bluuebunny/crossref_metadata_2025 huggingface dataset:
Lectin Isolated from Japanese Red Sword Beans (Canavalia gladiata) as a Potential Cancer Chemopreventive Agent
Authors: Une Satsuki , Nonaka Koji , Akiyama Junich
Published: February 2018

In this study, we investigated the chemical and biological profile of lectin isolated from Japanese red sword beans (Canavalia gladiata; RSBs). RSB lectin was purified using maltamyl‐Sepharose 4B and subjected to amino acid composition and partial amino acid sequencing analyses, and evaluated for blood and carbohydrate specificity, mitogenic activity, splenic natural killer (NK) cell activity, and its effect on B16 melanoma cell proliferation, compared with Concanavalin A (Con A). The amino acid composition and sequences of RSB lectin were similar to those of Con A. RSB lectin showed specificity to mannose, glucose, maltose, methyl‐D‐mannoside, and thyroglobulin, but not rhamnose, using mouse, sheep, and rabbit erythrocytes. Compared with Con A, RSB lectin showed low resistance to proteases and to temperatures greater than 70 °C, but high mitogenic activity for mouse splenic cells. Notably, while treatment with RSB lectin and Con A (0.01 and 0.1 μg/mL) promoted similar levels of splenic NK cell activity, which were higher than that observed in the control (0 μg/mL) and interleukin 2 (IL‐2) (25 U)‐treated populations, RBS lectin exerted a significantly stronger anti‐proliferative effect than Con A at a concentration of 125.0 μg per well. Overall, our results show that RSB lectin might exert immunological effects on mouse splenic cells and could thus be used as a potential cancer chemopreventive agent.

Practical Application

Japanese red sword bean (RSB) is a tropical perennial legume consumed in many Asian countries. RSB lectin shows specificity to mannose, glucose, maltose, methyl‐d‐mannoside, and thyroglobulin, but not to rhamnose, using mouse, sheep, and rabbit erythrocytes. RSB lectin exhibits similarities to Concanavalin A in amino acid composition and sequence, shows mitogenic activity for mouse splenic cells and strong anti‐proliferative activity for B16 melanoma cells, and also enhances the activity of splenic natural killer (NK) cells against YAC‐1 cells. Thus, RSB lectin has the potential to be used as a bioactive protein in medical research.
Prediction of Firmness and pH for “Golden Delicious” Apple Based on Elasticity Index from Modal Analysis
Authors: Hou Jumin , Zhang Yuxia , Sun Yonghai , Xu Na , Leng Yue
Published: February 2018

An experimental modal test system was established to extract the natural frequencies of “Golden Delicious” apple, after which the elasticity index was calculated to predict the apple quality parameters based on the orthogonal polynomials method. The elasticity index in every vibration mode changed dramatically (P = 0.01) along time revolution. The multivariate regression methods were used to model the predictive relationship between the elasticity index and the apple quality parameters. The models of the apple juice pH based on support vector regression presented adequate determination coefficients of calibration set (Q2 = 0.68) and prediction set (R2 = 0.55), respectively. The models based on partial least squares regression could be used for predicting the apple firmness parameter offset gradient (Q2 = 0.76 andR2 = 0.72). It helped understanding the fruit dynamic properties of the fruit and spontaneously obtaining the fruit chemical parameters. A nondestructive and portable device was viable for fruit quality estimation by the modal test system during storage, transport, and even growth on the tree.

Practical Application

A nondestructive and portable device was provided for fruit quality detection during storage, transport and even growth based on experimental modal analysis. A systematic statistical analysis method about outlier detection, data set partitioning, parameter optimization, and multiple regression models were provided.
Effects of Pulsatile Blood Flow on Oxygenator Performance
Authors: Schraven Lotte , Kaesler Andreas , Flege Christian , Kopp Rüdger , Schmitz‐Rode Thomas , Steinseifer Ulrich , Arens Jutta
Published: February 2018

Extracorporeal membrane oxygenation (ECMO) is mainly used for the therapy of acute respiratory distress syndrome and chronic obstructive lung disease. In the last years, the development of these systems underwent huge steps in optimization, but there are still problems with thrombus formation, clogging, and thus insufficient gas exchange. One idea of ECMO optimization is a pulsatile blood flow through the oxygenator, but this is still a controversy discussion. Analyzing available publications, it was not possible to identify a general statement about the effect of pulsatile blood flow on the gas exchange performance. The variety of parameters and circuit components have such a high influence on the outcome that a direct comparison of the studies is difficult. For this reason, we performed a structured study to evaluate the effects of pulsatile blood flow on the gas exchange performance of oxygenator. In in vitro tests according to DIN EN ISO 7199, we tested a small oxygenator (0.25 m2 exchange surface, polymethylpentene fibers, 33 mL priming volume) with constant and pulsatile blood flow in comparison. Therefore, we varied the mean blood flow from 250 to 1200 mL/min, the amplitude of 0, 20, and 50%, and the frequency of 30, 60, and 90 bpm. The results demonstrate that the gas transfer for pulsatile and constant blood flow was similar (oxygen: 36–64 mLO2/LBlood; carbon dioxide 35–80 mLCO2/LBlood) for the same mean blood flow ranges. Over all, the results and analyses showed a statistically nonsignificant difference between pulsatile and nonpulsatile flow. Consequently, we conclude that the implementation of pulsatile blood flow has only a small to no effect on the gas exchange performance in an oxygenator. As the results were obtained using an oxygenator with a coiled fiber bundle, the test must be verified for a stacked fiber oxygenator.
Changes in Total Cardiac Output and Oxygen Extraction During Exercise in Patients Supported With an HVAD Left Ventricular Assist Device
Authors: Schmidt Thomas , Bjarnason‐Wehrens Birna , Mommertz Stephanie , Hannig Meike , Schulte‐Eistrup Sebastian , Willemsen Detlev , Reiss Nils
Published: February 2018

