bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive‐pressure ventilation during transport: a randomized crossover study of self‐inflating and flow‐inflating resuscitators in a simulation model
Authors: Lucy Malcolm J. , Gamble Jonathan J. , Daku Brian L. , Bryce Rhonda D. , Rana Masud 
Published: June 2014

SummaryBackgroundPositive‐pressure ventilation during transport of intubated patients is generally delivered via a hand‐pressurized device. Of these devices, self‐inflating resuscitators (SIR) and flow‐inflating resuscitators (FIR) constitute the two major types used. Selection of a particular device for transport, however, remains largely an institutional practice.ObjectiveTo evaluate the hypothesis that transport ventilation goals of intubated pediatric patients are better achieved using an FIR compared to an SIR.MethodsThis randomized crossover simulation study compared the performance of SIR and FIR among anesthesia providers in a pediatric transport scenario. Subjects hand‐ventilated a test lung while simultaneously maneuvering a stretcher bed to simulate patient transport. Hand ventilation was carried out using a Jackson–Rees circuit (FIR) and a Laerdal pediatric silicone resuscitator (SIR). The primary outcome was the proportion of total breaths delivered within the predefined target PIP/PEEP range (30+/− 3, 10+/− 3 cm H2O). Secondary outcomes included proportion of total breaths delivered with operationally defined unacceptable breath variables (PIP > 35 cm H2O or PEEP < 5 cm H2O).ResultsOverall, participants were four times more likely to deliver target breaths and one‐third less likely to deliver unacceptable breaths using the FIR compared to the SIR. When comparing device performance, a 44% increase in the proportions of target breaths and a 40.4% decrease in unacceptable breaths using the FIR were observed (P < 0.0001 for both).ConclusionsHand ventilation during patient transport is superior using the FIR compared to the SIR to achieve target ventilatory goals and avoid unacceptable ventilatory cycles.
Treatment planning: A key milestone to prevent treatment dropout in adolescents with borderline personality disorder
Authors: Desrosiers Lyne , Saint‐Jean Micheline , Breton Jean‐Jacques 
Published: June 2014

ObjectiveThe aim of this study was to gain a broader appreciation of processes involved in treatment dropout in adolescents with borderline personality disorder (BPD).DesignA constructivist grounded theory was chosen using a multiple‐case research design with three embedded levels of analysis (adolescent, parent, and care setting).MethodTheoretical sampling and the different stages of analysis specific to grounded theory were performed according to the iterative process of constant comparative analysis. Twelve cases were examined (nine dropouts among adolescents with BPD and for the purpose of falsification, one dropout of suicidal adolescent without BPD and two completed treatments among adolescents with BPD). To document the cases, three groups of informants were recruited (adolescents, parents, and therapists involved in the treatment) and 34 interviews were conducted.ResultsPsychological characteristics, perception of mental illness and mental health care, and help‐seeking context were the specific treatment dropout vulnerabilities identified in adolescents with BPD and in their parents. However, their disengagement became an issue only when care‐setting response – including mitigation of accessibility problems, adaptation of services to needs of adolescents with BPD, preparation for treatment, and concern for clinicians' disposition to treat – was ill‐suited to these treatment dropout vulnerabilities. Treatment planning proves to be a key milestone to properly engage adolescents with BPD and their parent.ConclusionsSystematic assessment of treatment dropout vulnerabilities before the intervention plan is laid out could foster better‐suited responses of the care setting thus decreasing the incidence of treatment discontinuation in adolescents with BPD.Practitioner points

Treatment dropout vulnerabilities specific to adolescents with BPD and their parents can be detected before the beginning of treatment.

Premature treatment termination may be prevented if the care setting considers these vulnerabilities at treatment planning.

Fears and negative reaction to treatment can be attenuated if the reasons behind the therapeutic orientation are explained and if the adolescent understand how the treatment will affect his condition.

