bluuebunny/crossref_metadata_2025 huggingface dataset:
Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia
Authors: Travaglino Antonio , Raffone Antonio , Saccone Gabriele , Mollo Antonio , De Placido Giuseppe , Mascolo Massimo , Insabato Luigi , Zullo Fulvio
Published: February 2019

The 2014 World Health Organization (WHO) classification of endometrial hyperplasia (EH) defines premalignant EH based on only cytologic atypia, disregarding architecture complexity. We aimed to assess the impact of architecture complexity on the risk of cancer in non‐atypical EH. A systematic review and meta‐analysis was performed by searching electronic databases form their inception to October 2018. All studies assessing the rates of progression to cancer in non‐atypical EH (simple vs complex) were included. Pooled relative risk (RR) for cancer progression was calculated; a p‐value < 0.05 was considered significant. Eight studies with 1066 women were included. The risk for progression of non‐atypical EH to cancer was significantly higher in complex EH than in simple EH (p < 0.0001), with an RR of 4.90. In conclusion, the complexity of glandular architecture significantly increases the risk of cancer in non‐atypical EH. Complex non‐atypical EH may be regarded as a low‐risk premalignant lesion rather than a benign condition.
Setting the Foundations for Theoretical Progress toward Understanding the Role of Values in Organisational Behaviour: Commentary on “Values at Work: The Impact of Personal Values in Organisations” by Arieli, Sagiv, and Roccas
Authors: Maio Gregory R. , Hanel Paul H.P. , Martin Robin , Lee Allan , Thomas Geoff
Published: February 2019

Arieli, Sagiv, and Roccas’s lead article provides a timely and important review of the role of individual values and their role in organisations. At the same time as identifying several key areas of progress, the review identifies significant gaps. In this commentary, we focus on additional gaps that merit attention. In particular, we highlight a need for greater theoretical clarity in the literature about the concrete ways in which values are instantiated in different organisational contexts, roles, and cultural settings. We argue that the growing importance of values in studies of organisational contexts would be well‐served by more precision in how they are conceptualised and operationalised in studies of organisational behaviour.
Outcomes following restrictive or liberal red blood cell transfusion in patients with lower gastrointestinal bleeding
Authors: Kherad Omar , Restellini Sophie , Martel Myriam , Sey Michael , Murphy Michael F. , Oakland Kathryn , Barkun Alan , Jairath Vipul
Published: February 2019

Background

Restrictive red blood cell (RBC) transfusion reduces mortality and rebleeding after upper gastrointestinal bleeding (UGIB). However, there is no evidence to guide transfusion strategies in lower gastrointestinal bleeding (LGIB).

Aim

To assess the association between RBC transfusion strategies and outcomes in patients with LGIB

Methods

This was a post hoc analysis of the UK National Comparative Audit of LGIB and the Use of Blood. The relationships between liberal RBC transfusion and clinical outcomes of rebleeding, mortality and a composite outcome for safe discharge were examined. Transfusion strategy was dichotomised and defined as “liberal” when transfusion was administered for haemoglobin (Hb) ≥80 g/L (or ≥90 g/L in patients with acute coronary syndrome) or major haemorrhage, and “restrictive” otherwise. Multivariable logistic regression models were used to assess the independent association between liberal RBC transfusion and outcomes.

Results

Of 2528 consecutive patients enrolled from 143 hospitals in the original study, 666 (26.3%) received RBC transfusion (mean age 73.3 ± 16 years, 49% female, initial mean haemoglobin 90 ± 24 g/L, 2.3% had haemodynamic instability). The rebleeding rate in transfused patients was 42.3%. After adjusting for potential confounders, there was no difference between liberal and restrictive RBC transfusion strategies for the odds of rebleeding (OR 0.89, 95% CI 0.6‐1.22), in‐hospital mortality (OR 0.54, 95% CI 0.3‐1.1) or of achieving the composite outcome (OR 0.72, 95% CI 0.5‐1.1).

Conclusion

Although these results could be due to residual confounding, they provide an important foundation for the design of randomised trials to evaluate transfusion strategies for LGIB.
The impact of human CES1 genetic variation on enzyme activity assessed by ritalinic acid/methylphenidate ratios
Authors: Stage Claus , Dalhoff Kim , Rasmussen Henrik Berg , Schow Guski Louise , Thomsen Ragnar , Bjerre Ditte , Ferrero‐Miliani Laura , Busk Madsen Majbritt , Jürgens Gesche
Published: February 2019

The present clinical trial investigated the impact of selected SNPs in CES1 on the metabolic activity of the enzyme. For this purpose, we used methylphenidate (MPH) as a pharmacological probe and the d‐RA/d‐MPH (metabolite/parent drug) ratios as a measure of enzymatic activity. This metabolic ratio (MR) was validated against the AUC ratios (AUCd‐RA/AUCd‐MPH). CES1 SNPs from 120 volunteers were identified, and 12 SNPs fulfilling predefined inclusion criteria were analysed separately, comparing the effect of each genotype on the metabolic ratios. The SNP criteria were as follows: presence of Hardy‐Weinberg equilibrium, a minor allele frequency ≥ 0.01 and a clearly interpretable sequencing result in at least 30% of the individuals. Each participant ingested 10 mg of racemic methylphenidate, and blood samples were drawn prior to and 3 hours after drug administration. The SNP analysis confirmed the considerable impact of rs71647871 (G143E) in exon 4 on drug metabolism. In addition, three volunteers with markedly lower median MR, indicating decreased CES1 activity, harboured the same combination of three SNPs in intron 5. The median MR for these SNPs was 8.2 for the minor allele compared to 16.4 for the major alleles (P = 0.04). Hence, one of these or the combination of these SNPs could be of clinical significance considering that the median MR of the G143E group was 5.4. The precise genetic relationship of this finding is currently unknown, as is the clinical significance.
Histamine, histamine H3 receptor, and alcohol use disorder
Authors: Panula Pertti
Published: February 2019

