bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophilia, gelatinase release and microvascular leakage induced by human mast cell tryptase in a mouse model: Lack of a role of protease‐activated receptor 2 (PAR2)
Authors: Khedr M. E. M. S. , Abdelmotelb A. M. , Pender S. L. F. , Zhou X. , Walls A. F. 
Published: January 2018

SummaryBackgroundTryptase, the most abundant protease of the human mast cell, has been implicated as a key mediator of allergic inflammation that acts through activation of PAR2.ObjectivesTo investigate the contribution of PAR2 in the pro‐inflammatory actions mediated by tryptase in a mice model.MethodsWe have injected recombinant human βII‐tryptase into the peritoneum of PAR2‐deficient and wild‐type C57BL/6 mice. After 6, 12 and 24 hours, mice were killed, peritoneal lavage performed and inflammatory changes investigated.ResultsTryptase stimulated an increase in neutrophil numbers in the peritoneum, but responses did not differ between PAR2‐deficient and wild‐type mice. Heat inactivation of tryptase or pre‐incubation with a selective tryptase inhibitor reduced neutrophilia, but neutrophil accumulation was not elicited with a peptide agonist of PAR2 (SLIGRL‐NH2). Zymography indicated that tryptase stimulated the release of matrix metalloproteinases (MMP) 2 and 9 in the peritoneum of both mouse strains. Studies involving immunomagnetic isolation of neutrophils suggested that neutrophils represent the major cellular source of tryptase‐induced MMP2 and MMP9. At 24 hours after tryptase injection, there was increased microvascular leakage as indicated by high levels of albumin in peritoneal lavage fluid, and this appeared to be partially abolished by heat‐inactivating tryptase or addition of a protease inhibitor. There was no corresponding increase in levels of histamine or total protein. The extent of tryptase‐induced microvascular leakage or gelatinase release into the peritoneum did not differ between PAR2‐deficient and wild‐type mice.ConclusionsOur findings indicate that tryptase is a potent stimulus for neutrophil accumulation, MMP release and microvascular leakage. Although these actions required an intact catalytic site, the primary mechanism of tryptase in vivo would appear to involve processes independent of PAR2.
Obese asthmatics are characterized by altered adipose tissue macrophage activation
Authors: Periyalil H. A. , Wood L. G. , Wright T. A. , Karihaloo C. , Starkey M. R. , Miu A. S. , Baines K. J. , Hansbro P. M. , Gibson P. G. 
Published: January 2018

SummaryBackgroundAdipose tissue‐derived inflammation is linked to obesity‐related comorbidities. This study aimed to quantify and immuno‐phenotype adipose tissue macrophages (ATMs) from obese asthmatics and obese non‐asthmatics and to examine associations between adipose tissue, systemic and airway inflammation.MethodsVisceral (VAT) adipose tissue and subcutaneous (SAT) adipose tissue were collected from obese adults undergoing bariatric surgery and processed to obtain the stromovascular fraction. Pro‐inflammatory (M1) and anti‐inflammatory (M2) macrophages were quantified by flow cytometry. Cytospins of induced sputum were stained for differential cell counts. Plasma C‐reactive protein (CRP) and CD163 were measured by ELISA.ResultsVAT contained a higher number of ATMs compared to SAT. A higher percentage of M1 ATMs was observed in VAT of obese asthmatics compared to obese non‐asthmatics. The M1:M2 ratio in VAT was negatively associated with FEV1%. Sputum macrophage count was correlated positively with M1 ATMs and negatively with M2 ATMs in VAT. In obese asthmatics, CRP was positively associated with M1:M2 ratio in VAT. There were no associations with CD163. An elevated ratio of M1:M2 ATMs was observed in VAT of obese asthmatics with increased disease severity.Conclusions and Clinical RelevanceVisceral inflammation with increased pro‐inflammatory macrophages (M1) occurs in obese asthma and may be a determinant of systemic inflammation and asthma severity.
Epigenetic changes and their implications in autoimmune hepatitis
Authors: Czaja Albert J. 
Published: January 2018

