bluuebunny/crossref_metadata_2025_split huggingface dataset:
Red blood cell storage affects the stability of cytosolic native protein complexes
Authors: Pallotta Valeria , Rinalducci Sara , Zolla Lello 
Published: March 2015

BACKGROUNDRefrigerated storage of red blood cell (RBC) units promotes the progressive accumulation of the so‐called storage lesions, a widespread series of alterations to morphology, metabolism, and proteome integrity of stored RBCs. However, while storage lesions targeting the RBC membrane fraction have been widely documented, the cytosolic fraction is as yet an underinvestigated cause of the technical inconveniences related to the high abundance of hemoglobin.STUDY DESIGN AND METHODSBy exploiting a recently ideated preparative two‐dimensional clear native electrophoresis, followed by mass spectrometry analysis, we could monitor the changes of soluble multiprotein complexes (MPCs) in RBCs after 0, 21, and 35 days of storage under standard blood banking conditions.RESULTSData indicate a substantial storage‐dependent alteration of RBC MPCs, particularly of those involved in energy and redox metabolism, confirming previous evidence about the progressive dysregulation of these pathways in long‐stored units.CONCLUSIONThe use of native gel–based proteomics to investigate MPCs present in the RBC cytosolic fraction proved to be a powerful tool. Results collected represent a preliminary advance in the knowledge of the key role of native cytosolic MPCs in context of RBC storage lesion. Multiprotein organization and interacting partners of some key enzymes have been found to change during storage duration, suggesting that future studies will be needed to assess whether such alterations could influence their activity and efficiency.
Western immunoblotting as a new tool for investigating direct antiglobulin test–negative autoimmune hemolytic anemias
Authors: Bloch Evgenia M. , Sakac Darinka , Branch Haley A. , Cserti‐Gazdewich Christine , Pendergrast Jacob , Pavenski Katerina , Branch Donald R. 
Published: March 2015

BACKGROUNDDirect antiglobulin test–negative (DAT(–)) autoimmune hemolytic anemia, characterized by hemolysis without detectable immunoglobulin or complement on patient red blood cells (RBCs), poses a diagnostic challenge. To select therapy, classification of the hemolysis as immune‐ or non–immune‐mediated is important. We developed a method using Western immunoblot (WB) to classify DAT(–) patients by measuring and comparing levels of RBC immunoglobulin (Ig)G to normal donors.STUDY DESIGN AND METHODSRBC samples from 42 normal donors were made into ghosts and analyzed by WB and densitometry to establish a normal mean relative quantity of IgG (RQIgG) on the RBCs. RQIgG on eight DAT(–) and eluate‐negative patients with hemolytic anemia was determined and compared to RQIgG on normal RBCs.RESULTSRQIgG of 42 normal donors indicated a calculated mean ± SD of 0.0016 ± 0.0015 and we used a cutoff of 0.0047, the mean + 2SD. This was compared with a receiver operating curve cutoff of 0.0041 with 100% sensitivity and 93% specificity. Of the eight patients tested, three were classified as non–immune‐mediated (one had pyruvate kinase deficiency) and five as immune‐mediated. Two of the patients in the latter group underwent splenectomy, followed by remission.CONCLUSIONWB analysis is more sensitive than conventional test tube DAT or elution analysis. Our assay confirms: 1) previous studies showing normal RBCs are sensitized with IgG, perhaps due to natural autoantibody to senescence; 2) that some normal RBCs have increased levels of IgG without signs of disease; and 3) that WB distinguishes between non–immune‐ and immune‐mediated hemolytic anemia in DAT(–) patients and may be useful for clinical diagnosis.
Cost‐effectiveness of becaplermin gel on wound healing of diabetic foot ulcers
Authors: Gilligan Adrienne M. , Waycaster Curtis R. , Motley Travis A. 
Published: March 2015