Concerns for autonomy of the adolescent, parental help‐seeking context as well as ensuring that the clinician has the skills, interest, and motivation to work with the family may have a positive effect on families' commitment to treatment.
Stop and revive? The effectiveness of nap and active rest breaks for reducing driver sleepiness
Authors: Watling Christopher N. , Smith Simon S. , Horswill Mark S. 
Published: June 2014

AbstractThe purpose of this study was to compare the effects of two commonly utilized sleepiness countermeasures: a nap break and an active rest break. The effects of the countermeasures were evaluated by physiological (EEG), subjective, and driving performance measures. Participants completed 2 h of simulated driving, followed by a 15‐min nap break or a 15‐min active rest break, then completed the final hour of simulated driving. The nap break reduced EEG and subjective sleepiness. The active rest break did not reduce EEG sleepiness, with sleepiness levels eventually increasing, and resulted in an immediate reduction of subjective sleepiness. No difference was found between the two breaks for the driving performance measure. The immediate reduction of subjective sleepiness after the active rest break could leave drivers with erroneous perceptions of their sleepiness, particularly with increases of physiological sleepiness after the break.
Epidemiology, clinical manifestations, and outcomes of Scedosporium infections among solid organ transplant recipients
Authors: Johnson L.S. , Shields R.K. , Clancy C.J. 
Published: June 2014

AbstractBackgroundFew studies of Scedosporium infections following solid organ transplantation have been performed in the era of induction immunosuppression and widespread antifungal prophylaxis.MethodsWe performed a single‐center, retrospective study of transplant recipients from 2000 through 2010 who had a positive Scedosporium culture.ResultsAmong 27 patients, 67% (n = 18) and 33% (n = 9) were infected with Scedosporium apiospermum and Scedosporium prolificans, respectively. A total of 67% received induction immunosuppression and 74% received prior antifungal therapy. Isolates were broadly resistant to antifungals. Of these patients, 59% (n = 16) were colonized by Scedosporium, and 41% (n = 11) had disease (scedosporiosis). No significant clinical differences were seen between species. Colonization occurred exclusively in the lungs of lung transplant recipients (LTR). Scedosporiosis followed lung transplantation in 55%, and other organ transplants (multivisceral [18%]; and heart, liver, small intestine [9% each]) in 45%. Scedosporiosis was preceded by colonization in 36%. Diseases included pneumonia (64%), mediastinitis (18%), and fungemia/disseminated infections (18%). The 6‐month outcomes were death in 55%, progression in 18%, stability in 9%, and resolution in 18%. Patients who died had earlier onset scedosporiosis post transplant (median: 80.5 vs. 1388 days; P = 0.04), and were more likely to have mediastinitis or disseminated infections than pneumonia (100% vs. 29%; P = 0.06). The 3 patients who developed scedosporiosis >1 year post transplant survived. All patients who survived were treated with a voriconazole‐containing regimen.ConclusionsLTR were most susceptible to Scedosporium colonization and scedosporiosis, particularly within the lungs. Death was common with scedosporiosis in the first year after all types of organ transplants, consistent with profound immunosuppression and antifungal resistance, but not encountered thereafter.
Disseminated Cunninghamella bertholletiae infection with spinal epidural abscess in a kidney transplant patient: case report and literature review
Authors: Navanukroh O. , Jitmuang A. , Chayakulkeeree M. , Ngamskulrungroj P. 
Published: June 2014

AbstractCunninghamella bertholletiae is a rare cause of invasive mucormycosis. We report the case of a 42‐year‐old Thai woman who suffered from disseminated C. bertholletiae infection. The patient developed dry cough, sharp shooting pain in the left buttock referred to the left leg, and fever 1 month after undergoing deceased‐donor kidney transplantation. Radiographic studies exhibited multiple pulmonary cavities, osteomyelitis of the sacral spine, epidural abscess along the lumbrosacral spine, and paravertebral soft tissue involvement. Surgical debridement of the epidural abscess concurrent with prolonged intravenous administration of amphotericin B resulted in a good outcome.
Population Pharmacokinetics of Bedaquiline (TMC207), a Novel Antituberculosis Drug
Authors: McLeay Sarah C. , Vis Peter , van Heeswijk Rolf P. G. , Green Bruce 
Published: June 2014