AbstractBackgroundThe genetic risk of autoimmune hepatitis is insufficient to explain the observed risk, and epigenetic changes may explain disparities in disease occurrence in different populations within and between countries. The goal of this review was to examine how epigenetic changes induced by the environment or inherited as a phenotypic trait may affect autoimmune hepatitis and be amenable to therapeutic intervention.Materials and methodsPertinent abstracts were identified in PubMed by multiple search terms. The number of abstracts reviewed was 1689, and the number of full‐length articles reviewed exceeded 150.ResultsActivation of pro‐inflammatory genes in autoimmune disease is associated with hypomethylation of deoxyribonucleic acid and modification of histones within chromatin. Organ‐specific microribonucleic acids can silence genes by marking messenger ribonucleic acids for degradation, and they can promote inflammatory activity or immunosuppression. High circulating levels of the microribonucleic acids 21 and 122 have been demonstrated in autoimmune hepatitis, and they may increase production of pro‐inflammatory cytokines. Microribonucleic acids are also essential for maintaining regulatory T cells. Drugs, pollutants, infections, diet and ageing can induce inheritable epigenetic changes favouring autoimmunity. Reversal is feasible by manipulating enzymes, transcription factors, gene‐silencing molecules and toxic exposures or by administering methyl donors and correcting vitamin D deficiency. Gene targets, site specificity, efficacy and consequences are uncertain.ConclusionsPotentially reversible epigenetic changes may affect the occurrence and outcome of autoimmune hepatitis, and investigations are warranted to determine the nature of these changes, key genomic targets, and feasible interventions and their consequences.
Within‐diet variation in rates of macronutrient consumption and reproduction does not accompany changes in lifespan in Drosophila melanogaster
Authors: Semaniuk Uliana , Feden'ko Khrystyna , Yurkevych Ihor S. , Storey Kenneth B. , Simpson Stephen J. , Lushchak Oleh 
Published: January 2018

AbstractInterventions such as caloric or dietary restriction extend lifespan in organisms spanning from yeast to primates. Despite its positive influence on longevity, dietary restriction has been found to negatively affect reproduction. Many studies have reported negative correlations between lifespan and reproductive characteristics (such as mating rate, fecundity, reproductive period, and others). Such correlation gives the appearance of a resource‐based trade‐off between these two life‐history traits. Here, we have used nutritional geometry to confirm previous findings in flies that dietary macronutrient balance (protein‐to‐carbohydrate ratio, P:C) impacts both lifespan and reproduction, such that across a series of diets differing in P:C, maximum lifespan was observed at a lower P:C (1:8) than that which supported highest fecundity (1:1.5). We have then addressed the question whether variation among Drosophila melanogasterMeigen (Diptera: Drosophilidae) fruit flies in food intake and egg production within a single dietary treatment is negatively associated with within‐diet variation in lifespan, as might be expected under a resource‐based trade‐off. There was no such association between intake rate, egg production, and longevity. We noted that the smaller sample sizes and smaller inter‐individual variance apparent within — as compared to across — diet treatments may have weakened any signature of a trade‐off between lifespan and reproduction. Thus, we conclude that, whereas dietary macronutrient ratio is a primary determinant of both reproduction and longevity, neither eating less nor laying fewer eggs per se predicted lifespan. This supports the view that there is not a simple quantitative resource‐based trade‐off between lifespan and reproduction, but rather these represent life‐history traits with qualitatively different nutritional optima.
Ambulatory blood pressure in the dash diet trial: Effects of race and albuminuria
Authors: Tyson Crystal C. , Barnhart Huiman , Sapp Shelly , Poon Victor , Lin Pao‐Hwa , Svetkey Laura P. 
Published: January 2018

We evaluated whether low‐grade albuminuria or black race modulates ambulatory blood pressure (BP) or nocturnal BP response to the DASH diet. Among 202 adults enrolled in the DASH multicenter trial who were fed the DASH or control diet for 8 weeks, reductions in 24‐hour daytime and nighttime SBP and DBP were significantly larger for DASH compared to control. Median changes in nocturnal BP dipping were not significant. Compared to urine albumin excretion of <7 mg/d, ≥7 mg/d was associated with larger significant median reductions in 24‐hour SBP (−7.3 vs −3.1 mm Hg), all measures of DBP (24‐hour: −5.9 vs −1.8 mm Hg; daytime: −9.9 vs −4.0 mm Hg; nighttime −9.0 vs −2.0 mm Hg), and with increased nocturnal SBP dipping (2.3% vs −0.5%). Black race was associated with larger median reduction in 24‐hour SBP only (−5.5 vs −2.4 mm Hg). This analysis suggests greater effect of DASH on ambulatory BP in the presence of low‐grade albuminuria.
Human‐simulation‐based learning to prevent medication error: A systematic review
Authors: Sarfati Laura , Ranchon Florence , Vantard Nicolas , Schwiertz Vérane , Larbre Virginie , Parat Stéphanie , Faudel Amélie , Rioufol Catherine 
Published: January 2018

