bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomewide mechanisms of chronological longevity by dietary restriction in budding yeast
Authors: Campos Sergio E. , Avelar‐Rivas J. Abraham , Garay Erika , Juárez‐Reyes Alejandro , DeLuna Alexander
Published: March 2018

Dietary restriction is arguably the most promising nonpharmacological intervention to extend human life and health span. Yet, only few genetic regulators mediating the cellular response to dietary restriction are known, and the question remains which other regulatory factors are involved. Here, we measured at the genomewide level the chronological lifespan of Saccharomyces cerevisiae gene deletion strains under two nitrogen source regimens, glutamine (nonrestricted) and γ‐aminobutyric acid (restricted). We identified 473 mutants with diminished or enhanced extension of lifespan. Functional analysis of such dietary restriction genes revealed novel processes underlying longevity by the nitrogen source quality, which also allowed us to generate a prioritized catalogue of transcription factors orchestrating the dietary restriction response. Importantly, deletions of transcription factors Msn2, Msn4, Snf6, Tec1, and Ste12 resulted in diminished lifespan extension and defects in cell cycle arrest upon nutrient starvation, suggesting that regulation of the cell cycle is a major mechanism of chronological longevity. We further show that STE12 overexpression is enough to extend lifespan, linking the pheromone/invasive growth pathway with cell survivorship. Our global picture of the genetic players of longevity by dietary restriction highlights intricate regulatory cross‐talks in aging cells.
Evidence that miR‐146a attenuates aging‐ and trauma‐induced osteoarthritis by inhibiting Notch1, IL‐6, and IL‐1 mediated catabolism
Authors: Guan Ying‐Jie , Li Jing , Yang Xu , Du Shaohua , Ding Jing , Gao Yun , Zhang Ying , Yang Kun , Chen Qian
Published: March 2018

Primary osteoarthritis (OA) is associated with aging, while post‐traumatic OA (PTOA) is associated with mechanical injury and inflammation. It is not clear whether the two types of osteoarthritis share common mechanisms. We found that miR‐146a, a microRNA‐associated with inflammation, is activated by cyclic load in the physiological range but suppressed by mechanical overload in human articular chondrocytes. Furthermore, miR‐146a expression is decreased in the OA lesions of human articular cartilage. To understand the role of miR‐146a in osteoarthritis, we systemically characterized mice in which miR‐146a is either deficient in whole body or overexpressed in chondrogenic cells specifically. miR‐146a‐deficient mice develop early onset of OA characterized by cartilage degeneration, synovitis, and osteophytes. Conversely, miR‐146a chondrogenic overexpressing mice are resistant to aging‐associated OA. Loss of miR‐146a exacerbates articular cartilage degeneration during PTOA, while chondrogenic overexpression of miR‐146a inhibits PTOA. Thus, miR‐146a inhibits both OA and PTOA in mice, suggesting a common protective mechanism initiated by miR‐146a. miR‐146a suppresses IL‐1β of catabolic factors, and we provide evidence that miR‐146a directly inhibits Notch1 expression. Therefore, such inhibition of Notch1 may explain suppression of inflammatory mediators by miR‐146a. Chondrogenic overexpression of miR‐146a or intra‐articular administration of a Notch1 inhibitor alleviates IL‐1β‐induced catabolism and rescues joint degeneration in miR‐146a‐deficient mice, suggesting that miR‐146a is sufficient to protect OA pathogenesis by inhibiting Notch signaling in the joint. Thus, miR‐146a may be used to counter both aging‐associated OA and mechanical injury‐/inflammation‐induced PTOA.
The mitochondrial unfolded protein response is activated upon hematopoietic stem cell exit from quiescence
Authors: Mohrin Mary , Widjaja Andrew , Liu Yufei , Luo Hanzhi , Chen Danica
Published: March 2018

The mitochondrial unfolded protein response (UPRmt), a cellular protective program that ensures proteostasis in the mitochondria, has recently emerged as a regulatory mechanism for adult stem cell maintenance that is conserved across tissues. Despite the emerging genetic evidence implicating the UPRmt in stem cell maintenance, the underlying molecular mechanism is unknown. While it has been speculated that the UPRmt is activated upon stem cell transition from quiescence to proliferation, the direct evidence is lacking. In this study, we devised three experimental approaches that enable us to monitor quiescent and proliferating hematopoietic stem cells (HSCs) and provided the direct evidence that the UPRmt is activated upon HSC transition from quiescence to proliferation, and more broadly, mitochondrial integrity is actively monitored at the restriction point to ensure metabolic fitness before stem cells are committed to proliferation.
One way or another: predictors of wolf poaching in a legally harvested wolf population
Authors: Suutarinen J. , Kojola I.
Published: March 2018