Alcohol use disorder is associated with several mental, physical, and social problems. Its treatment is difficult and often requires a combination of pharmacological and behavioural therapy. The brain histaminergic system, one of the wake‐active systems that controls whole‐brain activity, operates through three neuronal GPCRs. The histamine H3 receptor (Hrh3), which is expressed in many brain areas involved in alcohol drinking and alcohol reward, can be targeted with a number of drugs developed initially for cognitive disorders and/or disorders related to sleep, wakefulness, and alertness. In all rodent alcohol drinking models tested so far, H3 receptor antagonists have reduced alcohol drinking and alcohol‐induced place preference and cue‐induced alcohol reinstatement. Several H3 receptor antagonists tested and found to be safe for humans could be subjected to clinical tests to treat alcohol use disorder. Preference should be given to short‐acting drugs to avoid the sleep problems associated with the wake‐maintaining effects of the drugs.

Linked Articles

This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc
Therapeutic efficacy evaluation of radioimmunotherapy with 90Y‐labeled anti‐podoplanin antibody NZ‐12 for mesothelioma
Authors: Sudo Hitomi , Tsuji Atsushi B. , Sugyo Aya , Saga Tsuneo , Kaneko Mika K. , Kato Yukinari , Higashi Tatsuya
Published: February 2019

Podoplanin is a type I transmembrane sialomucin‐like glycoprotein that is highly expressed in malignant mesothelioma. The rat‐human chimeric antibody NZ‐12 has high affinity for human podoplanin and antibody‐dependent cellular cytotoxicity and is applicable for radioimmunotherapy (RIT) to enhance the antitumor effect. In the present study, we evaluated the in vivo and in vitro properties of radiolabeled NZ‐12 and the antitumor effect of RIT with 90Y‐labeled NZ‐12 in an NCI‐H226 (H226) malignant mesothelioma xenograft mouse model. 111In‐labeled NZ‐12 bound specifically to H226 cells with high affinity, and accumulation was high in H226 tumors but low in major organs. RIT with 90Y‐labeled NZ‐12 significantly suppressed tumor growth and prolonged survival without body weight loss and obvious adverse effects. Higher podoplanin expression levels were observed in human mesothelioma specimens, suggesting higher tumor accumulation of 90Y‐labeled NZ‐12 in patients compared with the H226 tumor xenografts. Our findings suggest that 90Y‐labeled NZ‐12 is a promising RIT agent as a new therapeutic option for malignant mesothelioma that warrants further clinical studies to evaluate the dosimetry and efficacy in patients.
Mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance
Authors: Takaoka Yuji , Konno Masamitsu , Koseki Jun , Colvin Hugh , Asai Ayumu , Tamari Keisuke , Satoh Taroh , Mori Masaki , Doki Yuichiro , Ogawa Kazuhiko , Ishii Hideshi
Published: February 2019

Mitochondrial pyruvate carrier (MPC) is known to cause different expressions in normal and cancer cells. We observed a change in phenotype with the suppression of MPC expression. We knocked down MPC1 and/or MPC2 using siRNA or shRNA. We observed its cell morphology and accompanying molecular marker. Furthermore, the radioresistance of the MPC knockdown cell line was examined using a colony formation assay. MPC1‐suppressed cells changed their morphology to a spindle shape. Epithelial‐mesenchymal transition (EMT) was suspected, and examination of the EMT marker by PCR showed a decrease in E‐cadherin and an increase in fibronectin. Focusing on glutamine metabolism as the mechanism of this phenomenon, we knocked down the glutamine‐metabolizing enzyme glutaminase (GLS). EMT was also observed in GLS‐suppressed cells. Furthermore, when MPC1‐suppressed cells were cultured in a glutamine‐deficient medium, changes in EMT markers were suppressed. In addition, MPC1‐suppressed cells also increased with a significant difference in radioresistance. Decreased MPC1 expression favorably affects EMT and radioresistance of cancer.
Gender differences in Australasian ophthalmologists' experiences of the workplace
Authors: Jain Neeranjali S. , Kersten Hannah M. , Watson Stephanie L. , Danesh‐Meyer Helen V.
Published: February 2019

Importance

Gender differences were identified in experiences of the workplace and family responsibilities amongst Australian and New Zealand ophthalmologists.

Background

To survey ophthalmologists regarding their balance of career, family and workplace experiences and to identify gender differences.

Design

Online questionnaire sent to 1000 randomly selected Royal Australian and New Zealand College of Ophthalmologists (RANZCO) Fellows in 2017.

Participants

The response rate was 28% (n = 282) with 192 males.

Methods

Confidential questionnaire.

Main Outcome Measures

Questionnaire responses.

Results

Gender differences were noted in working hours (59% of males worked greater than 40 hours a week vs 26% of females, P < 0.001) and frequency of private practice work (mean of 6.6 half‐day sessions per week for men vs 4.9 sessions for women, P < 0.001). Female ophthalmologists reported additional obstacles to career advancement including difficulty receiving mentorship (57% vs 40%, P = 0.027), travel difficulties due to family responsibilities (59% vs 34%, P < 0.001) and rigid timelines for promotion/tenure (38% vs 19%, P = 0.005). Female ophthalmologists delayed child‐bearing, with 59% becoming parents after fellowship training. Women spent more time child‐rearing (67% vs 8% of men cared for children >20 hours per week, P < 0.001). Female ophthalmologists were more likely to report experiencing discrimination (31% vs 8% of men, P < 0.001).

