bluuebunny/crossref_metadata_2025 huggingface dataset:
HOTAIR but not ANRIL long non‐coding RNA contributes to the pathogenesis of multiple sclerosis
Authors: Pahlevan Kakhki Majid , Nikravesh Abbas , Shirvani Farsani Zeinab , Sahraian Mohammad Ali , Behmanesh Mehrdad
Published: October 2017

Studies have revealed that dysregulation in gene expression is one of the main aspects of multiple sclerosis (MS) pathogenesis. Although the molecular pathways underlying the immunomodulatory role of vitamin D (VD) in MS is not completely elucidated, VD has more recently become a topic of interest in immune regulation and is widely administered to patients with MS as an immunomodulatory supplement. Long non‐coding RNAs (lncRNAs) are known to play important roles in regulation of gene expression via different mechanisms. Given that VD‐related genes are regulated by epigenetic mechanisms, here we aimed to evaluate the role of VD in combination with HOTAIR and ANRIL lncRNAs using in vivo, in vitro and in silico experiments in MS pathogenesis. Our data revealed that HOTAIR but not ANRIL lncRNA is probably involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis through an unclear mechanism and it seems that by affecting the expression, inflammation and VD can influence HOTAIR‐related mechanisms, which require further study.
The competitive nature of signal transducer and activator of transcription complex formation drives phenotype switching of T cells
Authors: Sadreev Ildar I. , Chen Michael Z. Q. , Umezawa Yoshinori , Biktashev Vadim N. , Kemper Claudia , Salakhieva Diana V. , Welsh Gavin I. , Kotov Nikolay V.
Published: October 2017

Signal transducers and activators of transcription (STATs) are key molecular determinants of T‐cell fate and effector function. Several inflammatory diseases are characterized by an altered balance of T‐cell phenotypes and cytokine secretion. STATs, therefore, represent viable therapeutic targets in numerous pathologies. However, the underlying mechanisms by which the same STAT proteins regulate both the development of different T‐cell phenotypes and their plasticity during changes in extracellular conditions remain unclear. In this study, we investigated the STAT‐mediated regulation of T‐cell phenotype formation and plasticity using mathematical modelling and experimental data for intracellular STAT signalling proteins. The close fit of our model predictions to the experimental data allows us to propose a potential mechanism for T‐cell switching. According to this mechanism, T‐cell phenotype switching is the result of the relative redistribution of STAT dimer complexes caused by the extracellular cytokine‐dependent STAT competition effects. The developed model predicts that the balance between the intracellular STAT species defines the amount of the produced cytokines and thereby T‐cell phenotypes. The model predictions are consistent with the experimentally observed interferon‐γ to interleukin‐10 switching that regulates human T helper type 1/type 1 regulatory T‐cell responses. The proposed model is applicable to a number of STAT signalling circuits.
Phylogenetic distribution of a male pheromone that may exploit a nonsexual preference in lampreys
Authors: Buchinger T. J. , Bussy U. , Li K. , Wang H. , Huertas M. , Baker C. F. , Jia L. , Hayes M. C. , Li W. , Johnson N. S.
Published: October 2017

Pheromones are among the most important sexual signals used by organisms throughout the animal kingdom. However, few are identified in vertebrates, leaving the evolutionary mechanisms underlying vertebrate pheromones poorly understood. Pre‐existing biases in receivers' perceptual systems shape visual and auditory signalling systems, but studies on how receiver biases influence the evolution of pheromone communication remain sparse. The lamprey Petromyzon marinus uses a relatively well‐understood suite of pheromones and offers a unique opportunity to study the evolution of vertebrate pheromone communication. Previous studies indicate that male signalling with the mating pheromone 3‐keto petromyzonol sulphate (3kPZS) may exploit a nonsexual attraction to juvenile‐released 3kPZS that guides migration into productive rearing habitat. Here, we infer the distribution of male signalling with 3kPZS using a phylogenetic comparison comprising six of 10 genera and two of three families. Our results indicate that only P. marinus and Ichthyomyzon castaneus release 3kPZS at high rates. Olfactory and behavioural assays with P. marinus, I. castaneus and a subset of three other species that do not use 3kPZS as a sexual signal indicate that male signalling might have driven the evolution of female adaptations to detect 3kPZS with specific olfactory mechanisms and respond to 3kPZS with targeted attraction relevant during mate search. We postulate that 3kPZS communication evolved independently in I. castaneus and P. marinus, but cannot eliminate the alternative that other species lost 3kPZS communication. Regardless, our results represent a rare macroevolutionary investigation of a vertebrate pheromone and provide insight into the evolutionary mechanisms underlying pheromone communication.
Antagonistic pleiotropy can maintain fitness variation in annual plants
Authors: Brown K. E. , Kelly J. K.
Published: October 2017

Antagonistic pleiotropy (AP) is a genetic trade‐off between different fitness components. In annual plants, a trade‐off between days to flower (DTF) and reproductive capacity often determines how many individuals survive to flower in a short growing season, and also influences the seed set of survivors. We develop a model of viability and fecundity selection informed by many experiments on the yellow monkeyflower, Mimulus guttatus, but applicable to many annual species. A viability/fecundity trade‐off maintains stable polymorphism under surprisingly general conditions. We also introduce both spatial heterogeneity and temporal stochasticity in environmental parameters. Neither is necessary for polymorphism, but spatial heterogeneity allows polymorphism while also generating the often observed non‐negative correlations in fitness components.
Adropin preserves the blood‐brain barrier through a Notch1/Hes1 pathway after intracerebral hemorrhage in mice
Authors: Yu Lingyan , Lu Zhengyang , Burchell Sherrefa , Nowrangi Derek , Manaenko Anatol , Li Xue , Xu Yang , Xu Ningbo , Tang Jiping , Dai Haibin , Zhang John H.
Published: October 2017

