bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective antagonism of TRPA1 produces limited efficacy in models of inflammatory- and neuropathic-induced mechanical hypersensitivity in rats
Authors: Lehto Sonya G , Weyer Andy D , Youngblood Beth D , Zhang Maosheng , Yin Ruoyuan , Wang Weiya , Teffera Yohannes , Cooke Melanie , Stucky Cheryl L , Schenkel Laurie , Geuns-Meyer Stephanie , Moyer Bryan D , Wild Kenneth D , Gavva Narender R 
Published: November 2016

The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in pathophysiological processes that include asthma, cough, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and rodents, and TRPA1 antagonists have been reported to be effective in rodent models of pain. In our pursuit of TRPA1 antagonists as potential therapeutics, we generated AMG0902, a potent (IC90 of 300 nM against rat TRPA1), selective, brain penetrant (brain to plasma ratio of 0.2), and orally bioavailable small molecule TRPA1 antagonist. AMG0902 reduced mechanically evoked C-fiber action potential firing in a skin-nerve preparation from mice previously injected with complete Freund’s adjuvant, supporting the role of TRPA1 in inflammatory mechanosensation. In vivo target coverage of TRPA1 by AMG0902 was demonstrated by the prevention of AITC-induced flinching/licking in rats. However, oral administration of AMG0902 to rats resulted in little to no efficacy in models of inflammatory, mechanically evoked hypersensitivity; and no efficacy was observed in a neuropathic pain model. Unbound plasma concentrations achieved in pain models were about 4-fold higher than the IC90 concentration in the AITC target coverage model, suggesting that either greater target coverage is required for efficacy in the pain models studied or TRPA1 may not contribute significantly to the underlying mechanisms.
An exploratory factor analysis of the spontaneous reporting of severe cutaneous adverse reactions
Authors: Hauben Manfred , Hung Eric , Hsieh Wen-Yaw 
Published: November 2016

Background: Severe cutaneous adverse reactions (SCARs) are prominent in pharmacovigilance (PhV). They have some commonalities such as nonimmediate nature and T-cell mediation and rare overlap syndromes have been documented, most commonly involving acute generalized exanthematous pustulosis (AGEP) and drug rash with eosinophilia and systemic symptoms (DRESS), and DRESS and toxic epidermal necrolysis (TEN). However, they display diverse clinical phenotypes and variations in specific T-cell immune response profiles, plus some specific genotype–phenotype associations. A question is whether causation of a given SCAR by a given drug supports causality of the same drug for other SCARs. If so, we might expect significant intercorrelations between SCARs with respect to overall drug-reporting patterns. SCARs with significant intercorrelations may reflect a unified underlying concept. Methods: We used exploratory factor analysis (EFA) on data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) to assess reporting intercorrelations between six SCARs [AGEP, DRESS, erythema multiforme (EM), Stevens–Johnson syndrome (SJS), TEN, exfoliative dermatitis (ExfolDerm)]. We screened the data using visual inspection of scatterplot matrices for problematic data patterns. We assessed factorability via Bartlett’s test of sphericity, Kaiser-Myer-Olkin (KMO) statistic, initial estimates of communality and the anti-image correlation matrix. We extracted factors via principle axis factoring (PAF). The number of factors was determined by scree plot/Kaiser’s rule. We also examined solutions with an additional factor. We applied various oblique rotations. We assessed the strength of the solution by percentage of variance explained, minimum number of factors loading per major factor, the magnitude of the communalities, loadings and crossloadings, and reproduced- and residual correlations. Results: The data were generally adequate for factor analysis but the amount of variance explained, shared variance, and communalities were low, suggesting caution in general against extrapolating causality between SCARs. SJS and TEN displayed most shared variance. AGEP and DRESS, the other SCAR pair most often observed in overlap syndromes, demonstrated modest shared variance, along with maculopapular rash (MPR). DRESS and TEN, another of the more commonly diagnosed pairs in overlap syndromes, did not. EM was uncorrelated with SJS and TEN. Conclusions: The notion that causality of a drug for one SCAR bolsters support for causality of the same drug with other SCARs was generally not supported.
Relationship of ACL Injury and Posterior Tibial Slope With Patient Age, Sex, and Race
Authors: Waiwaiole Alana , Gurbani Ajay , Motamedi Kambiz , Seeger Leanne , Sim Myung Shin , Nwajuaku Patricia , Hame Sharon L. 
Published: November 2016