Following implantation of a left ventricular assist device (LVAD), acceptable functional performance is now being achieved; however, peak VO2 and peak work load (watts) remain considerably limited. Maximum physical capacity is essentially dependent on generated cardiac output (CO) and arteriovenous oxygen difference (avDO2). We investigated the changes in CO and avDO2 during exercise in LVAD patients with an HVAD pump (HeartWare Inc., Framingham, MA, USA). Approximately 6 weeks after implantation, 20 patients (100% male, 60.8 ± 7.3 years old, BMI 25.7 ± 3.3) underwent a six‐minute walk test (6MWT), a cardiopulmonary exercise test (CPET), and noninvasive hemodynamic measurement. The mean six‐minute walking distance (6MWD) was 403 m (68% of predicted), and mean peak VO2 was 10.9 mL/kg/min (39% of predicted). Mean total CO improved from 3.8 L at rest to 7.0 L at maximum exercise. The mean avDO2 increased from 7.4 mL/dL (44% of oxygen content) at rest to 13.2 mL/dL (75% of oxygen content) at maximum exercise. There was a significant increase in both total CO (P < 0.01) and avDO2 (P < 0.05) between rest and sub‐maximum exercise. As exercise levels increased, however, no further significant changes were achieved. Long‐term studies, especially in combination with exercise programs, would be desirable in order to observe the development of these parameters.
Recurrent rearrangements of the PLAG1 and HMGA2 genes in lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma
Authors: Andreasen Simon , von Holstein Sarah L. , Homøe Preben , Heegaard Steffen
Published: February 2018

Purpose

Lacrimal gland tumours constitute a wide spectrum of neoplastic lesions that are histologically similar to tumours of the salivary gland. In the salivary gland, pleomorphic adenoma (PA) is frequently characterized by recurrent chromosomal rearrangements of the PLAG1 and HMGA2 genes, a genetic feature retained in carcinoma ex pleomorphic adenoma (ca‐ex‐PA) that makes it possible to distinguish ca‐ex‐PA from de novo carcinomas. However, whether PLAG1 and HMGA2 gene rearrangements are found in lacrimal gland PA and ca‐ex‐PA is not known.

Methods

Twenty‐one lacrimal gland PAs and four ca‐ex‐PAs were retrospectively reviewed and subjected to break‐apart fluorescence in situ hybridization (FISH) for rearrangements of the PLAG1 gene. Cases without PLAG1 abnormalities were subjected to HMGA2 break‐apart FISH. Immunohistochemical staining for PLAG1 and HMGA2 protein was performed and correlated with gene status.

Results

Sixteen of 21 PAs showed rearrangement of PLAG1 and were all positive for PLAG1 protein. Two of the remaining five PAs showed rearrangement of HMGA2 and were the only cases positive for HMGA2 with immunohistochemistry. The three FISH‐negative PAs expressed PLAG1 protein. All four ca‐ex‐PAs showed rearrangement of PLAG1 and expressed PLAG1 protein. None of the de novo carcinomas showed rearrangement of either of the two genes or expression of the two proteins.

Conclusion

Rearrangement of PLAG1 and HMGA2 and expression of the corresponding proteins are frequent and specific findings in lacrimal gland PA and ca‐ex‐PA. The mechanism for PLAG1 overexpression in FISH‐negative PAs is yet to be clarified.
Nutraceuticals: opening the debate for a regulatory framework
Authors: Santini Antonello , Cammarata Silvia Miriam , Capone Giacomo , Ianaro Angela , Tenore Gian Carlo , Pani Luca , Novellino Ettore
Published: February 2018

