bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Global Regulatory Cyclic AMP Receptor Protein (CRP) Controls Multifactorial Fluoroquinolone Susceptibility in Salmonella enterica Serovar Typhimurium
Authors: Kary Stefani C. , Yoneda Joshua R. K. , Olshefsky Stephen C. , Stewart Laura A. , West Steven B. , Cameron Andrew D. S. 
Published: September 2017

ABSTRACT

Fluoroquinolone antibiotics are prescribed for the treatment of
Salmonella enterica
infections, but resistance to this family of antibiotics is growing. Here we report that loss of the global regulatory protein cyclic AMP (cAMP) receptor protein (CRP) or its allosteric effector, cAMP, reduces susceptibility to fluoroquinolones. A Δ
crp
mutation was synergistic with the primary fluoroquinolone resistance allele
gyrA83
, thus able to contribute to clinically relevant resistance. Decreased susceptibility to fluoroquinolones could be partly explained by decreased expression of the outer membrane porin genes
ompA
and
ompF
with a concomitant increase in the expression of the ciprofloxacin resistance efflux pump gene
acrB
in Δ
crp
cells. Expression of
gyrAB
, which encode the DNA supercoiling enzyme GyrAB, which is blocked by fluoroquinolones, and expression of
topA
, which encodes the dominant supercoiling-relaxing enzyme topoisomerase I, were unchanged in Δ
crp
cells. Yet Δ
crp
cells maintained a more relaxed state of DNA supercoiling, correlating with an observed increase in topoisomerase IV (
parCE
) expression. Surprisingly, the Δ
crp
mutation had the unanticipated effect of enhancing fitness in the presence of fluoroquinolone antibiotics, which can be explained by the observation that exposure of Δ
crp
cells to ciprofloxacin had the counterintuitive effect of restoring wild-type levels of DNA supercoiling. Consistent with this, Δ
crp
cells did not become elongated or induce the SOS response when challenged with ciprofloxacin. These findings implicate the combined action of multiple drug resistance mechanisms in Δ
crp
cells: reduced permeability and elevated efflux of fluoroquinolones coupled with a relaxed DNA supercoiling state that buffers cells against GyrAB inhibition by fluoroquinolones.
Revisiting the Role of Csp Family Proteins in Regulating Clostridium difficile Spore Germination
Authors: Kevorkian Yuzo , Shen Aimee 
Published: September 2017

ABSTRACT

Clostridium difficile
causes considerable health care-associated gastrointestinal disease that is transmitted by its metabolically dormant spore form. Upon entering the gut,
C. difficile
spores germinate and outgrow to produce vegetative cells that release disease-causing toxins.
C. difficile
spore germination depends on the Csp family of (pseudo)proteases and the cortex hydrolase SleC. The CspC pseudoprotease functions as a bile salt germinant receptor that activates the protease CspB, which in turn proteolytically activates the SleC zymogen. Active SleC degrades the protective cortex layer, allowing spores to outgrow and resume metabolism. We previously showed that the CspA pseudoprotease domain, which is initially produced as a fusion to CspB, controls the incorporation of the CspC germinant receptor in mature spores. However, study of the individual Csp proteins has been complicated by the polar effects of TargeTron-based gene disruption on the
cspBA-cspC
operon. To overcome these limitations, we have used
pyrE
-based allelic exchange to create individual deletions of the regions encoding CspB, CspA, CspBA, and CspC in strain 630Δ
erm
. Our results indicate that stable CspA levels in sporulating cells depend on CspB and confirm that CspA maximizes CspC incorporation into spores. Interestingly, we observed that
csp
and
sleC
mutants spontaneously germinate more frequently in 630Δ
erm
than equivalent mutants in the JIR8094 and UK1 strain backgrounds. Analyses of this phenomenon suggest that only a subpopulation of
C. difficile
630Δ
erm
spores can spontaneously germinate, in contrast with
Bacillus subtilis
spores. We also show that
C. difficile
clinical isolates that encode truncated CspBA variants have sequencing errors that actually produce full-length CspBA.