ABSTRACT

Bedaquiline is a novel agent for the treatment of pulmonary multidrug-resistant
Mycobacterium tuberculosis
infections, in combination with other agents. The objective of this study was to develop a population pharmacokinetic (PK) model for bedaquiline to describe the concentration-time data from phase I and II studies in healthy subjects and patients with drug-susceptible or multidrug-resistant tuberculosis (TB). A total of 5,222 PK observations from 480 subjects were used in a nonlinear mixed-effects modeling approach. The PK was described with a 4-compartment disposition model with dual zero-order input (to capture dual peaks observed during absorption) and long terminal half-life (
t
1/2
). The model included between-subject variability on apparent clearance (CL/F), apparent central volume of distribution (
V
c
/F), the fraction of dose via the first input, and bioavailability (F). Bedaquiline was widely distributed, with apparent volume at steady state of >10,000 liters and low clearance. The long terminal
t
1/2
was likely due to redistribution from the tissue compartments. The final covariate model adequately described the data and had good simulation characteristics. The CL/F was found to be 52.0% higher for subjects of black race than that for subjects of other races, and
V
c
/F was 15.7% lower for females than that for males, although their effects on bedaquiline exposure were not considered to be clinically relevant. Small differences in F and CL/F were observed between the studies. The residual unexplained variability was 20.6% and was higher (27.7%) for long-term phase II studies.
Exposure of Staphylococcus aureus to Subinhibitory Concentrations of β-Lactam Antibiotics Induces Heterogeneous Vancomycin-Intermediate Staphylococcus aureus
Authors: Roch Mélanie , Clair Perrine , Renzoni Adriana , Reverdy Marie-Elisabeth , Dauwalder Olivier , Bes Michèle , Martra Annie , Freydière Anne-Marie , Laurent Frédéric , Reix Philippe , Dumitrescu Oana , Vandenesch François 
Published: June 2014

ABSTRACT

Glycopeptides are known to select for heterogeneous vancomycin-intermediate
Staphylococcus aureus
(h-VISA) from susceptible strains. In certain clinical situations, h-VISA strains have been isolated from patients without previous exposure to glycopeptides, such as cystic fibrosis patients, who frequently receive repeated treatments with beta-lactam antibiotics. Our objective was to determine whether prolonged exposure to beta-lactam antibiotics can induce h-VISA. We exposed 3 clinical vancomycin-susceptible methicillin-resistant
Staphylococcus aureus
(MRSA) strains to ceftazidime, ceftriaxone, imipenem, and vancomycin (as a control) at subinhibitory concentrations for 18 days
in vitro
. Population analyses showed progressive increases in vancomycin resistance; seven of the 12 derived strains obtained after induction were classified as h-VISA according to the following criteria: area under the curve (AUC) on day 18/AUC of Mu3 of ≥90% and/or growth on brain heart infusion (BHI) agar with 4 mg/liter vancomycin. The derived isolates had thickened cell walls proportional to the level of glycopeptide resistance. Genes known to be associated with glycopeptide resistance (
vraSR
,
yvqF
, SA1703,
graRS
,
walKR
, and
rpoB
) were PCR sequenced; no
de novo
mutations were observed upon beta-lactam exposure. To determine whether
trfA
, a gene encoding a glycopeptide resistance factor, was essential in the selection of h-VISA upon beta-lactam pressure, a
trfA
-knockout strain was generated by allelic replacement. Indeed, beta-lactam exposure of this mutated strain showed no capacity to induce vancomycin resistance. In conclusion, these results showed that beta-lactam antibiotics at subinhibitory concentrations can induce intermediate vancomycin resistance
in vitro
. This induction required an intact
trfA
locus. Our results suggest that prior use of beta-lactam antibiotics can compromise vancomycin efficacy in the treatment of MRSA infections.
Fosmidomycin Decreases Membrane Hopanoids and Potentiates the Effects of Colistin on Burkholderia multivorans Clinical Isolates
Authors: Malott Rebecca J. , Wu Chia-Hung , Lee Tracy D. , Hird Trevor J. , Dalleska Nathan F. , Zlosnik James E. A. , Newman Dianne K. , Speert David P. 
Published: June 2014

