bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychophysiological Responses to Repeated-Sprint Training in Normobaric Hypoxia and Normoxia
Authors: Brocherie Franck , Millet Grégoire P. , Girard Olivier 
Published: May 2016

Purpose:To compare psychophysiological responses to 6 repeated-sprint sessions in normobaric hypoxia (RSH) and normoxia (RSN) in team-sport athletes during a 2-wk “live high–train low” training camp.Methods:While residing under normobaric hypoxia (≥14 h/d, FiO2 14.5–14.2%), 23 lowland elite field hockey players performed, in addition to their usual training, 6 sessions (4 × 5 × 5-s maximal sprints, 25-s passive recovery, 5 min rest) under either RSH (FiO2 ~14.5%) or RSN (FiO2 21%). Sprint 1 and 5 times, physiological strain (heart rate [HR], arterial oxyhemoglobin saturation [SpO2]), and perceptual responses (overall peripheral discomfort, difficulty breathing, and lower-limb discomfort) were monitored.Results:During the 1st session, HR increased across sets (P < .001) independently of the conditions, while SpO2 was globally lower (P < .001) for RSH (averaged value: 91.9% ± 1.2%) vs RSN (96.9% ± 0.6%). Thereafter, SpO2 and HR remained similar across sessions for each condition. While 1st-sprint time remained similar, last-sprint time and fatigue index significantly decreased across sets (P < .01) and sessions (P < .05) but not between conditions. Ratings of overall perceived discomfort, difficulty breathing, and lower-limb discomfort were higher (P < .05) in RSH vs RSN at the 1st session. During subsequent sessions, values for overall perceived discomfort (time [P < .001] and condition [P < .05] effects), difficulty breathing (time effect; P < .001), and lower-limb discomfort (condition [P < .001] and interaction [P < .05] effects) decreased to a larger extent in RSH vs RSN.Conclusion:Despite higher hypoxia-induced physiological and perceptual strain during the 1st session, perceptual responses improved thereafter in RSH so as not to differ from RSN. This indicates an effective acclimation and tolerance to this innovative training.
A Silenced
vanA
Gene Cluster on a Transferable Plasmid Caused an Outbreak of Vancomycin-Variable Enterococci
Authors: Sivertsen Audun , Pedersen Torunn , Larssen Kjersti Wik , Bergh Kåre , Rønning Torunn Gresdal , Radtke Andreas , Hegstad Kristin 
Published: May 2016

ABSTRACT

We report an outbreak of vancomycin-variable
vanA
+
enterococci (VVE) able to escape phenotypic detection by current guidelines and demonstrate the molecular mechanisms for
in vivo
switching into vancomycin resistance and horizontal spread of the
vanA
cluster. Forty-eight
vanA
+
Enterococcus faecium
isolates and one
Enterococcus faecalis
isolate were analyzed for clonality with pulsed-field gel electrophoresis (PFGE), and their
vanA
gene cluster compositions were assessed by PCR and whole-genome sequencing of six isolates. The susceptible VVE strains were cultivated in brain heart infusion broth containing vancomycin at 8 μg/ml for
in vitro
development of resistant VVE. The transcription profiles of susceptible VVE and their resistant revertants were assessed using quantitative reverse transcription-PCR. Plasmid content was analyzed with S1 nuclease PFGE and hybridizations. Conjugative transfer of
vanA
was assessed by filter mating. The only genetic difference between the
vanA
clusters of susceptible and resistant VVE was an IS
L3
-family element upstream of
vanHAX
, which silenced
vanHAX
gene transcription in susceptible VVE. Furthermore, the VVE had an insertion of IS
1542
between
orf2
and
vanR
that attenuated the expression of
vanHAX
. Growth of susceptible VVE occurred after 24 to 72 h of exposure to vancomycin due to excision of the IS
L3
-family element. The
vanA
gene cluster was located on a transferable broad-host-range plasmid also detected in outbreak isolates with different pulsotypes, including one
E. faecalis
isolate. Horizontally transferable silenced
vanA
able to escape detection and revert into resistance during vancomycin therapy represents a new challenge in the clinic. Genotypic testing of invasive vancomycin-susceptible enterococci by
vanA
-PCR is advised.
Involvement of Antibiotic Efflux Machinery in Glutathione-Mediated Decreased Ciprofloxacin Activity in Escherichia coli
Authors: Goswami Manish , Subramanian Mahesh , Kumar Ranjeet , Jass Jana , Jawali Narendra 
Published: May 2016