AbstractRationale, aims and objectivesIn the past 2 decades, there has been an increasing interest in simulation‐based learning programs to prevent medication error (ME). To improve knowledge, skills, and attitudes in prescribers, nurses, and pharmaceutical staff, these methods enable training without directly involving patients. However, best practices for simulation for healthcare providers are as yet undefined. By analysing the current state of experience in the field, the present review aims to assess whether human simulation in healthcare helps to reduce ME.MethodsA systematic review was conducted on Medline from 2000 to June 2015, associating the terms “Patient Simulation,” “Medication Errors,” and “Simulation Healthcare.” Reports of technology‐based simulation were excluded, to focus exclusively on human simulation in nontechnical skills learning.ResultsTwenty‐one studies assessing simulation‐based learning programs were selected, focusing on pharmacy, medicine or nursing students, or concerning programs aimed at reducing administration or preparation errors, managing crises, or learning communication skills for healthcare professionals.The studies varied in design, methodology, and assessment criteria. Few demonstrated that simulation was more effective than didactic learning in reducing ME. This review highlights a lack of long‐term assessment and real‐life extrapolation, with limited scenarios and participant samples. These various experiences, however, help in identifying the key elements required for an effective human simulation‐based learning program for ME prevention: ie, scenario design, debriefing, and perception assessment. The performance of these programs depends on their ability to reflect reality and on professional guidance.ConclusionProperly regulated simulation is a good way to train staff in events that happen only exceptionally, as well as in standard daily activities. By integrating human factors, simulation seems to be effective in preventing iatrogenic risk related to ME, if the program is well designed.
Reflectance difference microscopy for nanometre thickness microstructure measurements
Authors: HU C. , HUO S. , SHEN W. , LI Y. , HU X. 
Published: January 2018

AbstractThe discontinuity of medium at the boundary produces optically anisotropic response which makes reflectance difference microscopy (RDM) a potential method for nanometre‐thickness microstructure measurements. Here, we present the methodology of RDM for the edge measurement of ultrathin microstructure. The RD signal of microstructure's boundary is mathematically deduced according to boundary condition and polarization optics theory. A normal‐incidence RDM setup was built simply with one linear polarizer, one liquid crystal variable retarder and one 5 × objective. Then, the performance of the developed setup was identified using homogenous reflection mirror and high quality linear polarizer. For demonstration, microstructures array with 100 nm step height was measured. The results show that the RD signal is sensitive to the edge and its sign reflects the change direction of the edge. Furthermore, a height sensitivity of better than 10 nm and a spatial resolution of ∼3 m offer this technique a good candidate for characterizing ultrathin microstructures.
Itraconazole induced hypertension and hypokalemia: Mechanistic evaluation
Authors: Hoffmann Wesley J. , McHardy Ian , Thompson George R. 
Published: January 2018

SummaryWe describe a case of apparent mineralocorticoid excess (hypertension, hypokalemia, metabolic alkalosis and low plasma renin activity) secondary to itraconazole therapy. Inhibition of 11β‐hydroxysteroid dehydrogenase 2 was demonstrated, and withholding itraconazole led to resolution of adverse effects that did not recur with voriconazole. This report adds to a growing body of evidence linking apparent mineralocorticoid excess with certain triazoles.
Diagnostic patterns and delays in autoimmune blistering diseases of the mouth: A cross‐sectional study
Authors: Hassona Y , Cirillo N , Taimeh D , Al Khawaldeh H , Sawair F 
Published: January 2018