Adropin is expressed in the CNS and plays a crucial role in the development of stroke. However, little is currently known about the effects of adropin on the blood‐brain barrier (BBB) function after intracerebral hemorrhage (ICH). In this study, the role of adropin in collagenase‐induced ICH was investigated in mice. At 1‐h post‐ICH, mice were administered with recombinant human adropin by intranasal. Brain water +content, BBB permeability, and neurological function were measured at different time intervals. Proteins were quantified using western blot analysis, and the localizations of adropin and Notch1 were visualized via immunofluorescence staining. It is shown that adropin reduced brain water content and improved neurological functions. Adropin preserved the functionality of BBB by increasing N‐cadherin expression and reducing extravasation of albumin. Moreover, in vivo knockdown of Notch1 and Hes1 both abolished the protective effects of adropin. Taken together, our data demonstrate that adropin constitutes a potential treatment value for ICH by preserving BBB and improving functional outcomes through the Notch1 signaling pathway.

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How does dietary particle size affect carnivore gastrointestinal transit: A dog model
Authors: De Cuyper A. , Hesta M. , Tibosch S. , Wanke C. , Clauss M. , Janssens G. P. J.
Published: October 2017

The effect of dietary particle size on gastrointestinal transit in carnivores has not been studied and might offer more insight into their digestive physiology. This study evaluated the effect of two dietary particle sizes (fine = 7.8 mm vs. coarse = 13 mm) of chunked day‐old chicks on transit parameters in dogs. Six beagle dogs were fed both dietary treatments in a crossover design of 7 days with transit testing on the fifth day. Transit parameters were assessed using two markers, that is a wireless motility capsule (IntelliCap®) and titanium oxide (TiO2). Dietary particle size did not affect gastric emptying time (GRT), small bowel transit time (SBTT), colonic transit time (CTT) and total transit time (aTTT) of the capsule (p > .05). There was no effect of dietary particle size on TiO2 mean retention time (MRT) (p > .05). The time of last TiO2 excretion (MaxRT) differed (p = .013) between diets, being later for the coarse diet. Both MRT (R = 0.617, p = .032) and MaxRT (R = 0.814; p = .001) were positively correlated to aTTT. The ratio MRT/aTTT tended towards a difference between diets (p = .059) with the coarse diet exceeding fine diet values. Results show that the difference between capsule measurements and TiO2 is larger for the fine than the coarse diet suggesting that the capsule becomes more accurate when dietary particle size approaches marker size. Dietary particle size might have affected transit parameters but differences are too small to claim major physiological consequences.
Polyunsaturated fatty acids influence inflammatory markers in a cellular model for canine osteoarthritis
Authors: Adler N. , Schoeniger A. , Fuhrmann H.
Published: October 2017

Although it is well recognized that dietary supplementation with fish oil improves clinical symptoms in dogs suffering from osteoarthritis, the molecular basis for the dietary benefit is not yet completely resolved in dogs. This study was designed to further clarify how polyunsaturated fatty acids (PUFA) affect key factors of cartilage degeneration in a canine cell culture system mimicking osteoarthritis. Canine chondrocytes were incubated either without or with 10 μm of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) or 3.6 μm ibuprofen (Ibu) as positive control for 6 days. After the supplementation, cells were stimulated with 10 ng/ml interleukin‐1β (IL‐1β) for another 48 hr to induce osteoarthritic changes, or left unstimulated. We analysed fatty acid uptake via gas–liquid chromatography, nitric oxide (NO) production via Griess assay, prostaglandin E (PGE) production via ELISA and relative gene expression of several cartilage matrix proteinases, inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 via RT‐qPCR. After supplementation, the chondrocytes rapidly incorporated the PUFA into their fatty acid pools. The stimulation with IL‐1β caused a marked increase of most of the inflammatory markers measured. N‐3 PUFA EPA reduced IL‐induced gene expression of iNOS and corresponding production of NO. N‐6 PUFA AA also decreased iNOS and NO, but furthermore lowered gene expression of matrix metalloproteinase‐3. On the other hand, AA upregulated the aggrecanase ADAMTS‐5 and augmented the release of PGE. The effect of n‐3 PUFA DHA turned out to be negligible. Our results reveal molecular mechanisms by which PUFA affect degenerative joint disease in dogs. Of particular importance is that not only EPA but also AA decreased several inflammatory markers in our model. Thus, we conclude that an appropriate balance of both n‐3 and n‐6 fatty acids deserves more attention in dietary interventions.
The impact of direct‐fed microbials and enzymes on the health and performance of dairy cows with emphasis on colostrum quality and serum immunoglobulin concentrations in calves
Authors: Ort S. B. , Aragona K. M. , Chapman C. E. , Shangraw E. , Brito A. F. , Schauff D. J. , Erickson P. S.
Published: October 2017

