bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor‐specific individuality of red blood cell performance during storage is partly a function of serum uric acid levels
Authors: Tzounakas Vassilis L. , Karadimas Dimitrios G. , Anastasiadi Alkmini T. , Georgatzakou Hara T. , Kazepidou Eleftheria , Moschovas Dimitris , Velentzas Athanassios D. , Kriebardis Anastasios G. , Zafeiropoulos Nikolaos E. , Avgeropoulos Apostolos , Lekka Marilena , Stamoulis Konstantinos E. , Papassideri Issidora S. , Antonelou Marianna H. 
Published: October 2017

BACKGROUNDPrevious investigations in leukoreduced units of red blood cells (RBCs) in mannitol additive solution revealed the close association of uric acid (UA) levels in vivo with the susceptibility of RBCs to storage lesion markers. In this study, we examined whether UA has a similar correlation with the capability of RBCs to cope with the oxidative provocations of storage under different conditions, namely, in CPDA‐1 and in the absence of leukoreduction.STUDY DESIGN AND METHODSThe UA‐dependent antioxidant capacity of the supernatant was measured in nonleukoreduced units of RBCs in CPDA (n = 47). The possible effect of UA variability on the storage lesion profile was assessed by monitoring several physiologic properties of RBCs and supernatant, including cell shape, reactive oxygen species, and size distribution of extracellular vesicles, in units exhibiting the lowest or highest levels of UA activity (n = 16) among donors, throughout the storage period.RESULTSIn stored RBC units, the UA‐dependent antioxidant activity of the supernatant declined as a function of storage duration but always in strong relation to the UA levels in fresh blood. Contrary to units of poor‐UA activity, RBCs with the highest levels of UA activity exhibited better profile of calcium‐ and oxidative stress–driven modifications, including a significant decrease in the percentages of spherocytes and of 100‐ to 300‐nm‐sized vesicles, typically associated with the exovesiculation of stored RBCs.CONCLUSIONThe antioxidant activity of UA is associated with donor‐specific differences in the performance of RBCs under storage in nonleukoreduced CPDA units.
Comparison of albumin, colloid osmotic pressure, von Willebrand factor, and coagulation factors in canine cryopoor plasma, cryoprecipitate, and fresh frozen plasma
Authors: Culler Christine A. , Iazbik Cristina , Guillaumin Julien 
Published: October 2017

AbstractObjectiveTo compare albumin concentrations, coagulation factors activity, and colloid osmotic pressure (COP) of cryoprecipitate (CRYO) and cryopoor plasma (CPP) to that of source fresh frozen plasma (FFP).DesignProspective in vitro study.SettingUniversity teaching hospital.AnimalsTen healthy, non‐Greyhound dogs enrolled in an academic teaching hospital blood donor program.InterventionsFresh blood was obtained from canine blood donors and separated into FFP and packed red blood cells. The source FFP was further separated into CRYO and CPP. Albumin and fibrinogen concentrations, COP, activities of coagulation factors II, V, VII, VIII, IX, X, and von Willebrand factor (vWf) were assessed for each FFP, CRYO, and CPP.Measurements and Main ResultsThe mean albumin concentration and COP in CPP were significantly higher compared with those found in FFP, with 31.7 g/L (±6) in CPP compared to 28.9 g/L (±0.5) in FFP (P< 0.001) and 14.5 mm Hg (±0.7) in CPP compared to 12.7 mm Hg (±0.3) in FFP (P= 0.03), respectively. CRYO had significantly higher concentrations of fibrinogen (median 3.46 g/L, 95% CI 2.65–4.27), and higher activities of factor VIII (mean activity 427.0%, ±95.4) and vWf (mean activity 504.7%, ±41.39) as compared to the other products. The activities of vitamin K dependent factors II, VII, and X were similar in CPP compared to FFP, although factor IX activity was lower in CPP. There was no significant difference in factor II or VII activities between the 3 products.ConclusionsThe mean albumin concentration and COP were highest in CPP, suggesting that CPP may be a potential alternative to FFP for oncotic support and albumin replacement. CRYO contained higher activities of vWf and factor VIII than other products and could be used to treat vWf deficiency and hemophilia A. As vitamin K dependent coagulation factors II, VII, and X in CPP were similar to FFP, CPP may be an option for replacement of most of vitamin K dependent factors.
Reductions in margin length after excision of grade II mast cell tumors and grade I and II soft tissue sarcomas in dogs
Authors: Milovancev Milan , Townsend Katy L. , Bracha Shay , Gorman Elena , Curran Kaitlin , Russell Duncan S. 
Published: October 2017

