on the metabolites available for cell envelope synthesis, so growth medium selection is a critical consideration when designing and interpreting experiments related to morphogenesis. (iii) Perturbations in pathways relying on commonly shared and limiting metabolites, like undecaprenyl phosphate (Und-P), can lead to pleotropic phenotypes in unrelated pathways.
Replication Restart in Bacteria
Authors: Michel Bénédicte , Sandler Steven J. 
Published: March 2017

ABSTRACT

In bacteria, replication forks assembled at a replication origin travel to the terminus, often a few megabases away. They may encounter obstacles that trigger replisome disassembly, rendering replication restart from abandoned forks crucial for cell viability. During the past 25 years, the genes that encode replication restart proteins have been identified and genetically characterized. In parallel, the enzymes were purified and analyzed
in vitro
, where they can catalyze replication initiation in a sequence-independent manner from fork-like DNA structures. This work also revealed a close link between replication and homologous recombination, as replication restart from recombination intermediates is an essential step of DNA double-strand break repair in bacteria and, conversely, arrested replication forks can be acted upon by recombination proteins and converted into various recombination substrates. In this review, we summarize this intense period of research that led to the characterization of the ubiquitous replication restart protein PriA and its partners, to the definition of several replication restart pathways
in vivo
, and to the description of tight links between replication and homologous recombination, responsible for the importance of replication restart in the maintenance of genome stability.
The psychological features of patellofemoral pain: a systematic review
Authors: Maclachlan Liam R. , Collins Natalie J. , Matthews Mark L.G. , Hodges Paul W. , Vicenzino Bill 
Published: March 2017

BackgroundPatellofemoral pain (PFP) is prevalent in adolescence and adulthood and often persists. In contrast to other persistent musculoskeletal conditions, for which non-physical, psychological features are implicated, PFP remains largely conceptualised in mechanical terms.AimsTo (1) identify whether the psychological characteristics of individuals with PFP differs from asymptomatic controls and (2) evaluate the correlations between psychological characteristics and PFP severity.Study designSystematic reviewMethodsA systematic review of the literature was conducted according to PRISMA guidelines. The Epidemiological Appraisal Instrument was used to evaluate quality. Studies measuring psychological constructs with patient-reported measures were included. Standardised mean differences were calculated and supported by narrative synthesis.ResultsTwenty-five studies were eligible. Quality results ranged from 28.3% to 61.7%. Psychological constructs were reported under four groupings: mental health, cognitive factors, behavioural factors and other factors. There is limited evidence of mental health and cognitive differences in some individuals with PFP. Features demonstrating linear correlations with pain and physical function included anxiety/depression, catastrophising, praying and hoping and pain-related fear.ConclusionsAnxiety, depression, catastrophising and fear of movement may be elevated in individuals with PFP and correlate with pain and reduced physical function. These results derive from a limited number of studies. Future research should aim to evaluate if and how psychological factors contribute to PFP.Clinical relevancePatients are likely to benefit from clinician vigilance to the presence of psychological factors.
Exploring similarities and differences in hospital adverse event rates between Norway and Sweden using Global Trigger Tool
Authors: Deilkås Ellen Tveter , Risberg Madeleine Borgstedt , Haugen Marion , Lindstrøm Jonas Christoffer , Nylén Urban , Rutberg Hans , Michael Soop 
Published: March 2017

ObjectivesIn this paper, we explore similarities and differences in hospital adverse event (AE) rates between Norway and Sweden by reviewing medical records with the Global Trigger Tool (GTT).DesignAll acute care hospitals in both countries performed medical record reviews, except one in Norway. Records were randomly selected from all eligible admissions in 2013. Eligible admissions were patients 18 years of age or older, undergoing care with an in-hospital stay of at least 24 hours, excluding psychiatric and care and rehabilitation. Reviews were done according to GTT methodology.SettingSimilar contexts for healthcare and similar socioeconomic and demographic characteristics have inspired the Nordic countries to exchange experiences from measuring and monitoring quality and patient safety in healthcare. The co-operation has promoted the use of GTT to monitor national and local rates of AEs in hospital care.Participants10 986 medical records were reviewed in Norway and 19 141 medical records in Sweden.ResultsNo significant difference between overall AE rates was found between the two countries. The rate was 13.0% (95% CI 11.7% to 14.3%) in Norway and 14.4% (95% CI 12.6% to 16.3%) in Sweden. There were significantly higher AE rates of surgical complications in Norwegian hospitals compared with Swedish hospitals. Swedish hospitals had significantly higher rates of pressure ulcers, falls and ‘other’ AEs. Among more severe AEs, Norwegian hospitals had significantly higher rates of surgical complications than Swedish hospitals. Swedish hospitals had significantly higher rates of postpartum AEs.ConclusionsThe level of patient safety in acute care hospitals, as assessed by GTT, was essentially the same in both countries. The differences between the countries in the rates of several types of AEs provide new incentives for Norwegian and Swedish governing bodies to address patient safety issues.
Investigating skin-to-skin care patterns with extremely preterm infants in the NICU and their effect on early cognitive and communication performance: a retrospective cohort study
Authors: Gonya Jenn , Ray William C , Rumpf R Wolfgang , Brock Guy 
Published: March 2017