Thirty‐six cows were blocked by calving date and randomly assigned to one of three treatments. Cows were on treatments 3 weeks prepartum through 8 weeks post‐partum. Treatments were as follows: (i) no direct‐fed microbial (DFM) or cellulase and amylase enzymes (C), (ii) 45.4 g/day of DFM (D) or (iii) 45.4 g/day of DFM and 18.2 g/day of enzyme (DE). Total mixed ration fed and refused were measured daily to determine dry matter intake (DMI). Blood samples were taken three times weekly and analysed for β‐hydroxybutyrate, glucose and non‐esterified fatty acids. Body weight (BW) was measured weekly. Colostrum was weighed and analysed for IgA and IgG concentration. Calves were fed 4 L of colostrum within 2 hr of birth. Calf blood samples were taken at 0 and 24 hr for analysis of IgA and IgG concentrations and apparent efficiency of absorption. Milk yield was measured daily and samples collected weekly. Initial BW was different among treatments with D being lesser than C or DE treatments. Body weight, weight gain, efficiency of gain, DMI and blood parameters were unaffected. Treatment did not affect colostrum yield. Ash percentage of colostrum tended to increase with D and DE, while IgA and total solids yield decreased with D. Colostrum fat yield was decreased in D and DE. Treatments did not impact BW, serum IgA and IgG concentrations or apparent efficiency of absorption of calves. Post‐partum BW, DMI, blood parameters, milk production and composition were unaffected by treatment. However, cows on D gained more BW and tended to have greater efficiency of gain compared to those on DE, but were similar to C. Somatic cell scores were greatest for D. Results indicate that DFM and enzyme supplementation did not improve health and performance of dairy cattle during the pre‐ and post‐partum periods under conditions of this study.
Effect of water restriction on milk yield and quality in Lacaune breed ewes
Authors: Casamassima D. , Palazzo M. , Nardoia M. , D'Alessandro A. G. , Vizzarri F.
Published: October 2017

The effect of water restriction on body weight, body condition score, milk yield, and milk composition and rheological characteristics in intensively reared Lacaune ewes was evaluated. After 7 days of adaptation, the trial lasted 28 days. Thirty lactating ewes (48 ± 5 months of age; mean value ± standard deviation) at the beginning of third lactation month were divided into three groups (n = 10), corresponding to the following water restriction treatment: a group control received no drinking water restriction (W100), and two groups received water to the extent of 80% and 60% of W100 daily consumption (W80 and W60 group respectively). The effects of water restriction were assessed at the beginning of experiment (D0), at D14 and D28. The W60 group resulted in a significant decrease in body weight, body condition score, milk yield and feed consumption of hay due to the experimental treatment; whereas a marked increase in both W60 and W80 groups of milk lactose, urea, sodium, sodium chloride content and titratable acidity was observed. Rheological parameters of milk, rennet coagulation time and curd‐firming time were positively affected by water restriction treatments, with a decrease in both experimental groups of the time required for the formation of a stable and firm curd. Results highlight the importance of water consumption in dairy sheep. The scarce availability of water, significantly affecting ewes milk production, is worthy of particular attention in arid area where water stress‐resistant breeds should be considered. This study underlines that milk yield, being closely linked to the availability of water of the breeding habitat due to its high water content (about 81%), could be reached in area where water is not a limiting factor without reducing the genetic expression of the animals. Less severe water restrictions, such as 20% of daily voluntary water intake, produce no detrimental effect on milk yield.
Effects of dietary Greek oregano (Origanum vulgare ssp. hirtum) supplementation on rumen fermentation, enzyme profile and microbial communities in goats
Authors: Paraskevakis N.
Published: October 2017

This study was conducted to examine in vivo long‐term effects of dietary dried oregano (Origanum vulgare ssp. hirtum) whole plant on rumen fermentation, enzyme profile and microbial communities. For this purpose, eight healthy, adult, non‐lactating Alpine goats were kept in tie stalls equipped for individual feeding and randomly divided into two homogeneous groups: one fed 0.6 kg of a concentrate mixture and 0.6 kg of wheat straw without any supplementation and served as control group (CON) while the other group (OR) fed the same diet of CON but supplemented with 20 g of dried oregano plants (OPs) to provide daily dosage of 1 ml of essential oil (EO) per animal. The experimental period lasted 69 days and individual rumen fluid samples were obtained every 2 weeks at 0 and 4 hr after feeding. The results showed that dietary supplementation with OPs increased the protease activity (p < .001) and ammonia concentration (p < .05) in the rumen. Among the studied microbial populations, Peptostreptococcus anaerobius (p = .028) and Clostridium sticklandii (p < .001) were found to be the most sensitive to oregano at the current dosage. Furthermore, the total methanogen population significantly decreased (p < .05). It is concluded that a long‐term dietary administration of OPs can suppress specific rumen micro‐organisms and modify rumen fermentation favourably at least by means of suppressing methanogens.
Developing Moral Emotion Attributions in Happy Victimizer Task: Role of Victim Information
Authors: Hasegawa Mari
Published: October 2017

Previous happy victimizer (HV) studies have shown that preschool and early elementary school children attribute happy emotions to the violator of moral rules. This study examines the effects of information pertaining to the victim in HV stories on children's emotion attributions. In Study 1, 55 children (aged 5–6 and 7–8 years) participated. Participants heard three types of stories: (a) victim sadness resulting from a character's wrongdoing (normal HV story); (b) victim happiness resulting from a character's wrongdoing (non‐canonical HV story); and (c) victim sadness resulting from an accident (accident story). The children were required to infer the victimizer's feelings and to justify their attributions. Children demonstrated more positive emotion attributions for non‐canonical HV stories than the normal and accident versions. In Study 2, 57 children (aged 5–6 and 7–8 years) judged two types of HV tasks (a story featuring a younger child as victim and a normal HV story). Both groups demonstrated more negative emotion attributions for the young victim stories than the normal HV stories, indicating that children's judgment varied according to contexts and different information in determining emotion attributions.
Measurement Variation and Repeatability of Echocardiographic Variables Used to Estimate Pulmonary Artery Pressure in Dogs
Authors: Abbott J.A. , Gentile‐Solomon J.M.
Published: October 2017

Background

Pulmonary hypertension (PH) is an important clinical entity in dogs. Pulmonary hypertension is generally identified based on echocardiographic findings, but measurement variation of the variables most often used in this context has not been reported.