AbstractObjectiveQuantify changes in the circumferential lengths of surgical margins of resected canine mast cell tumors (MCT) and soft tissue sarcomas (STS) between the time of collection and histopathology.Study designProspective, hypothesis‐driven, clinical study.Sample populationTwo hundred and thirty‐seven margins from 69 excised tumors (50 MCT and 19 STS) in 51 client‐owned dogs.MethodsThe lengths of surgical margins were recorded (eg, cranial, caudal, dorsal, and ventral) for each tumor at 5 time points: intraoperatively (in vivo), immediately after excision (ex vivo), after formalin fixation (postfixation), once mounted on glass slides (subgross), and as histologically tumor‐free margins (HTFMs).ResultsCompared to in vivo dimensions, the length of surgical margins at each processing step (ie, ex vivo, postfixation, subgross, and HTFM) was reduced by a median of 3.0, 5.0, 6.0, and 8.8 mm for MCT; 2.5, 2.0, 5.0, and 5.0 mm for STS. All processing steps resulted in significant reductions among MCT samples (P < .0001), except between postfixation vs subgross, and for STS samples (P < .0001), except between ex vivo vs postfixation and subgross vs HTFM. The maximum reduction in the total length of margins (from in vivo to HTFM) was 29.6 and 24.2 mm for MCT and STS, respectively.ConclusionSurgical margin length reductions occur due to a combination of physical factors (eg, tissue elasticity, myofibril contraction, and histologic processing) and biological factors (eg, microscopic tumor infiltration into the grossly normal surgical margin).Clinical significanceThese data provide information relevant to evidence‐based surgical planning and may influence patient morbidity in the most commonly encountered cutaneous malignancies of dogs.
Accuracy of a patient‐specific 3D printed drill guide for placement of cervical transpedicular screws
Authors: Hamilton‐Bennett Sinead E. , Oxley Bill , Behr Sebastien 
Published: October 2017

AbstractObjectiveTo develop a patient‐specific 3‐dimensional (3D) printed drill guide for placement of cervical transpedicular screws and to assess its accuracy.Study designProspective case‐series.Sample PopulationThirty‐two cervical pedicle screws (CPS) placed in 3 large breed dogs.MethodsComputed tomographic (CT) data of the cervical vertebrae were exported to a medical image processing software and 3D virtual vertebral models were created for each vertebra. These models were processed in a computer aided design (CAD) software to determine the optimal trajectory and size of the CPS. Virtual drill guides were created for each patient, 3D‐printed, and used intraoperatively. Locking titanium screw heads were bonded with polymethylmethacrylate cement to stabilize affected vertebral segments. Postoperative CT was used to assess the radiological accuracy of CPS placement in each dog. For each screw, CAD files were analyzed to determine a screw‐diameter‐to‐pedicle‐width‐ratio (SDPWR) at the narrowest point of the pedicle.ResultsA total of 32 CPS were placed, measuring 3.5 mm (n = 20), 2.7 mm (n = 11), and 2.4 mm (n = 1) in diameter. The majority (29/32) of these screws were placed without evidence of vertebral canal breach (grade 0), whereas a vertebral canal breach <2 mm (grade 1) was detected in 3/32 screws. This outcome was achieved despite a mean SDPWR of 0.75 (range 0.58‐0.93).ConclusionThe use of a 3D‐printed patient‐specific drill guide permitted accurate placement of 32 bicortical pedicle screws in the caudal cervical vertebrae of 3 dogs. This technique may improve clinical outcome through superior biomechanical properties of screws, reduced surgical time, and reduced morbidity. These results warrant evaluation of patient outcome in a larger population.
Manganese coprecipitation/adsorption behaviour and sludge volume ratios in chemical treatment systems for mine drainage: a review of the literature and a pilot‐scale experiment
Authors: Kim Duk‐Min , Kim Dong‐Kwan , Lee Sang‐Hwan 
Published: October 2017