ABSTRACT

Burkholderia cepacia
complex (Bcc) pulmonary infections in people living with cystic fibrosis (CF) are difficult to treat because of the extreme intrinsic resistance of most isolates to a broad range of antimicrobials. Fosmidomycin is an antibacterial and antiparasitic agent that disrupts the isoprenoid biosynthesis pathway, a precursor to hopanoid biosynthesis. Hopanoids are involved in membrane stability and contribute to polymyxin resistance in Bcc bacteria. Checkerboard MIC assays determined that although isolates of the Bcc species
B. multivorans
were highly resistant to treatment with fosmidomycin or colistin (polymyxin E), antimicrobial synergy was observed in certain isolates when the antimicrobials were used in combination. Treatment with fosmidomycin decreased the MIC of colistin for isolates as much as 64-fold to as low as 8 μg/ml, a concentration achievable with colistin inhalation therapy. A liquid chromatography-tandem mass spectrometry technique was developed for the accurate quantitative determination of underivatized hopanoids in total lipid extracts, and bacteriohopanetetrol cyclitol ether (BHT-CE) was found to be the dominant hopanoid made by
B. multivorans
. The amount of BHT-CE made was significantly reduced upon fosmidomycin treatment of the bacteria. Uptake assays with 1-
N
-phenylnaphthylamine were used to determine that dual treatment with fosmidomycin and colistin increases membrane permeability, while binding assays with boron-dipyrromethene-conjugated polymyxin B illustrated that the addition of fosmidomycin had no impact on polymyxin binding. This work indicates that pharmacological suppression of membrane hopanoids with fosmidomycin treatment can increase the susceptibility of certain clinical
B. multivorans
isolates to colistin, an agent currently in use to treat pulmonary infections in CF patients.
Levofloxacin-Ceftriaxone Combination Attenuates Lung Inflammation in a Mouse Model of Bacteremic Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae via Inhibition of Cytolytic Activities of Pneumolysin and Autolysin
Authors: Majhi Arnab , Adhikary Rana , Bhattacharyya Aritra , Mahanti Sayantika , Bishayi Biswadev 
Published: June 2014

ABSTRACT

In this study, our objective was to determine whether a synergistic antimicrobial combination
in vitro
would be beneficial in the downregulation of pneumococcal virulence genes and whether the associated inflammation of the lung tissue induced by multidrug-resistant
Streptococcus pneumoniae
infection
in vivo
needs to be elucidated in order to consider this mode of therapy in case of severe pneumococcal infection. We investigated
in vivo
changes in the expression of these virulence determinants using an efficacious combination determined in previous studies. BALB/c mice were infected with 10
6
CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone at 50 mg/kg were initiated 18 h postinfection; the animals were sacrificed 0 to 24 h after the initiation of treatment. The levels of cytokines, chemokines, and C-reactive protein (CRP) in the serum and lungs, along with the levels of myeloperoxidase and nitric oxide the inflammatory cell count in bronchoalveolar lavage fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and inducible nitric oxide synthase (iNOS) protein expression in the lungs were estimated. Combination therapy downregulated inflammation and promoted bacterial clearance. Pneumolysin and autolysin expression was downregulated, with a concomitant decrease in the expression of COX-2 and iNOS in lung tissue. Thus, the combination of levofloxacin and ceftriaxone can be considered for therapeutic use even in cases of pneumonia caused by drug-resistant isolates.
Synergy of Streptogramin Antibiotics Occurs Independently of Their Effects on Translation
Authors: Noeske Jonas , Huang Jian , Olivier Nelson B. , Giacobbe Robert A. , Zambrowski Mark , Cate Jamie H. D. 
Published: June 2014