Background: Posterior tibial slope (PTS) has been proposed as a potential risk factor for anterior cruciate ligament (ACL) injury; however, studies that have examined this relationship have provided inconclusive and sometimes contradictory results. Further characterization of this relationship may enable the medical community to identify individuals at greater risk for ACL injury and possibly characterize an anatomic target during surgical reconstruction. Purpose: The primary goal was to investigate the relationship between PTS and ACL injury. The secondary goal was to determine whether there are any patient factors, such as age, race, or sex, that correlate with ACL injury and PTS. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Medical records of 221 patients who underwent magnetic resonance imaging (MRI) of the knee between January 2003 and December 2009 were reviewed. Patients were separated into 2 groups: a study group of those subjects who had undergone surgery for ACL injury (n = 107) and a control group of patients diagnosed with patellofemoral syndrome (n = 114). Demographic data were collected, and MRI images from both groups were analyzed using imaging software to obtain medial and lateral tibial slope measurements. Data were then analyzed using analysis of variance (ANOVA) comparison and a multivariable regression model to determine which, if any, patient factors were related to probability of having an ACL injury. Results: ANOVA comparison demonstrated that the study group had significantly greater values for lateral PTS (6° ± 4°; P < .001) and medial PTS (7° ± 4°; P = .002) compared with controls (5° ± 3° and 5° ± 4°, respectively). After stepwise elimination of nonsignificant variables, the final multivariable logistic regression model determined that age (odds ratio [OR], 0.94; P < .001) and lateral PTS (OR, 1.12; P = .002) had statistically significant relationships with ACL injury. Medial PTS, race, and sex were not demonstrated to be significant predictors of ACL injury in this final model. Conclusion: This study demonstrates a relationship between increased lateral PTS and ACL injury, which corroborates the findings of previously published studies. The findings presented in this article may help identify patients who are at greater risk of ACL injury and could potentially benefit from treatments aimed at modification of PTS.
The impact of post-stroke complications on in-hospital mortality depends on stroke severity
Authors: Bustamante Alejandro , Giralt Dolors , García-Berrocoso Teresa , Rubiera Marta , Álvarez-Sabín José , Molina Carlos , Serena Joaquín , Montaner Joan 
Published: November 2016

Introduction Controversies remain on whether post-stroke complications represent an independent predictor of poor outcome or just a reflection of stroke severity. We aimed to identify which post-stroke complications have the highest impact on in-hospital mortality by using machine learning techniques. Secondary aim was identification of patient’s subgroups in which complications have the highest impact. Patients and methods Registro Nacional de Ictus de la Sociedad Española de Neurología is a stroke registry from 42 centers from the Spanish Neurological Society. Data from ischemic stroke patients were used to build a random forest by combining 500 classification and regression trees, to weight up the impact of baseline characteristics and post-stroke complications on in-hospital mortality. With the selected variables, a logistic regression analysis was performed to test for interactions. Results 12,227 ischemic stroke patients were included. In-hospital mortality was 5.9% and median hospital stay was 7(4–10) days. Stroke severity [National Institutes of Health Stroke Scale > 10, OR = 5.54(4.55–6.99)], brain edema [OR = 18.93(14.65–24.46)], respiratory infections [OR = 3.67(3.02–4.45)] and age [OR = 2.50(2.07–3.03) for >77 years] had the highest impact on in-hospital mortality in random forest, being independently associated with in-hospital mortality. Complications have higher odds ratios in patients with baseline National Institutes of Health Stroke Scale <10. Discussion Our study identified brain edema and respiratory infections as independent predictors of in-hospital mortality, rather than just markers of more severe strokes. Moreover, its impact was higher in less severe strokes, despite lower frequency. Conclusion Brain edema and respiratory infections were the complications with a greater impact on in-hospital mortality, with the highest impact in patients with mild strokes. Further efforts on the prediction of these complications could improve stroke outcome.
A long-term experimental study of the reactivity of basement rock with highly alkaline cement waters: Reactions over the first 15 months
Authors: Rochelle C. A. , Milodowski A. E. , Bateman K. , Moyce E. B. A. , Kilpatrick A. 
Published: November 2016