IMPORTANCE
Clostridium difficile
is a leading cause of health care-associated infections. Initiation of
C. difficile
infection depends on spore germination, a process controlled by Csp family (pseudo)proteases. The CspC pseudoprotease is a germinant receptor that senses bile salts and activates the CspB protease, which activates a hydrolase required for germination. Previous work implicated the CspA pseudoprotease in controlling CspC incorporation into spores but relied on plasmid-based overexpression. Here we have used allelic exchange to study the functions of CspB and CspA. We determined that CspA production and/or stability depends on CspB and confirmed that CspA maximizes CspC incorporation into spores. Our data also suggest that a subpopulation of
C. difficile
spores spontaneously germinates in the absence of bile salt germinants and/or Csp proteins.
Is external fixation a better way than plaster to supplement K-wires in non-comminuted distal radius fractures?
Authors: Athar Sajjad M , Ashwood Neil , Aerealis George , Bain Gregory I 
Published: September 2017

AbstractBackgroundDistal radius fractures represent about one-sixth of all fractures. There is still no consensus on the treatment of this fracture. We have several issues to assess and address; one of them is the fixation method. We tried to compare the effectiveness of two methods of stabilisation of distal radial fracture. Comparison between the techniques of Kirschner wire (K-wire) fixation with plaster and K-wire fixation with external fixation (Ex-Fix) was undertaken to assess which treatment modality gives better results in patients with distal radius fracture Frykman VII and VIII with no metaphyseal comminution.MethodFifty-six patients were chosen randomly and then allocated to two different modalities of stabilisation randomly as well, they were followed up; three of them were lost to follow-up because of death and two moved away from the area. Fifty-one patients were randomised in two groups: 24 were treated with K-wire and spanning Ex-Fix supplementation and 27 were treated with K-wires and plaster. Patients were prospectively monitored following the operation with a minimum follow-up of 1 year. Measurement of range of motion was obtained after surgery. Visual Analogue Scale (VAS) scores for pain and satisfaction levels were also recorded.ResultsThere was statistically significant difference in favour of the Ex-Fix patient group for pain (VAS, Ex-Fix group: mean 14.9; plaster group: mean 28.1) and satisfaction (Ex-Fix group: mean 89.7;plaster group: mean 76.3). Although one would expect that range of motion would be reduced in the Ex-Fix group, there were no statistically significant differences found, with the exception of supination where results were in favour of the Ex-Fix group (mean 54.4; plaster group: mean 45.2).ConclusionIn our study, xternal fixator (Ex-Fix) supplementation of K-wiring favoured patients with distal radius fracture, even though there was no metaphyseal comminution, and therefore is suggested in contrast to plaster supplementation.
Evaluation of adiponectin and leptin levels and oxidative stress in bipolar disorder patients with metabolic syndrome treated by valproic acid
Authors: Akgün Sema , Köken Tülay , Kahraman Ahmet 
Published: September 2017

Introduction: An increased risk for metabolic syndrome (MS) has been described for people with psychotic and mood disorders. The aim of this study was to determine the influence of valproic acid (VPA) treatment on adiponectin, leptin levels and oxidative stress in bipolar disorder (BD). Methods: Forty patients with BD receiving VPA monotherapy and 20 healthy control subjects were included in this study. BD patients were divided into two groups with and without MS as group 1 and group 2, respectively. Twenty BD patients diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM IV) were assessed for MS according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria. Adiponectin, leptin, protein carbonyls, sulfhydryl (–SH) and malondialdehyde (MDA) levels were measured in 40 BD patients and 20 control subjects. Results: Serum adiponectin levels were significantly lower in group 1 patients than in group 2 and control subjects ( p<.001). Serum leptin levels were significantly higher in group 1 patients than in group 2 and control subjects ( p<.001). Serum –SH levels were significantly lower in group 2 patients than in group 1 ( p<.001) and control subjects ( p<.05). Serum carbonyl levels were significantly higher in group 1 and group 2 patients than in control subjects ( p<.001). Serum MDA levels were significantly higher in group 1 patients than in group 2 and control subjects ( p<.001). Conclusion: These results provide further evidence that VPA treatment for patients with BD contributed to the metabolic disturbances, such as the decreased serum adiponectin and –SH levels, as well as the increased serum leptin, MDA and carbonyl levels.
Impaired vagal activity to meal in patients with functional dyspepsia and delayed gastric emptying
Authors: Guo W-J , Yao S-K , Zhang Y-L , Du S-Y , Wang H-F , Yin L-J , Li H-L 
Published: September 2017