Conclusions and Relevance

Female ophthalmologists worked fewer hours, mainly in the private sector, to fulfil their greater family commitments. Female ophthalmologists reported additional obstacles to career advancement and were more likely to report experiencing discrimination in the workplace.
New Zealand childhood ocular trauma study: Analysis of 75 601 cases of ocular injury from 2007 to 2016
Authors: Ferguson Reid A. , Sung Justin , McKelvie James
Published: February 2019

Importance

Childhood ocular injury is a common, preventable cause of potentially severe permanent disability.

Background

This study evaluates the nationwide incidence, demographics and visual outcomes of children with ocular injury in New Zealand.

Design

Nationwide retrospective review.

Participants

All children in New Zealand aged 0 to 17 years from 2007 to 2016 with ocular injury requiring assessment by a medical practitioner.

Methods

New Zealand national and regional datasets were used to evaluate population‐level statistics for ocular injury over a 10‐year period. Visual and clinical outcome data were assessed using a randomized sample of 150 patients.

Main Outcome Measures

Annual incidence, aetiology, demographics, injury location, visual outcomes, protective eyewear use, surgical intervention and follow‐up.

Results

A national total of 75 601 cases were included with a mean incidence of 719/100 000 children/year. Cases were predominantly male (63.2%) and of New Zealand‐European ethnicity (60.8%), aged 0 to 4 years (30.66%). Injury cause was most commonly “struck by object” (53.7%) and occurred in the home (50.9%). Tertiary hospital assessment and treatment was required in 17.7% where final visual acuity of 6/12 or worse was noted in 19.7% and protective eyewear use was reported in 2.7%. Maori and Pacific ethnicities were associated with higher rates of permanent visual impairment.

Conclusions and Relevance

Children with the highest risk of ocular injury are males aged 0 to 4 years. Children of Maori or Pacific Island ethnicity and aged 15 to 17 years have the highest risk of ocular injury resulting in permanent visual impairment. Protective eyewear use is uncommon in children presenting with ocular injury. Promotion of appropriate injury prevention strategies is an important public health message.
Phylogenomic analysis of Calyptratae: resolving the phylogenetic relationships within a major radiation of Diptera
Authors: Narayanan Kutty Sujatha , Meusemann Karen , Bayless Keith M. , Marinho Marco A. T. , Pont Adrian C. , Zhou Xin , Misof Bernhard , Wiegmann Brian M. , Yeates David , Cerretti Pierfilippo , Meier Rudolf , Pape Thomas
Published: February 2019

The Calyptratae, one of the most species‐rich fly clades, only originated and diversified after the Cretaceous–Palaeogene extinction event and yet exhibit high species diversity and a diverse array of life history strategies including predation, phytophagy, saprophagy, haematophagy and parasitism. We present the first phylogenomic analysis of calyptrate relationships. The analysis is based on 40 species representing all calyptrate families and on nucleotide and amino acid data for 1456 single‐copy protein‐coding genes obtained from shotgun sequencing of transcriptomes. Topologies are overall well resolved, robust and largely congruent across trees obtained with different approaches (maximum parsimony, maximum likelihood, coalescent‐based species tree, four‐cluster likelihood mapping). Many nodes have 100% bootstrap and jackknife support, but the true support varies by more than one order of magnitude [Bremer support from 3 to 3427; random addition concatenation analysis (RADICAL) gene concatenation size from 10 to 1456]. Analyses of a Dayhoff‐6 recoded amino acid dataset also support the robustness of many clades. The backbone topology Hippoboscoidea+(Fanniidae+(Muscidae+((Anthomyiidae–Scathophagidae)+Oestroidea))) is strongly supported and most families are monophyletic (exceptions: Anthomyiidae and Calliphoridae). The monotypic Ulurumyiidae is either alone or together with Mesembrinellidae as the sister group to the rest of Oestroidea. The Sarcophagidae are sister to Mystacinobiidae+Oestridae. Polleniinae emerge as sister group to Tachinidae and the monophyly of the clade Calliphorinae+Luciliinae is well supported, but the phylogenomic data cannot confidently place the remaining blowfly subfamilies (Helicoboscinae, Ameniinae, Chrysomyinae). Compared to hypotheses from the Sanger sequencing era, many clades within the muscoid grade are congruent but now have much higher support. Within much of Oestroidea, Sanger era and phylogenomic data struggle equally with regard to finding well‐supported hypotheses.
Comanagement of small‐scale fisheries and ecosystem services
Authors: Gelcich Stefan , Martínez‐Harms Maria José , Tapia‐Lewin Sebastián , Vasquez‐Lavin Felipe , Ruano‐Chamorro Cristina
Published: February 2019

Marine ecosystem services are in global decline, which requires new transformational changes in governance to cope with multiple anthropogenic stressors. We perform a systematic literature review of the biodiversity and ecosystem services outcomes of a governance transformation toward comanagement through the allocation of territorial user rights to artisanal fisher associations (TURFs) in Chile. We synthesize the implications of more than 25 years of establishing a TURF policy over ecosystem services. Results show TURFs sustain biodiversity and all typologies of ecosystem services when they are well enforced. Research on provisioning services is most prevalent, however cultural services have been gaining traction with studies assessing the role of leadership, sanctions, and social capital in determining TURF outcomes. The results suggest that TURFs can play an important role in creating social and ecological enabling conditions for local stewardship. While this is encouraging, there is a bias toward positive results and few studies address negative consequences of TURFs aimed at identifying constraints for further development. The review shows that there has been a continuous transition toward interdisciplinary social–ecological research. Research on TURFs faced with drivers of global change and uncertainty are urgently needed, in order to anticipate unintended outcomes and adapt accordingly.
Comparing the effects and compliance between volume‐assured and pressure support non‐invasive ventilation in patients with chronic respiratory failure
Authors: Huang Xu An , Du Yan Ping , Li Liu Xia , Wu Fang Fang , Hong Shao Qing , Tang Fang Xuan , Ye Zhang Qiang
Published: February 2019

Introduction

Standard bi‐level non‐invasive ventilation with fixed‐level pressure support (PS) delivery may not maintain ventilation during the changes in pulmonary mechanics that occur throughout day and night, so average volume‐assured pressure support (AVAPS) modes that target a preset volume by adjustment of PS may be effective.