AbstractManganese removal at lower pH and sludge volume in settling ponds are some of the major issues affecting chemical treatment systems for mine drainage. First, Fe and Al existing in mine drainage coprecipitate with and/or adsorb Mn. Eight chemical treatment facilities were reviewed from literature and a pilot‐scale experiment was also conducted in the Daedeok mine in South Korea. The Mn/(Fe + Al) ratio revealed a positive linear relationship with the lowest pH at discharge, and regression lines were generated. This relationship may be used to predict the pH required to remove Mn considering coprecipitation/adsorption. Second, the ratios of the generation rate of sludge to the required settling volume at five semi‐active treatment facilities were evaluated from literature. This ratio is referred to as the sludge‐settling volume ratio, which can be used as one of the factors in deciding between semi‐active and active treatment systems.
Study on Slip Phenomenon of Pumps As Turbines in Different Working Conditions
Authors: Xiaohui Wang , Junhu Yang , Zhengting Xia 
Published: October 2017

Slip phenomenon is known to strongly influence the performance of pump as turbine (PAT). It is of interest to investigate the influence of flow parameters on the slip factor and obtain the effective value of slip factor over the whole range of their working conditions.
In the present work, the slip phenomenon of PAT at different working condition was studied, slip factor was calculated in every point of the flow. Furthermore, the relative eddy within the impeller passage was evaluated and the hydraulic performance of PAT was analyzed.
The result shows that the slip factor decreases with the increasing flow rate, slip phenomenon induces additional hydraulic loss in impeller passage, it weakened in over-load region, as a consequence, hydraulic efficiency is relatively high. On the contrary, the slip phenomenon strengthened in part-load region, therefore, hydraulic efficiency of PAT is relatively low. It was observed that a relative eddy take place within the impeller passage, the eddy occurs near pressure side of blade at design-point condition, it motions to suction side at high discharge, and divides into two separated eddy at partial discharge condition. The relative eddy cause pressure fluctuate in PAT impeller, which affects the energy recovery of PAT.
Axial Thrust Prediction for a Multi-Stage Centrifugal Pump
Authors: Bruurs K. A. J. , van Esch B. P. M. , van der Schoot M. S. , van der Zijden E. J. J. 
Published: October 2017

The prediction of axial thrust for centrifugal pumps has been an important topic for many years. This is especially the case for multi-stage pumps with opposed or inline impellers, as the correct selection of balancing device(s) and bearings depends highly on the accuracy of the calculated thrust.
Up till now, many investigations regarding axial thrust have focused on fully analytical or (semi-)empirical relations while others have tried to predict the axial thrust using CFD simulations. Full analytical or empirical methods tend to give poor results or need tuning for each specific pump, while the full CFD methods are costly in both setup time and computer resources.
This paper presents a hybrid method to calculate the axial thrust of a multi-stage pump with an inline impeller design. The hybrid method combines analytical methods and CFD to reduce the required setup time and computation costs. The CFD calculation of the main flow is used as a boundary condition for the semi-empirical models for the side chambers and the inter-stage seals, such that these tight regions can be excluded from the CFD calculation.
To verify and validate the hybrid method, results are compared with measurements and with full CFD calculations that include the side chambers and seals. These results show that the hybrid method and the full CFD method give comparable results, but there is still some difference with the measurements.
Impact of Rifabutin or Rifampin on Bedaquiline Safety, Tolerability, and Pharmacokinetics Assessed in a Randomized Clinical Trial with Healthy Adult Volunteers
Authors: Healan Amanda M. , Griffiss J. McLeod , Proskin Howard M. , O'Riordan Mary Ann , Gray Wesley A. , Salata Robert A. , Blumer Jeffrey L. 
Published: October 2017

ABSTRACT

Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial ATP synthase. Bedaquiline has been used to effectively treat tuberculosis (TB) caused by drug-susceptible and drug-resistant
Mycobacterium tuberculosis
. Rifamycins are a cornerstone of combination drug regimens for the treatment of TB. This phase 1, open-label, randomized, controlled trial evaluated the effect of steady-state dosing of rifabutin or rifampin on the safety, tolerability, and pharmacokinetics of bedaquiline given as a single dose. Thirty-three healthy subjects were enrolled to receive a 400-mg single oral dose of bedaquiline at two time points, on study days 1 and 29. Subjects were randomly assigned to once daily oral doses of rifabutin (300 mg/day,
n
= 17) or rifampin (600 mg/day,
n
= 16) during period 2 from days 20 to 41. Serial blood sampling for bedaquiline measurement occurred on days 1 and 29 through 336 h after bedaquiline administration. The day 29 bedaquiline pharmacokinetic parameter estimates were compared to the corresponding day 1 estimates for each rifamycin group. Steady-state rifampin reduced bedaquiline AUC
0–336
approximately 45%, from 47.69 h·μg/ml in period 1 to 26.33 h·μg/ml in period 2. Bedaquiline apparent clearance accelerated 24% in rifampin-treated subjects from 6.59 liters/h in period 1 to 8.19 liters/h in period 2. Steady-state rifabutin resulted in little quantitative impact on bedaquiline exposure but was associated with grade 3 and 4 adverse events before and after the day 29 bedaquiline dose. Dosage adjustments may therefore be necessary to ensure that bedaquiline plasma concentrations reach therapeutic levels safely when combining bedaquiline and rifamycins in TB treatment regimens. (This single-site, randomized, open-label, prospective study in healthy adult volunteers was registered at Clinicaltrials.gov under registration no. NCT01341184.)
Interplay between Antibiotic Efficacy and Drug-Induced Lysis Underlies Enhanced Biofilm Formation at Subinhibitory Drug Concentrations
Authors: Yu Wen , Hallinen Kelsey M. , Wood Kevin B. 
Published: October 2017