Poaching is a major threat to large predator populations, but the predictors of poaching are poorly mapped in developed countries where illegal killing is motivated by social reasons. Poaching can be common although the species is legally hunted, such as in the case of the wolf (Canis lupus). Our goal was to identify crucial motives of poaching to find possible solutions to the ongoing wolf conflict. We studied predictors of poaching on two spatial scales – countrywide (76 wolves) and territory [30 Global Positioning System (GPS)‐wolves] – during 2001–2016 in Finland. The countrywide factors predicting illegal kill were as follows: (1) lifestage, with adult wolves showing a remarkably high probability of being illegally killed in comparison with juveniles; (2) the number of wolves killed legally in the local scale, that is, licensed wolf hunting at the local scale decreased the likelihood of illegal killing, as did the total number of legally hunted wolves; (3) total legal bag in the whole country; and (4) density of the local human population, that is, low human density increased the probability of illegal kill. For breeding adult GPS‐collared wolves at the territory level, there was a positive relationship between the tendency to cross roads and likelihood of being illegally killed. Our results provided evidence that poaching is a matter of local intolerance toward wolves and that the problem is mainly related to wolf hunting. Legal hunting might decrease poaching, but seems inefficient as a long‐term solution. To maintain a viable wolf population, the poaching risk of breeding adults should be decreased. Predicted poaching probabilities could be used to tackle poaching in a preventive manner by involving both decision makers and local residents in anti‐poaching actions.
Clozapine reduces nicotine self‐administration, blunts reinstatement of nicotine‐seeking but increases responding for food
Authors: Abela Andrew R. , Li Zhaoxia , Lê Anh D. , Fletcher Paul J.
Published: March 2018

People with schizophrenia display significantly higher rates of smoking than the general population, which may be due to an interaction between nicotine and antipsychotic medication. While the conventional antipsychotic drug haloperidol sometimes increases cigarette smoking in patients with schizophrenia, there is some evidence suggesting that clozapine, an atypical antipsychotic drug, may reduce nicotine use in these patients. However, the effects of antipsychotic drugs like clozapine on aspects of nicotine self‐administration and reinstatement have not been systematically examined. In the current study, we assessed the effect of clozapine on nicotine self‐administration under fixed ratio and progressive ratio schedules of reinforcement, as well as reinstatement of nicotine‐seeking following a period of abstinence. To determine the specificity of its effect on nicotine reward, we also tested the effect of clozapine on responding for food reinforcement under fixed ratio and progressive ratio schedules. For comparison, we also examined the effects of haloperidol, a first‐generation antipsychotic drug, under some of the same behavioral conditions as clozapine. We show that clozapine inhibits nicotine self‐administration and reinstatement of nicotine‐seeking but also increases the amount of effort that rats will exert for food reward. In contrast, haloperidol at a wide range of doses attenuated responding for nicotine and food reward, suggestive of a non‐specific reduction in reinforcer efficacy. These results show the potential utility of clozapine as a smoking cessation treatment for patients with schizophrenia, in addition to its antipsychotic properties.
Denise Kandel's classic work on the gateway sequence of drug acquisition
Authors: Lynskey Michael T. , Agrawal Arpana
Published: March 2018

During the early 1970s Denise Kandel and her colleagues documented an ‘invariant sequence’ in initiation of drug use: starting with alcohol and tobacco, progressing to cannabis and then to other illicit, or ‘harder’ drugs. This observation, which became known as the ‘gateway sequence’ of drug use, has been influential in policy debates but remains highly contentious, with the area of greatest controversy focusing upon whether cannabis use increases risk causally for initiation of other illicit drugs. While numerous studies have replicated Kandel's initial findings (sequence of onset) and reported that associations between cannabis use and the use of other illicit drugs remain after controlling for potentially confounding factors, the mechanisms underlying these observed associations remain hotly debated. In particular, it is possible that the observed associations are non‐causal but reflect the influence of confounding factors which influence both early‐onset drug use and subsequent progressions. However, research employing a range of techniques to address this issue has been unable to discount the possibility that associations between earlier and subsequent drug use reflect causal processes. This paper reviews Kandel's ongoing contributions to this field, which span 45 years, and discusses both the influence of her work and the controversy that it has aroused.
Important patient and public (PPI) perspectives on addiction as a reason for performing euthanasia
Authors: Irving Andy
Published: March 2018

Commentary to: The need to exercise caution in accepting addiction as a reason for performing euthanasia
Women‐only treatment? Epistemologies of ignorance, intersectionality and the need for a feminist embodiment approach
Authors: Ettorre Elizabeth
Published: March 2018

Commentary to: Do women with complex alcohol and other drug use histories want women-only residential treatment?
Attempts to reduce alcohol intake and treatment needs among people with probable alcohol dependence in England: a general population survey
Authors: Dunne Jacklyn , Kimergård Andreas , Brown Jamie , Beard Emma , Buykx Penny , Michie Susan , Drummond Colin
Published: March 2018

Aims

To compare the proportion of people in England with probable alcohol dependence [Alcohol Use Disorders Identification Test (AUDIT) score ≥ 20] with those with other drinking patterns (categorized by AUDIT scores) in terms of motivation to reduce drinking and use of alcohol support resources.

Design

A combination of random probability and simple quota sampling to conduct monthly cross‐sectional household computer‐assisted interviews between March 2014 and August 2017.

Setting

The general population in all nine regions of England.

Participants

Participants in the Alcohol Toolkit Study (ATS), a monthly household survey of alcohol consumption among people aged 16 years and over in England (n = 69 826). The mean age was 47 years [standard deviation (SD) = 18.78; 95% confidence interval (CI) = 46.8–47] and 51% (n = 35 560) were female.

