bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional repressor DREAM regulates trigeminal noxious perception
Authors: Benedet Tomaso , Gonzalez Paz , Oliveros Juan C. , Dopazo Jose M. , Ghimire Kedar , Palczewska Malgorzata , Mellstrom Britt , Naranjo Jose R. 
Published: February 2016

AbstractExpression of the downstream regulatory element antagonist modulator (DREAM) protein in dorsal root ganglia and spinal cord is related to endogenous control mechanisms of acute and chronic pain. In primary sensory trigeminal neurons, high levels of endogenous DREAM protein are preferentially localized in the nucleus, suggesting a major transcriptional role. Here, we show that transgenic mice expressing a dominant active mutant of DREAM in trigeminal neurons show increased responses following orofacial sensory stimulation, which correlates with a decreased expression of prodynorphin and brain‐derived neurotrophic factor in trigeminal ganglia. Genome‐wide analysis of trigeminal neurons in daDREAM transgenic mice identified cathepsin L and the monoglyceride lipase as two new DREAM transcriptional targets related to pain. Our results suggest a role for DREAM in the regulation of trigeminal nociception.This article is part of the special article series “Pain”.
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Retromer and Rab2‐dependent trafficking mediate PS1 degradation by proteasomes in endocytic disturbance
Authors: Ueda Naoya , Tomita Taisuke , Yanagisawa Katsuhiko , Kimura Nobuyuki 
Published: February 2016

AbstractAccumulating evidence suggests that endocytic pathway deficits are involved in Alzheimer's disease pathogenesis. Several reports show that endocytic disturbance affects β‐amyloid peptide (Aβ) cleavage from β‐amyloid precursor protein (APP). Presenilin‐1 (PS1) is the catalytic core of the γ‐secretase complex required for Aβ generation. Previously, we showed that aging induces endocytic disturbance, resulting in the accumulation of Aβ and APP in enlarged endosomes. It remains unclear, however, whether PS1 localization and function are affected with endocytic disturbance. Here, we report that in endocytic disturbance, PS1 is transported from endosomes to ER/Golgi compartments via retromer trafficking, and that PS1 interacts with vacuolar protein sorting‐associated protein 35 both in vitro and in vivo. Moreover, PS1 is degraded by proteasomes via a Rab2‐dependent trafficking pathway, only during endocytic disturbance. These findings suggest that PS1 levels and localization in endosomes are regulated by retromer trafficking and ER‐associated degradation system, even if endocytic disturbance significantly induces the endosomal accumulation of APP and β‐site APP‐cleaving enzyme 1. Results of this study also suggest that retromer deficiency can affect PS1 localization in endosomes, where Aβ cleavage mainly occurs, possibly leading to enhanced Aβ pathology.
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We proposed the following mechanism for intracellular transport of presenilin‐1 (PS1). When endosome/lysosome trafficking is disturbed, PS1 is transported from endosome to endoplasmic reticulum (ER)/Golgi compartments via retromer and Rab2‐mediated trafficking, and then degraded by endoplasmic reticulum‐associated degradation (ERAD). Perturbations in this trafficking can cause abnormal endosomal accumulation of PS1, and then may lead to exacerbated Aβ pathology.Cover Image for this issue: doi: 10.1111/jnc.13318.
CONSUMER‐DIRECTED HEALTH PLANS: A REVIEWOF THE EVIDENCE
Authors: Bundorf M. Kate 
Published: February 2016

AbstractThe number of people enrolled in consumer‐directed health plans (CDHPs) has increased dramatically over the last decade. We review the empirical literature on the effects of CDHPs, which is based on the experience of these plans in the employer‐sponsored market. Studies indicate that CDHPs reduce health care spending by approximately 5–15 percent relative to similar plans with lower deductibles and without spending accounts. Spending reductions are concentrated among healthier enrollees and are driven by reductions in the use of outpatient services and pharmaceuticals. There is little evidence on whether they reduce the use of low‐value services.
Diagnostic Value of Right Pulmonary Artery Distensibility Index in Dogs with Pulmonary Hypertension: Comparison with Doppler Echocardiographic Estimates of Pulmonary Arterial Pressure
Authors: Visser L.C. , Im M.K. , Johnson L.R. , Stern J.A. 
Published: February 2016