Objective

Our meta‐analysis wants to compare AVAPS and pressure support non‐invasive ventilation (PS‐NIV) regarding arterial blood gases (ABGs), sleep efficiency and compliance.

Method

Relevant publications indexed in PubMed, Cochrane Library, Embase, Web of Science, Wanfang Data, China National Knowledge Infrastructure and VIPI were identified. Appropriate articles identified from the reference lists of the above searches were also reviewed. We included randomized controlled trials involved the use of AVAPS and PS‐NIV ventilation for chronic respiratory failure. Each included study weighted mean differences, and 95% confidence intervals (CI) were calculated for continuous outcomes. Statistical heterogeneity was assessed using the I2 value ≤ 50% were considered as no statistical heterogeneity and used fixed effects model. Otherwise, a random effects model was used.

Results

Eight trials were eligible. No significant difference was observed between AVAPS and PS‐NIV groups to compare PaCO2 (OR −0.97, CI‐2.54‐0.61, P = 0.23) and PaO2 (OR −1.81, CI‐4.29‐0.67, P = 0.15) in ABGs. There was no significant difference between the two groups with sleep efficiency (OR −3.31, CI‐7.58‐0.95, P = 0.13) and visual analog scale (OR 0.32, CI‐6.97‐7.61, P = 0.93).

Conclusions

The evidence shows there is no significant difference in clinical outcomes when comparing AVAPS and PS‐NIV used for chronic respiratory failure patients.
Early adversity in rural India impacts the brain networks underlying visual working memory
Authors: Wijeakumar Sobanawartiny , Kumar Aarti , Delgado Reyes Lourdes M. , Tiwari Madhuri , Spencer John P.
Published: February 2019

There is a growing need to understand the global impact of poverty on early brain and behavioural development, particularly with regard to key cognitive processes that emerge in early development. Although the impact of adversity on brain development can trap children in an intergenerational cycle of poverty, the massive potential for brain plasticity is also a source of hope: reliable, accessible, culturally agnostic methods to assess early brain development in low resource settings might be used to measure the impact of early adversity, identify infants for timely intervention and guide the development and monitor the effectiveness of early interventions. Visual working memory (VWM) is an early marker of cognitive capacity that has been assessed reliably in early infancy and is predictive of later academic achievement in Western countries. Here, we localized the functional brain networks that underlie VWM in early development in rural India using a portable neuroimaging system, and we assessed the impact of adversity on these brain networks. We recorded functional brain activity as young children aged 4–48 months performed a VWM task. Brain imaging results revealed localized activation in the frontal cortex, replicating findings from a Midwestern US sample. Critically, children from families with low maternal education and income showed weaker brain activity and poorer distractor suppression in canonical working memory areas in the left frontal cortex. Implications of this work are far‐reaching: it is now cost‐effective to localize functional brain networks in early development in low‐resource settings, paving the way for novel intervention and assessment methods.
Predictive value of global and territorial longitudinal strain imaging in detecting significant coronary artery disease in patients with myocardial infarction without persistent ST‐segment elevation
Authors: Atici Adem , Barman Hasan Ali , Durmaz Eser , Demir Koray , Cakmak Ramazan , Tugrul Sevil , Elitok Ali , Onur İmran , Sahin İrfan , Oncul Aytac
Published: February 2019

Introduction

Two‐dimensional (2D) speckle‐tracking echocardiographic (STE) imaging is frequently performed in the assessment of cardiovascular diseases. We aim to investigate the role of the global and territorial longitudinal strain (GLS and TLS) values assessed via 2D STE imaging to detect significant coronary artery disease (CAD) in non‐ST‐segment elevation myocardial infarction (NSTEMI) patients without wall‐motion abnormalities.

Methods

This study enrolled 150 patients with the diagnosis of NSTEMI. Patients who had typical chest pain with unstable angina characteristics within the last 24 hours were 18–80 years of age and had a typical rise and/or fall of cardiac biomarkers were included. Myocardial functions were assessed via myocardial deformation analyses of 2D STE images.

Results

The mean age of the CAD group was 52.91 ± 9.11, vs 50.31 ± 8.32 in the control group. In the CAD group, 56 patients were male (65%), whereas 21 were male (60%) in control group. GLS and TLS assessments demonstrated a statistically significant difference between CAD and control groups, with GLS values of −16.27 ± 1.91 and −18.74 ± 1.93 (P < 0.001), TLS‐LAD values of −15.67 ± 1.83 and −18.54 ± 1.97 (P < 0.001), TLS‐RCA values of −17.04 ± 1.81 and −19.20 ± 1.86 (P < 0.001), and TLS‐Cx values of −17.40 ± 2.08 and −18.34 ± 2.18 (P = 0.028), respectively. Correlation analyses revealed that as high‐sensitivity troponin (hsTnT) values increased, GLS decreased significantly, and further, an increase in severity of CAD resulted in decreased TLS‐LAD, ‐CX and ‐RCA (TLS‐LAD: P < 0.001, r = −0.743; TLS‐CX: P < 0.001, r = −0.449; TLS‐RCA: P < 0.001, r = −0.737). Multivariate analyses indicated that GLS and GRACE ACS risk scores are independent predictors of CAD in patients with NSTEMI (GLS: OR = 0.514, P < 0.001; GRACE score: OR = 0.938, P = 0.007).