AbstractA series of long-term laboratory experiments was started in 1995 to investigate longer-term dissolution/ precipitation reactions that may occur in the alkaline disturbed zone surrounding a cementitious repository for radioactive waste. They consist of samples of UK basement rock reacting with either Na-K-Ca-OH water ('young' cement porewater) or Ca-OH water ('evolved' cement porewater) at 70°C. This paper summarizes results of reactions occurring over the first 15 months. Experiments of both fluid types showed many similar features, though primary mineral dissolution and secondary mineral precipitation were more extensive in the experiments involving Na-K-Ca (younger) cement porefluids compared to more evolved (Ca-rich) cement porefluids. Dissolution of dolomite, and to a lesser extent silicates (probably K-feldspar, but also possibly mica) occurred relatively rapidly at 70°C. Dolomite dissolution may have been a key factor in reducing pH values, and may be a key mineral in controlling the extent of alkaline disturbed zones. Dissolution was followed by precipitation of brucite close to dolomite grains, at least two generations of C-S-H phases (which may have contained variable amounts of K, Al and Mg); overgrowths of calcite; small crystals of hydroxyapophyllite; and elongate crystals of celestite. Though hydroxyapophyllite was observed (a phase commonly associated with zeolites), there was no evidence for the formation of zeolites in the experiments. Fluid chemical changes track the mineralogical changes, with C-S-H phases being a major control on fluid chemistry. In the 'young' porewater experiments there were decreases in pH, and K, Ca and Mg concentrations, together with transitory increases in SiO2 concentrations. In the 'evolved' porewater experiments there were decreases in pH, Mg, Ca and Sr concentrations, together with small increases in K and SiO2 concentrations. A number of experiments are still running, and will be sampled in coming years.
On the origin of 'iron-cross' twins of pyrite from Mt. Katarina, Slovenia
Authors: Rečnik Aleksander , Zavašnik Janez , Jin Lei , Čobić Andrea , Daneu Nina 
Published: November 2016

AbstractIron-cross twins of pyrite are well known among mineralogists, however it is quite surprising that the conditions of their formation remain unexplored. To address this question we studied pyrite twins from the Upper Permian silts of Mt. Katarina near Ljubljana (Slovenia), which represent one of the most typical geological environments for twinned pyrite. Mineralization of pyrite starts with a reduction of the primary red-coloured hematite-rich sediment by sulfide-rich fluids that penetrated the strata. A short period of magnetite crystallization is observed prior to pyrite crystallization, which indicates a gradual reduction process. Sulfur isotope analysis of pyrite shows an enrichment in δ34S, suggesting its origin from the neighbouring red-bed deposit. Other sulfides, such as chalcopyrite and galena, formed at the end of pyrite crystallization. Remnants of mineralizing fluids trapped at the interfaces between the inclusions and host pyrite show trace amounts of Pb and Cu, indicating their presence in the solutions throughout the period of pyrite crystallization. An electron microscopy and spectroscopy study of twin boundaries showed that interpenetration twinning is accomplished through a complex 3D intergrowth of primary {110} Cu-rich twin boundaries, and secondary {100} boundaries that are pure. We show that approximately one monolayer of Cu atoms is necessary to stabilize the {110} twin structure. When the source of Cu is interrupted, the two crystal domains continue to form {100} interfaces, that are more favourable for pure pyrite.
Targeted deep sequencing in polycythemia vera and essential thrombocythemia
Authors: Tefferi Ayalew , Lasho Terra L. , Guglielmelli Paola , Finke Christy M. , Rotunno Giada , Elala Yoseph , Pacilli Annalisa , Hanson Curtis A. , Pancrazzi Alessandro , Ketterling Rhett P. , Mannarelli Carmela , Barraco Daniela , Fanelli Tiziana , Pardanani Animesh , Gangat Naseema , Vannucchi Alessandro M. 
Published: November 2016

Key Points
More than half of patients with PV or ET harbor DNA mutations/variants other than JAK2/CALR/MPL. The presence of some of these mutations adversely affects overall, leukemia-free, or myelofibrosis-free survival.
Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology
Authors: Maphis Nicole , Jiang Shanya , Xu Guixiang , Kokiko-Cochran Olga N. , Roy Saktimayee M. , Van Eldik Linda J. , Watterson D. Martin , Lamb Bruce T. , Bhaskar Kiran 
Published: November 2016

Abstract
Background
Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method
We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results
First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 (pS199/pS202) site tau phosphorylation, with the maximum effect peaking at 60–90 min after stimulation. Second, treatment of old (~20 months of age) hTau mice with MW181 (1 mg/kg body weight; 14 days via oral gavage) significantly reduced p38α MAPK activation compared with vehicle-administered hTau mice. This also resulted in a significant reduction in AT180 (pT231) site tau phosphorylation and Sarkosyl-insoluble tau aggregates. Third, MW181 treatment significantly increased synaptophysin protein expression and resulted in improved working memory. Fourth, MW181 administration reduced phosphorylated MAPK-activated protein kinase 2 (pMK2) and phosphorylated activating transcription factor 2 (pATF2), which are known substrates of p38α MAPK. Finally, MW181 reduced the expression of interferon-γ and interleukin-1β.

