bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of ELN recommendations in the management of first‐line treated chronic myeloid leukaemia patients: a French cross‐sectional study
Authors: Etienne Gabriel , Huguet Francoise , Guerci‐Bresler Agnès , Nicolini Franck E. , Maloisel Frédéric , Coiteux Valérie , Dauriac Charles , Carpentier Nathalie , Bourdeix Isabelle , Tulliez Michel , Cony‐Makhoul Pascale
Published: April 2016

The availability of tyrosine kinase inhibitors has extended therapeutic options for chronic myeloid leukaemia (CML) patients. Monitoring recommendations and clinical response goals have recently been updated. The objective of this study was to describe the profile of CML patients in chronic phase currently receiving first‐line therapy, including treatment, monitoring and response kinetics. A multicentre, cross‐sectional, epidemiological survey in unselected chronic phase CML patients in France attending consultations during a one‐month period was performed. 438 of 697 (62·8%) reported patients were currently receiving first‐line treatment and were analysed. Imatinib was the most frequently received treatment (72·4% of patients). Retrospective cytogenetic and molecular assessments at 3, 6, 12 or 18 months were available in 88·4% of patients. At the 12‐month assessment, 32·2% were not in major molecular response (MMR). At last assessment, among 355 patients with duration of treatment ≥ 12 months, 91·5% had achieved MMR and 66·5% were in deep molecular response. This study, performed in everyday practice population of CML patients, suggests that monitoring of molecular responses in real‐life practice is aligned with European LeukaemiaNet recommendations. The majority of patients still receiving first‐line treatment are in optimal response, with a few being classified as in the warning area or responding to failure.
Cell cycle status in AML blast cells from peripheral blood, bone marrow aspirates and trephines and implications for biological studies and treatment
Authors: Sellar Rob S. , Fraser Laura , Khwaja Asim , Gale Rosemary E. , Marafioti Teresa , Akarca Ayse , Hubank Mike , Brooks Tony , Stoeber Kai , Williams Gareth , Linch David C.
Published: April 2016

Using immunohistochemistry and flow cytometry to define phases of the cell cycle, this study shows that a high proportion of acute myeloid leukaemia (AML) blasts obtained from trephine biopsies are cycling, whereas >95% of peripheral blood‐derived blasts are arrested in G1. Results obtained from bone marrow aspirates are more similar to those from blood rather than from trephine biopsies. These differences were confirmed by gene expression profiling in a patient with high count AML. This has implications for cell cycle and other biological studies using aspirates rather than trephine biopsies and for the use of cell mobilising agents before chemotherapy.
Characterizing clients' verbal statements in behavioural support interventions: The case of smoking cessation
Authors: Gainforth Heather L. , Lorencatto Fabiana , Erickson Karl , West Robert , Michie Susan
Published: April 2016

Background

Reliable methods have been developed for characterizing behavioural interventions in terms of component practitioner‐delivered behaviour change techniques (BCTs). As yet, no corresponding methods have been developed for characterizing client responses.

Purpose

To develop a method for characterizing clients’ verbal statements in audio‐recordings of smoking cessation behavioural support consultations.

Methods

An established framework for specifying practitioner‐delivered BCTs was adapted to account for corresponding BCTs in clients’ verbal statements. A total of 1,429 client statements within 15 transcripts of audio‐recorded consultations were independently coded using the framework.

Results

Of the 58 BCT categories in the practitioner framework, 53 corresponding client BCTs were included and five codes unrelated to smoking cessation were added. Forty client BCTs were reliably identified at least once across sessions (75.1% agreement; PABAK = .77).

Conclusions

It is possible to reliably categorize clients’ verbal statements in smoking cessation consultations in terms of responses to BCTs delivered by the practitioner. When used alongside the taxonomy of practitioner‐delivered BCTs, this method could provide a basis for investigating the dyadic interaction between the practitioner and client.

Statement of contribution

What is already known on this subject?

Taxonomies exist for characterizing practitioner‐delivered behaviour change techniques (BCTs) in interventions.

Client responses and contributions are an important part of the behaviour change process.

Examining clients’ receipt of BCTs can add explanatory value to the outcomes of interventions.

Current taxonomies and methods do not characterize client responses in terms of BCTs.

What does this study add?

First method to characterize clients’ statements corresponding to a practitioner BCT taxonomy.

Provides a method for investigating the dyadic practitioner–client interaction using BCTs.

A method that has potential to add explanatory value to the outcomes of interventions.
Too much of a good thing? Overexertion of self‐control and dietary adherence in individuals with Type 2 diabetes
Authors: Jenkins Brooke N. , Rook Karen S. , Borges‐Garcia Raquel , Franks Melissa M. , Stephens Mary Ann Parris
Published: April 2016

Objectives

The resource model of self‐control posits that self‐control is a finite resource that can be depleted. Individuals with diabetes must continually restrict their diet, requiring self‐control. As a result, dietary adherence is difficult, and lapses are common. People with diabetes who overexert self‐control following a lapse may be especially likely to experience a subsequent relapse, as suggested by the resource model. This investigation used the resource model of self‐control to test whether overexertion of dietary self‐control following a lapse would be predictive of a subsequent relapse in dietary control.

Design

We tested this prediction in a daily diary study of 128 individuals with diabetes (Mage = 66.12).

Methods

Participants' reports of their daily dietary adherence were used to define lapses in adherence, post‐lapse adherence, and relapses.

Results

Individuals who overexerted self‐control after a lapse were more likely to experience a subsequent relapse (OR = 3.276, p = .016) and to do so sooner (HR = 2.12, p = .023).

Conclusions

People with diabetes may seek to compensate for a lapse in adherence by overexerting self‐control, but doing so may deplete their self‐control and increase the risk of a future relapse.