Currently, nutraceuticals do not have a specific definition distinct from those of other food‐derived categories, such as food supplements, herbal products, pre‐ and probiotics, functional foods, and fortified foods. Many studies have led to an understanding of the potential mechanisms of action of pharmaceutically active components contained in food that may improve health and reduce the risk of pathological conditions while enhancing overall well‐being. Nevertheless, there is a lack of clear information and, often, the claimed health benefits may not be properly substantiated by safety and efficacy information or in vitro and in vivo data, which can induce false expectations and miss the target for a product to be effective, as claimed. An officially shared and accepted definition of nutraceuticals is still missing, as nutraceuticals are mostly referred to as pharma‐foods, a powerful toolbox to be used beyond the diet but before the drugs to prevent and treat pathological conditions, such as in subjects who may not yet be eligible for conventional pharmaceutical therapy. Hence, it is of utmost importance to have a proper and unequivocal definition of nutraceuticals and shared regulations. It also seems wise to assess the safety, mechanism of action and efficacy of nutraceuticals with clinical data. A growing demand exists for nutraceuticals, which seem to reside in the grey area between pharmaceuticals and food. Nonetheless, given specific legislation from different countries, nutraceuticals are experiencing challenges with safety and health claim substantiation.
Adverse events linked with the use of chimeric and humanized anti‐CD20 antibodies in children with idiopathic nephrotic syndrome
Authors: Bonanni Alice , Calatroni Marta , D'Alessandro Matteo , Signa Sara , Bertelli Enrica , Cioni Michela , Di Marco Eddi , Biassoni Roberto , Caridi Gianluca , Ingrasciotta Giulia , Bertelli Roberta , Di Donato Armando , Bruschi Maurizio , Canepa Alberto , Piaggio Giorgio , Ravani Pietro , Ghiggeri Gian Marco
Published: February 2018

Aims

Anti‐CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin inhibitor withdrawal, repeated infusions of anti‐CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed, to consider repeated infusions.

Methods

We investigated the side effects associated with the use of rituximab (a chimeric antibody; 130 patients) and ofatumumab (a humanized antibody; 37 patients) in children with INS (steroid‐dependent and steroid/calcineurin inhibitor‐dependent disease) treated at a national referral centre over a 9‐year period (400 treatments; follow‐up 1–9 years).

Results

Infusion reactions were mainly absent in children with steroid‐dependent disease. Rash, dyspnoea, fever, cough and itchy throat (5% and 18% following rituximab and ofatumumab infusion, respectively) were resolved by using premedication with salbutamol. Other short‐term reactions (up to 3 months), including arthritis (2%) and lung injury (1%), were more common with rituximab. Infections were observed 3–9 months following infusion, were similarly common in the two groups and resolved with targeted therapies [antibiotic, fluconazole, immunoglobulins (Igs), etc.]. The number of circulating CD19/20 cells fell to 0 at month 1 and were reconstituted at month 3; circulating IgG antibodies remained within the normal range for 1 year. Tetanus and hepatitis B virus immunization was not modified by either treatment; Epstein–Barr virus and John Cunningham virus activation markers were occasionally observed.

Conclusion

Overall, the toxicity of anti‐CD20 monoclonal antibodies was limited to post‐infusion side effects in children with more complex disease. The relatively safe profile of anti‐CD20 antibodies supports their use as steroid‐sparing agents in children with INS.
Care associated with stillbirth for the most disadvantaged women: A multi‐method study of care in England
Authors: Redshaw Maggie , Henderson Jane
Published: February 2018

Background

Most research on women experiencing stillbirth relies on online user group surveys or qualitative interviews. The objective of this study was to investigate the experience of women who are at a higher risk of stillbirth, living in areas of greatest deprivation, and are commonly not well represented.

Methods

This study used birth and death registrations in 2012‐2013 to identify a sample of mothers whose babies had died as a result of stillbirth. These women were sent a survey 6‐9 months after the stillbirth. We undertook descriptive analysis of quantitative data and used binary logistic regression with the Index of Multiple Deprivation as a measure of disadvantage. We used thematic analysis to describe free text responses.

Results

The survey response rate was 30% (N = 473). Ethnic minority, younger age, and single parenthood were associated with disadvantage. Women residents in the most deprived areas perceived care more negatively: during labor they were significantly less likely to be spoken to by medical staff so they could understand (73% compared with 90%, adjusted odds ratio [aOR] 0.33 [95% confidence interval {CI} 0.18‐0.65]), or treated with respect by midwives (79% compared with 90%, aOR 0.41 [95% CI 0.22‐0.77]). The qualitative themes identified were: “Difficulty in accessing care,” “More could have been done,” “Ineffective communication,” and “Cared for and not cared for” which support the quantitative findings.

Conclusion

Women living in the most deprived areas reported poorer experiences of care compared with more advantaged women. All women need compassionate and sensitive care around the time of a stillbirth.
Home birth integration into the health care systems of eleven international jurisdictions
Authors: Comeau Amanda , Hutton Eileen K. , Simioni Julia , Anvari Ella , Bowen Megan , Kruegar Samantha , Darling Elizabeth K.
Published: February 2018

Background

The purpose of this study was to develop assessment criteria that could be used to examine the level of integration of home birth within larger health care systems in developed countries across 11 international jurisdictions.

Methods

An expert panel developed criteria and a definition to assess home birth integration within health care systems. We selected jurisdictions based on the publications that were eligible for inclusion in our systematic review and meta‐analysis on planned place of birth. We sent the authors of the included publications a questionnaire about home birth practitioners and practices in their respective health care system at the time of their studies. We searched published peer‐reviewed, non–peer‐reviewed, and gray literature, and the websites of professional bodies to document information about home birth integration in each jurisdiction based on our criteria. Where information was lacking, we contacted experts in the field from the relevant jurisdiction.