Conclusions
Taken together, these studies support p38α MAPK as a valid therapeutic target for the treatment of tauopathies.
Νευροεπιστήμες και εκπαίδευση: Απόψεις φοιτητών Παιδαγωγικών Τμημάτων
Authors: Χάλιου Ελένη , Παπαδάτου - Παστού Μαριέττα , Βλάχος Φίλιππος 
Published: November 2016

<p><em>Εισαγωγή</em>: Ο χώρος της εκπαίδευσης έχει ως αντικείμενο τη διδασκαλία και τη μάθηση. Οι Νευροεπιστήμες, από την άλλη μεριά, μελετούν το πώς ο εγκέφαλος μαθαίνει, γιατί κάποιοι μαθητές εμφανίζουν μαθησιακές δυσκολίες και το τι μπορεί να γίνει για να αντιμετωπιστούν οι δυσκολίες αυτές. Δεν αποτελεί, λοιπόν, έκπληξη, ότι το ενδιαφέρον των δασκάλων για την εφαρμογή των ευρημάτων από το χώρο των Νευροεπιστημών στην εκπαίδευση είναι μεγάλο διεθνώς.</p><p><em>Σκοπός</em>: Σκοπός της παρούσας έρευνας είναι η διερεύνηση των απόψεων φοιτητών Παιδαγωγικών Τμημάτων της χώρας μας για την αναγκαιότητα και τη χρησιμότητα παροχής σε αυτούς γνώσεων σχετικά με τις Νευροεπιστήμες.</p><p><em>Ευρήματα</em>: Σε δείγμα 257 προπτυχιακών και 94 μεταπτυχιακών78+﷽﷽﷽﷽﷽﷽﷽φρουδ διδάσκονται σχετικ φοιτητών από το Παιδαγωγικό Τμήμα Δημοτικής Εκπαίδευσης του Πανεπιστημίου Αθηνών, 117 προπτυχιακών φοιτητών από Παιδαγωγικό Τμήμα Ειδικής Αγωγής του Πανεπιστημίου Θεσσαλίας και 105 προπτυχιακών φοιτητών από το Παιδαγωγικό Τμήμα Προσχολικής Εκπαίδευσης του Πανεπιστημίου Θεσσαλίας, δόθηκαν ερωτηματολόγια για τη διερεύνηση των παραπάνω ερωτημάτων. Ενδεικτικά, το ενδιαφέρον των φοιτητών για τις Νευροεπιστήμες φάνηκε να είναι μεγάλο, με το 78,4% να δηλώνει ότι ενδιαφέρεται για την επιστημονική γνώση σχετικά με τις λειτουργίες του εγκεφάλου και το πώς αυτές επηρεάζουν τη διαδικασία της μάθησης. Το 83,6% των φοιτητών απάντησε ότι πρέπει να υπάρχει μάθημα πάνω στις λειτουργίες του εγκεφάλου στο πρόγραμμα σπουδών των Παιδαγωγικών Τμημάτων.</p><p><em>Συμπεράσματα</em><strong>:</strong> Τα ευρήματα από τη χώρα μας είναι σύμφωνα με ευρήματα από τη διεθνή βιβλιογραφία. Η επιθυμία των μελλοντικών δασκάλων να αποκτήσουν γνώσεις πάνω σε θέματα Νευροεπιστημών φαίνεται να είναι μεγάλη. </p>
Matching target dose to target organ
Authors: Bannon Desmond I. , Williams Marc A. 
Published: November 2016

In vitro assays have become a mainstay of modern approaches to toxicology with the promise of replacing or reducing the number of in vivo tests required to establish benchmark doses, as well as increasing mechanistic understanding. However, matching target dose to target organ is an often overlooked aspect of in vitro assays, and the calibration of in vitro exposure against in vivo benchmark doses is often ignored, inadvertently or otherwise. An example of this was recently published in Environmental Health Perspectives by Wagner et al., where neural stems cells were used to model the molecular toxicity of lead. On closer examination of the in vitro work, the doses used in media reflected in vivo lead doses that would be at the highest end of lead toxicity, perhaps even lethal. Here we discuss the doses used and suggest more realistic doses for future work with stem cells or other neuronal cell lines.
The impact of wearing single vision soft contact lenses on the peripheral refractive error
Authors: Allinjawi Kareem , Sharanjeet-Kaur Sharanjeet-Kaur , Akhir Saadah Mohamed , Abdul Mutalib Haliza 
Published: November 2016