ObjectivesTo describe the natural history and factors influencing diagnostic delays among patients with autoimmune blistering diseases of the mouth.Materials and MethodsIn this cross‐sectional study, 27 newly diagnosed patients were interviewed, and professional and patient delays were calculated. Disease extent and severity scores were determined using Saraswat scoring system.ResultsTwenty‐seven patients were interviewed and examined. Patient delay was significantly longer in patients who had desquamative gingivitis as initial presentation, in those who tried to use home remedies and over the counter medications, and in patients with less severe disease. Most patients (n = 21 [77.7%]) made more than one consultation, and the mean time needed to reach a definitive diagnosis (i.e. professional delay) was 83.2 ± 21.4 days (range from 21 to 130 days). Professional delay was significantly correlated with the number of previous consultations (r = .78) and was significantly longer in patients who had desquamative gingivitis as initial presentation.ConclusionDiagnosis of oral blistering diseases is often delayed. Diagnostic delay is more common in patients presenting with desquamative gingivitis and those with less severe disease. Improving patients and healthcare professionals’ awareness about oral blistering diseases might help reduce diagnostic delay.
Validity and Test–Retest Reliability of the Dutch Modified Perceived Deficits Questionnaire to Examine Cognitive Symptoms in Women with Chronic Whiplash, Chronic Idiopathic Neck Pain, and Fibromyalgia
Authors: Lenoir D. , De Pauw R. , Ickmans K. , Schumacher C. , Timmers I. , Kregel J. , Coppieters I. 
Published: January 2018

AbstractIntroductionUntil now, only reliability and validity of the English version of the modified Perceived Deficits Questionnaire (mPDQ) have been investigated.ObjectiveThe aim of this study was to translate the mPDQ into Dutch and evaluate its validity and reliability as an assessment tool for self‐perceived cognitive problems in patients with chronic whiplash‐associated disorders (CWAD), chronic idiopathic neck pain (CINP), and fibromyalgia (FM).MethodsA case–control study was performed with a volunteer sample of 13 women with CWAD, 18 with CINP, and 33 with FM, and 33 women who were healthy and free of pain. The mPDQ was first translated into Dutch, and its test–retest reliability, internal consistency, and discriminative power were examined.ResultsThe intraclass correlation coefficients were higher than 0.74. Cronbach's α values ranged between 0.71 and 0.95. Total mPDQ scores were significantly higher (P < 0.017) in FM and CWAD patients compared to healthy controls. Furthermore, participants performed the Stroop task and the psychomotor vigilance task (PVT), 2 neuropsychological computer‐based cognitive performance tests. Correlations between the mPDQ total score and the cognitive performance tests were evaluated. Significant moderate to high correlations were found in all study samples between total mPDQ score and objective cognitive tests (Spearman correlation coefficient = 0.35 to 0.80; P < 0.05).ConclusionTherefore, the Dutch version of the mPDQ showed high test–retest reliability and high internal consistency, and was able to distinguish CWAD and FM patients from healthy controls.PerspectiveThis article presents the validity and test–retest reliability of the Dutch mPDQ. This measure could help clinicians who seek a reliable and user‐friendly way to assess cognitive symptoms in chronic pain patients.
If or when? Uncertainty's role in anxious anticipation
Authors: Bennett Ken P. , Sinclair Jac V. , Larson Christine L. 
Published: January 2018

AbstractUncertainty is often associated with subjective distress and a potentiated anxiety response. Occurrence uncertainty, or the inability to predict if a threat will occur, has rarely been compared experimentally with temporal uncertainty, or the inability to predict when a threat will occur. The current study aimed to (a) directly compare the anxiogenic effects of anticipating these two types of uncertain threat, as indexed by the eyeblink startle response, and (b) assess the relationship between startle response to occurrence and temporal uncertainty and individual differences in self‐reported intolerance of uncertainty and anxiety. The findings indicated that anticipation during occurrence uncertainty elicited a larger startle response than anticipating a certain threat, but anticipation during temporal uncertainty was superior at potentiating startle blink overall. Additional analyses of the effects of order and habituation further highlighted temporal uncertainty's superiority in eliciting greater startle responding. This suggests that, while uncertainty is physiologically anxiety provoking, some level of certainty that the threat will occur enhances the robustness of the physiological anxiety response. However, self‐reported anxiety was equivalent for temporal and occurrence uncertainty, suggesting that, while defensive responding may be more affected by temporal uncertainty, people perceive both types of uncertainty as anxiogenic. Individual differences in the intolerance of uncertainty and other anxiety measures were not related to anticipatory startle responsivity during any of the conditions.
High‐frequency ultrasonography—New non‐invasive method in assessment of skin lymphomas
Authors: Polańska A. , Dańczak‐Pazdrowska A. , Olek‐Hrab K. , Osmola‐Mańkowska A. , Bowszyc‐Dmochowska M. , Żaba R. , Adamski Z. 
Published: January 2018