Results

Home birth is well integrated into the health care system in British Columbia (Canada), England, Iceland, the Netherlands, New Zealand, Ontario (Canada), and Washington State (USA). Home birth is less well integrated into the health care system in Australia, Japan, Norway, and Sweden.

Conclusions

This paper is the first to propose criteria for the evaluation of home birth integration within larger maternity care systems. Application of these criteria across 11 international jurisdictions indicates differences in the recognition and training of home birth practitioners, in access to hospital facilities, and in the supplies and equipment available at home births, which give rise to variation in the level of integration across different settings. Standardized criteria for the evaluation of systems integration are essential for interpreting planned home birth outcomes that emerge from contextual differences.
Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results
Authors: Richardson Paul G. , Bensinger William I. , Huff Carol Ann , Costello Caitlin L. , Lendvai Nikoletta , Berdeja Jesus G. , Anderson Larry D. , Siegel David S. , Lebovic Daniel , Jagannath Sundar , Laubach Jacob P. , Stockerl‐Goldstein Keith E. , Kwei Long , Clow Fong , Elias Laurence , Salman Zeena , Graef Thorsten , Bilotti Elizabeth , Vij Ravi
Published: February 2018

Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first‐in‐class, once‐daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low‐dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2‐stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0–14·7). Progression‐free survival was 4·6 months (range, 0·4–17·3). Grade 3–4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3–4 non‐haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre‐treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment.
Early movement restriction leads to enduring disorders in muscle and locomotion
Authors: Delcour Maxime , Massicotte Vicky S. , Russier Michaël , Bras Hélène , Peyronnet Julie , Canu Marie‐Hélène , Cayetanot Florence , Barbe Mary F. , Coq Jacques‐Olivier
Published: February 2018

Motor control and body representation in the central nervous system (CNS) as well as musculoskeletal architecture and physiology are shaped during development by sensorimotor experience and feedback, but the emergence of locomotor disorders during maturation and their persistence over time remain a matter of debate in the absence of brain damage. By using transient immobilization of the hind limbs, we investigated the enduring impact of postnatal sensorimotor restriction (SMR) on gait and posture on treadmill, age‐related changes in locomotion, musculoskeletal histopathology and Hoffmann reflex in adult rats without brain damage. SMR degrades most gait parameters and induces overextended knees and ankles, leading to digitigrade locomotion that resembles equinus. Based on variations in gait parameters, SMR appears to alter age‐dependent plasticity of treadmill locomotion. SMR also leads to small but significantly decreased tibial bone length, chondromalacia, degenerative changes in the knee joint, gastrocnemius myofiber atrophy and muscle hyperreflexia, suggestive of spasticity. We showed that reduced and atypical patterns of motor outputs, and somatosensory inputs and feedback to the immature CNS, even in the absence of perinatal brain damage, play a pivotal role in the emergence of movement disorders and musculoskeletal pathologies, and in their persistence over time. Understanding how atypical sensorimotor development likely contributes to these degradations may guide effective rehabilitation treatments in children with either acquired (ie, with brain damage) or developmental (ie, without brain injury) motor disabilities.
Improving disease knowledge in 6‐ to 10‐year‐olds with sickle cell disease: A quasi‐experimental study
Authors: Morrison‐Levy N. , Knight‐Madden J. , Royal‐Thomas T. , King L. , Asnani M.
Published: February 2018

Background

Increasing knowledge and understanding of disease is known to improve outcomes in persons living with a chronic illness. In this paper, we aim to compare the disease knowledge of children with sickle cell disease (SCD), age 6–10 years, who received an intervention (an educational colouring book on SCD) geared towards improving disease knowledge, to those who did not received the colouring book.

Methods

A quasi‐experimental study was conducted where disease knowledge was determined in 56 children who had received the colouring book and compared to 60 children who did not receive this intervention.

Results

The mean knowledge score was significantly higher in the intervention group (mean difference = 2.65; 95% CI [1.43, 3.86]), as well as in older children and in those in higher grades but there was no difference between sexes. In a multiple regression model (adjusted R2: 0.39; p value < .001), knowledge score was significantly higher in those who received the intervention (β: 2.62; 95% CI [1.48, 3.76]) while adjusting for age, gender, persons living at home, and the father's employment status.