ABSTRACT

We have analyzed the contribution of different efflux components to glutathione-mediated abrogation of ciprofloxacin's activity in
Escherichia coli
and the underlying potential mechanism(s) behind this phenomenon. The results indicated that glutathione increased the total active efflux, thereby partially contributing to glutathione-mediated neutralization of ciprofloxacin's antibacterial action in
E. coli
. However, the role of glutathione-mediated increased efflux becomes evident in the absence of a functional TolC-AcrAB efflux pump.
Dynamics of Mutations during Development of Resistance by Pseudomonas aeruginosa against Five Antibiotics
Authors: Feng Yanfang , Jonker Martijs J. , Moustakas Ioannis , Brul Stanley , ter Kuile Benno H. 
Published: May 2016

ABSTRACT

Pseudomonas aeruginosa
is an opportunistic pathogen that causes considerable morbidity and mortality, specifically during intensive care. Antibiotic-resistant variants of this organism are more difficult to treat and cause substantial extra costs compared to susceptible strains. In the laboratory,
P. aeruginosa
rapidly developed resistance to five medically relevant antibiotics upon exposure to stepwise increasing concentrations. At several time points during the acquisition of resistance, samples were taken for whole-genome sequencing. The increase in the MIC of ciprofloxacin was linked to specific mutations in
gyrA
,
parC
, and
gyrB
, appearing sequentially. In the case of tobramycin, mutations in
fusA
,
HP02880
,
rplB
, and
capD
were induced. The MICs of the beta-lactam compounds meropenem and ceftazidime and the combination of piperacillin and tazobactam correlated linearly with beta-lactamase activity but not always with individual mutations. The genes that were mutated during the development of beta-lactam resistance differed for each antibiotic. A quantitative relationship between the frequency of mutations and the increase in resistance could not be established for any of the antibiotics. When the adapted strains are grown in the absence of the antibiotic, some mutations remained and others were reversed, but this reversal did not necessarily lower the MIC. The increased MIC came at the cost of moderately reduced cellular functions or a somewhat lower growth rate. In all cases except ciprofloxacin, the increase in resistance seems to be the result of complex interactions among several cellular systems rather than individual mutations.
Synergy between Colistin and the Signal Peptidase Inhibitor MD3 Is Dependent on the Mechanism of Colistin Resistance in Acinetobacter baumannii
Authors: Martínez-Guitián Marta , Vázquez-Ucha Juan C. , Odingo Joshua , Parish Tanya , Poza Margarita , Waite Richard D. , Bou German , Wareham David W. , Beceiro Alejandro 
Published: May 2016

ABSTRACT

Synergy between colistin and the signal peptidase inhibitor MD3 was tested against isogenic mutants and clinical pairs of
Acinetobacter baumannii
isolates. Checkerboard assays and growth curves showed synergy against both colistin-susceptible strains (fractional inhibitory concentration index [FIC
index
] = 0.13 to 0.24) and colistin-resistant strains with mutations in
pmrB
and phosphoethanolamine modification of lipid A (FIC
index
= 0.14 to 0.25) but not against colistin-resistant Δ
lpx
strains with loss of lipopolysaccharide (FIC
index
= 0.75 to 1). A colistin/MD3 combination would need to be targeted to strains with specific colistin resistance mechanisms.
Mycophenolic Acid and Its Derivatives as Potential Chemotherapeutic Agents Targeting Inosine Monophosphate Dehydrogenase in Trypanosoma congolense
Authors: Suganuma Keisuke , Sarwono Albertus Eka Yudistira , Mitsuhashi Shinya , Jąkalski Marcin , Okada Tadashi , Nthatisi Molefe , Yamagishi Junya , Ubukata Makoto , Inoue Noboru 
Published: May 2016

ABSTRACT

This study aimed to evaluate the trypanocidal activity of mycophenolic acid (MPA) and its derivatives for
Trypanosoma congolense
. The proliferation of
T. congolense
was completely inhibited by adding <1 μM MPA and its derivatives. In addition, the IMP dehydrogenase in
T. congolense
was molecularly characterized as the target of these compounds. The results suggest that MPA and its derivatives have the potential to be new candidates as novel trypanocidal drugs.
Chitinase 3-Like 1 (Chil1) Regulates Survival and Macrophage-Mediated Interleukin-1β and Tumor Necrosis Factor Alpha during Pseudomonas aeruginosa Pneumonia
Authors: Marion Chad R. , Wang Jianmiao , Sharma Lokesh , Losier Ashley , Lui Wei , Andrews Nathaniel , Elias Jack A. , Kazmierczak Barbara I. , Roy Craig R. , Dela Cruz Charles S. 
Published: May 2016