BackgroundNoninvasive diagnosis of pulmonary hypertension (PH) primarily relies upon Doppler echocardiography of tricuspid regurgitation (TR). However, TR might be absent or difficult to measure.Hypothesis/ObjectivesTo determine the diagnostic value of right pulmonary artery distensibility (RPAD) index for prediction of Doppler‐derived estimates of pulmonary artery (PA) pressure compared to other indices of PH in dogs.AnimalsSixty‐nine client‐owned dogs with TR.MethodsProspective observational study. Dogs were allocated to groups according to TR pressure gradient (TRPG): TRPG <36 mmHg (control, n = 22), TRPG 36–50 (n = 16), TRPG 50–75 (n = 14) and TRPG >75 mmHg (n = 17). Right pulmonary artery distensibility index, acceleration time to peak PA flow (AT), AT: ejection time of PA flow (AT:ET) and main PA size: aorta size (MPA:Ao) were calculated in each dog.ResultsRight pulmonary artery distensibility index demonstrated the strongest correlation (r = −0.90; P < .0001) to TRPG followed by MPA:Ao (r = 0.78; P < .0001), AT (r = −0.69; P < .0001) and AT:ET (r = −0.68; P < .0001). RPAD index possessed the most accurate cutoff (<29.5%; Sensitivity [Sn] 0.84, Specificity [Sp] 0.95) to predict TRPG >50 mmHg compared to AT (<53.9 ms; Sn 0.74, Sp 0.87), AT:ET (<0.30; Sn 0.61, Sp 0.97) and MPA:Ao (>1.04; Sn 0.94, Sp 0.74). All intra‐ and interobserver measurement variabilities exhibited coefficients of variation ≤13%.Conclusions and Clinical ImportanceRight pulmonary artery distensibility index is an accurate predictor of TRPG and should be particularly useful if TR is absent or difficult to measure.
Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs
Authors: KuKanich B. 
Published: February 2016

The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combination administered orally to six healthy greyhounds. Antinociception was assessed using an electronic von Frey (vF) device as a mechanical/pressure model. Acetaminophen was administered at a dose of 600 mg (14.4–23.1 mg/kg) and codeine phosphate at 90 mg (2.1–3.3 mg/kg) equivalent to 67.5 mg codeine base (1.6–2.5 mg/kg). The geometric mean maximum plasma concentrations of acetaminophen, codeine, and codeine‐6‐glucuronide were 7.95 μg/mL, 11.0 ng/mL, and 3819 ng/mL, respectively. Morphine concentrations were <1 ng/mL. The terminal half‐lives of acetaminophen, codeine, and codeine‐6‐glucuronide were 0.94, 1.71, and 3.12 h. There were no significant changes in vF thresholds, except at 12 h which decreased on average by 17% compared to baseline. The decrease in vF thresholds at 12 h could be due to aversion, hyperalgesia, or random variability. The lack of antinociception in this study could be due to a true lack of antinociception, lack of model sensitivity, or specificity. Further studies using different models (including clinical trials), different dog breeds, multiple dose regimens, and a range of dosages are needed prior to recommended use or concluding lack of efficacy for oral acetaminophen/codeine in dogs.
Correlations and zoning patterns of phosphorus and chromium in olivine from H chondrites and the LL chondrite Semarkona
Authors: McCanta M. C. , Beckett J. R. , Stolper E. M. 
Published: February 2016