Objective

To define measurement variation of echocardiographic variables that are used to estimate pulmonary artery pressure.

Animals

Four dogs with subclinical tricuspid valve regurgitation were selected from a hospital population.

Methods

Prospective descriptive study ‐ dogs were subject to repeated echocardiographic examination by 2 operators. Each dog was echocardiographically examined 12 times, once by each operator during mornings and afternoons of 3 nonconsecutive days. Measurement variation was defined by coefficients of variation and by mean square errors (MSE) from ANOVA models. Repeatability coefficients (RC) were calculated from MSE.

Results

Of 50 within‐day, between‐day, and interoperator coefficients of variation (CVs), 37 were less than 10% and 46 were less than 15%. The range of peak velocity of tricuspid valve regurgitation (VTR) VTR was 1.87–3.34 m/s. Analysis of variance revealed a significant effect (P < 0.05) of operator for 7 of 10 measurements. Within‐operator/between‐day/within‐subject and between‐operator/between‐day/within‐subject RCs of VTR were, respectively, 0.3 and 0.6 m/s.

Conclusions and Clinical Importance

With regard to repeatability, VTR is superior to other methods used for echocardiographic estimation of systolic pulmonary artery pressure. When TR is absent, the acceleration time of pulmonary ejection and the acceleration‐to‐ejection time ratio are alternative measures. A change in VTR exceeding 0.3 m/s might be outside the range of expected within‐operator variation.
Glutathione Peroxidase Activity, Plasma Total Antioxidant Capacity, and Urinary F2‐ Isoprostanes as Markers of Oxidative Stress in Anemic Dogs
Authors: Kendall A. , Woolcock A. , Brooks A. , Moore G.E
Published: October 2017

Background

Oxidative stress plays a role in the pathophysiology of several diseases and has been documented as a contributor to disease in both the human and veterinary literature. One at‐risk cell is the erythrocyte, however, the role of oxidative stress in anemia in dogs has not been widely investigated.

Hypothesis/Objective

Anemic dogs will have an alteration in the activity of glutathione peroxidase (GPx), a decrease in of total antioxidant capacity (TAC), and an increased concentration of urinary 15‐F2‐isoprostanes (F2‐IsoP) when compared to healthy dogs.

Animals

40 client‐owned dogs with anemia (PCV <30%) age‐matched to 40 client‐owned healthy control dogs.

Methods

Prospective, cross‐sectional study. Whole blood GPx activity, plasma TAC, and urinary F2‐isoprostane concentrations were evaluated in each dog and compared between groups.

Results

Anemic dogs had significantly lower GPx activity (43.1 × 103 +/‐ 1.6 × 103 U/L) than did dogs in the control group (75.8 × 103 +/‐ 2.0 × 103 U/L; P < 0.0001). The GPx activity in dogs with hemolysis (103 +/‐ 0.8 × 103 U/L) was not significantly different (P = 0.57) than in dogs with nonhemolytic anemia (43.5 × 103 +/‐ 1.1 × 103 U/L). The TAC concentrations (P = 0.15) and urinary F2‐isoprostanes (P = 0.73) did not significantly differ between groups.

Conclusions and Clinical Importance

Glutathione peroxidase activity was significantly decreased in anemic dogs indicating oxidative stress. Additional studies are warranted to determine if antioxidant supplementation would improve survival and overall outcome as part of a therapeutic regimen for anemic dogs.
Evaluation of Renal Perfusion in Hyperthyroid Cats before and after Radioiodine Treatment
Authors: Stock E. , Daminet S. , Paepe D. , Buresova E. , Vandermeulen E. , Smets P. , Duchateau L. , Saunders J.H. , Vanderperren K.
Published: October 2017

Background

Hyperthyroidism and chronic kidney disease (CKD) are common in elderly cats. Consequently, both diseases often occur concurrently. Furthermore, renal function is affected by thyroid status. Because changes in renal perfusion play an important role in functional renal changes in hyperthyroid cats, investigation of renal perfusion may provide novel insights.

Objectives

To evaluate renal perfusion in hyperthyroid cats with contrast‐enhanced ultrasound (CEUS).

Animals

A total of 42 hyperthyroid cats was included and evaluated before and 1 month after radioiodine treatment.

Methods

Prospective intrasubject clinical trial of contrast‐enhanced ultrasound using a commercial contrast agent (SonoVue) to evaluate renal perfusion. Time‐intensity curves were created, and perfusion parameters were calculated by off‐line software. A linear mixed model was used to examine differences between pre‐ and post‐treatment perfusion parameters.