Conclusion

The study highlights that a simple, inexpensive (cost: US$1/book) child‐friendly intervention can significantly improve knowledge about SCD even in young children. It also underlines various social factors that are associated with children's understanding of their disease.
IL-27: a double agent in the IL-6 family
Authors: Jones G W , Hill D G , Cardus A , Jones S A
Published: February 2018

The cytokine interleukin (IL)-6 is a major therapeutic target for the treatment of various inflammatory and autoimmune diseases. While IL-6 receives considerable attention in studies of innate and adaptive immunity, the IL-6-related family member IL-27 is recognized increasingly for its effects on cellular proliferation, differentiation and leucocyte effector functions. Both cytokines activate responses in myeloid and stromal tissue cells, where they direct the transition from innate to adaptive immunity. However, they are identified frequently as lymphokines that control responses in T cells and B cells. In this regard, IL-27 often opposes the action of IL-6. Here, we will review the role of IL-6 and IL-27 in inflammation, with a particular focus on inflammatory arthritis, and discuss their importance in the diagnosis, stratification and treatment of autoimmune disease.
Random walk grey wolf optimizer for constrained engineering optimization problems
Authors: Gupta Shubham , Deep Kusum
Published: February 2018

Swarm intelligence is one of the most promising area of numerical optimization to solve real‐world optimization problems. Grey wolf optimizer (GWO), which is based on leadership hierarchy of grey wolves, is one of the relatively new algorithm in the field of swarm intelligence–based algorithms. In order to solve constrained real‐world optimization problems, in this paper, a constrained version of GWO has been proposed by incorporating a simple constraint handling technique in GWO, and then an attempt is made to improve the ability of the leaders in original GWO by proposing random walk GWO (RW‐GWO) by pointing out some drawbacks in their process of searching prey. (To the best of the knowledge of the authors, a constrained version of GWO has not been developed yet. The unconstrained version of RW‐GWO has been proposed in the authors' earlier work.) The efficiency of both these proposed algorithms have been tested on the Institute of Electrical and Electronics Engineers Congress on Evolutionary Computation 2006 benchmark problems and on 3 engineering application problems to observe their comparative performance. It is concluded from the results that the proposed improved version of GWO, namely, RW‐GWO, has better potential to solve these constraint problems compared to GWO very efficiently as a constrained optimizer.
Asthma and its related socioeconomic factors: The Shiraz Adult Respiratory Disease Study 2015
Authors: Masoompour Seyed Masoom , Mahdaviazad Hamideh , Ghayumi Seiyed Mohammad Ali
Published: February 2018

Objective

This study aimed to explore the association between the prevalence of asthma and the socioeconomic factors using data from the Shiraz Adult Respiratory Disease Study, 2015(SARDS).

Methods

The SARDS was conducted from June to October 2015 among adult subjects of the general population of Shiraz, Iran. Current asthma was defined as the presence of at least 1 of the following factors in the preceding 12 months: (1) being awakened by an attack of shortness of breath, coughing, or chest tightness without any identifiable cause; (2) having an asthma attack; (3) currently using medication for asthma; or (4) having wheezing or whistling in the chest not associated with a cold or the flu. Information on individual socioeconomic status was derived from self‐reported education level, occupation, income, and residence location. A value of P < .05 was considered statistically significant.

Results

A total of 4582 respondents aged 20‐60 years were included in the analysis. The overall prevalence of adult asthma was 7.8%. The prevalence of asthma was higher significantly among female and subjects with higher body mass index, allergic rhinitis, smokers, jobless, and individuals who live in suburban areas. In the adjusted logistic regression model, being jobless (odds ratio [OR], 2.256; 95% confidence interval [CI], 1.123‐4.535) and living in a suburban area (OR, 1.735; 95% CI, 1.058‐2.845) were the most significant socioeconomic predictive factors for adult current asthma.

Conclusions

It can be concluded that lower socioeconomic status is associated with higher adult current asthma prevalence. Target interventions are necessary to reduce disparities in healthcare systems.
Intraoperative transesophageal echocardiographic predictors of recurrent left ventricular outflow tract obstruction in children undergoing subaortic stenosis resection
Authors: Nawaytou Hythem M. , Mercer‐Rosa Laura , Channing Alexandra , Cohen Meryl S.
Published: February 2018

Background

Intraoperative transesophageal echocardiography (iTEE) is used to assess for residual left ventricular outflow tract obstruction (LVOTO) after surgical resection of subaortic membrane causing subaortic stenosis (sub‐AS). We aimed to identify the iTEE features associated with recurrence of LVOTO.

Methods

We conducted a retrospective study of children undergoing sub‐AS resection from June 2006 to June 2014. Doppler assessment of the flow velocity and the anatomical features of the left ventricular outflow tract were analyzed from stored echocardiograms. Recurrent LVOTO was defined as an increase in the mean pressure gradient across the left ventricular outflow tract of > 15 mm Hg on the most recent follow‐up echocardiogram from the mean pressure gradient on the predischarge echocardiogram or as doubling of the mean pressure gradient to a value ≥20 mm Hg.

Results

Thirty‐five patients were included, with median age at surgery was 8.1 years (range: 0.7–29 years) and median follow‐up was 47 months (2–91 months). Ten patients (29%) had recurrent LVOTO, which was associated with a shorter distance between the narrowest diameter of the outflow tract and the aortic valve on iTEE [median 0.59 cm (range 0.39–0.74) vs 0.98 cm (0.75–1.5), P = .03]. No patients with more than mild residual LVOTO on iTEE regressed to mild or no LVOTO on follow‐up echocardiograms.