Measurements

χ2 tests were used to investigate associations with demographic variables, motivation to quit drinking, attempts to quit drinking, general practitioner (GP) engagement and types of support accessed in the last 12 months across AUDIT risk zones.

Findings

A total of 0.6% were classified as people with probable alcohol dependence (95% CI = 0.5–0.7). Motivation to quit (χ2 = 1692.27, P < 0.001), current attempts (χ2 = 473.94, P < 0.001) and past‐year attempts (χ2 = 593.67, P < 0.001) differed by AUDIT risk zone. People with probable dependence were more likely than other ATS participants to have a past‐year attempt to cut down or quit (51.8%) and have received a specialist referral from their GP about drinking (13.7%), and less likely to report no motivation to reduce their drinking (26.2%). Those with probable dependence had higher use of self‐help books and mobile applications (apps) than other ATS participants; however, 27.7% did not access any resources during their most recent attempt to cut down.

Conclusions

Adults in England with probable alcohol dependence, measured through the Alcohol Use Disorders Identification Test, demonstrate higher motivation to quit drinking and greater use of both specialist treatment and self‐driven support compared with those in other Alcohol Use Disorders Identification Test zones, but most do not access treatment resources to support their attempts.
Keeping secrets: Leslie E. Keeley, the gold cure and the 19th‐century neuroscience of addiction
Authors: Hickman Timothy A.
Published: March 2018

Background and Aims

Dr Leslie E. Keeley was perhaps the world's most famous addiction cure doctor at the turn of the 20th century, but mainstream medicine dismissed him as a quack because he dispensed a secret cure. This paper aims to describe Keeley's now largely forgotten story and to draw attention to the role of contextual issues in the acceptance or rejection of any theory of addiction, particularly the neuroscientific theories of the early 21st century.

Methods

This study is a qualitative assessment and contextualization of historical documents. Its main sources are archival and are, for the most part, unknown to historians. The paper also offers intellectual and historical context that is drawn from leading historical and sociological analyses.

Results

Keeley's addiction cure was dismissed as quackery because it failed to meet the changing standards of late 19th‐century professional medicine. This begs us to consider contextual issues in any assertion of the viability of addiction therapeutics, in the present as well the past.

Conclusions

Keeley's near erasure from the historical record was a consequence of a broader, late 19th‐century medical power struggle that took precedence over the testimony of tens of thousands of satisfied patients who claimed that Keeley's cure worked. Context matters in the assessment of the viability of theories of addiction from the past, but also from the present. Historians and social scientists are well placed to make those assessments.
Treatment response and non‐response in CBT and Network Support for alcohol disorders: targeted mechanisms and common factors
Authors: Litt Mark D. , Kadden Ronald M. , Tennen Howard
Published: March 2018

Aims

To determine whether mechanisms of drinking behavior change that are targeted by specific treatments mediate the effects of Packaged Cognitive Behavior Therapy (PCBT) and Network Support (NS) on abstinence rates throughout 27 months.

Design

Secondary analysis of data from two Network Support Project randomized clinical trials, in which participants were assigned to either a case management control treatment (control) or NS treatment in trial 1, or to PCBT or NS treatment in trial 2.

Setting

An out‐patient substance abuse treatment site at a university medical center in the United States.

Participants

A total of 249 men and 154 women (n = 403) with alcohol use disorder.

Measurements

The primary outcome was membership in a treatment responder class determined by growth mixture modeling (GMM) of monthly proportion days abstinent (PDA) to 27 months. Key predictors of responder class membership included network change variables, and changes in coping scores and self‐efficacy.

Findings

GMM analyses indicated that a three‐class solution provided the best fit to the data: a treatment responder class comprising almost 55% of patients, a late relapsing class that showed post‐treatment gains followed by a return to baseline drinking (12.7% of patients) and a non‐responder class (32% of patients). Analyses indicated that treatment effects on responder class membership were moderated by baseline drinking (P < 0.001). PCBT effects were mediated by changes in coping scores (P < 0.05). NS treatment effects were also mediated by coping change, as well as by increases in self‐efficacy and in number of abstinent friends (P < 0.05).

Conclusions

Long‐term success in Packaged Cognitive Behavior Therapy and Network Support treatments for alcohol use disorder appears to be mediated by both general mechanisms (developing coping skills and self‐efficacy) and treatment‐targeted mechanisms (developing network strategies that emphasize social support and avoiding friends who drink).
Effects of chelating agent and acids on Biodentine
Authors: Ballal V , Marques JN , Campos CN , Lima CO , Simão RA , Prado M
Published: March 2018

Background

To evaluate the effect of distilled water, ethylenediaminetetraacetic acid (EDTA), phosphoric acid and maleic acid on Biodentine regarding surface topography, microhardness and push‐out bond strength (POBS).

Methods

Fifty‐two cylindrical shaped Biodentine specimens were divided into groups: control (distilled water); EDTA (17% EDTA); PA (37% phosphoric acid); and MA (7% maleic acid). Surfaces were evaluated by topographic analysis and Vickers microhardness test. Topographic changes were evaluated qualitatively and microhardness was statistically analyzed by Kruskal–Wallis test. Forty mandibular molars were used to simulate clinical conditions. The crowns were removed and a perforation was created at the furcal floor. The Biodentine was packed into the root perforations and the roots were divided into four groups (DW, EDTA, PA, MA). Samples were stored and subjected to interfacial analysis. POBS data were analyzed by Kruskal–Wallis and Dunn tests.