AbstractPhosphorus zoning is observed in olivines in high‐FeO (type IIA) chondrules in H chondrites over the entire range of petrologic grades: H3.1–H6. Features in P concentrations such as oscillatory and sector zoning, and high P cores are present in olivines that are otherwise unzoned in the divalent cations. Aluminum concentrations are low and not significantly associated with P zoning in chondrule olivines. In highly unequilibrated H chondrites, phosphorus zoning is generally positively correlated with Cr. Atomic Cr:P in olivine is roughly 1:1 (3:1 for one zone in one olivine in RC 075), consistent with Cr3+ charge‐balancing P5+ substituting for Si4+. Normal igneous zonation involving the dominant chrome species Cr2+ was observed only in the LL3.0 chondrite Semarkona. In more equilibrated chondrites (H3.5–H3.8), Cr spatially correlated with P is occasionally observed but it is diffuse relative to the P zones. In H4–H6 chondrites, P‐correlated Cr is absent. One signature of higher metamorphic grades (≥H3.8) is the presence of near matrix olivines that are devoid of P oscillatory zoning. The restriction to relatively high metamorphic grade and to grains near the chondrule–matrix interface suggests that this is a response to metasomatic processes. We also observed P‐enriched halos near the chondrule–matrix interface in H3.3–H3.8 chondrites, likely reflecting the loss of P and Ca from mesostasis and precipitation of Ca phosphate near the chondrule surface. These halos are absent in equilibrated chondrites due to coarsening of the phosphate and in unequilibrated chondrites due to low degrees of metasomatism. Olivines in type IA chondrules show none of the P‐zoning ubiquitous in type IIA chondrules or terrestrial igneous olivines, likely reflecting sequestration of P in reduced form within metallic alloys and sulfides during melting of type IA chondrules.
Mind, Brain, and Education: A Transdisciplinary Field
Authors: Knox Rockey 
Published: February 2016

ABSTRACTThe emerging field of mind, brain, and education (MBE) is grappling with core issues associated with its identity, scope, and method. This article examines some of the most pressing issues that structure the development of MBE as a transdisciplinary effort. Rather than representing the ongoing debates in MBE as superficial squabbles to eventually be “overcome,” this article argues that the politics of MBE language, discourse, and validity suggest profound epistemological differences that transcend a traditional interdisciplinary approach. Instead, MBE would benefit from a transdisciplinary approach that contextually accords equal and differential weight to a range of knowledge inputs from education studies, neuroscience, and other academic and practitioner spheres beneath the broad umbrella of MBE. Specifically, this article suggests that some of the key tasks for those involved in MBE studies require a transdisciplinary approach to knowledge translation and knowledge development.
“I was so worried about every drop of milk” – feeding problems at home are a significant concern for parents after major heart surgery in infancy
Authors: Tregay Jenifer , Brown Katherine , Crowe Sonya , Bull Catherine , Knowles Rachel , Wray Jo 
Published: February 2016

AbstractIncreasing numbers of operations in small infants with complex congenital heart disease are being carried out in the UK year on year, with more surviving the initial operation. However, even after successful surgery some of these infants remain fragile when they are discharged home. The aim of the study was to elicit parents' experiences of caring for a child with complex needs after major congenital heart surgery. We conducted a qualitative study involving semi‐structured interviews with parents of 20 children (aged <1–5 months at hospital discharge), who had undergone open heart surgery and subsequently died or been readmitted unexpectedly to intensive care following their initial discharge home. Feeding difficulties following discharge from the specialist surgical centre emerged as one of the most significant parental concerns spontaneously raised in interviews. For some parents the impact of feeding difficulties overshadowed any other cardiac concerns. Key themes centred around feeding management (particularly the practical challenges of feeding their baby), the emotional impact of feeding for parents and the support parents received or needed after discharge with respect to feeding. Caring for a child with congenital heart disease following surgery is demanding, with feeding difficulties being one of the most significant parent stressors. Local health professionals can be a good source of support for parents provided that they are well informed about the needs of a cardiac baby and have realistic expectations of weight gain. Specialist surgical centres should consider addressing issues of parental stress around feeding and weight gain prior to hospital discharge. © 2016 Blackwell Publishing Ltd
‘We disputed every word’: how Kyrgyzstan's moderates tame ethnic nationalism
Authors: Marat Erica 
Published: February 2016

AbstractIn post‐violence Kyrgyzstan, a small group of civic‐minded nationalists are fighting to tame extremist voices by formulating their own reconciliation policies. These moderates have adopted several strategies, including persuasion and bargaining with nationalistic elites. This process is not without its limitations. Important issues, such as forging a civic identity for the majority ethnic group, remain unaddressed. Still, moderates' policy achievements and concrete actions are likely to continue to undercut nationalist rhetoric. The case of Kyrgyzstan offers one possible alternative to the Soviet paradigm of framing nationhood alongside citizenship.
An autopsy case of invasive sino‐orbital aspergillosis presenting the “tram‐track” sign and “donut configuration” in the orbital magnetic resonance imaging
Authors: Morimoto Nobutoshi , Morimoto Mizuki , Takahashi Yoshiaki , Kageyama Yasuhiko , Nakamura Satoko , Ando Midori , Mano Shohei , Mizobuchi Koichi , Abe Koji 
Published: February 2016