Results

An increase in several time‐related perfusion parameters was observed after radioiodine treatment, indicating a decreased blood velocity upon resolution of the hyperthyroid state. Furthermore, a small post‐treatment decrease in peak enhancement was present in the renal medulla, suggesting a lower medullary blood volume.

Conclusions and Clinical Importance

Contrast‐enhanced ultrasound indicated a higher cortical and medullary blood velocity and higher medullary blood volume in hyperthyroid cats before radioactive treatment in comparison with 1‐month post‐treatment control.
Ectopic Bone as a Nidus for Calcium Oxalate Urocystolithiasis in a Cat
Authors: Lulich J.P. , Prasad H.S. , Manno M. , Bagley B.
Published: October 2017

A 7‐year‐old female spayed domestic shorthair cat was referred to the urology service for nonsurgical urocystolith removal. A urolith was attached to the urothelium by ectopic bone. Interventional removal without surgery was successful. Follow‐up evaluation 3 years after urolith removal revealed recurrent uroliths, bladder wall mineralization, and marked renal mineralization. This case illustrates the metaplastic potential of the urothelium and that ectopic bone should be included among the pathological factors that promote lithogenesis.
Spatial transcriptomes within the Pseudomonas aeruginosa biofilm architecture
Authors: Heacock‐Kang Yun , Sun Zhenxin , Zarzycki‐Siek Jan , McMillan Ian A. , Norris Michael H. , Bluhm Andrew P. , Cabanas Darlene , Fogen Dawson , Vo Hung , Donachie Stuart P. , Borlee Bradley R. , Sibley Christopher D. , Lewenza Shawn , Schurr Michael J. , Schweizer Herbert P. , Hoang Tung T.
Published: October 2017

Bacterial cooperative associations and dynamics in biofilm microenvironments are of special interest in recent years. Knowledge of localized gene‐expression and corresponding bacterial behaviors within the biofilm architecture at a global scale has been limited, due to a lack of robust technology to study limited number of cells in stratified layers of biofilms. With our recent pioneering developments in single bacterial cell transcriptomic analysis technology, we generated herein an unprecedented spatial transcriptome map of the mature in vitro Pseudomonas aeruginosa biofilm model, revealing contemporaneous yet altered bacterial behaviors at different layers within the biofilm architecture (i.e., surface, middle and interior of the biofilm). Many genes encoding unknown functions were highly expressed at the biofilm‐solid interphase, exposing a critical gap in the knowledge of their activities that may be unique to this interior niche. Several genes of unknown functions are critical for biofilm formation. The in vivo importance of these unknown proteins was validated in invertebrate (fruit fly) and vertebrate (mouse) models. We envisage the future value of this report to the community, in aiding the further pathophysiological understanding of P. aeruginosa biofilms. Our approach will open doors to the study of bacterial functional genomics of different species in numerous settings.
Adenine‐induced chronic kidney disease in rats
Authors: Diwan Vishal , Brown Lindsay , Gobe Glenda C
Published: October 2017

Summary at a Glance

This invited review article describes the adenine model of chronic kidney disease in rodents and compares its features with other rodent models of kidney disease.
Opioid use disorder and misuse: A review of the epidemiology and medical implications for pediatric anesthesiologists
Authors: Knipper Emily , Banta‐Green Caleb J. , Jimenez Nathalia
Published: October 2017

This educational review presents an overview of opioid use disorder, misuse and overdose among adolescents, and the clinical implications for anesthesiologists. It provides definitions, discusses the epidemiology worldwide, (focusing on North America), and emphasizes the clinical implications of patients with chronic opioid exposure, including perioperative pain management, as well as opioid overdose and prolonged use of opioids after acute exposure. In the USA, opioid use disorder and negative outcomes related to opioids rose dramatically from 1999‐2010; concomitantly heroin use and fatal overdoses have increased as heroin use is associated with the disordered use of licit opioids. Among adolescents and young adults, opioid use disorder is significant, with continued increases in disordered use specifically among young adults. Acute opioid intoxication may have multiple medical implications in addition to respiratory depression, and children are susceptible to acute intoxication via accidental ingestion of prescription opioids. Novel opioid formulations, such as acetyl fentanyl, with unpredictable pharmacology may also be present in acute intoxication. Chronically, opioid use presents challenges for safe and adequate pain management, in the presence of opioid‐induced hyperalgesia and differential tolerance as well as mental health issues including depression and anxiety. Predictors of prolonged opioid use in adolescents and adults after surgery is an area of ongoing research. Young patients encountered by pediatric anesthesiologists may be involved in diversion and disordered use of opioids. Increased awareness among anesthesiologists is important, as perioperative discussions often provide an opportunity to detect at risk patients.
Changes in blood volume indicators and dynamic indicators measured with transpulmonary ultrasound velocity during blood depletion and repletion in a neonatal swine model
Authors: Martin‐Flores Manuel , Cisternas Alvaro F. , Gleed Robin D.
Published: October 2017

Background

Dynamic indicators such as pulse pressure and stroke volume variations can be measured to track changes in preload during hemorrhage, and evaluate fluid therapy. However, these dynamic indicators require mechanical ventilation, and might be affected by cardiac dysrhythmias and changes in vascular tone. Blood volume indicators may offer alternatives for assessing changes in volume status.

Aims

The aims of this study were to measure changes in blood volume indicators and dynamic indicators during removal of blood in two stages and subsequent blood replacement in anesthetized, mechanically ventilated, neonatal pigs.