Results

Ethylenediaminetetraacetic acid, MA and PA changed the morphology of the Biodentine surface. PA showed microhardness similar to distilled water (P > 0.05), while MA and EDTA demonstrated reduced values when compared with PA (P < 0.05). PA improved the POBS of Biodentine in comparison with the control.

Conclusions

Changes in the topography, microhardness and POBS of Biodentine are associated with irrigant agent used.
Differential seedling regeneration patterns across forest–grassland ecotones in two tropical treeline species (Polylepis spp.)
Authors: Morales Laura V. , Sevillano‐Rios Cristian Steven , Fick Stephen , Young Truman P.
Published: March 2018

Successful forest expansion into grassland can be limited by seed dispersal and adverse conditions for tree seedlings in the grassland environment. In the high‐elevation Andes, human‐induced fragmentation has exacerbated the patchy distribution of Polylepis forests, threatening their unique biological communities and spurring restoration interest. Studies of Polylepis forest extent in Peru suggest that forest borders have remained stable over the past century despite decreasing anthropogenic disturbance, suggesting that tree seedling recruitment is being limited in the open grassland habitat. We studied natural seedling dispersion patterns of Polylepis sericea and Polylepis weberbaueri (Rosaceae) at forest–grassland edges across a range of environmental conditions to examine seedling recruitment and colonization of grasslands in Huascaran National Park (Peru). Using data from 2367 seedlings found in 48 forest–grassland edge plots (15 m × 15 m) at forest patches between 3900–4500 masl, we employed generalized mixed modelling to identify the significant associations of seedling densities with environmental covariates. In addition, we compared these associations to patterns of adult presence on the landscape. Seedling densities were associated with a combination of variables varying within (distance to forest edge) and among (elevation and dry season solar irradiation) plots across the landscape. For both species, seedling densities decreased with increasing distance away from the forest in a manner consistent with short‐distance seed dispersal by wind. Our results suggest that such short‐distance dispersal may slow forest expansion, but that there also appear to be substantial post‐dispersal limitations to seedling establishment in the grassland. Polylepis sericea densities decreased with elevation, while P. weberbaueri increased with elevation and decreased with solar irradiation. Associations of adult presence with elevation and solar irradiation mirrored those of seedling densities. Management of areas with forest patches dominated by these species should consider these differences in their environmental tolerances, particularly during species selection and zonation for reforestation.
Promoting and developing insect conservation in Australia's urban environments
Authors: New Tim R
Published: March 2018

Accelerating pressures to accommodate rapidly increasing human populations in Australia pose major problems for insect conservation in urban and periurban regions from loss of natural habitats, alien species impacts and a variety of other causes. Several urban insects have become notable flagships for promoting wider conservation interests, leading to wider appreciation of environmental benefits of ‘open spaces’, urban forests, connectivity, ‘green architecture’ and other landscape features as relevant planning considerations in urban development. Their conservation, under a range of ecological contexts and threats, occurs in conjunction with energetic advocacy and educational programs that can emphasise the roles and diversity of Australia's unique insect fauna. Approaches to conserving native insects amidst urban intensification are discussed from selected case studies and citizen science projects that illustrate principles and complexities of single‐species conservation, the values of indicator and diversity surrogate taxa and the implications of alien species on native insect diversity and its losses in urban environments. Important lessons and implications include the following: (1) recognition that taxonomic and ecological diversity of insects can be high in urban areas; (2) acknowledgment that insect diversity in urban environments is vulnerable to changes and a variety of threatening processes; (3) mitigation responses that involve reducing threats, preserving open spaces with natural vegetation, creating new open areas and promoting connectivity; (4) establishment of partnerships that enhance conservation values and prospects through individual people, local authorities and government agencies; and (5) increasing awareness of insects as integral components of ecological sustainability contributing to the wider values of urban environments.
In silico characterization of functional single nucleotide polymorphisms of folate pathway genes
Authors: Vohra Manik , Sharma Anu Radha , Paul Bobby , Bhat Manoj K , Satyamoorthy Kapaettu , Rai Padmalatha S.
Published: March 2018

Folate metabolism genes are pivotal to critical biological processes and are related to several conditions, including developmental, cognitive, and cardiovascular anomalies. A systematic catalog of genetic polymorphisms in protein coding regions, regulatory transcription factor binding sites, and miRNA binding sites associated with folate pathway genes may contribute to personalized medicine. We performed a comprehensive computational survey of single nucleotide polymorphisms (SNPs) of folate pathway genes to highlight functional polymorphisms in the coding region, transcription factor binding sites, and miRNAs binding sites. Folate pathway genes were searched through PubMed and Kyoto Encyclopedia of Genes and Genomes pathway databases. SNPs were identified and characterized using the University of California, Santa Cruz genome browser and SNPnexus tool. Functional characterization of nonsynonymous SNPs (nsSNPS) was performed using bioinformatics tools, and common deleterious nsSNPs were identified. We identified 48 genes of folate pathway containing 287 SNPs in the coding regions. Out of these SNPs, rs5742905, rs45511401, and rs1801133 were predicted to be deleterious through four different bioinformatics tools. Three‐dimensional structures of two proteins with and without deleterious nsSNPs were predicted by SWISSPDB viewer and SuperPose. Besides, a total of 237 SNPs was identified in transcription factor binding sites using the Genomatix software suite and six miRNA target site SNPs using miRNASNP. This systematic and extensive in silico analysis of functional SNPs of folate pathway may provide a foundation for future targeted mechanistic, structure‐function, and genetic epidemiological studies.
Exosomal tetraspanins as regulators of cancer progression and metastasis and novel diagnostic markers
Authors: Malla Rama Rao , Pandrangi Santhi , Kumari Seema , Gavara Murali Mohan , Badana Anil Kumar
Published: March 2018