AbstractAn 84‐year‐old man with diabetes mellitus presented with a right orbital apex syndrome. In the orbital magnetic resonance imaging, the fat‐suppressed T2‐weighted image showed a hyperintense parallel linear lesion on the right optic nerve and a ring lesion around it, producing the “tram‐track” sign on the axial view and the “donut configuration” on the coronal view. A trans‐sphenoid endoscopic orbital biopsy showed an infection of Aspergillus fumigatus. Despite treatment with oral voriconazole, the patient died from deterioration of chronic heart failure. An autopsy found normal tissue around the orbital portion of bilateral optic nerves, while Aspergillus was found around the optic chiasm. The “tram‐track” sign and the “donut configuration” in the orbital magnetic resonance imaging were beneficial for the diagnosis of invasive sino‐orbital aspergillosis.
Objective prediction of pharyngeal swallow dysfunction in dysphagia through artificial neural network modeling
Authors: Kritas S. , Dejaeger E. , Tack J. , Omari T. , Rommel N. 
Published: February 2016

AbstractBackgroundPharyngeal pressure‐flow analysis (PFA) of high resolution impedance‐manometry (HRIM) with calculation of the swallow risk index (SRI) can quantify swallow dysfunction predisposing to aspiration. We explored the potential use of artificial neural networks (ANN) to model the relationship between PFA swallow metrics and aspiration and to predict swallow dysfunction.MethodsTwo hundred consecutive dysphagia patients referred for videofluoroscopy and HRIM were assessed. Presence of aspiration was scored and PFA software derived 13 metrics and the SRI. An ANN was created and optimized over training cycles to achieve optimal classification accuracy for matching inputs (PFA metrics) to output (presence of aspiration on videofluoroscopy). Application of the ANN returned a value between 0.00 and 1.00 reflecting the degree of swallow dysfunction.Key ResultsTwenty one patients were excluded due to insufficient number of swallows (<4). Of 179, 58 aspirated and 27 had aspiration pneumonia history. The SRI was higher in aspirators (aspiration 24 [9, 41] vs no aspiration 7 [2, 18], p < 0.001) and patients with pneumonia (pneumonia 27 [5, 42] vs no pneumonia 8 [3, 24], p < 0.05). The ANN Predicted Risk was higher in aspirators (aspiration 0.57 [0.38, 0.82] vs no aspiration 0.13 [0.4, 0.25], p < 0.001) and in patients with pneumonia (pneumonia 0.46 [0.18, 0.60] vs no pneumonia 0.18 [0.6, 0.49], p < 0.01). Prognostic value of the ANN was superior to the SRI.Conclusions & InferencesIn a heterogeneous cohort of dysphagia patients, PFA with ANN modeling offers enhanced detection of clinically significant swallowing dysfunction, probably more accurately reflecting the complex interplay of swallow characteristics that causes aspiration.
Probiotic Lactobacillus casei strain Shirota relieves stress‐associated symptoms by modulating the gut–brain interaction in human and animal models
Authors: Takada M. , Nishida K. , Kataoka‐Kato A. , Gondo Y. , Ishikawa H. , Suda K. , Kawai M. , Hoshi R. , Watanabe O. , Igarashi T. , Kuwano Y. , Miyazaki K. , Rokutan K. 
Published: February 2016