ABSTRACT

Subinhibitory concentrations of antibiotics have been shown to enhance biofilm formation in multiple bacterial species. While antibiotic exposure has been associated with modulated expression of many biofilm-related genes, the mechanisms of drug-induced biofilm formation remain a focus of ongoing research efforts and may vary significantly across species. In this work, we investigate antibiotic-induced biofilm formation in
Enterococcus faecalis
, a leading cause of nosocomial infections. We show that biofilm formation is enhanced by subinhibitory concentrations of cell wall synthesis inhibitors but not by inhibitors of protein, DNA, folic acid, or RNA synthesis. Furthermore, enhanced biofilm is associated with increased cell lysis, increases in extracellular DNA (eDNA) levels, and increases in the density of living cells in the biofilm. In addition, we observe similar enhancement of biofilm formation when cells are treated with nonantibiotic surfactants that induce cell lysis. These findings suggest that antibiotic-induced biofilm formation is governed by a trade-off between drug toxicity and the beneficial effects of cell lysis. To understand this trade-off, we developed a simple mathematical model that predicts changes in antibiotic-induced biofilm formation due to external perturbations, and we verified these predictions experimentally. Specifically, we demonstrate that perturbations that reduce eDNA (DNase treatment) or decrease the number of living cells in the planktonic phase (a second antibiotic) decrease biofilm induction, while chemical inhibitors of cell lysis increase relative biofilm induction and shift the peak to higher antibiotic concentrations. Overall, our results offer experimental evidence linking cell wall synthesis inhibitors, cell lysis, increased eDNA levels, and biofilm formation in
E. faecalis
while also providing a predictive quantitative model that sheds light on the interplay between cell lysis and antibiotic efficacy in developing biofilms.
Peptidoglycan Cross-Linking Activity of
l
,
d
-Transpeptidases from Clostridium difficile and Inactivation of These Enzymes by β-Lactams
Authors: Sütterlin Laetitia , Edoo Zainab , Hugonnet Jean-Emmanuel , Mainardi Jean-Luc , Arthur Michel 
Published: October 2017

ABSTRACT

In most bacteria, the essential targets of β-lactam antibiotics are the
d
,
d
-transpeptidases that catalyze the last step of peptidoglycan polymerization by forming 4→3 cross-links. The peptidoglycan of
Clostridium difficile
is unusual since it mainly contains 3→3 cross-links generated by
l
,
d
-transpeptidases. To gain insight into the characteristics of
C. difficile
peptidoglycan cross-linking enzymes, we purified the three putative
C. difficile
l
,
d
-transpeptidase paralogues Ldt
Cd1
, Ldt
Cd2
, and Ldt
Cd3
, which were previously identified by sequence analysis. The catalytic activities of the three proteins were assayed with a disaccharide-tetrapeptide purified from the
C. difficile
cell wall. Ldt
Cd2
and Ldt
Cd3
catalyzed the formation of 3→3 cross-links (
l
,
d
-transpeptidase activity), the hydrolysis of the C-terminal
d
-Ala residue of the disaccharide-tetrapeptide substrate (
l
,
d
-carboxypeptidase activity), and the exchange of the C-terminal
d
-Ala for
d
-Met. Ldt
Cd1
displayed only
l
,
d
-carboxypeptidase activity. Mass spectrometry analyses indicated that Ldt
Cd1
and Ldt
Cd2
were acylated by β-lactams belonging to the carbapenem (imipenem, meropenem, and ertapenem), cephalosporin (ceftriaxone), and penicillin (ampicillin) classes. Acylation of Ldt
Cd3
by these β-lactams was not detected. The acylation efficacy of Ldt
Cd1
and Ldt
Cd2
was higher for the carbapenems (480 to 6,600 M
−1
s
−1
) than for ampicillin and ceftriaxone (3.9 to 82 M
−1
s
−1
). In contrast, the efficacy of the hydrolysis of β-lactams by Ldt
Cd1
and Ldt
Cd2
was higher for ampicillin and ceftriaxone than for imipenem. These observations indicate that Ldt
Cd1
and Ldt
Cd2
are inactivated only by β-lactams of the carbapenem class due to a combination of rapid acylation and the stability of the resulting covalent adducts.
Mechanism of Action of Miltefosine on Leishmania donovani Involves the Impairment of Acidocalcisome Function and the Activation of the Sphingosine-Dependent Plasma Membrane Ca
2+
Channel
Authors: Pinto-Martinez Andrea K. , Rodriguez-Durán Jessica , Serrano-Martin Xenon , Hernandez-Rodriguez Vanessa , Benaim Gustavo 
Published: October 2017