Exosomes are cell–cell communicators emerging as a new paradigm for noninvasive diagnosis and prognosis of treatment response. Exosomal tetraspanin proteins like CD63, CD9 and CD81 play a critical role in sorting, selective recruitment of biomolecules, target selection, cell‐specific entry, capturing, angiogenesis and vasculogenesis. These tetraspanins are being used as markers for oral, colorectal and colon cancers and glioblastoma. However, exosomal markers with robust specificity for early detection of carcinomas are the furthest along. EXO CARTA database shows the presence of CD151 in exosomes of colorectal, melanoma, ovarian and prostate cancers. CD151 preferentially targets exosomes to lung, lymph node and stroma cells. The present review discussed the possible role of tetraspanins in the formation, cargo selection, target selection and uptake of exosomes and suggests exciting new directions for future research.
Making Austerity Popular: The Media and Mass Attitudes toward Fiscal Policy
Authors: Barnes Lucy , Hicks Timothy
Published: March 2018

What explains variation in individual attitudes toward government deficits? Although macroeconomic stance is of paramount importance for contemporary governments, our understanding of its popular politics is limited. We argue that popular attitudes regarding austerity are influenced by media (and wider elite) framing. Information necessary to form preferences on the deficit is not provided neutrally, and its provision shapes how voters understand their interests. A wide range of evidence from Britain between 2010 and 2015 supports this claim. In the British Election Study, deficit attitudes vary systematically with the source of news consumption, even controlling for party identification. A structural topic model of two major newspapers' reporting shows that content varies systematically with respect to coverage of public borrowing—in ways that intuitively accord with the attitudes of their readership. Finally, a survey experiment suggests causation from media to attitudes: deficit preferences change based on the presentation of deficit information.
Sectarian Framing in the Syrian Civil War
Authors: Corstange Daniel , York Erin A.
Published: March 2018

How do civilians respond to civil war narratives? Do they react to ethnic frames more strongly than to alternatives? Governments and rebels battle for hearts and minds as well as strategic terrain, and winning the narrative war can shift legitimacy, popular support, and material resources to the sympathetically framed side. We examine the effect of one‐sided and competing war discourses on ordinary people's understandings of the Syrian civil war—a conflict with multiple narratives, but which has become more communal over time. We conduct a framing experiment with a representative sample of Syrian refugees in Lebanon in which we vary the narrative that describes the reasons for the conflict. We find that sectarian explanations, framed in isolation, strongly increase the importance government supporters place on fighting. When counterframed against competing narratives, however, the rallying effect of sectarianism drops and vanishes.
Childhood asthma clusters reveal neutrophil‐predominant phenotype with distinct gene expression
Authors: Su M.‐W. , Lin W.‐C. , Tsai C.‐H. , Chiang B.‐L. , Yang Y.‐H. , Lin Y.‐T. , Wang L.‐C. , Lee J.‐H. , Chou C.‐C. , Wu Y.‐F. , Yeh Y.‐L. , Lee Y. L.
Published: March 2018

Background

Childhood asthma comprises different phenotypes with complex pathophysiology. Different asthma phenotypes evoke various clinical symptoms and vary in their responses to treatments.

Methods

We applied k‐means clustering algorithm of twelve objective laboratory tests among 351 asthmatic children enrolled in the Taiwanese Consortium of Childhood Asthma Study (TCCAS). We constructed gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with different asthma phenotypes.

Results

Five distinct phenotypes of childhood asthma were identified and can be characterized by either eosinophil‐predominant or neutrophil‐predominant inflammatory characteristics. In the gene expression profile analysis, significant differences were noted for neutrophil‐predominant asthma, compared with samples from all the other asthma phenotypes. The vast majority of the differentially expressed genes in neutrophil‐predominant asthma was associated with corticosteroid response. From an independent inhaled corticosteroid (ICS) response cohort, we also found neutrophils could be activated in this severe asthma phenotype and neutrophil‐predominant asthma may be associated with corticosteroid nonresponsiveness.