Methods

In eight anesthetized, mechanically ventilated piglets (5‐6 weeks old), cardiac index, stroke volume index, total end‐diastolic volume, central blood volume, active circulating volume, pulse pressure variation, and stroke volume variation were measured during blood removal in two stages (15 mL kg−1 each stage) and blood replacement (30 mL kg−1). Values after each intervention were measured for each parameter.

Results

All indicators differed from baseline after removal of 15 mL kg−1 of blood, except for stroke volume variation. Differences between both stages of hemorrhage were only observed for indexed stroke volume, total end‐diastolic volume, central blood volume, and pulse pressure variation.

Conclusion

Total end‐diastolic volume and central blood volume changed during blood depletion and repletion, and differed between stages of hemorrhage. These indicators might be useful for assessing volume status instead of, or in addition to cardiac index and dynamic indicators.
Rapid Response Team activation for pediatric patients on the acute pain service
Authors: Teets Maxwell , Tumin Dmitry , Walia Hina , Stevens Jenna , Wrona Sharon , Martin David , Bhalla Tarun , Tobias Joseph D.
Published: October 2017

Introduction

Untreated pain or overly aggressive pain management may lead to adverse physiologic consequences and activation of the hospital's Rapid Response Team. This study is a quality improvement initiative that attempts to identify patient demographics and patterns associated with Rapid Response Team consultations for patients on the acute pain service.

Methods

A retrospective review of all patients on the acute pain service from February 2011 until June 2015 was cross‐referenced with inpatients requiring consultation from the Rapid Response Team. Two independent practitioners reviewed electronic medical records to determine which events were likely associated with pain management interventions.

Results

Over a 4‐year period, 4872 patients were admitted to the acute pain service of whom 135 unique patients required Rapid Response Team consults. There were 159 unique Rapid Response Team activations among 6538 unique acute pain service consults. A subset of 27 pain management‐related Rapid Response Team consultations was identified. The largest percentage of patients on the acute pain service were adolescents aged 12‐17 (36%). Compared to this age group, the odds of Rapid Response Team activation were higher among infants <1 year old (odds ratio = 2.85; 95% confidence interval: 1.59, 5.10; P < .001) and adults over 18 years (odds ratio = 1.68; 95% confidence interval: 1.01, 2.80; P = .046).

Discussion

Identifying demographics and etiologies of acute pain service patients requiring Rapid Response Team consultations may help to identify patients at risk for clinical decompensation.
Pharmacokinetics of S‐ketamine during prolonged sedation at the pediatric intensive care unit
Authors: Flint Robert B. , Brouwer Carole N. M. , Kränzlin Anne S. C. , Lie‐A‐Huen Loraine , Bos Albert P. , Mathôt Ron A. A.
Published: October 2017

Background

S‐ketamine is the S(+)‐enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S‐ketamine is observed during long‐term sedation.

Aims

The aim of this study was to evaluate the pharmacokinetic variability of S‐ketamine in children aged 0‐18 years during long‐term sedation. Twenty‐five children (median age: 0.42 years, range: 0.02‐12.5) received continuous intravenous administrations of 0.3‐3.6 mg/kg/h S‐ketamine for sedation during mechanical ventilation. Infusion rates were adjusted to the desired level of sedation and analgesia based on the COMFORT‐B score and Visual Analog Scale. Blood samples were drawn once daily at random time‐points, and at 1 and 4 hours after discontinuation of S‐ketamine infusion. Time profiles of plasma concentrations of S‐ketamine and active metabolite S‐norketamine were analyzed using nonlinear mixed‐effects modeling software. Clearance and volume of distribution were allometrically scaled using the ¾ power model.

Results

A total of 86 blood samples were collected. A 2‐compartment and 1‐compartment model adequately described the PK of S‐ketamine and S‐norketamine, respectively. The typical parameter estimates for clearance and central and peripheral volumes of distribution were: CLS‐KETAMINE=112 L/h/70 kg, V1S‐KETAMINE=7.7 L/70 kg, V2S‐KETAMINE=545L/70 kg, QS‐kETAMINE=196 L/h/70 kg, and CLS‐NORKETAMINE=53 L/h/70 kg. Interpatient variability of CLS‐KETAMINE and CLS‐NORKETAMINE was considerable with values of 40% and 104%, respectively, leading to marked variability in steady‐state plasma concentrations.

Conclusion

Substantial interpatient variability in pharmacokinetics in children complicates the development of adequate dosage regimen for continuous sedation.
Infection prevention in pediatric anesthesia practice
Authors: Martin Lizabeth D. , Kallile Michael , Kanmanthreddy Siri , Zerr Danielle M.
Published: October 2017

Healthcare‐associated infections are an important source of morbidity and mortality in pediatric patients. Anesthesiologists have a unique role in infection prevention. Hand hygiene and anesthesia workspace decontamination decrease infection rates in surgical patients. Standard protocols exist for insertion and handling of central lines, arterial lines, and regional procedures, which should be strictly adhered to in order to prevent infectious complications. Temperature control and timely administration of antibiotics contribute to the prevention of surgical site infections. Education, culture shift, staff engagement, and effective change management are necessary for successful implementation of infection prevention strategies.
Sternal malformations and anesthetic management
Authors: Nichols John H. , Nasr Viviane G.
Published: October 2017