Objective This study was performed to investigate impaired vagal activity to meal in patients with functional dyspepsia (FD) with delayed gastric emptying (GE). Methods Eighty-five patients were studied. GE parameters, including those in the overall and proximal stomach, were measured by GE functional tests at the Department of Nuclear Medicine. Autonomic nervous function was tested by spectral analysis of heart rate variability (HRV). The vagal activity and sympathetic activity were analyzed by recording the power in the high-frequency component (HF), low-frequency component (LF), and LF/HF ratio. Results Overall and proximal GE were delayed in 47.2% and 50.9% of the patients, respectively. Spectral analysis of HRV showed that the HF in patients with delayed proximal GE was significantly lower and that the LF/HF ratio was significantly higher than those in patients with normal proximal GE after a meal. Conclusion Delayed proximal GE might be caused by disrupted sympathovagal balance as a result of decreased vagal activity after a meal. Improvement in vagal activity may constitute an effective treatment method for patients with FD.
Impact of Multiple Daily Clinical Pharmacist-Enforced Assessments on Time in Target Sedation Range
Authors: Lizza Bryan D. , Jagow Benjamin , Hensler David , Cooper Craig J. , Short Elizabeth J. , Maas Matthew B. , Naidech Andrew M. , Wunderink Richard G. 
Published: September 2017

Objectives: Incorporation of a single daily assessment by a clinical pharmacist to improve adherence with a sedation protocol is associated with reduced duration of mechanical ventilation and intensive care unit (ICU) length of stay (LOS). We test the feasibility of incorporating a clinical pharmacist into more frequent sedation assessments and observed whether there are any potential differences in the sedatives administered. Methods: Prospective, quasi-experimental, pilot study of patients admitted to the medical ICU. Patients were included in the analysis if ≥18 years of age within the first 24 hours of initiation of mechanical ventilation. Our primary intent was to test the clinical feasibility surrounding more frequent sedation assessments by a clinical pharmacist by evaluating potential differences in time in target sedation range and sedative administration. Exploratory efficacy end points included time in target sedation range (0 to −2) using the Richmond Agitation Sedation Scale (RASS) and sedative exposure. Patients were assigned to receive either 3 assessments with a clinical pharmacist per day (intervention) or a single assessment by a clinical pharmacist per day (standard of care). During the assessments, clinical pharmacists participated in the RASS administration and made dosing adjustments according to an established sedation protocol. Main Results: Seventeen patients were enrolled (n = 6 intervention group, n = 11 standard of care). Duration of mechanical ventilation was similar in the 2 groups (intervention 100.0 hours [52.5-197.5] vs control 76.0 hours [46.0-201.0], P = .95), but patients in the intervention group exhibited a greater percentage time in the target RASS range (intervention 76.0% [53.7-81.5%] vs control 45.2% [35.3-67.0], P = .11) that was not statistically significant. Patients in the intervention group received less fentanyl per day (820.9 µg [227.3-1579.4] vs 1997 µg [1648.2-2477.2], P = .02) than in the control group. Conclusion: Incorporating a clinical pharmacist into more frequent daily sedation assessments was associated with a reduction in fentanyl administration. There were no observed differences in time in target sedation range or reduction in duration of mechanical ventilation.
The combination of words in compound nouns by Spanish-Japanese bilingual children: Transfers in unambiguous structure
Authors: Kutsuki Aya 
Published: September 2017