Conclusion

Phenotype clustering of childhood asthma can be helpful to identify clinically relevant patients and reveal different inflammatory characteristics in asthmatic children. Neutrophil‐predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Gene expression profile of different asthma phenotypes not only improve our knowledge of childhood asthma, but also can guide asthma precision medicine.
Topical application of corticosteroids to tracheal tubes to prevent postoperative sore throat in adults undergoing tracheal intubation: a systematic review and meta‐analysis
Authors: Kuriyama A. , Maeda H. , Sun R. , Aga M.
Published: March 2018

Postoperative sore throat negatively affects patient satisfaction and recovery. Numerous randomised trials have tested the efficacy of corticosteroids applied to tracheal tubes to prevent postoperative sore throat. We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Wanfang Database, and the China Academic Journal Network Publishing Database from inception to 7 December 2017. We included randomised controlled trials that assessed the efficacy and safety of corticosteroids applied to tracheal tubes, compared either with non‐analgesic controls and analgesic agents, in adults undergoing elective surgery under general anaesthesia. We pooled the data using a random‐effects model and assessed the risk of random error by applying trial sequential analysis. Our primary outcomes were postoperative sore throat 24 h after surgery/extubation, and adverse events. The evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We included 20 randomised controlled trials involving 2200 patients. Compared with non‐analgesic controls, corticosteroids applied to tracheal tubes were associated with a reduced incidence of postoperative sore throat, risk ratio (95%CI) 0.39 (0.32–0.49) (18 trials, 1506 patients). Two randomised trials reported no adverse events. Compared with lidocaine, corticosteroids applied to tracheal tubes were associated with reduced incidence of postoperative sore throat, risk ratio (95%CI) 0.42 (0.35–0.51) (nine trials, 706 patients). Trial sequential analyses suggested the presence of firm evidence that corticosteroids applied to tracheal tubes were superior both to non‐analgesic controls and lidocaine, in preventing postoperative sore throat. Evidence for postoperative sore throat for both comparisons was assessed as high quality. Only two trials sought adverse events; none were recorded.
Obstetric synthetic oxytocin use and subsequent hyperactivity/inattention problems in Danish children
Authors: Stokholm Lonny , Juhl Mette , Lønfeldt Nicole N. , Mikkelsen Susanne H. , Obel Carsten , Strandberg‐Larsen Katrine
Published: March 2018

Introduction

The objective was to examine the association between obstetric synthetic oxytocin use and hyperactivity/inattention problems in offspring.

Material and methods

We identified children born in 2000–2003, enrolled in the Danish National Birth Cohort, with data on the Strengths and Difficulties Questionnaire (SDQ) reported by parents at age seven (n = 33 896) and age 11 (n = 27 561) and the children themselves around age 11 (n = 27 251). Information on oxytocin administration was provided in the Medical Birth Register. We estimated mean differences and odds ratios for childhood hyperactivity/inattention problems according to oxytocin exposure.

Results

Synthetic oxytocin was administered in 26% of the deliveries. We did not find the use of synthetic oxytocin during birth to be associated with childhood hyperactivity/inattention problems, whether analyzed in linear or logistic regression models.

Conclusions

Our findings do not support any effects of obstetric use of synthetic oxytocin on hyperactivity/inattention problems in children when measured with the SDQ subscale at 7 or 11 years of age.
Investigation of the Relationship Between Electrical Stimulation Frequency and Muscle Frequency Response Under Submaximal Contractions
Authors: Papcke Caluê , Krueger Eddy , Olandoski Marcia , Nogueira‐Neto Guilherme Nunes , Nohama Percy , Scheeren Eduardo Mendonça
Published: March 2018

Neuromuscular electrical stimulation (NMES) is a common tool that is used in clinical and laboratory experiments and can be combined with mechanomyography (MMG) for biofeedback in neuroprostheses. However, it is not clear if the electrical current applied to neuromuscular tissues influences the MMG signal in submaximal contractions. The objective of this study is to investigate whether the electrical stimulation frequency influences the mechanomyographic frequency response of the rectus femoris muscle during submaximal contractions. Thirteen male participants performed three maximal voluntary isometric contractions (MVIC) recorded in isometric conditions to determine the maximal force of knee extensors. This was followed by the application of nine modulated NMES frequencies (20, 25, 30, 35, 40, 45, 50, 75, and 100 Hz) to evoke 5% MVIC. Muscle behavior was monitored by the analysis of MMG signals, which were decomposed into frequency bands by using a Cauchy wavelet transform. For each applied electrical stimulus frequency, the mean MMG spectral/frequency response was estimated for each axis (X, Y, and Z axes) of the MMG sensor with the values of the frequency bands used as weights (weighted mean). Only with respect to the Z (perpendicular) axis of the MMG signal, the stimulus frequency of 20 Hz did not exhibit any difference with the weighted mean (P = 0.666). For the frequencies of 20 and 25 Hz, the MMG signal displayed the bands between 12 and 16 Hz in the three axes (P < 0.050). In the frequencies from 30 to 100 Hz, the muscle presented a higher concentration of the MMG signal between the 22 and 29 Hz bands for the X and Z axes, and between 16 and 34 Hz bands for the Y axis (P < 0.050 for all cases). We observed that MMG signals are not dependent on the applied NMES frequency, because their frequency contents tend to mainly remain between the 20‐ and 25‐Hz bands. Hence, NMES does not interfere with the use of MMG in neuroprosthesis.
Evaluation and Comparison of Hemodynamic Performance of Three ECLS Systems in a Simulated Adult Cardiogenic Shock Model
Authors: Ündar Akif , Wang Shigang , Moroi Morgan , Kunselman Allen R. , Brehm Christoph E.
Published: March 2018