Conclusions

Global longitudinal strain (GLS) assessed with 2D STE is a promising, easy to perform and quick imaging method to predict CAD in patients with NSTEMI.
The acute effects of edge‐to‐edge percutaneous mitral valve repair on the shape and size of the mitral annulus and its relation to mitral regurgitation
Authors: Donmez Esra , Salcedo Ernesto E. , Quaife Robert A. , Burke Joseph M. , Gill Edward A. , Carroll John D.
Published: February 2019

Background

The effects of edge‐to‐edge percutaneous mitral valve repair on the shape and size of the mitral annulus and its relation to mitral regurgitation (MR) have not been well characterized. We evaluated acute changes in mitral annular shape and dimensions, and their effect on MR severity, in patients with functional and degenerative MR following MitraClip®.

Methods

Patients that underwent MitraClip® between January 2013 and May 2016 at our institution were retrospectively reviewed. Exclusions: inadequate images, prior mitral valve repair, and rapid atrial fibrillation. Intra‐procedure TEE 3D images acquired prior to and after implantation of MitraClip® were analyzed using software to model the mitral valve apparatus.

Results

Of seventy‐eight patients that underwent MitraClip® procedure, 60 were eligible. Mean age was 78.3 ± 11 years. Severe MR (4+) was present in 37 patients, moderately/severe MR (3+) in 23. All patients achieved MR reduction to ≤2. 3D annular circumference, bicommissural diameter, and anteroposterior diameter had a significant size reduction after MitraClip®. None of the mitral annular measures had significantly different mean change between the large and small MR change groups at the 0.05 significance level.

Conclusions

In patients with functional or degenerative MR, the MitraClip® significantly affect mitral annular dimensions; however, these changes do not correlate with the immediate MR reduction.
Fetal and postnatal echocardiographic imaging of transposition of the great arteries with the aortic valve posterior to the pulmonary valve
Authors: Castellanos Daniel A. , McKenzie Emmett Dean , Morris Shaine A.
Published: February 2019

Transposition of the great arteries (TGA) with a posterior aorta is an uncommon but historically important variant of TGA. In this arrangement, the aorta is posterior to the pulmonary valve, maintains fibrous continuity with the mitral valve, and arises from the right ventricle. We present a case of fetal echocardiography demonstrating TGA with a posterior aorta. Postnatal transthoracic echocardiography and intra‐operative assessment confirm the anatomy. To the best of our knowledge, this is the first published case of this anatomic lesion by fetal echocardiography.
Morphological characterization of vegetation by real‐time three‐dimensional transesophageal echocardiography in infective endocarditis: Prognostic impact
Authors: Pérez‐García Carlos Nicolás , Olmos Carmen , Islas Fabián , Marcos‐Alberca Pedro , Pozo Eduardo , Ferrera Carlos , García‐Arribas Daniel , Pérez de Isla Leopoldo , Vilacosta Isidre
Published: February 2019

Purpose

Vegetation size is a prognostic predictor in infective endocarditis (IE) and guides surgical management. The aim of this study was to evaluate the accuracy of real‐time 3‐dimensional transesophageal echocardiography (RT3DTEE) compared to 2DTEE in the diagnosis and characterization of vegetation, as well as its potential clinical impact.

Methods

Two hundred and three consecutive patients with IE were recruited (2009–2016) and retrospectively analyzed. Vegetation diameters and area from 68 patients were measured by 2DTEE and RT3DTEE at admission. The association between size and systemic embolisms was evaluated with logistic regression models. Differences in the discriminative power for the best dimensions’ cutoff points were assessed by comparing the area under the ROC curves (AUC).

Results

Vegetation size and area were larger by RT3DTEE (P < 0.001) than by 2DTEE, and RT3DTEE was especially relevant in the characterization of nonfiliform vegetation, Morphology was strongly associated with friability, being sessile vegetation less likely to embolize, compared to filiform and raceme‐shaped ones (15.4% vs 46% vs 50%). Major diameter by RT3DTEE had better embolic predictive performance than 2DTEE (AUC 0.76 [0.57–0.89] vs 0.71 [0.53–0.86]; P = 0.611). The best cutoff points associated with embolic events during the infection were 17 mm for RT3DTEE and 15 mm for 2DTEE. Based exclusively on vegetation size, the proportion of patients meeting a surgical indication according to current guidelines is higher using RT3DTEE.