ABSTRACTWe sought to determine the long‐term cost effectiveness (payer's perspective) of becaplermin gel plus good wound care (BGWC) vs. good wound care (GWC) alone in terms of wound healing and risk of amputation in patients with diabetic foot ulcers (DFUs). Outcomes data were derived from a propensity score‐matched cohort from the Curative Health Services database between 1998 and 2004, which was followed for 20 weeks. A four‐state Markov model was used to predict costs and outcomes of wound healing and risk of amputation for BGWC vs. GWC alone over 1 year in patients with DFU. The primary outcome was closed‐wound weeks. Transition probabilities for healing and amputation were derived from the aforementioned propensity score‐matched cohorts. Ulcer recurrence was estimated from the medical literature. Utilization for becaplermin was calculated using the dosing algorithm in the product labeling. Of 24,898 eligible patients, 9.6% received BGWC. Based on the model, patients treated with BGWC had substantially more closed‐wound weeks compared with GWC (16.1 vs. 12.5 weeks, respectively). More patients receiving BGWC had healed wounds at 1 year compared with those receiving GWC (48.1% vs. 38.3%). Risk of amputation was lower in the BGWC cohort (6.8% vs. 9.8%). Expected annual direct costs for DFU were $21,920 for BGWC and $24,640 for GWC. BGWC was economically dominant over GWC, providing better outcomes at a lower cost in patients with DFU. Compared with GWC alone, BGWC is more effective in healing wounds and lowering amputation risk, thereby decreasing long‐term costs for DFU.
Cryptosporidium parvum Caused a Large Outbreak Linked to Frisée Salad in Finland, 2012
Authors: Åberg R. , Sjöman M. , Hemminki K. , Pirnes A. , Räsänen S. , Kalanti A. , Pohjanvirta T. , Caccio S. M. , Pihlajasaari A. , Toikkanen S. , Huusko S. , Rimhanen‐Finne R. 
Published: March 2015

SummaryOver 250 individuals fell ill in five outbreaks caused by Cryptosporidium parvum in Finland, October–November 2012. The cases were connected by lunch meals at restaurants in four different cities. In two outbreaks, the same C. parvumIIdA17G1 subtype was found in patients’ stool samples which supports a single source of infection. Frisée salad was the only common food item served at the restaurants, and consumption of lunch salad containing the frisée salad was associated with the illness. Lunch customers who responded that they had eaten lunch salad were three times more likely to have become ill than those who had not answered whether they had eaten the salad or not (RR 2.66; 95% Cl 1.02–6.9, P‐value <0.01). Cryptosporidiosis should be considered as a causal agent in long‐lasting watery diarrhoea combined with abdominal cramps, and clinical samples should be tested for Cryptosporidium at the same time bacteria and viruses are tested. Measures to prevent contamination of ‘ready‐to‐eat vegetables’ with Cryptosporidium oocysts and methods to test frozen food samples should be developed.
Large Ca2+‐dependent facilitation of CaV2.1 channels revealed by Ca2+ photo‐uncaging
Authors: Lee Shin‐Rong , Adams Paul J. , Yue David T. 
Published: March 2015

Key points
CaV2.1 channels constitute a dominant Ca2+ entry pathway into brain neurons, triggering downstream Ca2+‐dependent processes such as neurotransmitter release.
CaV2.1 is itself modulated by Ca2+, resulting in activity‐dependent enhancement of channel opening termed Ca2+‐dependent facilitation (CDF).
Real‐time Ca2+ imaging and Ca2+ uncaging here reveal that CDF turns out to be strikingly faster, more Ca2+ sensitive, and larger than anticipated on previous grounds.
Robust resolution of the quantitative profile of CDF enables deduction of a realistic biophysical model for this process.
These results suggest that CaV2.1 CDF would figure most prominently in short‐term synaptic plasticity and cerebellar Purkinje cell rhythmicity.
AbstractCaV2.1 (P‐type) voltage‐gated Ca2+ channels constitute a major source of neuronal Ca2+ current, strongly influencing rhythmicity and triggering neurotransmitter release throughout the central nervous system. Fitting with such stature among Ca2+ entry pathways, CaV2.1 is itself feedback regulated by intracellular Ca2+, acting through calmodulin to facilitate channel opening. The precise neurophysiological role of this calcium‐dependent facilitation (CDF) remains uncertain, however, in large measure because the very magnitude, Ca2+ dependence and kinetics of CDF have resisted quantification by conventional means. Here, we utilize the photo‐uncaging of Ca2+ with CaV2.1 channels fluxing Li+ currents, so that voltage‐dependent activation of channel gating is no longer conflated with Ca2+ entry, and CDF is then driven solely by light‐induced increases in Ca2+. By using this strategy, we now find that CDF can be unexpectedly large, enhancing currents by as much as twofold at physiological voltages. CDF is steeply Ca2+ dependent, with a Hill coefficient of approximately two, a half‐maximal effect reached by nearly 500 nm Ca2+, and Ca2+ on/off kinetics in the order of milliseconds to tens of milliseconds. These properties were established for both native P‐type currents in cerebellar Purkinje neurons, as well as their recombinant channel counterparts under heterologous expression. Such features suggest that CDF of CaV2.1 channels may substantially enhance the regularity of rhythmic firing in cerebellar Purkinje neurons, where regularity is believed crucial for motor coordination. In addition, this degree of extensive CDF would be poised to exert large order‐of‐magnitude effects on short‐term synaptic plasticity via rapid modulation of presynaptic Ca2+ entry.
Passive motion reduces vestibular balance and perceptual responses
Authors: Fitzpatrick Richard C. , Watson Shaun R. D. 
Published: March 2015