The objective of this study was to evaluate three commercially available ECLS systems with rotary pumps in terms of circuit pressure, pressure drop, perfusion modes, and hemodynamic energy transmission in a simulated adult cardiogenic shock model. One circuit consisted of a Cardiohelp system, which included a Cardiohelp console and HLS Module Advanced 7.0 tubing set with integrated centrifugal pump and oxygenator. The alternative circuit was composed of a Quadrox‐D Adult oxygenator connected in series with either an i‐cor diagonal pump and console or a Rotaflow centrifugal pump and console. The circuit was primed with lactated Ringer's solution and packed red blood cells (hematocrit 40%). The trials were conducted at flow rates of 1‐5 L/min with pseudo patient pressures of 60 mm Hg and 80 mm Hg. Pulsatile flow was tested when using the i‐cor system. Mean pre‐oxygenator pressure and pressure drop across ECLS circuit (including oxygenator and arterial tubing) were lower when using the Cardiohelp system as compared to the Rotaflow and i‐cor systems (P < 0.01). The i‐cor system was able to deliver more hemodynamic energy to the pseudo patient because of its ability to produce pulsatile flow (P < 0.01). The Cardiohelp HLS Module Advanced 7.0 integrated oxygenator had a lower resistance than the Quadrox‐D oxygenator. Although the compact Cardiohelp system had a better hemodynamic performance when compared to Rotaflow and i‐cor systems, the pulsatile flow of the i‐cor system delivered more hemodynamic energy to the pseudo patient. This may render more physiological benefits in high‐risk patients on ECLS.
Correlation between observation task performance and visual acuity, contrast sensitivity and environmental light in a simulated maritime study
Authors: Koefoed Vilhelm F. , Assmuss Jörg , Høvding Gunnar
Published: March 2018

Purpose

To examine the relevance of visual acuity (VA) and index of contrast sensitivity (ICS) as predictors for visual observation task performance in a maritime environment.

Methods

Sixty naval cadets were recruited to a study on observation tasks in a simulated maritime environment under three different light settings. Their ICS were computed based on contrast sensitivity (CS) data recorded by Optec 6500 and CSV‐1000E CS tests. The correlation between object identification distance and VA/ICS was examined by stepwise linear regression.

Results

The object detection distance was significantly correlated to the level of environmental light (p < 0.001), but not to the VA or ICS recorded in the test subjects. Female cadets had a significantly shorter target identification range than the male cadets.

Conclusion

Neither CS nor VA were found to be significantly correlated to observation task performance. This apparent absence of proven predictive value of visual parameters for observation tasks in a maritime environment may presumably be ascribed to the normal and uniform visual capacity in all our study subjects.
Evaluation of two‐dimensional Bruch's membrane opening minimum rim area for glaucoma diagnostics in a large patient cohort
Authors: Enders Philip , Adler Werner , Kiessling David , Weber Vincent , Schaub Friederike , Hermann Manuel M. , Dietlein Thomas , Cursiefen Claus , Heindl Ludwig M.
Published: March 2018

Purpose

To characterize the two‐dimensional parameter Bruch's membrane opening minimum rim area (BMO‐MRA) in spectral domain optical coherence tomography (SD‐OCT) of the optic nerve head (ONH) compared to minimum rim width (BMO‐MRW) and retinal nerve fibre layer (RNFL) thickness in a large patient cohort.

Methods

Case–control, cross‐sectional study of 705 eyes of 445 participants. A total of 449 eyes with glaucoma, 67 eyes with ocular hypertension and 189 healthy controls, underwent SD‐OCT and confocal laser scanning tomography (CSLT), visual field testing and clinical examination. Morphometric ONH parameters, visual field function and diagnostic power were compared. Main outcome measures were SD‐OCT‐derived BMO‐MRA, BMO‐MRW, RNFL thickness and CSLT‐derived rim area (DM‐RA).

Results

Mean ONH area was 2.11 ± 0.57 mm2; mean BMO area was 1.89 ± 0.45 mm2. Correlation of mean deviation in visual field to morphometric parameters was ρ = 0.70, (p < 0.001) for RNFL thickness, ρ = 0.68 (p < 0.001) for BMO‐MRA, ρ = 0.66 (p < 0.001) for BMO‐MRW. These correlations were not significantly different (p > 0.05), while DM‐RA correlated significantly worse (ρ = 0.55; p < 0.001). In receiver operating characteristics, the calculated area under the curve (AUC) and sensitivity at 90% specificity to differentiate glaucoma were 0.87% and 70.1% for BMO‐MRA, 0.86% and 68.1% for RNFL thickness, 0.84% and 66.0% for BMO‐MRW, 0.82% and 51.3% for DM‐RA.

Conclusions

In a heterogenous clinical cohort of glaucoma patients, all analysed SD‐OCT parameters excel DM‐RA of CSLT. The two‐dimensional parameter BMO‐MRA shows comparable levels of diagnostic power to detect glaucoma compared to established parameters BMO‐MRW and RNFL thickness. Given higher comparability between ONH sizes, BMO‐MRA might become an additional standard tool in SD‐OCT imaging for glaucoma.
Consensus on procedures to include in a simulation‐based curriculum in ophthalmology: a national Delphi study
Authors: Thomsen Ann Sofia Skou , la Cour Morten , Paltved Charlotte , Lindorff‐Larsen Karen Gilboe , Nielsen Bjørn Ulrik , Konge Lars , Nayahangan Leizl Joy
Published: March 2018

Purpose

The number of available simulation‐based models for technical skills training in ophthalmology is rapidly increasing, and development of training programmes around these procedures should follow a structured approach. The aim of this study was to identify all technical procedures that should be integrated in a simulation‐based curriculum in ophthalmology.