ABSTRACT

Streptogramin antibiotics are divided into types A and B, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin) and NXL 103 (type A, flopristin; type B, linopristin) with the
Escherichia coli
70S ribosome by X-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. The streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that the synergistic antimicrobial activity of streptogramins can occur independently of the effects of streptogramin on translation.
Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner
Authors: Dulek Daniel E. , Newcomb Dawn C. , Goleniewska Kasia , Cephus Jaqueline , Zhou Weisong , Reiss Sara , Toki Shinji , Ye Fei , Zaynagetdinov Rinat , Sherrill Taylor P. , Blackwell Timothy S. , Moore Martin L. , Boyd Kelli L. , Kolls Jay K. , Peebles R. Stokes 
Published: June 2014

ABSTRACTThe Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, includingKlebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminishex vivoandin vivoIL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection withK. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acuteK. pneumoniaeinfection and thereby increases the lungK. pneumoniaeburden. As hypothesized, we found that allergic airway inflammation decreased the number ofK. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lungK. pneumoniaeburden and postinfection mortality. We showed that the decreased lungK. pneumoniaeburden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lungK. pneumoniaeburden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity againstK. pneumoniaeand suggest new mechanisms of orchestrating lung antibacterial immunity.
Intestinal Epithelium-Specific MyD88 Signaling Impacts Host Susceptibility to Infectious Colitis by Promoting Protective Goblet Cell and Antimicrobial Responses
Authors: Bhinder Ganive , Stahl Martin , Sham Ho Pan , Crowley Shauna M. , Morampudi Vijay , Dalwadi Udit , Ma Caixia , Jacobson Kevan , Vallance Bruce A. 
Published: June 2014

ABSTRACT

Intestinal epithelial cells (IECs), including secretory goblet cells, form essential physiochemical barriers that separate luminal bacteria from underlying immune cells in the intestinal mucosa. IECs are common targets for enteric bacterial pathogens, with hosts responding to these microbes through innate toll-like receptors that predominantly signal through the MyD88 adaptor protein. In fact, MyD88 signaling confers protection against several enteric bacterial pathogens, including
Salmonella enterica
serovar Typhimurium and
Citrobacter rodentium
. Since IECs are considered innately hyporesponsive, it is unclear whether MyD88 signaling within IECs contributes to this protection. We infected mice lacking MyD88 solely in their IECs (
IEC-Myd88
−/−
) with
S.
Typhimurium. Compared to wild-type (WT) mice, infected
IEC-Myd88
−/−
mice suffered accelerated tissue damage, exaggerated barrier disruption, and impaired goblet cell responses (Muc2 and RELMβ). Immunostaining revealed
S.
Typhimurium penetrated the IECs of
IEC-Myd88
−/−
mice, unlike in WT mice, where they were sequestered to the lumen. When isolated crypts were assayed for their antimicrobial actions, crypts from
IEC-Myd88
−/−
mice were severely impaired in their antimicrobial activity against
S.
Typhimurium. We also examined whether MyD88 signaling in IECs impacted host defense against
C. rodentium
, with
IEC-Myd88
−/−
mice again suffering exaggerated tissue damage, impaired goblet cell responses, and reduced antimicrobial activity against
C. rodentium
. These results demonstrate that MyD88 signaling within IECs plays an important protective role at early stages of infection, influencing host susceptibility to infection by controlling the ability of the pathogen to reach and survive at the intestinal mucosal surface.