Conclusions

RT3DTEE allows a better characterization of IE vegetation than 2DTEE, what may have a clinical impact on surgical management and also prognostic due to a more accurate prediction of embolic risk.
Added value of three‐dimensional transthoracic echocardiography in assessment of an adult patient with atrioventricular septal defect
Authors: Surkova Elena , West Cathy , Flick Caroline , Ilagan Liberty , Gatzoulis Michael A. , Senior Roxy , Li Wei
Published: February 2019

Transthoracic echocardiography is the principal imaging modality for assessment of patients with atrioventricular septal defects. Three‐dimensional echocardiography streamlines and simplifies data acquisition offering a unique realistic en‐face display of heart valves and septal defects and enables accurate evaluation of the cardiac anatomy, dynamic, and function. We demonstrated an added value of three‐dimensional echocardiography in assessment of an adult patient with atrioventricular septal defect and its advantages over conventional echocardiography.
Detecting neuroinflammation in the brain following chronic alcohol exposure in rats: A comparison between in vivo and in vitro TSPO radioligand binding
Authors: Tyler Ryan E. , Kim Sung Won , Guo Min , Jang Yeon Joo , Damadzic Ruslan , Stodden Tyler , Vendruscolo Leandro F. , Koob George F. , Wang Gene‐Jack , Wiers Corinde E. , Volkow Nora D.
Published: February 2019

Excessive alcohol consumption is associated with neuroinflammation, which likely contributes to alcohol‐related pathology. However, positron emission tomography (PET) studies using radioligands for the 18‐kDa translocator protein (TSPO), which is considered a biomarker of neuroinflammation, reported decreased binding in alcohol use disorder (AUD) participants compared to controls. In contrast, autoradiographic findings in alcohol exposed rats reported increases in TSPO radioligand binding. To assess if these discrepancies reflected differences between in vitro and in vivo methodologies, we compared in vitro autoradiography (using [3H]PBR28 and [3H]PK11195) with in vivo PET (using [11C]PBR28) in male, Wistar rats exposed to chronic alcohol‐vapor (dependent n = 10) and in rats exposed to air‐vapor (nondependent n = 10). PET scans were obtained with [11C]PBR28, after which rats were euthanized and the brains were harvested for autoradiography with [3H]PBR28 and [3H]PK11195 (n = 7 dependent and n = 7 nondependent), and binding quantified in hippocampus, thalamus, and parietal cortex. Autoradiography revealed significantly higher binding in alcohol‐dependent rats for both radioligands in thalamus and hippocampus (trend level for [3H]PBR28) compared to nondependent rats, and these group differences were stronger for [3H]PK11195 than [3H]PBR28. In contrast, PET measures obtained in the same rats showed no group difference in [11C]PBR28 binding. Our in vitro data are consistent with neuroinflammation associated with chronic alcohol exposure. Failure to observe similar increases in [11C]PBR28 binding in vivo suggests the possibility that a mechanism mediated by chronic alcohol exposure interferes with [11C]PBR28 binding to TSPO in vivo. These data question the sensitivity of PBR28 PET as a methodology to assess neuroinflammation in AUD.
Effects of an epilepsy‐specific Internet intervention (Emyna) on depression: Results of the ENCODE randomized controlled trial
Authors: Meyer Björn , Weiss Mario , Holtkamp Martin , Arnold Stephan , Brückner Katja , Schröder Johanna , Scheibe Franziska , Nestoriuc Yvonne
Published: February 2019

Objective

Depression and anxiety are highly prevalent among people with epilepsy (PwE) but often remain unrecognized and treated inadequately. Effective psychosocial treatments such as cognitive behavioral therapy (CBT) are rarely available to most PwE, which is one reason electronically delivered CBT (eCBT) is regarded as promising. This study examined an eCBT intervention, termed Emyna, that was tailored to suit the needs of PwE. It includes CBT‐related content on depression, stress and anxiety, seizure triggers and auras, and lifestyle habits. The trial examined the efficacy of Emyna in reducing symptoms of depression (primary outcome) and anxiety as well as improving quality of life.

Methods

Participants (N = 200) with epilepsy, a diagnosis of a depressive disorder, and at least moderate depressive symptoms were randomized to Emyna or care as usual. At baseline and after 3, 6, and 9 months, participants were invited to complete online questionnaires. The primary outcome was improvement of depressive symptoms at 3 months.

Results

Relative to the control group, intervention group participants experienced significantly greater improvements in depression, anxiety, stress, social‐occupational impairment, and epilepsy‐related quality of life, in both intention‐to‐treat (ITT) and per‐protocol analyses. In ITT analyses, effects of medium magnitude were observed, as measured by the Patient Health Questionnaire–9 items (Cohen d = 0.54, 95% confidence interval [CI] = 0.25‐0.82, P < 0.001) and the Neurological Disorders Depression Inventory for Epilepsy (d = 0.51, 95% CI = 0.23‐0.79, P < 0.01). At 3 months, intervention group participants also reported fewer illness‐related days off work and fewer days hospitalized over the preceding months, compared to control group participants (P ≤ 0.05), whereas no such differences were present at baseline (P > 0.30).

Significance

These findings showed that Emyna, used adjunctively to usual care, could help improve mental health, social‐occupational functioning, and quality of life among PwE. The program provides an additional treatment option that could produce clinically relevant symptom reductions and reduce key cost drivers (ie, hospitalization rates and illness‐related inability to work).
The complex role of mast cells in fungal infections
Authors: Jiao Qingqing , Luo Ying , Scheffel Jörg , Zhao ZuoTao , Maurer Marcus
Published: February 2019

In addition to their critical role in allergic disorders, mast cells (MCs) are well recognized for their protective effector functions during bacteria and parasite infections. This review describes recent advancements of our understanding of the complex role ofMCs in fungal infections. Specifically, we outline key features of the contribution ofMCs to infections with six fungal pathogens, namelySporothrix,Paracoccidioides,Aspergillus,Malassezia,CandidaandDermatophytes. Evidence from studies of these pathogens suggests thatMCs can function as positive regulators that detect and contain fungi at the site of infection. However, it appears that the inflammation induced byMCs following fungal infections may not always and only be beneficial to the host.MCresponses during fungal infections may primarily benefit the pathogen by facilitating its spreading and contributing to a greater severity of fungal infections. This review also highlights key drivers ofMCs activation and effector mechanisms that have been identified for the multidimensional function ofMCs in fungal diseases and in allergic diseases combined with fungal infection.
Conversation Analysis and Family Therapy: A Critical Review of Methodology
Authors: Ong Ben , Barnes Scott , Buus Niels
Published: February 2019