Methods

Key opinion leaders involved in the education of ophthalmologists in Denmark including heads of departments, heads of clinical education, professors and board members of the society were invited to participate in a three‐round Delphi process. Round 1 aimed at identifying technical procedures that physicians should be able to perform competently when completing specialty training; round 2 involved characterization of each procedure including frequency, number of operators, risk and/or discomfort for patients associated with an inexperienced physician, and feasibility of simulation‐based training; round 3 included a priority ranking of procedures.

Results

The response rate for each round was 71%, 64% and 64%, respectively. Sixty‐five procedures were reduced to 25 prioritized procedures during the three rounds. Two‐thirds of the procedures that were identified and highly prioritized were therapeutic procedures such as intravitreal injection therapy, yttrium–aluminium–garnet laser iridotomy/capsulotomy, minor ocular surface procedures and retinal argon laser therapy. The diagnostic procedures that were prioritized were ocular ultrasound, superficial keratectomy and optical coherence tomography (OCT).

Conclusion

The Delphi process identified and prioritized 25 procedures that should be practised in a simulation‐based environment to achieve competency before working with patients. The list may be used to guide the development of future training programmes for ophthalmologists.
Beta‐peripapillary atrophy of the optic disc and its determinants in Japanese eyes: a population‐based study
Authors: Mataki Naomi , Tomidokoro Atsuo , Araie Makoto , Iwase Aiko
Published: March 2018

Purposes

To assess β‐zone of peripapillary atrophy (β‐PPA) and its relationship between systemic and ocular factors, especially glaucoma, in a Japanese population.

Methods

Fundus photographs obtained from 2129 normal, 84 primary open‐angle glaucoma (POAG) and 10 primary angle closure glaucoma subjects from 3021 participants aged 40 years or older in the Tajimi Study were analysed planimetrically. If both eyes of a subject met inclusion criteria, one eye was randomly chosen.

Results

The presence rates of β‐PPA were 54.7 and 77.4% (p < 0.001) and β‐PPA area averaged 0.67 and 1.06 mm2 (p < 0.001), in normal and POAG eyes, respectively. Myopia was closely related to disc ovality and β‐PPA. In normal eyes, logistic analysis showed that the presence of β‐PPA was correlated with older age, female gender, myopic refraction, thicker central corneal thickness (CCT), greater disc ovality and disc centre to fovea (disc‐fovea) distance and lower intraocular pressure (IOP) (p = 0.039 ~ <0.001); and multiple regression analysis showed that β‐PPA area was correlated with older age, myopic refraction, greater disc area and ovality, disc‐fovea distance and lower IOP (p = 0.004 ~ <0.001) after adjusting other factors.

Conclusions

The presence and size of β‐PPA in normal eyes were correlated with older age, greater disc ovality and disc‐fovea distance and lower IOP. Further, its presence was associated with female gender, thicker CCT and its size with greater disc area. β‐zone of peripapillary atrophy (β‐PPA) was also associated with POAG. These results provide reference data of the β‐PPA in a Japanese population and possibly indicate clinical importance of β‐PPA in glaucoma clinic.
Noninvasive evaluation of cerebrospinal fluid pressure in ocular hypertension: a preliminary study
Authors: Xie Xiaobin , Chen Weiwei , Li Zhen , Thomas Ravi , Li Yong , Xian Junfang , Yang Diya , Wang Huaizhou , Zhang Shoukang , Kang Zefeng , Wang Ningli ,   the Beijing Intraocular and Intracranial Study Group
Published: March 2018

Purpose

To compare the orbital cerebral spinal fluid pressure (CSFP) and trans‐lamina cribrosa pressure difference (TLCPD) determined noninvasively in ocular hypertensive (OH) subjects and controls.

Methods

Cross‐sectional observational study. Magnetic resonance imaging was used to measure orbital subarachnoid space width (OSASW). The CSFP (mm Hg) was estimated from a published formula as 17.54 × MRI derived OSASW at 15 mm behind the globe + 0.47 × body mass index + 0.13 × mean arterial blood pressure −21.52. Estimated TLCPD was calculated as IOP‐ CSFP.

Results

The orbital subarachnoid space width was significantly wider (p = 0.01) in the OH group than in the control group at all three measurement locations. The MRI derived CSFP value in OH (14.9 ± 2.9 mm Hg) was significantly higher than in the normal group (12.0 ± 2.8 mm Hg; p < 0.01). The estimated TLCPD value in OH (9.0 ± 4.2 mm Hg) was significantly higher than in controls (3.6 ± 3.0 mm Hg; p < 0.01).

Conclusion

The wider OSASW and higher estimated CSFP in OH subjects suggest a higher orbital CSFP. Despite a higher orbital CSFP that could be protective, the higher TLCPD in OH may play a significant role in the risk of developing glaucoma.