AbstractBackgroundThis study aimed to examine the effects of Lactobacillus casei strain Shirota (LcS) on gut–brain interactions under stressful conditions.MethodsThree double‐blind, placebo‐controlled trials were conducted to examine the effects of LcS on psychological and physiological stress responses in healthy medical students under academic examination stress. Subjects received LcS‐fermented milk or placebo daily for 8 weeks prior to taking a national standardized examination. Subjective anxiety scores, salivary cortisol levels, and the presence of physical symptoms during the intervention were pooled and analyzed. In the animal study, rats were given feed with or without LcS for 2 weeks, then submitted to water avoidance stress (WAS). Plasma corticosterone concentration and the expression of cFos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) were measured immediately after WAS. In an electrophysiological study, gastric vagal afferent nerve activity was monitored after intragastric administration of LcS to urethane‐anesthetized rats.Key ResultsAcademic stress‐induced increases in salivary cortisol levels and the incidence rate of physical symptoms were significantly suppressed in the LcS group compared with the placebo group. In rats pretreated with LcS, WAS‐induced increases in plasma corticosterone were significantly suppressed, and the number of CRF‐expressing cells in the PVN was reduced. Intragastric administration of LcS stimulated gastric vagal afferent activity in a dose‐dependent manner.Conclusions & InferencesThese findings suggest that LcS may prevent hypersecretion of cortisol and physical symptoms under stressful conditions, possibly through vagal afferent signaling to the brain and reduced stress reactivity in the PVN.
Dissection of expression‐quantitative trait locus and allele specificity using a haploid/diploid plant system – insights into compensatory evolution of transcriptional regulation within populations
Authors: Verta Jukka‐Pekka , Landry Christian R. , MacKay John 
Published: February 2016

Summary

Regulation of gene expression plays a central role in translating genotypic variation into phenotypic variation. Dissection of the genetic basis of expression variation is key to understanding how expression regulation evolves. Such analyses remain challenging in contexts where organisms are outbreeding, highly heterozygous and long‐lived such as in the case of conifer trees.

We developed an RNA sequencing (RNA‐seq)‐based approach for both expression‐quantitative trait locus (eQTL) mapping and the detection of cis‐acting (allele‐specific) vs trans‐acting (non‐allele‐specific) eQTLs. This method can be potentially applied to many conifers.

We used haploid and diploid meiotic seed tissues of a single self‐fertilized white spruce (Picea glauca) individual to dissect eQTLs according to linkage and allele specificity. The genetic architecture of local eQTLs linked to the expressed genes was particularly complex, consisting of cis‐acting, trans‐acting and, surprisingly, compensatory cis‐trans effects. These compensatory effects influence expression in opposite directions and are neutral when combined in homozygotes. Nearly half of local eQTLs were under compensation, indicating that close linkage between compensatory cis‐trans factors is common in spruce. Compensated genes were overrepresented in developmental and cell organization functions.

Our haploid–diploid eQTL analysis in spruce revealed that compensatory cis‐trans eQTLs segregate within populations and evolve in close genetic linkage.
Comparing self‐reported optometric dry eye clinical practices in Australia and the United Kingdom: is there scope for practice improvement?
Authors: Downie Laura E. , Rumney Nicholas , Gad Anne , Keller Peter R. , Purslow Christine , Vingrys Algis J. 
Published: February 2016

AbstractPurposeThe aim of this study was to compare the self‐reported clinical practice behaviours of optometrists in Australia and the United Kingdom (UK) with respect to the diagnosis and management of dry eye disease (DED). We also sought to examine whether the reported practices of clinicians in each region were consistent with current evidence‐based recommendations for DED.MethodsAn online survey was distributed to optometrists (Australia, n = 654; UK, n = 1006). Respondents provided information about practice modality, years of optometric experience, preferred diagnostic and management strategies (stratified by DED severity) and the information/evidence base used to guide patient care.ResultsA total of 317 completed surveys were received (response rates, Australia: 21%, UK: 17%). Optometrists in both regions demonstrated similarly strong knowledge of tear film assessment and adopted both subjective and objective techniques to diagnose DED. Patient symptoms were considered the most important, valuable and commonly performed assessment by both Australian and UK respondents. UK practitioners valued and utilised conjunctival signs and tear meniscus height assessments more than Australian optometrists (p < 0.05), who placed relatively greater emphasis on sodium fluorescein tear break‐up time to diagnose DED (p < 0.05). Clinicians in both locations tailored DED therapy to severity. While practitioners in both regions predominantly managed mild DED with eyelid hygiene and tear supplementation, Australian optometrists indicated prescribing topical corticosteroid therapy significantly more often than UK practitioners for moderate (14% vs 6%) and severe (52% vs 8%) disease (p < 0.05). The major source of information used to guide practitioners’ dry eye management practices was continuing education conferences.ConclusionsThis study highlights a range of parallels and divergences in dry eye clinical practice between Australian and UK optometrists. Our data identify both areas of strength in the adoption of evidence‐based practice, as well as some potential to improve international translation of dry eye research evidence into practice.