Shamberger and Welch classify sternal malformations into four types: thoracic ectopia cordis, cervical ectopia cordis, thoraco‐abdominal ectopia cordis, and cleft sternum. Cleft sternum is the most common subset, with a reported incidence of 1 in 50,000 to 100,000 live births, representing 0.15% of all anterior chest wall malformations. Acostello et al further classify cleft sternum into complete or partial (superior, medium, inferior) with a simple superior partial cleft sternum being by far the most common with an orthotopic heart, intact pericardium, and normal skin coverage. Associated anomalies with superior partial cleft sternum are rare, but can include cervicofacial hemangiomas, midline raphe from the tip of the cleft to the umbilicus, and PHACES (posterior fossa malformations, facial hemangiomas, arterial anomalies with coarctation of aorta, cardiac defects, eye abnormalities, sternal cleft, and supraumbilical raphe) syndrome. The more rare inferior partial clefts are associated with thoraco‐abdominal ectopia cordis as part of the Pentalogy of Cantrell (omphalocele, anterior diaphragmatic hernia, sternal cleft, ectopia cordis, ventricular septal defect/left ventricular diverticulum). This review summarizes the current knowledge of all four types of sternal malformations, and provides guidance for optimal anesthetic and perioperative care of these children.
A prospective audit of pain profiles following general and urological surgery in children
Authors: Wilson Caroline A. , Sommerfield David , Drake‐Brockman Thomas F. E. , Lagrange Claudia , Ramgolam Anoop , von Ungern‐Sternberg Britta S.
Published: October 2017

Background

Postoperative pain is frequently undertreated in children both in hospital and at home following discharge. Pain has both short‐ and long‐term consequences for children, their families, and the healthcare system. A greater understanding of procedure‐specific postoperative pain trajectories is required to improve pain management.

Aim

To determine the duration and severity of acute postoperative pain experienced by children undergoing 8 different general and urological procedures (primary outcomes). Behavioral disturbance rates, nausea and vomiting scores, and parental satisfaction were also examined during the follow‐up period (secondary outcomes).

Method

Families of children (0‐18 years) undergoing common general and urological procedures were invited to enroll in the study. Children's pain scores, measured using a parental proxy 0‐10 numerical rating scale, were collected by telephone interview until pain was resolved. Analgesia prescribed and given, behavioral disturbance, nausea and vomiting scores, the method of medication education communication, and parental satisfaction were also measured.

Results

Of 360 patients recruited, 326 complete datasets were available. Patients underwent laparoscopic appendicectomy (57), open appendicectomy (19), circumcision (50), cystoscopy (52), hypospadias repair (22), inguinal hernia repair (51), orchidopexy (51), or umbilical hernia repair (24). Postoperative pain peaked on the day of or the day after surgery in all groups, and decreased over time. Pain lasted a median duration of 5 postoperative days following open appendicectomy, and 0‐2 postoperative days for other procedures. Behavioral disturbance rates closely followed pain scores. Analgesia administration at home varied widely between and within groups.

Conclusion

Pain management was inadequate in most of the groups studied, particularly after appendicectomy or umbilical hernia repair, with most children experiencing at least moderate pain on the day of and day after surgery. There was a need for a standardized management, with increased dual analgesia prescribing, to ensure that children receive adequate postoperative analgesia in hospital and at home.
Description of four new HLA alleles in the Finnish population: A*03:283N, A*68:167, C*03:327, C*03:361
Authors: Polvi A. , Peräsaari J. , Linjama T. , Saarinen T. , Koskela S. , Voorter C. E. M. , Jaatinen T.
Published: October 2017

New HLA alleles found in the Finnish population: A*03:283N, A*68:167, C*03:327 and C*03:361.
Identification of the novel HLA‐B*57:91 allele, by next‐generation sequencing in a Spanish individual
Authors: Enrich E. , Campos E. , Caro‐Oleas J. L. , Herrero‐Mata M. J. , Rudilla F.
Published: October 2017

HLA‐B*57:91 differs from HLA‐B*57:01:01 by a single nucleotide substitution resulting in an amino acid change.
Seasonal below‐ground metabolism in switchgrass
Authors: Palmer Nathan A. , Saathoff Aaron J. , Scully Erin D. , Tobias Christian M. , Twigg Paul , Madhavan Soundararajan , Schmer Marty , Cahoon Rebecca , Sattler Scott E. , Edmé Serge J. , Mitchell Robert B. , Sarath Gautam
Published: October 2017

Switchgrass (Panicum virgatum), a perennial, polyploid, C4 warm‐season grass is among the foremost herbaceous species being advanced as a source of biomass for biofuel end uses. At the end of every growing season, the aerial tissues senesce, and the below‐ground rhizomes become dormant. Future growth is dependent on the successful over‐wintering of the rhizomes. Although the importance of rhizome health to overall year‐upon‐year plant productivity has been long recognized, there is limited information on seasonal changes occurring during dormancy at both the transcriptome and metabolite levels. Here, global changes in transcriptomes and metabolites were investigated over two growing seasons in rhizomes harvested from field‐grown plants. The objectives were: (a) synthesize information on cellular processes that lead to dormancy; and (b) provide models that could account for major metabolic pathways present in dormant switchgrass rhizomes. Overall, metabolism during dormancy appeared to involve discrete but interrelated events. One was a response to abscisic acid that resulted in dehydration, increases in osmolytes and upregulation of autophagic processes, likely through the target of rapamycin complex and sucrose non‐fermentative‐related kinase‐based signaling cascades. Another was a recalibration of energy transduction through apparent reductions in mitochondrial oxidative phosphorylation, increases in substrate level generation of ATP and reducing equivalents, and recycling of N and possibly CO2 through refixation. Lastly, transcript abundances indicated that cold‐related signaling was also occurring. Altogether, these data provide a detailed overview of rhizome metabolism, especially during dormancy, which can be exploited in the future to improve winter survival in switchgrass.
RiceAntherNet: a gene co‐expression network for identifying anther and pollen development genes
Authors: Lin Hong , Yu Jing , Pearce Simon P. , Zhang Dabing , Wilson Zoe A.
Published: October 2017