ABSTRACT

Leishmania donovani
is the causing agent of visceral leishmaniasis, a common infection that affects millions of people from the most underdeveloped countries. Miltefosine is the only oral drug to treat infections caused by
L. donovani
. Nevertheless, its mechanism of action is not well understood. While miltefosine inhibits the synthesis of phosphatidylcholine and also affects the parasite mitochondrion, inhibiting the cytochrome
c
oxidase, it is to be expected that this potent drug also produces its effect through other targets. In this context, it has been reported that the disruption of the intracellular Ca
2+
homeostasis represents an important object for the action of drugs in trypanosomatids. Recently, we have described a plasma membrane Ca
2+
channel in
Leishmania mexicana
, which is similar to the L-type voltage-gated Ca
2+
channel (VGCC) present in humans. Remarkably, the parasite Ca
2+
channel is activated by sphingosine, while the L-type VGCC is not affected by this sphingolipid. In the present work we demonstrated that, similarly to sphingosine, miltefosine is able to activate the plasma membrane Ca
2+
channel from
L. donovani
. Interestingly, nifedipine, the classical antagonist of the human channel, was not able to fully block the parasite plasma membrane Ca
2+
channel, indicating that the mechanism of interaction is not identical to that of sphingosine. In this work we also show that miltefosine is able to strongly affect the acidocalcisomes from
L. donovani
, inducing the rapid alkalinization of these important organelles. In conclusion, we demonstrate two new mechanisms of action of miltefosine in
L. donovani
, both related to disruption of parasite Ca
2+
homeostasis.
Vitamin D Compounds Are Bactericidal against Streptococcus mutans and Target the Bacitracin-Associated Efflux System
Authors: Saputo S. , Faustoferri R. C. , Quivey R. G. 
Published: October 2017

ABSTRACT

Vitamin D analogs were identified as compounds that induced lysis of planktonic cultures of
Streptococcus mutans
in a high-throughput screen of FDA-approved drugs. Previous studies have demonstrated that certain derivatives of vitamin D possess lytic activity against other bacteria, though the mechanism has not yet been established. Through the use of a combinatorial approach, the vitamin D derivative doxercalciferol was shown to act synergistically with bacitracin, a polypeptide-type drug that is known to interfere with cell wall synthesis, suggesting that doxercalciferol may act in a bacitracin-related pathway. Innate resistance to bacitracin is attributed to efflux by a conserved ABC-type transporter, which in
S. mutans
is encoded by the
mbrABCD
operon.
S. mutans
possesses two characterized mechanisms of resistance to bacitracin, the ABC transporter,
S. mutans
bacitracin resistance (Mbr) cassette, consisting of MbrABCD, and the rhamnose-glucose polysaccharide (Rgp) system, RgpABCDEFGHI. Loss of function of the transporter in
ΔmbrA
and
ΔmbrD
mutants exacerbated the effect of the combination of doxercalciferol and bacitracin. Despite conservation of a transporter homologous to
mbrABCD
, the combination of doxercalciferol and bacitracin appeared to be synergistic only in streptococcal species. We conclude that vitamin D derivatives possess lytic activity against
S. mutans
and act through a mechanism dependent on the bacitracin resistance mechanism of MbrABCD.