AbstractBackgroundMycosis fingoides (MF) is the most common subtype of primary cutaneous T‐cell lymphomas. Current evaluation of disease extent and severity is based on mSWAT scoring system, which seems to be relatively subjective. The aim of this subject was to present the usefulness of 20 MHz in objective 5‐year long monitoring of response to therapy in MF patients.Materials and methodsThe 5‐years long follow‐up based on 19 skin USG images of patients diagnosed as early stages of MF was studied. The assessed USG parameter was the mean diameter of subepidermal low echogenic band (SLEB).ResultsIn every MF patient during exacerbation within lesional skin we could observe SLEB, which thinning or complete disappearance was detected after finishing the therapy. Lack of complete absence of SLEB was related to the lack of complete remission assessed by mSWAT.ConclusionWe present for the first time the possibility of monitoring patients’ clinical state on the base of non‐invasive USG imaging. We recommend additional use of 20 MHz USG to reduce intra‐observer variability and to assess residual disease. USG imaging can complement evaluation of skin lesions in MF and can support clinical judgement.
Probability Theory Plus Noise: Descriptive Estimation and Inferential Judgment
Authors: Costello Fintan , Watts Paul 
Published: January 2018

AbstractWe describe a computational model of two central aspects of people's probabilistic reasoning: descriptive probability estimation and inferential probability judgment. This model assumes that people's reasoning follows standard frequentist probability theory, but it is subject to random noise. This random noise has a regressive effect in descriptive probability estimation, moving probability estimates away from normative probabilities and toward the center of the probability scale. This random noise has an anti‐regressive effect in inferential judgement, however. These regressive and anti‐regressive effects explain various reliable and systematic biases seen in people's descriptive probability estimation and inferential probability judgment. This model predicts that these contrary effects will tend to cancel out in tasks that involve both descriptive estimation and inferential judgement, leading to unbiased responses in those tasks. We test this model by applying it to one such task, described by Gallistel et al. ). Participants' median responses in this task were unbiased, agreeing with normative probability theory over the full range of responses. Our model captures the pattern of unbiased responses in this task, while simultaneously explaining systematic biases away from normatively correct probabilities seen in other tasks.
Enhancing heterologous expression in Chlamydomonas reinhardtii by transcript sequence optimization
Authors: Weiner Iddo , Atar Shimshi , Schweitzer Shira , Eilenberg Haviva , Feldman Yael , Avitan Meital , Blau Mor , Danon Avihai , Tuller Tamir , Yacoby Iftach 
Published: January 2018

SUMMARYVarious species of microalgae have recently emerged as promising host‐organisms for use in biotechnology industries due to their unique properties. These include efficient conversion of sunlight into organic compounds, the ability to grow in extreme conditions and the occurrence of numerous post‐translational modification pathways. However, the inability to obtain high levels of nuclear heterologous gene expression in microalgae hinders the development of the entire field. To overcome this limitation, we analyzed different sequence optimization algorithms while studying the effect of transcript sequence features on heterologous expression in the model microalga Chlamydomonas reinhardtii, whose genome consists of rare features such as a high GC content. Based on the analysis of genomic data, we created eight unique sequences coding for a synthetic ferredoxin–hydrogenase enzyme, used here as a reporter gene. Following in silico design, these synthetic genes were transformed into the C. reinhardtii nucleus, after which gene expression levels were measured. The empirical data, measured in vivo show a discrepancy of up to 65‐fold between the different constructs. In this work we demonstrate how the combination of computational methods and our empirical results enable us to learn about the way gene expression is encoded in the C. reinhardtii transcripts. We describe the deleterious effect on overall expression of codons encoding for splicing signals. Subsequently, our analysis shows that utilization of a frequent subset of preferred codons results in elevated transcript levels, and that mRNA folding energy in the vicinity of translation initiation significantly affects gene expression.