ABSTRACT

Pseudomonas aeruginosa
causes hospital-acquired pneumonia and is associated with high mortality. An effective response to such an infection includes efficient clearance of pathogenic organisms while limiting collateral damage from the host inflammatory response, known as host resistance and host tolerance, respectively.
P. aeruginosa
expresses a type III secretion system (T3SS) needle complex that induces NLRC4 (NOD-like receptor C4) activation, interleukin-1β (IL-1β) production, and host tissue damage. Chitinase 3-like-1 (Chil1) is expressed during infection and binds to its receptor, IL-13 receptor α2 (IL-13Rα2), to regulate the pathogen-host response during
Streptococcus pneumoniae
infection, but the role Chil1 plays in balancing the host resistance and host tolerance during
P. aeruginosa
pneumonia is not known. We conducted experiments using C57BL/6 mice with or without a genetic deficiency of Chil1 and demonstrated that Chil1-deficient mice succumb to
P. aeruginosa
infection more rapidly than the wild type (WT). The decreased survival time in infected Chil1-deficient mice is associated with more neutrophils recruited to the airways, more lung parenchymal damage, and increased pulmonary consolidation while maintaining equivalent bacterial killing compared to WT mice. Infected Chil1-deficient mice and bone marrow-derived macrophages (BMDMs) from Chil1-deficient mice have increased production of tumor necrosis factor alpha (TNF-α) and IL-1β compared to infected WT mice and macrophages. Infection of Chil1-deficient BMDMs with non-NLRC4-triggering
P. aeruginosa
, which is deficient in the T3SS needle complex, did not alter the excessive IL-1β production compared to BMDMs from WT mice. The addition of recombinant Chil1 decreases the excessive IL-1β production but only partially rescues stimulated BMDMs from IL-13Rα2-deficient mice. Our data provide mechanistic insights into how Chil1 regulates
P. aeruginosa
-induced host responses.
Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of
rocA
Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes
Authors: Zhu Luchang , Olsen Randall J. , Horstmann Nicola , Shelburne Samuel A. , Fan Jia , Hu Ye , Musser James M. 
Published: May 2016

ABSTRACT

Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in
Streptococcus pyogenes
. The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of the
rocA
gene encoding a sensor kinase.
S. pyogenes
strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins
S. pyogenes
NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the
rocA
gene. In summary, we identified and characterized an intergenic VNTR polymorphism in
S. pyogenes
that affects toxin production and virulence. These new findings enhance understanding of
rocA
biology and the function of VNTR polymorphisms in
S. pyogenes
.
Initial US evaluation of second-generation capsule colonoscopy for detecting colon polyps
Authors: Morgan Douglas R , Malik Pramod R , Romeo David P , Rex Douglas K 
Published: May 2016

ObjectivesCapsule colonoscopy is an additional screening modality for colorectal cancer. Second-generation capsule colonoscopy (CC2) may have improved efficacy in the detection of colon adenomas as compared with prior devices. The purpose of this study was to evaluate the performance of CC2 in the detection of polyps in symptomatic and screening patients in the USA.DesignProspective, multicentre study.Setting and participantsTwo academic medical centres and two private practice facilities, evaluating patients with indications for colonoscopy.MethodsPatients underwent capsule colonoscopy procedure using magnesium citrate as a boost, followed by colonoscopy on the same day. The main outcome measurement was accuracy of CC2 for the detection of colorectal polyps ≥6 and ≥10 mm as compared with conventional colonoscopy.Results51 patients were enrolled, 50 of whom had CC2 and colonoscopy examinations and were included in the accuracy analysis. 30% and 14% of patients had polyps ≥6 and ≥10 mm, respectively. For lesions ≥10 mm identified on conventional colonoscopy, CC2 sensitivity was 100% (95% CI 56.1% to 100%) with a specificity of 93.0% (79.9% to 98.2%). For polyps ≥6 mm, the CC2 sensitivity was 93.3% (66.0% to 99.7%) and the specificity was 80.0% (62.5% to 90.9%). There was a 61% adequate cleansing rate with 64% of CC2 procedures being complete.ConclusionsIn the initial US experience with CC2 there was adequate sensitivity for detecting patients with polyps ≥6 mm in size. Magnesium citrate was inadequate as a boost agent.Trial registration numberNCT01087528.
Cost-effectiveness of adalimumab, infliximab or vedolizumab as first-line biological therapy in moderate-to-severe ulcerative colitis
Authors: Yokomizo Lauren , Limketkai Berkeley , Park K T 
Published: May 2016