Key points
Human activity exposes the vestibular organs to a wide dynamic range of motion.
We aimed to discover whether the CNS regulates sensitivity to vestibular afference during exposure to ambient motion.
Balance and perceptual responses to vestibular stimulation were measured before and after a 10 min period of imposed, moderate intensity, stochastic whole‐body rotation.
After this conditioning, vestibular balance reflexes evoked by galvanic vestibular stimulation were halved in amplitude.
Conditioning doubled the thresholds for perceiving small rotations, and reduced perceptions of the amplitude of real rotations, and illusory rotation evoked by galvanic stimulation.
We conclude that the CNS auto‐regulates sensitivity to vestibular sensory afference and that this probably involves central and peripheral mechanisms, as might arise from vestibular efferent regulation.
Failure of these regulatory mechanisms at different levels could lead to disorders of movement perception and balance control during standing.
AbstractWith the hypothesis that vestibular sensitivity is regulated to deal with a range of environmental motion conditions, we explored the effects of passive whole‐body motion on vestibular perceptual and balance responses. In 10 subjects, vestibular responses were measured before and after a period of imposed passive motion. Vestibulospinal balance reflexes during standing evoked by galvanic vestibular stimulation (GVS) were measured as shear reaction forces. Perceptual tests measured thresholds for detecting angular motion, perceptions of suprathreshold rotation and perceptions of GVS‐evoked illusory rotation. The imposed conditioning motion was 10 min of stochastic yaw rotation (0.5–2.5 Hz ≤ 300 deg s−2) with subjects seated. This conditioning markedly reduced reflexive and perceptual responses. The medium latency galvanic reflex (300–350 ms) was halved in amplitude (48%; P = 0.011) but the short latency response was unaffected. Thresholds for detecting imposed rotation more than doubled (248%; P < 0.001) and remained elevated after 30 min. Over‐estimation of whole‐body rotation (30–180 deg every 5 s) before conditioning was significantly reduced (41.1 to 21.5%; P = 0.033). Conditioning reduced illusory vestibular sensations of rotation evoked by GVS (mean 113 deg for 10 s at 1 mA) by 44% (P < 0.01) and the effect persisted for at least 1 h (24% reduction; P < 0.05). We conclude that a system of vestibular sensory autoregulation exists and that this probably involves central and peripheral mechanisms, possibly through vestibular efferent regulation. We propose that failure of these regulatory mechanisms at different levels could lead to disorders of movement perception and balance control during standing.
Training-Load Distribution in Endurance Runners: Objective Versus Subjective Assessment
Authors: Manzi Vincenzo , Bovenzi Antonio , Castagna Carlo , Salimei Paola Sinibaldi , Volterrani Maurizio , Iellamo Ferdinando 
Published: March 2015

Purpose:To assess the distribution of exercise intensity in long-distance recreational athletes (LDRs) preparing for a marathon and to test the hypothesis that individual perception of effort could provide training responses similar to those provided by standardized training methodologies.Methods:Seven LDRs (age 36.5 ± 3.8 y) were followed during a 5-mo training period culminating with a city marathon. Heart rate at 2.0 and 4.0 mmol/L and maximal heart rate were used to establish 3 intensity training zones. Internal training load (TL) was assessed by training zones and TRIMPi methods. These were compared with the session-rating-of-perceived-exertion (RPE) method.Results:Total time spent in zone 1 was higher than in zones 2 and 3 (76.3% ± 6.4%, 17.3% ± 5.8%, and 6.3% ± 0.9%, respectively; P = .000 for both, ES = 0.98, ES = 0.99). TL quantified by session-RPE provided the same result. The comparison between session-RPE and training-zones-based methods showed no significant difference at the lowest intensity (P = .07, ES = 0.25). A significant correlation was observed between TL RPE and TL TRIMPi at both individual and group levels (r = .79, P < .001). There was a significant correlation between total time spent in zone 1 and the improvement at the running speed of 2 mmol/L (r = .88, P < .001). A negative correlation was found between running speed at 2 mmol/L and the time needed to complete the marathon (r = –.83, P < .001).Conclusions:These findings suggest that in recreational LDRs most of the training time is spent at low intensity and that this is associated with improved performances. Session-RPE is an easy-to-use training method that provides responses similar to those obtained with standardized training methodologies.
Development and Evaluation of a Simple, Multifactorial Model Based on Landing Performance to Indicate Injury Risk in Surfing Athletes
Authors: Lundgren Lina E. , Tran Tai T. , Nimphius Sophia , Raymond Ellen , Secomb Josh L. , Farley Oliver R.L. , Newton Robert U. , Steele Julie R. , Sheppard Jeremy M. 
Published: March 2015