In plants, normal anther and pollen development involves many important biological events and complex molecular regulatory coordination. Understanding gene regulatory relationships during male reproductive development is essential for fundamental biology and crop breeding. In this work, we developed a rice gene co‐expression network for anther development (RiceAntherNet) that allows prediction of gene regulatory relationships during pollen development. RiceAntherNet was generated from 57 rice anther tissue microarrays across all developmental stages. The microarray datasets from nine rice male sterile mutants, including msp1‐4, ostdl1a, gamyb‐2, tip2, udt1‐1, tdr, eat1‐1, ptc1 and mads3‐4, were used to explore and test the network. Among the changed genes, three clades showing differential expression patterns were constructed to identify genes associated with pollen formation. Many of these have known roles in pollen development, for example, seven genes in Clade 1 (OsABCG15, OsLAP5, OsLAP6, DPW, CYP703A3, OsNP1 and OsCP1) are involved in rice pollen wall formation. Furthermore, Clade 1 contained 12 genes whose predicted orthologs in Arabidopsis have been reported as key during pollen development and may play similar roles in rice. Genes in Clade 2 are expressed earlier than Clade 1 (anther stages 2–9), while genes in Clade 3 are expressed later (stages 10–12). RiceAntherNet serves as a valuable tool for identifying novel genes during plant anther and pollen development. A website is provided (https://www.cpib.ac.uk/anther/riceindex.html) to present the expression profiles for gene characterization. This will assist in determining the key relationships between genes, thus enabling characterization of critical genes associated with anther and pollen regulatory networks.
An international investigation into AB plasma administration in hospitals: how many AB plasma units were infused? The HABSWIN study
Authors: Zeller Michelle P. , Barty Rebecca , Dunbar Nancy M. , Elahie Allahna , Flanagan Peter , Garritsen Henk , Kutner José Mauro , Pagano Monica B. , Pogłód Ryszard , Rogers Thomas S. , Staves Julie , van Wordragen‐Vlaswinkel Maria , Zwaginga Jaap Jan , Murphy Michael F. , Heddle Nancy M. , Yazer Mark H. ,   on behalf of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Published: October 2017

BACKGROUND

Typical practice is to transfuse group‐specific plasma units; however, there are situations where group AB plasma (universal donor) is issued to group A, B, or O recipients. If demand for group AB plasma exceeds collections, there is potential for shortage. This project explored the patterns of group AB plasma utilization at hospitals around the world.

STUDY DESIGN AND METHODS

The study had two phases: a survey that inquired about hospital group AB plasma inventory, policies, and transfusion practices and a retrospective review of 2014 calendar year data where participants submitted information on plasma disposition including ABO group of unit and recipient, transfusion location, and select indications. Recruitment occurred through snowball sampling. Descriptive analyses were performed.

RESULTS

Survey data were received from 25 centers across 10 countries; of those, 15 participants contributed to the data collection component. These 15 centers transfused a total of 43,369 AB plasma units during the study period. Only 1496 of 5541 (27%) group AB plasma units were transfused to group AB recipients. Transfusion policies, practices, and patterns were variable across sites.

CONCLUSION

Group AB plasma units are frequently transfused to non‐AB recipients. Whether transfusing 73% of group AB plasma units to non‐AB recipients is the ideal inventory management strategy remains to be determined.
Funding blood safety in the 21st century
Authors: Ifland Luke , Bloch Evan M. , Pitman John P.
Published: October 2017

BACKGROUND

Since 2000, there has been an historic increase in international development assistance, including blood safety projects. The result has been increased blood donations and infectious disease screening in many beneficiary countries. A comprehensive examination of international development assistance for blood safety has yet to be completed.

STUDY DESIGN AND METHODS

This report examines publicly available information, including donor agency websites and databases and data from the 2008 and 2012 World Health Organization Global Database on Blood Safety.

RESULTS

Between 2000 and 2015, from $602.4 million to $2.1 billion in international development assistance was allocated to blood safety programs worldwide, mostly as part of the global response to the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic. The US President's Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis, and Malaria were responsible for the majority of blood safety funding, which peaked in 2010 and declined through 2015.

CONCLUSION

Between 2000 and 2015, countries with high burdens of human immunodeficiency virus/acquired immunodeficiency syndrome received funding and technical assistance to improve national laboratories, increase blood component production, and strengthen clinical practice. Global trends in international development assistance at large, including aid for blood safety, suggest that funding will not rebound.
Three-dimensional supercritical resolved light-induced magnetic holography
Authors: Hao Chenglong , Nie Zhongquan , Ye Huapeng , Li Hao , Luo Yang , Feng Rui , Yu Xia , Wen Feng , Zhang Ying , Yu Changyuan , Teng Jinghua , Luk’yanchuk Boris , Qiu Cheng-Wei
Published: October 2017

3D supercritical resolved light-induced magnetic holography makes possible 1872 Tbit/in
3
ultrahigh-density data recording.