BackgroundThere are no head-to-head randomised controlled trials (RCTs) comparing the effectiveness of biologics in ulcerative colitis (UC). We aimed to assess the cost-effectiveness of adalimumab, infliximab and vedolizumab as first-line agents to induce clinical remission and mucosal healing (MH) in UC.MethodsWe constructed a decision tree based on a payer's perspective in the USA to estimate the first year costs of adalimumab, infliximab or vedolizumab to achieve clinical remission and MH in patients with moderate-to-severe UC. Transition probabilities were derived from ACT, ULTRA and GEMINI RCT data. Costs were derived from Medicare reimbursement rates and wholesale drug prices.ResultsAssuming a biological-naïve cohort, infliximab 5 mg/kg every 8 weeks was more cost-effective ($99 171 per MH achieved) than adalimumab 40 mg every other week ($316 378 per MH achieved) and vedolizumab every 8 weeks ($301 969 per MH achieved) at 1 year. Non-drug administration cost of infliximab exceeding $1974 per infusion would make adalimumab more cost-effective. First-line UC therapy with vedolizumab would be cost-effective if the drug acquisition price was <$2537 for each 300 mg administration during the 1-year time horizon.ConclusionsIf non-drug costs of infliximab administration are not excessive (<$2000), infliximab is the most cost-effective first-line biologic for moderate-to-severe UC. Exceeding this threshold infusion-related cost would make adalimumab the more cost-effective therapy. Considering its drug costs in the USA, vedolizumab appears to be appropriately used as a second-line biologic after antitumour necrosis factor failure.
Melatonin and cashmere growth in Inner Mongolian cashmere goats
Authors: Duan Chun-hui , Xu Jian-hai , Zhang Yu , Jia Zhi-hai , Zhang Wei 
Published: May 2016

The aim of the study was to investigate the effects of melatonin implants on cashmere growth and productive performance of cashmere goats. A total of thirty female goats were assigned to one of three treatments (n = 10), including control and two treatments where melatonin [2 mg kg−1 body weight (BW)] was implanted either in April and June or in June. Compared with the control, implantation in April and June increased cashmere yield and maximum cashmere length by 20.3% and 15.7%, respectively (P < 0.01), with an average initiation date of 22 May 2013 and cessation date of 26 Mar. 2014. In contrast, no cashmere growth was observed in control goats until 19 June 2013 and the growth ceased on 3 Apr. 2014. Melatonin only implanted in June had no effect on cashmere yield and maximum cashmere length, with an average initiation date of 5 June 2013 and cessation date of 27 Mar. 2014. Cashmere growth rate, cashmere fiber diameter, the final BW, and average daily gain were not influenced by melatonin implantation. Results suggested that melatonin implantation during the cashmere nongrowing period is an effective way to stimulate cashmere growth and extend the cashmere growth phase with April and June identified as the most appropriate time for implantation.
The Optimal Rehabilitation Period for Patients with Distal Radius Fractures According to the MCID in DASH Scores; A Preliminary Study
Authors: Iitsuka Terufumi , Iwatsuki Katsuyuki , Ota Hideyuki , Hirata Hitoshi 
Published: May 2016

Background: The statistical concept of minimal clinically important difference (MCID) enables the interpretation of small but meaningful changes that result from an intervention. This retrospective study aimed to examine the factors that influence the achievement of MCID after a distal radius fracture. Methods: A total of 45 patients (mean age: 54.2 ± 16 years) were included. Of these, 27 patients started rehabilitation within 3 days of surgery (Early group), and 18 patients underwent immobilization for 2 weeks after surgery, before starting rehabilitation (Non-early group). Functional outcomes and DASH scores at 4 weeks (baseline) were compared with those measured at 8 and 12 weeks for both groups, to determine whether the MCID had been achieved. Results: Our results showed that at 8 weeks after surgery in the early group, the grip strength, ulnar flexion, and baseline DASH score were significantly different between the groups that did and did not show an MCID ([Formula: see text]). There was also a significant difference in the baseline DASH score at 12 weeks after surgery ([Formula: see text]). None of these factors were significant in the non-early group. Logistic regression analysis revealed that the DASH score at 4 weeks (baseline) was an independent predictor for achieving a DASH MCID at 8 weeks postoperatively in the early group (odds ratio: 1.193). Those achieving a DASH MCID at 12 weeks postoperatively were completely separated by the baseline DASH score (≥ 29 points). Conclusions: If it is assumed that the effectiveness of rehabilitation depends upon achieving the DASH MCID by promoting functional recovery, early initiation might be recommended.
Pedicled Oblique Para-Umbilical Perforator (OPUP) Flap for Upper Limb Reconstruction
Authors: Naduthodikayil Praveen , Bhandari Laxminarayan , Sreedhar Sreelesh Lalitha 
Published: May 2016