Conclusions

LVOTO recurrence after sub‐AS resection is common, and residual LVOTO remains the same or increases over time. Proximity of the LVOTO to the aortic valve is a risk factor for recurrent LVOTO. These findings may be useful in counseling patients and to guide the frequency of postoperative follow‐up.
Consequences of relying on statistical significance: Some illustrations
Authors: Van Calster Ben , Steyerberg Ewout W. , Collins Gary S. , Smits Tim
Published: February 2018

Background

Despite regular criticisms of null hypothesis significance testing (NHST), a focus on testing persists, sometimes in the belief to get published and sometimes encouraged by journal reviewers. This paper aims to demonstrate known key limitations of NHST using simple nontechnical illustrations.

Design

The first illustration is based on simulated data of 20 000 studies that compare two groups for an outcome event. The true effect size (difference in event rates) and sample size (20‐100 per group) were varied. The second illustration used real data from a meta‐analysis on alpha‐blockers for the treatment of ureteric stones.

Results

The simulations demonstrated the large between‐study variability in P‐values (range between <.0001 and 1 for most simulation conditions). A focus on statistically significant effects (P < .05), notably in small to moderate samples, led to strongly overestimated effect sizes (up to 240%) and many false‐positive conclusions, that is statistically significant effects that were, in fact, true null effects. Effect sizes also exerted strong between‐study variability, but confidence intervals accounted for this: the interval width decreased with larger sample size, and the percentage of intervals that contained the true effect size was accurate across simulation conditions. Reducing alpha level, as recently suggested, reduced false‐positive conclusions but strongly increased the overestimation of significant effects (up to 320%).

Conclusions

Researchers and journals should abandon statistical significance as a pivotal element in most scientific publications. Confidence intervals around effect sizes are more informative, but should not merely be reported to comply with journal requirements.
Increasing clinical relevance in oral radiology: Benefits and challenges when implementing digital assessment
Authors: de Lange T. , Møystad A. , Torgersen G. R.
Published: February 2018

Aims

The aims of the study were to investigate benefits and challenges in implementing a digital examination and study the clinical relevance of the digital examination in relation to clinical training and practice.

Material and method

The study was based on semi‐structured focus‐group interviews from two distinct student populations (2016 and 2017) in a bachelor programme in dental hygiene. In addition, conversational data from a plenary discussion from the whole second student population (2017) were collected and analysed. The data were approached on basis of content analysis.

Results

A benefit experienced in the digital examination was the ease in typing and editing answers on the computer. This suggests an increased effectiveness in computer‐based compared to analogue examinations. An additional advantage was the experienced relevance of the examination related to the clinic. This finding refers not only to the digital presentations of images, but also to the entire setting in the clinic and dental practice. The limitations reported by the students were non‐optimal viewing conditions for presenting radiographic images and difficulties in obtaining an overview of the assignments compared to paper‐based examinations due to the linear digital examination format. The last finding on lacking overview revealed an influence on student performances which should be taken seriously in designing digital examinations.

Conclusion

In conclusion, the digital layout increases efficiency and clinical relevance of examinations to a certain extent. Obstacles were found in limitations related to image presentation and lack of overview of the examination. The latter challenge raises questions related to developing suitable assessment software.
Novel mutations in DNAJB6 cause LGMD1D and distal myopathy in French families
Authors: Jonson P. H. , Palmio J. , Johari M. , Penttilä S. , Evilä A. , Nelson I. , Bonne G. , Wiart N. , Meyer V. , Boland A. , Deleuze J.‐F. , Masson C. , Stojkovic T. , Chapon F. , Romero N. B. , Solé G. , Ferrer X. , Ferreiro A. , Hackman P. , Richard I. , Udd B.
Published: February 2018

Background and purpose

The aim was to determine the genetic background of unknown muscular dystrophy in five French families.

Methods

Twelve patients with limb girdle muscular dystrophy or distal myopathy were clinically evaluated. Gene mutations were identified using targeted exon sequencing and mutated DNAJB6 was tested in vitro.

Results

Five patients presented with distal lower limb weakness whilst others had proximal presentation with a variable rate of progression starting at the mean age of 38.5 years. Two novel mutations (c.284A>T, p.Asn95Ile, two families; and c.293_295delATG, p.Asp98del, one family) as well as the previously reported c.279C>G (p.Phe93Leu, two families) mutation in DNAJB6 were identified. All showed a reduced capacity to prevent protein aggregation.