Aims and Objectives: The current study’s aim was to test the ambiguity and dominance theories of transfer by examining compound noun production and comprehension by bilinguals acquiring Spanish and Japanese, as the word order of nominal compounds in these languages is always reversed, making them grammatically and theoretically unambiguous. Methodology: Ten Spanish-Japanese bilingual preschoolers completed production and comprehension elicitation tasks. Data and Analysis: The research subjects’ reversal rates were compared with those of age- and vocabulary-matched Japanese monolinguals. Findings/Conclusions: The results demonstrate that transfers occur from Spanish to Japanese in both production and comprehension, and that there are no dominance effects on the degree of cross-linguistic influence. Originality: There have been no previous studies on cross-linguistic transfer in Spanish-Japanese bilingual children. Significance/Implications: Transfer and directionality are not affected by relative vocabulary level; the concept of dominance should be (re)considered carefully especially for young bilinguals whose language inputs are greatly imbalanced and variable. Moreover, what is considered grammatically unambiguous by adults may be ambiguous for children acquiring such knowledge bilingually, which raises the need to consider structures in both languages as affecting the acquisition of language in young bilinguals.
Authentic Leadership Through an Ethical Prism
Authors: Gardiner Rita A. 
Published: September 2017

The Problem Authentic leadership (AL) focuses on enhancing the capabilities and capacities of leaders. Instead of focusing on the leader, this article considers the ethical challenges of fostering authenticity among employees. One such challenge is that marginalized groups may feel unable to be true to their values, a key premise of authentic leadership. To foster workplaces where marginalized groups feel able to be true to themselves, we must consider the cultural and structural barriers that can negatively affect people’s ability to express themselves in the workplace. Hence, when considering the merits of AL, it is important for human resource development (HRD) professionals to consider what occurs when employees do not fit institutional norms. The Solution Creating the conditions for a relational authentic approach to AL that allows authentic otherness to flourish is an important and complex ethical task, one that HRD scholars and practitioners are uniquely placed to encourage. The Stakeholders HRD scholars and practitioners interested in creating the conditions that encourage the flourishing of authentic otherness among employees.
Factors Influencing Patient Selection of a Foot and Ankle Surgeon
Authors: Manning Blaine T. , Bohl Daniel D. , Wang Kevin C. , Hamid Kamran S. , Holmes George B. , Lee Simon 
Published: September 2017

An increasingly consumer-centric health insurance market has empowered patients to select the providers of their choice. There is a lack of studies investigating the rationale by which patients select a foot and ankle surgeon. In the present study, 824 consecutive new patients seeking treatment from 3 foot-ankle surgeons were consecutively administered an anonymous questionnaire prior to their first appointment. It included rating the importance of 15 factors regarding specialist selection on a 1 to 10 scale, with 10 designated “ Very important” and 1 designated “ Not important at all.” The remaining questions were multiple choice regarding patient perspectives on other surgeon aspects (appointment availability, waiting room times, clinic proximity, etc). Of 824 consecutive patients administered the survey, 305 (37%) responded. Patients rated board certification (9.24 ± 1.87) and on-site imaging availability (8.48 ± 2.37)—on a 1 to 10 scale, with 10 designated “Very important— as the 2 most important criteria in choosing a foot and ankle surgeon. Patients rated advertisements as least important. Among the patients, 91% responded that a maximum of 30 minutes should elapse between clinic check-in and seeing their physician; 61% responded that a maximum of 20 minutes should elapse between clinic check-in and seeing their physician. In the context of an increasingly consumer-driven paradigm of health care delivery and reimbursement, it is important to understand patients’ preferences in specialist selection. Levels of Evidence: Level III: Prospective questionnaire
Changes in the Width of the Tibiofibular Syndesmosis Related to Lower Extremity Joint Dynamics and Neuromuscular Coordination on Drop Landing During the Menstrual Cycle
Authors: Okazaki Michie , Kaneko Masaaki , Ishida Yukisato , Murase Norio , Katsumura Toshihito 
Published: September 2017