Purpose:To develop and evaluate a multifactorial model based on landing performance to estimate injury risk for surfing athletes.Methods:Five measures were collected from 78 competitive surfing athletes and used to create a model to serve as a screening tool for landing tasks and potential injury risk. In the second part of the study, the model was evaluated using junior surfing athletes (n = 32) with a longitudinal follow-up of their injuries over 26 wk. Two models were compared based on the collected data, and magnitude-based inferences were applied to determine the likelihood of differences between injured and noninjured groups.Results:The study resulted in a model based on 5 measures—ankle-dorsiflexion range of motion, isometric midthigh-pull lower-body strength, time to stabilization during a drop-and-stick (DS) landing, relative peak force during a DS landing, and frontal-plane DS-landing video analysis—for male and female professional surfers and male and female junior surfers. Evaluation of the model showed that a scaled probability score was more likely to detect injuries in junior surfing athletes and reported a correlation of r = .66, P = .001, with a model of equal variable importance. The injured (n = 7) surfers had a lower probability score (0.18 ± 0.16) than the noninjured group (n = 25, 0.36 ± 0.15), with 98% likelihood, Cohen d = 1.04.Conclusions:The proposed model seems sensitive and easy to implement and interpret. Further research is recommended to show full validity for potential adaptations for other sports.
Assessment of Accelerometers for Measuring Upper-Extremity Physical Activity
Authors: Lawinger Elizabeth , Uhl Tim L. , Abel Mark , Kamineni Srinath 
Published: March 2015

Objective:The overarching goal of this study was to examine the use of triaxial accelerometers in measuring upper-extremity motions to monitor upper-extremity-exercise compliance. There were multiple questions investigated, but the primary objective was to investigate the correlation between visually observed arm motions and triaxial accelerometer activity counts to establish fundamental activity counts for the upper extremity.Study Design:Cross-sectional, basic research.Setting:Clinical laboratory.Participants:Thirty healthy individuals age 26 ± 6 y, body mass 24 ± 3 kg, and height 1.68 ± 0.09 m volunteered.Intervention:Participants performed 3 series of tasks: activities of daily living (ADLs), rehabilitation exercises, and passive shoulder range of motion at 5 specific velocities on an isokinetic dynamometer while wearing an accelerometer on each wrist. Participants performed exercises with their dominant arm to examine differences between sides. A researcher visually counted all arm motions to correlate counts with physical activity counts provided by the accelerometer.Main Outcome Measure:Physical activity counts derived from the accelerometer and visually observed activity counts recorded from a single investigator.Results:There was a strong positive correlation (r = .93, P < .01) between accelerometer physical activity counts and visual activity counts for all ADLs. Accelerometers activity counts demonstrated side-to-side difference for all ADLs (P < .001) and 5 of the 7 rehabilitation activities (P < .003). All velocities tested on the isokinetic dynamometer were shown to be significantly different from each other (P < .001).Conclusion:There is a linear relationship between arm motions counted visually and the physical activity counts generated by an accelerometer, indicating that arm motions could be potentially accounted for if monitoring arm usage. The accelerometers can detect differences in relatively slow arm-movement velocities, which is critical if attempting to evaluate exercise compliance during early phases of shoulder rehabilitation. These results provide fundamental information that indicates that triaxial accelerometers have the potential to objectively monitor and measure arm activities during rehabilitation and ADLs.
The Use of a Dynamic Elastomeric Fabric Orthosis in Supporting the Management of Athletic Pelvic and Groin Injury
Authors: Sawle Leanne , Freeman Jennifer , Marsden Jonathan 
Published: March 2015