Aim: The purpose of this study was to determine the changes in the relative peripheral refractive error produced by soft single vision contact lenses in myopic schoolchildren. Methods: 27 myopic schoolchildren aged between 13 to 15 years were included in this study. The measurements of central and peripheral refraction were made only on the right eye using a Grand-Seiko WR-5100K open-field autorefractometer without contact lens (WL), and with wearing single vision contact lens (SVCL). Refractive power was measured at center and horizontal eccentricity between 35° temporal to 35° nasal visual field (in 5° steps). Results: SVCL showed an increase in peripheral hyperopic defocus at the nasal and temporal visual field compare with baseline, but this change was not statistically significant (p=0.129). Conclusion: Wearing single vision soft contact lenses increases the relative peripheral hyperopic defocus in myopic schoolchildren.
Book review supplement
Authors: Groves Stephen , Morgan Clwyd , Sheppard Amanda , Hope Pam , Common Anne , Brown Roswyn , Walton Jane , Hunt Sheila C 
Published: November 2016

Orthopaedic Nursing (2nd edn) Nursing Diagnosis in Clinical Practice: Guides for Care Planning Critical Care Nursing (2nd edn) Nursing Care: The Challenge of Change Cancer Patient Care: Psychosocial Treatment Methods Practical Medical Ethics Accident and Emergency Nursing: A Nursing Model High Risk Pregnancy
Book Review Supplement
Authors: Hinchliff Sue , Hughes Roger B , Gee Kate , Biley Francis C , Farrington Andy , Rea Karen , MacAlister Lanette 
Published: November 2016

Interviewing Skills: Applying for a Job (video) Employment Law for Nurses Advanced Cardiac Life Support — The Practical Approach Nursing Process in Clinical Practice A Self-Help Guide to Managing Depression Patients' Rights, Responsibilities and the Nurse Professional Portfolio for Nurses
Care of a patient undergoing spinal anaesthesia
Authors: Betina Lympany Andrea 
Published: November 2016

Care study Christine was admitted for a left total knee replacement under spinal anaesthesia. She was a 72-year-old woman who lived on her own and had been widowed for some years. She was supported by her children who lived close by. She was a very independent lady, determined to do as much for herself as possible. Her medical history included an appendicectomy 27 years ago, a left breast abscess drained in 1952, a patellectomy of the left knee under general anaesthetic and a hiatus hernia for the past 9 years which only caused problems when bending down. She was on little medication apart from oral anti-inflammatory analgesic for the osteoarthritis in her left knee. She was overweight and had difficulty in reducing her weight. Her mobility was limited and she walked with the aid of a stick.
Book review supplement
Authors: Brown Roswyn , Phillips Jenny , Walton Margaret F , MacAlister Lanette , Marriott Janet D , Claxton Jenny , Sheehan Anthony , Sheppard Amanda , Papadopoulos Irena 
Published: November 2016

Study Skills for Nurses Nutritional Support — A Team Approach (Professional Nurse Clinical Skills Series) Behavioural Sciences for Carers Budgeting Skills: A Guide for Nurse Managers Preventing Cancers AIDS — Rights, Risks and Reason Introduction to Critical Care Nursing Teaching Transcultural Care. A Guide For Teachers of Nursing and Health Care
Educating a patient with diabetes about foot care
Authors: Mclntyre Margaret J , McDowell Joan RS 
Published: November 2016

Care study Mrs Rasul is a 55-year-old Asian woman who has had maturity onset diabetes for 17 years. At a hospital clinic appointment she was identified as being at risk of developing a neuropathic foot ulcer. She was referred to the diabetic nurse specialist for education and supervision. She lives at home with her husband, son and daughter. Religious factors dictate that she prays on her knees five times a day, which places pressure on her feet.
Book reviews
Authors: MacAlister Lanette , Ashurst Steve , Young Trudie , Ward Tom , Nolan Mike , Gorman Helen , Wilkinson Chris , Walton Jane 
Published: November 2016

Confusional States in Older People Unifying Nursing Practice and Theory The Care of Wounds Nursing and Social Policy: Care in Context Research and Its Application: Advanced Nursing Series Collaborative Care: Interprofessional, Interagency and Interpersonal The Clinical Nurse Specialist:Issues in Practice Critical Care Nursing