ObjectivesThe primary objective of the study was to investigate how patterns of skin-to-skin care might impact infant early cognitive and communication performance.DesignThis was a retrospective cohort study.SettingThis study took place in a level-IV all-referral neonatal intensive care unit in the Midwest USA specialising in the care of extremely preterm infants.ParticipantsData were collected from the electronic medical records of all extremely preterm infants (gestational age <27 weeks) admitted to the unit during 2010–2011 and who completed 6-month and 12-month developmental assessments in the follow-up clinic (n=97).Outcome measuresOutcome measures included the cognitive and communication subscales of the Bayley Scales of Infant Development, Third Edition (Bayley-III); and skin-to-skin patterns including: total hours of maternal and paternal participation throughout hospitalisation, total duration in weeks and frequency (hours per week).AnalysisExtracted data were analysed through a multistep process of logistic regressions, t-tests, χ2tests and Fisher's exact tests followed with exploratory network analysis using novel visual analytic software.ResultsInfants who received above the sample median in total hours, weekly frequency and total hours from mothersandfathers of skin-to-skin care were more likely to score ≥80 on the cognitive and communication scales of the Bayley-III. However, the results were not statistically significant (p>0.05). Mothers provided the majority of skin-to-skin care with a sharp decline at 30 weeks corrected age, regardless of when extremely preterm infants were admitted. Additional exploratory network analysis suggests that medical and skin-to-skin factors play a parallel, non-synergistic role in contributing to early cognitive and communication performance as assessed through the Bayley-III.ConclusionsThis study suggests an association between early and frequent skin-to-skin care with extremely preterm infants and early cognitive and communication performance.
Effectiveness of chronic care models for the management of type 2 diabetes mellitus in Europe: a systematic review and meta-analysis
Authors: Bongaerts Brenda W C , Müssig Karsten , Wens Johan , Lang Caroline , Schwarz Peter , Roden Michael , Rathmann Wolfgang 
Published: March 2017

ObjectivesWe evaluated the effectiveness of European chronic care programmes for type 2 diabetes mellitus (characterised by integrative care and a multicomponent framework for enhancing healthcare delivery), compared with usual diabetes care.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, Embase, CENTRAL and CINAHL from January 2000 to July 2015.Eligibility criteriaRandomised controlled trials focussing on (1) adults with type 2 diabetes, (2) multifaceted diabetes care interventions specifically designed for type 2 diabetes and delivered in primary or secondary care, targeting patient, physician and healthcare organisation and (3) usual diabetes care as the control intervention.Data extractionStudy characteristics, characteristics of the intervention, data on baseline demographics and changes in patient outcomes.Data analysisWeighted mean differences in change in HbA1c and total cholesterol levels between intervention and control patients (95% CI) were estimated using a random-effects model.ResultsEight cluster randomised controlled trials were identified for inclusion (9529 patients). One year of multifaceted care improved HbA1c levels in patients with screen-detected and newly diagnosed diabetes, but not in patients with prevalent diabetes, compared to usual diabetes care. Across all seven included trials, the weighted mean difference in HbA1c change was −0.07% (95% CI −0.10 to −0.04) (−0.8 mmol/mol (95% CI −1.1 to −0.4)); I2=21%. The findings for total cholesterol, LDL-cholesterol and blood pressure were similar to HbA1c, albeit statistical heterogeneity between studies was considerably larger. Compared to usual care, multifaceted care did not significantly change quality of life of the diabetes patient. Finally, measured for screen-detected diabetes only, the risk of macrovascular and mircovascular complications at follow-up was not significantly different between intervention and control patients.ConclusionsEffects of European multifaceted diabetes care patient outcomes are only small. Improvements are somewhat larger for screen-detected and newly diagnosed diabetes patients than for patients with prevalent diabetes.