Conclusions

The mutational and phenotypical spectrum of DNAJB6‐caused muscle disease is larger than previously reported, including also dysphagia. The originally reported c.279C>G (p.Phe93Leu) mutation is now identified in four different populations and appears to be a mutational hotspot. Our report confirms that some DNAJB6 mutations cause distal‐onset myopathy and hence DNAJB6 defects should be considered broadly in dominant muscular dystrophy families.
Melatonin attenuates homocysteine‐induced injury in human umbilical vein endothelial cells
Authors: Aminzadeh Azadeh , Mehrzadi Saeed
Published: February 2018

Homocysteine (Hcy) is a major risk factor for vascular disease and is closely associated with endothelial dysfunction. Melatonin is a neurohormone that is mostly produced by the pineal gland. Studies have reported that melatonin exhibits neuroprotective effects in several neurodegenerative disorders. The aim of the current study was to investigate the possible protective effect of melatonin against Hcy‐induced endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs) and to explore the underlying mechanisms. HUVECs were exposed to Hcy in the presence or absence of melatonin. The effect of melatonin on viability was examined by MTT assay. Intracellular reactive oxygen species (ROS) levels were determined by 2′,7′‐dichlorofluorescein diacetate (DCF‐DA). Further, expression of Bax, Bcl‐2, and caspase‐3 was analyzed by Western blot analysis. Lipid peroxidation (LPO) levels, total antioxidant power (TAP), and total thiol molecules were also evaluated. The results of this study revealed that melatonin significantly prevented Hcy‐induced loss in cell viability in HUVECs. It was found that ROS significantly increased in the presence of Hcy, whereas melatonin reduced ROS production. Melatonin also downregulated Bax, upregulated Bcl‐2, and decreased the expression and activity of caspase‐3. Hcy increased the levels of LPO, and this effect was significantly attenuated by melatonin. Melatonin also increased the levels of TAP and total thiol molecules. It was concluded that melatonin played a protective role against Hcy‐induced endothelium cell apoptosis through inhibition of ROS accumulation and the mitochondrial‐dependent apoptotic pathway.
Medical prescriptions falsified by the patients: a 12‐year national monitoring to assess prescription drug diversion
Authors: Jouanjus Emilie , Guernec Grégory , Lapeyre‐Mestre Maryse ,   the French Addictovigilance Network
Published: February 2018

Diversion of prescription drugs is difficult to assess in quality and quantity. This study aimed to characterize diversion of prescription drugs in France through a comparative analysis of falsified prescriptions collected during three periods from 2001 to 2012. The data recorded in a national program which records all falsified prescriptions presented to community pharmacies were studied. Included data regarded: subjects, prescription forms, and drugs. Description of the dataset in three periods (2001–2004, 2005–2008, and 2009–2012) was completed with clustering analyses to characterize profiles of prescriptions and subjects associated with the most reported drugs. The 4469 falsified prescriptions concerned most often females (51.6%). Average age was 46.5 years. Zolpidem, bromazepam, and buprenorphine were the most frequent drugs. Alone, 13 drugs (1.7%, 13/772) represented more than 40% of the total reports (3055/7272). They were associated with three diversion profiles: (i) buprenorphine, flunitrazepam, and morphine were mentioned on overlapping secure prescription forms presented by young men; (ii) alprazolam, bromazepam, zolpidem, codeine/acetaminophen were mentioned on simple prescription forms presented by experienced women; and (iii) acetaminophen and lorazepam were mentioned on modified prescription forms presented by elderly subjects. Clonazepam, clorazepate, dextropropoxyphene, zopiclone moved between those profiles. The patterns of falsified prescriptions provided in this study contribute to enhance the scientific knowledge on the most diverted prescription drugs. The latter follow distinct trajectories across time depending on their pharmacology (including their abuse/addiction potential) and on their regulation's history. The close and continuous analysis of falsified prescriptions is an excellent way to monitor prescription drug diversion.
mRNA expression of drug metabolism enzymes and transporter genes at birth using human umbilical cord blood
Authors: Neyro Virginia , Elie Valéry , Médard Yves , Jacqz‐Aigrain Evelyne
Published: February 2018

Growth and maturation changes are mainly responsible for differences in drug pharmacokinetics and pharmacodynamics observed between adults and children, especially neonates. Ontogeny of drug‐metabolizing enzymes and transporters plays an important role in drugs interindividual pharmacokinetic variability but data are limited in both term and preterm neonates. This study aimed to characterize mRNA expression of the main drug‐metabolizing enzymes and transport proteins involved in drug disposition, using umbilical cord blood (UCB), according to gender, gestational age, and genetic background. A large panel of genes was quantified as follows: cytochrome P450 system (n = 12), UGT family (n = 6), TPMT and transporters (n = 3), in 56 samples of UCB of twin neonates. Gene expression was measured using real‐time reverse transcription polymerase chain reaction with 18S rRNA as the endogenous control for normalization of data. Relative expression of the samples was expressed using the 2−ΔΔCt method for comparison of gene expression levels. Twenty genes were expressed in UCB at birth with variable levels of expression and tissue‐specific gene expression when compared to data on the fetal liver. Gestational age, gender, and genetic background influenced the expression of the genes tested. Easily accessible UCB samples will enable further studies to evaluate the influence of covariates. This suggests that these covariates need to be considered when assessing substrate drugs disposition mediated by these metabolizing enzymes and transporters in the neonatal population.
Teacher leadership and the advancement of teacher agency
Authors: Allen Linda Quinn
Published: February 2018