This article critiques the use of conversation analysis (CA) as applied to the study of family therapy. Searches of relevant databases and journals as well as citation searches were conducted in April 2018 for relevant articles. Inclusion criteria included the explicit use of CA either solely or in combination with discourse analysis and discursive psychology. This resulted in the inclusion of 25 articles that were reviewed against a guideline for the evaluation of qualitative research to which five items specific to CA were added to ensure a specific and balanced evaluation of the studies. Articles generally had a good application of quality criteria although there was a variation in detail of transcription, application of sequence analysis, and a limited use of validity testing. CA has the potential to complement existing research on family therapy but requires a rigorous application of process and quality criteria. The article provides recommendations for future CA research into family therapy.
Conformational analysis of apolipoprotein E3/E4 heteromerization
Authors: Tu Kai‐Han , Abhari Devan , Narayanaswami Vasanthy
Published: February 2019

Apolipoprotein E (apoE) is a 299 residue, exchangeable apolipoprotein that has essential roles in cholesterol homeostasis and reverse cholesterol transport. It is a two‐domain protein with the C‐terminal (CT) domain mediating protein self‐association via helix‐helix interactions. In humans, the APOE gene is polymorphic with three common alleles, ε2, ε3, and ε4, occurring in frequencies of ~ 5%, 77%, and 18%, respectively. Heterozygotes expressing apoE3 and apoE4 isoforms, which differ in residue at position 112 in the N‐terminal domain (C112 in apoE3 and R112 in apoE4), represent the highest population of ε4 carriers, an allele highly associated with Alzheimer's disease. The objective of this study was to determine if apoE3 and apoE4 have the ability to hybridize to form a heteromer in lipid‐free state. Refolding an equimolar mixture of His‐apoE3 and FLAG‐apoE4 (or vice versa) followed by pull‐down and immunoblotting indicated formation of apoE3/apoE4 heteromers. Förster resonance energy transfer between donor fluorophore on one isoform and acceptor on the other, both located in the respective CT domains, revealed a distance of separation of ~ 46 Å between the donor/acceptor pair. Similarly, a quencher placed on one was able to mediate significant quenching of fluorescence emission on the other, indicative of spatial proximity within collisional distance between the two. ApoE3/apoE4 heteromer association was also noted in lipid‐associated state in reconstituted lipoprotein particles. The possibility of heteromerization of apoE3/apoE4 bears implications in the potential mitigating role of apoE3 on the folding and physiological behavior of apoE4 and its role in maintaining cholesterol homeostasis.
SiberianMiscanthus sacchariflorusaccessions surpass the exceptional chilling tolerance of the most widely cultivated clone ofMiscanthusxgiganteus
Authors: Pignon Charles P. , Spitz Idan , Sacks Erik J. , Jørgensen Uffe , Kørup Kirsten , Long Stephen P.
Published: February 2019

Chilling temperatures (0–15°C) inhibit photosynthesis in most C4grasses, yet photosynthesis is chilling tolerant in the ‘Illinois’ clone of the C4grassMiscanthusxgiganteus, a candidate cellulosic bioenergy crop.M.xgiganteusis a hybrid betweenMiscanthus sacchariflorusandMiscanthus sinensis; therefore chilling‐tolerant parent lines might produce hybrids superior to the current clone. Recently a collection ofM. sacchariflorusfrom Siberia, the apparent low temperature limit of natural distribution,became available, which may be a source for chilling tolerance. The collection was screened for chilling tolerance of photosynthesis by measuring dark‐adapted maximum quantum yield of PSII photochemistry (Fv/Fm) on plants in the field in cool weather. Superior accessions were selected for further phenotyping: plants were grown at 25°C, transferred to 10°C (chilling) for 15 days, and returned to 25°C for 7 days (recovery). Two experiments assessed: (a) light‐saturated net photosynthetic rate (Asat) and operating quantum yield of PSII photochemistry (ΦPSII), (b) response of net leaf CO2uptake (A) to intercellular [CO2] (ci). Three accessions showed superior chilling tolerance: RU2012‐069 and RU2012‐114 achievedAsatup to double that ofM.xgiganteusprior to and during chilling, due to increasedci‐ saturated photosynthesis (Vmax). RU2012‐069 and RU2012‐114 also maintained greater levels of ΦPSIIduring chilling, indicating reduced photodamage. Additionally, accession RU2012‐112 maintained a stableAsatthroughout the 15‐day chilling period, whileAsatcontinuously declined in other accessions; this suggests RU2012‐112 could outperform others in lengthy chilling periods. Plants were returned to 25°C after the chilling period;M.xgiganteusshowed the weakest recovery after 1 day, but a strong recovery after 1 week. This study has therefore identified important genetic resources for the synthesis of improved lines ofM.xgiganteus, which could facilitate the displacement of fossil fuels by cellulosic bioenergy.
Female and foreign: An intersectional exploration of the experiences of skilled migrant women in Qatar
Authors: Rodriguez Jenny K. , Scurry Tracy
Published: February 2019

This article explores how the intersection of gender and foreignness shapes the experiences of skilled migrant women. Drawing on interviews with skilled migrant women working in Qatar, we situate their experiences in institutional, organizational and sociocultural terms to show how the intersection is articulated and mobilized to subordinate, marginalize and exclude them in work and social spaces. Findings show that the intersection is used to reinforce the status of the women as outsiders to the country (foreignness) and its cultural order (gender), resulting in structural and qualitative differences in the experiences of the group. In highlighting their nuanced experiences, we contribute to debates about gender, skilled migration and work in the Middle East. We also contribute to intersectionality debates by expanding the conceptual limits and analytical use of social categories of difference to explain experiences of work and unpack the simultaneity of subject positioning within institutional, organizational and sociocultural dynamics.
Effect of toothpaste containing amine fluoride and stannous chloride on the reduction of dental plaque and gingival inflammation. A randomized controlled 12‐week home‐use study
Authors: Lorenz Katrin , Hoffmann Thomas , Heumann Christian , Noack Barbara
Published: February 2019

Objectives

This single‐centre, controlled, randomized, double‐blinded clinical study in parallel groups was performed to assess the efficacy of an experimental toothpaste on plaque and gingivitis.