Background: Many injuries of the lower extremities, especially the knee and ankle, occur during sports activity, and the incidence rate is higher in women than in men. Hypothesis: The hypothesis was that phases of the menstrual cycle affect the width of the tibiofibular syndesmosis during drop landing in healthy young women and that such changes at the tibiofibular joint also affect the dynamics and neuromuscular coordination of the lower extremities. Study Design: Descriptive laboratory study. Methods: Participants included 28 healthy young women (mean age, 21.0 ± 0.8 years). Blood samples were collected to determine plasma levels of estradiol and progesterone immediately before the performance of the task: drop landing on a single leg from a 30-cm platform. Using ultrasonography, the distance between the tibia and the distal end of the fibula, regarded as the width of the tibiofibular syndesmosis, was measured in an upright position without flexion of the ankle. The peak ground-reaction force (GRF) on landing was measured using a force platform. The time to peak GRF (Tp-GRF) was measured as the time from initial ground contact to the peak GRF. Hip, knee, and ankle joint angles during the single-leg landing were calculated using a 3-dimensional motion analysis system. Muscle activities of the lower extremities were measured using surface electromyography. Results: The width of the tibiofibular syndesmosis was significantly greater in the luteal phase when compared with the menstrual, follicular, and ovulation phases (by 5%-8% of control). Also, during the luteal phase, the Tp-GRF was significantly shorter than in the follicular phase (by 6%); hip internal rotation and knee valgus were significantly greater than in the menstrual phase (by 43% and 34%, respectively); knee flexion was significantly less than in the menstrual and follicular phases (by 7%-9%); ankle dorsiflection was significantly less than in the follicular phase (by 11%); ankle adduction and eversion were significantly greater than in the menstrual and follicular phases (by 26%-46%, and 27%-33%, respectively); and activation of the gluteus maximus before landing was significantly lower than in the menstrual and follicular phases (by 20%-22%). Conclusion: The luteal phase appears to be associated with decreased strength and laxity of the ankle as well as lower extremity muscle activity in women. The changes presumably represent a greater risk for sports injuries. Clinical Relevance: The results of this study suggest that the luteal phase may be related to the greater incidence of lower extremity injuries in women.
The Tuberculosis Network European Trials Group (TBNET): new directions in the management of tuberculosis
Authors: Bothamley Graham 
Published: September 2017

The Tuberculosis Network European Trials Group (TBNET) is the largest clinical research organisation in Europe. Educational activities include the TBNET Academy and the European Advanced Course in Clinical Tuberculosis. Four of their publications are reviewed to show how the clinical management of tuberculosis is changing.Key pointsMost tuberculosis (TB) in contacts is found at their first visit.In contacts of pulmonary TB patients, the likelihood of later TB is ≤3%.Genetic tests can indicate when another antimycobacterial drug in the same class might be effective (e.g.rifabutin when there is rifampicin resistance or which injectable to choose).The short-course “Bangladesh” regimen can only be rarely used in Europe.Treatment completion in multidrug-resistant TB should not be included as a successful outcome.
The Global Lung Function Initiative (GLI) Network: bringing the world’s respiratory reference values together
Authors: Cooper Brendan G. , Stocks Janet , Hall Graham L. , Culver Bruce , Steenbruggen Irene , Carter Kim W. , Thompson Bruce Robert , Graham Brian L. , Miller Martin R. , Ruppel Gregg , Henderson John , Vaz Fragoso Carlos A. , Stanojevic Sanja 
Published: September 2017

The Global Lung Function Initiative (GLI) Network has become the largest resource for reference values for routine lung function testing ever assembled. This article addresses how the GLI Network came about, why it is important, and its current challenges and future directions. It is an extension of an article published inBreathein 2013 [1], and summarises recent developments and the future of the GLI Network.Key pointsThe Global Lung Function Initiative (GLI) Network was established as a result of international collaboration, and altruism between researchers, clinicians and industry partners. The ongoing success of the GLI relies on network members continuing to work together to further improve how lung function is reported and interpreted across all age groups around the world.The GLI Network has produced standardised lung function reference values for spirometry and gas transfer tests.GLI reference equations should be adopted immediately for spirometry and gas transfer by clinicians and physiologists worldwide.The recently established GLI data repository will allow ongoing development and evaluation of reference values, and will offer opportunities for novel research.Educational aimsTo highlight the advances made by the GLI Network during the past 5 years.To highlight the importance of using GLI reference values for routine lung function testing (e.g. spirometry and gas transfer tests).To discuss the challenges that remain for developing and improving reference values for lung function tests.