In keeping with the theme of this special issue, “Looking back, Moving forward,” the present article describes how Iowa is moving forward with its Teacher Leadership and Compensation (TLC) System. First implemented in school districts in the 2014–2015 year, the TLC System is designed to attract and support new teachers; make available meaningful teacher leadership roles, for which teachers receive supplemental salary; and provide high‐quality professional development. Today, every school district in the state of Iowa has a teacher leadership program in place with one of every four Iowa teachers holding a well‐defined, compensated leadership role. In order to participate fully in the new school culture created by the TLC System, it is imperative that teachers have agency, the ability and initiative to direct their own professional growth, and the opportunity to contribute to the growth of colleagues. Teacher education programs can advance preservice teacher agency by cultivating a growth mindset, implementing a dialogic pedagogy, and devoting attention to the construction of teacher identity.
Foreign language education policy on the horizon
Authors: Hult Francis M.
Published: February 2018

Language policy has developed into a major area of research that continues to expand and develop. This article examines potential directions for cross‐pollination between the fields of language policy and foreign language education. First, publication trends are examined. Database searches were conducted for the journals Foreign Language Annals, Modern Language Journal, Current Issues in Language Planning, Language Policy, and Language Problems and Language Planning. It is found that there is a dearth of studies on language policy in the foreign language–oriented journals and on foreign languages in language policy–oriented journals. Next, with these findings as a springboard, Spolsky's three‐component model of language policy—practices, beliefs, and management—is used to guide discussion about future research directions at the confluence of language policy and foreign language education. Finally, implications for political engagement with language education issues are raised, and it is suggested that professional associations might learn from the strategies of successful political action groups.
Arctic moistening provides negative feedbacks to riparian plants
Authors: Helama Samuli , Arppe Laura , Mielikäinen Kari , Oinonen Markku
Published: February 2018

Arctic moistening will affect the circumpolar forested riparian ecosystems. Upward trends observed for precipitation in high latitudes illustrate that the moistening may be underway to influence the woody biomass production near the inland waters, lakes and streams with effects on carbon pools and fluxes. Although the flooding and waterlogging tolerance of seedlings has been investigated, our understanding of responses in mature trees is still limited. Here we employ tree‐ring δ13C and width data from a subarctic riparian setting in Lapland, where artificially high lake level (HLL) has already altered the ecophysiological and growth responses of riparianPinus sylvestristrees to external drivers under conditions simulating moister environment. Prior to theHLLevent, the carbon assimilation rate was primarily limited by irradiance as reflected in the δ13C data and the radial growth of south‐facing riparian trees remained increased in comparison to shaded upland trees. By contrast, the riparian trees were not similarly benefited during theHLLperiod when reduced assimilation depleted the riparian in comparison to upland δ13C despite of increased irradiance. As a result, the radial growth of riparian trees was markedly reduced over theHLLevent while the upland trees benefited from increased irradiance and summer time warming. Although the production of biomass at high latitudes is commonly considered temperature‐limited, our results highlight the increasing role of Arctic moistening to limit the growth when increased precipitation (cloudiness) reduces the incoming solar radiation in general and when the riparian habitat becomes increasingly waterlogged in particular. The effects of high‐latitude warming to induce higher biomass productivity may be restricted by negative feedbacks.
Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors—A retrospective analysis
Authors: Carcao M. , Shapiro A. , Staber J. M. , Hwang N. , Druzgal C. , Lieuw K. , Belletrutti M. , Thornburg C. D. , Ahuja S. P. , Morales‐Arias J. , Dumont J. , Miyasato G. , Tsao E. , Jain N. , Pipe S. W.
Published: February 2018

Introduction

Immune tolerance induction (ITI) is the gold standard for eradication of factor VIII inhibitors in severe haemophilia A; however, it usually requires treatment for extended periods with associated high burden on patients and healthcare resources.

Aim

Review outcomes of ITI with recombinant factor VIII Fc fusion protein (rFVIIIFc) in patients with severe haemophilia A and high‐titre inhibitors.

Methods

Multicentre retrospective chart review of severe haemophilia A patients treated with rFVIIIFc for ITI.

Results

Of 19 patients, 7 were first‐time ITI and 12 were rescue ITI. Of 7 first‐time patients, 6 had at least 1 high‐risk feature for ITI failure. Four of 7 first‐time patients were tolerized in a median of 7.8 months. The remaining 3 patients continue on rFVIIIFc ITI. Of 12 rescue patients, 7 initially achieved a negative Bethesda titre (≤0.6) in a median of 3.3 months, 1 had a decrease in Bethesda titre and continues on rFVIIIFc ITI and 4 have not demonstrated a decrease in Bethesda titre. Of these 4, 3 continue on rFVIIIFc ITI and 1 switched to bypass therapy alone. Two initially responsive patients transitioned to other factors due to recurrence. Overall, 16 of 19 patients remain on rFVIIIFc (prophylaxis or ITI). For those still undergoing ITI, longer follow‐up is needed to determine final outcomes. No adverse events reported.

Conclusions

Recombinant factor VIII Fc fusion protein demonstrated rapid time to tolerization in high‐risk first‐time ITI patients. For rescue ITI, rFVIIIFc showed therapeutic benefit in some patients who previously failed ITI with other products. These findings highlight the need to further evaluate the use of rFVIIIFc for ITI.