Methods

In adult subjects with gingivitis, amine fluoride/stannous chloride toothpaste (test) and monofluorophosphate toothpaste (control) were applied twice daily by regular toothbrushing at home. Evaluations of plaque index (PI), gingival index (GI), modified sulcus bleeding index (mSBI) and safety took place at baseline and after 3 and 12 weeks of study product use. After study completion, all subjects received a dental prophylaxis. A descriptive statistical analysis included means and standard deviations. Unpaired t tests compared index reductions between groups at a significance level of 0.05.

Results

Intention‐to‐treat analysis included 240 out of 241 subjects. Baseline mean PI was reduced by 0.87 ± 0.35 in the test group and by 0.65 ± 0.41 in the control group. Within‐group differences and between‐group differences in index reduction were statistically significant (P < 0.001). Mean GI and mSBI were reduced significantly over time (P < 0.001) with no clinically meaningful differences between groups.

Conclusions

Both toothpastes reduced plaque and gingivitis statistically significant and clinically meaningful over 12 weeks. Compared to the control toothpaste, application of the amine fluoride/stannous chloride toothpaste led to a clinically meaningful and more pronounced plaque reduction.
Dental caries lesions in primary teeth without obvious cavitation: Treatment decision‐making process
Authors: Leal Soraya Coelho , Barros Brenda Viana , Cabral Renata Nunes , Ferrari Júnia Carolina Linhares , de Menezes Abreu Danielle Matos , Ribeiro Ana Paula Dias
Published: February 2019

Background

Dental caries diagnosis and management have changed over time.

Aim

To identify the treatment decision‐making process performed by paediatric dentists, after caries detection using CAST instrument (Caries Assessment Spectrum and Treatment), for enamel (CAST 3) and non‐cavitated dentin caries lesions (CAST 4) before and after analysing radiographic images.

Design

Seventy‐four paediatric dentists were invited to participate. Twelve clinical cases were presented online, and treatment decisions before and after the analysis of bitewing radiographs were evaluated.

Results

Sixty‐one specialists answered the questionnaire. The necessity for radiographs was significantly associated with the presence and depth of the caries lesion (P < 0.0001). CAST 3 lesions were preferentially monitored before and after the radiographic assessment. For CAST 4 lesions limited to the outer half of dentin, treatments indicated before and after radiographic analysis were sealant (33%) and restoration (40%). For the lesions in the inner half of dentin, restoration was the most cited before (45%) and after (84%) radiographs. The radiographic depth was the only significant independent variable when “change in the treatment option” was analysed by the regression model (P < 0.001).

Conclusions

Enamel lesions were treated through less invasive treatments. Radiographs influenced the decision, especially for the lesions that involved the inner half of dentin.
Influenza surveillance in Middle East, North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network
Authors: Abusrewil Suleiman , Algeer Abdulrahman , Aljifri Alanoud , Al Slail Fatima , Andrew Melissa K. , Awad Tag Eldin Mohamed , Al Awaidy Salah , Ben Alaya Nissaf , Ben Khelil Jalila , Dbaibo Ghassan , Derrar Fawzi , Elahmer Omar , Ghosn Nada , Gabriel Guelsah , Grasso Cindy , Hassan Mohamed , Hirve Siddhivinayak , Mirza Yusuf Kamal , Rateb Yousef Moh'd , Nourlil Jalal , Nunes Marta C. , Omaima Idris , Malande Oliver Ombeva , Saadatian‐Elahi Mitra , Sanchez‐Picot Valentina , Sk. Mamunur Rahman Malik , Tarraf Hesham , Walaza Sibongile
Published: February 2019

The Middle‐East and Africa Influenza Surveillance Network (MENA‐ISN), established in 2014, includes 15 countries at present. Country representatives presented their influenza surveillance programmes, vaccine coverage and influenza control actions achieved, and provided a list of country surveillance/control objectives for the upcoming 3 years. This report details the current situation of influenza surveillance and action plans to move forward in MENA‐ISN countries. Data were presented at the 8th MENA‐ISN meeting, organized by the Mérieux Foundation that was held on 10‐11 April 2018 in Cairo, Egypt. The meeting included MENA‐ISN representatives from 12 countries (Algeria, Egypt, Jordan, Kenya, Lebanon, Libya, Morocco, Pakistan, Saudi Arabia, South Africa, Tunisia and United Arab Emirates) and experts from the Canadian Centre for Vaccinology, and the World Health Organization. Meeting participants concluded that influenza remains a significant threat especially in high‐risk groups (children under‐5, elderly, pregnant women and immunosuppressed individuals) in the MENA‐ISN region. Additional funding and planning are required by member countries to contain this threat. Future meetings will need to focus on creative and innovative ways to inform policy and initiatives for vaccination, surveillance and management of influenza‐related morbidity and mortality especially among the most vulnerable groups of the population.