Background: Groin flap has been considered the workhorse flap for hand reconstruction. However it has certain drawbacks when covering defects over elbow or proximal forearm. Pedicled oblique paraumbilical perforator (OPUP) based flaps provide a good alternative in such cases. Methods: We performed OPUP flap in 11 cases of complex upper limb reconstructions over the past one year. We report our experience with this flap. Results: All flaps survived. One patient had marginal necrosis of 1 cm in the proximal end after flap division. Three patients had donor site scar hypertrophy. Conclusions: OPUP flap is superior to groin flap for larger defects or defects around the elbow. The major disadvantage is the donor site scar which is prone to hypertrophy.
Immunostimulatory Monoclonal Antibodies and Immunomodulation: Harvesting the Crop
Authors: Berraondo Pedro , Ochoa María Carmen , Rodriguez-Ruiz María Esperanza , Minute Luna , Lasarte Juan José , Melero Ignacio 
Published: May 2016

Abstract
The recent approval by the FDA of the combination of anti-CTLA4 and anti-PD-1 mAbs for the treatment of BRAF-unmutated unresectable or metastatic melanoma is a landmark for the development of cancer immunotherapy. On October 18 to 22, 2015, a symposium was held in Pamplona (Spain) to present and discuss the basic and clinical discoveries that have brought us to this milestone and to explore other targets and immunotherapy strategies aimed at attaining more efficacious oncology practice in the short term. Cancer Res; 76(10); 2863–7. ©2016 AACR.
Targeting Androgen Receptor Activation Function-1 with EPI to Overcome Resistance Mechanisms in Castration-Resistant Prostate Cancer
Authors: Yang Yu Chi , Banuelos Carmen Adriana , Mawji Nasrin R. , Wang Jun , Kato Minoru , Haile Simon , McEwan Iain J. , Plymate Stephen , Sadar Marianne D. 
Published: May 2016

Abstract
Purpose: Persistent androgen receptor (AR) transcriptional activity is clinically evident in castration-resistant prostate cancer (CRPC). Therefore, AR remains as a viable therapeutic target for CRPC. All current hormonal therapies target the C-terminus ligand-binding domain (LBD) of AR. By using EPI to target AR activation function-1 (AF-1), in the N-terminal domain that is essential for AR transactivation, we evaluate the ability of EPI to overcome several clinically relevant AR-related mechanisms of resistance.
Experimental Design: To study the effect of EPI on AR transcriptional activity against overexpressed coactivators, such as SRC1-3 and p300, luciferase reporter assays were performed using LNCaP cells. AR-negative COS-1 cells were employed for reporter assays to examine whether the length of polyglutamine tract affects inhibition by EPI. The effect of EPI on constitutively active AR splice variants was studied in LNCaP95 cells, which express AR-V7 variant. To evaluate the effect of EPI on the proliferation of LNCaP95 cells, we performed in vitro BrdUrd incorporation assay and in vivo studies using xenografts in mice.
Results: EPI effectively overcame several molecular alterations underlying aberrant AR activity, including overexpressed coactivators, AR gain-of-function mutations, and constitutively active AR-V7. EPI inhibited AR transcriptional activity regardless of the length of polyglutamine tract. Importantly, EPI significantly inhibited the in vitro and in vivo proliferation of LNCaP95 prostate cancer cells, which are androgen independent and enzalutamide resistant.
Conclusions: These findings support EPI as a promising therapeutic agent to treat CRPC, particularly against tumors driven by constitutively active AR splice variants that are resistant to LBD-targeting drugs. Clin Cancer Res; 22(17); 4466–77. ©2016 AACR.
See related commentary by Sharp et al., p. 4280