Context:Athletic pelvic and groin injuries are a common yet challenging problem. Pelvic belts have been successfully used to reduce pain and improve function but are not a practical solution for athletes. Therefore, there is scope to explore the use of a more dynamic intervention developed to aid in the management of this type of injury.Objectives:To undertake a preliminary investigation into the effectiveness of a dynamic elastomeric fabric orthosis (DEFO) in supporting the management of athletic pelvic and groin injury.Design:A case series with an AB design. Daily assessments were undertaken over 15 days; the onset of intervention was randomized with a minimum baseline period of 6 d. Follow-up assessment was undertaken after 1 mo.Settings:Community and university.Participants:8 athletes presenting with pelvic or groin injury confirmed through clinical screening.Intervention:A bespoke DEFO.Main Outcome Measures:Force produced on bilateral resisted hip adduction and self-scored pain (using a numerical rating scale of 0–10) at rest and during an active straight-leg raise and a broad jump.Results:In 7 cases a significant improvement was observed on at least 1 measure (2-SD method, celeration line, and/or the point of nonoverlapping data). The remaining case showed minimal symptoms during testing.
Brincidofovir (CMX001) Inhibits BK Polyomavirus Replication in Primary Human Urothelial Cells
Authors: Tylden Garth D. , Hirsch Hans H. , Rinaldo Christine Hanssen 
Published: March 2015

ABSTRACT

BK polyomavirus (BKPyV)-associated hemorrhagic cystitis (PyVHC) complicates 5 to 15% of allogeneic hematopoietic stem cell transplantations. Targeted antivirals are still unavailable. Brincidofovir (BCV; previously CMX001) has shown inhibitory activity against diverse viruses, including BKPyV in a primary human renal tubule cell culture model of polyomavirus-associated nephropathy. We investigated the effects of BCV in BKPyV-infected and uninfected primary human urothelial cells (HUCs), the target cells of BKPyV in PyVHC. The BCV concentrations causing 50 and 90% reductions (EC
50
and EC
90
) in the number of intracellular BKPyV genome equivalents per cell (icBKPyV) were 0.27 μM and 0.59 μM, respectively. At 0.63 μM, BCV reduced viral late gene expression by 90% and halted progeny release. Preinfection treatment for only 24 h reduced icBKPyV similarly to treatment from 2 to 72 h postinfection, while combined pre- and postinfection treatment suppressed icBKPyV completely. After investigating BCV's effects on HUC viability, mean selectivity indices at 50 and 90% inhibition (SI
50
and SI
90
) calculated for cellular DNA replication were 2.7 and 2.9, respectively, those for mitochondrial activity were 8.9 and 10.4, those for total ATP were 8.6 and 8.2, and those for membrane integrity were 25.9 and 16.7. The antiviral and cytostatic effects, but less so the cytotoxic effects, were inversely related to cell density. The cytotoxic effects at concentrations of ≥10 μM were rapid and likely related to BCV's lipid moiety. After carefully defining the antiviral, cytostatic, and cytotoxic properties of BCV in HUCs, we conclude that a preemptive or prophylactic approach in PyVHC is likely to give the best results.
Sodium Nitrite Blocks the Activity of Aminoglycosides against Pseudomonas aeruginosa Biofilms
Authors: Zemke Anna C. , Gladwin Mark T. , Bomberger Jennifer M. 
Published: March 2015

ABSTRACT

Sodium nitrite has broad antimicrobial activity at pH 6.5, including the ability to prevent biofilm growth by
Pseudomonas aeruginosa
on the surfaces of airway epithelial cells. Because of its antimicrobial activity, nitrite is being investigated as an inhaled agent for chronic
P. aeruginosa
airway infections in cystic fibrosis patients. However, the interaction between nitrite and commonly used aminoglycosides is unknown. This paper investigates the interaction between nitrite and tobramycin in liquid culture, abiotic biofilms, and a biotic biofilm model simulating the conditions in the cystic fibrosis airway. The addition of nitrite prevented killing by aminoglycosides in liquid culture, with dose dependence between 1.5 and 15 mM. The effect was not blocked by the nitric oxide scavenger CPTIO or dependent on efflux pump activity. Nitrite shifted the biofilm minimal bactericidal concentration (MBC-biofilm) from 256 μg/ml to >1,024 μg/ml in an abiotic biofilm model. In a biotic biofilm model, the addition of 50 mM nitrite decreased the antibiofilm activity of tobramycin by up to 1.2 log. Respiratory chain inhibition recapitulated the inhibition of aminoglycoside activity by nitrite, suggesting a potential mechanism of inhibition of energy-dependent aminoglycoside uptake. In summary, sodium nitrite induces resistance to both gentamicin and tobramycin in
P. aeruginosa
grown in liquid culture, as an abiotic biofilm, or as a biotic biofilm.