Statement of contribution

What is already known on this subject?

The resource model of self‐control posits that self‐control is a limited resource that can be temporarily depleted. Numerous experimental studies have demonstrated support for this model showing that when participants are instructed to engage in a self‐control task, they produce less self‐control on a subsequent task. The majority of the existing studies are not conducted in naturalistic settings and do not use patient populations.

What does this study add?

This study is an ecologically valid test of the resource model of self‐control.

This study applies the resource model of self‐control to a patient population.
Work‐Related Training and the Probability of Transitioning from Non‐Permanent to Permanent Employment
Authors: McVicar Duncan , Wooden Mark , Leung Felix , Li Ning
Published: April 2016

It is widely believed that work‐related training increases a worker's probability of moving up the job‐quality ladder. This is usually couched in terms of effects on wages, but it has also been argued that training increases the probability of moving from non‐permanent forms of employment to more permanent employment. This hypothesis is tested using nationally representative panel data for Australia, a country where the incidence of non‐permanent employment, and especially casual employment, is high by international standards. While a positive association between participation in work‐related training and the subsequent probability of moving from either casual or fixed‐term contract employment to permanent employment is observed among men, this is shown to be driven not by a causal impact of training on transitions but by differences between those who do and do not receive training, that is selection bias.
Relaxin and insulin‐like peptide 3 in the musculoskeletal system: from bench to bedside
Authors: Ferlin Alberto , De Toni Luca , Sandri Marco , Foresta Carlo
Published: April 2016

Skeletal muscles and bones form a joined functional unit sharing a complex mechanical, biochemical and hormonal crosstalk. A number of factors, including sex hormones, physiologically regulate the musculoskeletal system. Striking gender differences in muscle and bone mass, and function are mainly caused by distinct actions exerted by oestrogens and androgens. However, relaxin and relaxin‐related peptides, such as insulin‐like peptide 3 (INSL3), might contribute to these sex‐associated differences in physiological and pathological conditions (such as osteoporosis and sarcopenia). Relaxin is a ‘pregnancy’ hormone, but it is also produced from the prostate gland, and has recently attracted attention as a potential drug for cardiovascular disorders and fibrosis. In contrast, INSL3 is a male‐specific hormone produced by the Leydig cells of the testis with a fundamental role in testicular descent during fetal life. Recent evidence suggests that both hormones have interesting roles in the musculoskeletal system. Relaxin and INSL3, by finely tuning bone formation and resorption, are involved in bone remodelling processes, and relaxin contributes to the healing of injured ligaments and promotes skeletal muscle regeneration. Here, we review the most recent findings on the effects of relaxin and INSL3 on skeletal muscle and the cell components of bone. In the light of the experimental evidence available and animal models, their clinical implications are also discussed.

Linked Articles

This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc
The role of metformin and resveratrol in the prevention of hypoxia‐inducible factor 1α accumulation and fibrosis in hypoxic adipose tissue
Authors: Li Xiaole , Li Jia , Wang Lulu , Li Aiyun , Qiu Zhixia , Qi Lian‐wen , Kou Junping , Liu Kang , Liu Baolin , Huang Fang
Published: April 2016

Background and Purpose

Hypoxic activation of hypoxia‐inducible factor 1α (HIF‐1α) and fibrosis in adipose tissue contribute to adipose dysfunction. This study was designed to investigate the effects of metformin and resveratrol on the regulation of HIF‐1α and fibrosis in hypoxic adipose tissue.

Experimental Approach

Mice were fed a high‐fat diet to induce hypoxia and fibrosis in adipose tissue; adipose tissue incubated in vitro in 1% O2 showed a similar change. The effects of metformin and resveratrol on hypoxia, HIF‐1α accumulation, endoplasmic reticulum stress and gene expressions of extracellular matrix components and pro‐inflammatory cytokines were examined.

Key Results

Oral administration of metformin or resveratrol prevented hypoxia and reduced HIF‐1α accumulation with dephosphorylation of inositol‐requiring enzyme 1α and eukaryotic initiation factor 2α, indicative of suppression of hypoxic HIF‐1α activation and endoplasmic reticulum stress. Metformin and resveratrol down‐regulated gene expressions of Col3α, Col6α, elastin and lysyl oxidase and thereby reduced collagen deposition in adipose tissue. The increased gene expressions of TNF‐α, IL‐6, monocyte chemoattractant protein 1 and F4/80 were also down‐regulated by metformin and resveratrol. Metformin and resveratrol had similar effects in adipose tissue exposed to 1% O2. Metformin reduced ATP production and prevented the reduction in oxygen tension in 3T3‐L1 cells, suggesting that it prevented hypoxia by limiting oxygen consumption, whereas resveratrol reduced HIF‐1α accumulation by promoting its proteasomal degradation via the regulation of AMPK/SIRT1.

Conclusion and Implications

Hypoxia and fibrosis are early causes of adipose dysfunction in obesity. Both metformin and resveratrol effectively inhibited HIF‐1α activation‐induced fibrosis and inflammation in adipose tissue, although by different mechanisms.
Amylin structure–function relationships and receptor pharmacology: implications for amylin mimetic drug development
Authors: Bower Rebekah L , Hay Debbie L
Published: April 2016

Amylin is an important, but poorly understood, 37 amino acid glucoregulatory hormone with great potential to target metabolic diseases. A working example that the amylin system is one worth developing is the FDA‐approved drug used in insulin‐requiring diabetic patients, pramlintide. However, certain characteristics of pramlintide pharmacokinetics and formulation leave considerable room for further development of amylin‐mimetic compounds. Given that amylin‐mimetic drug design and development is an active area of research, surprisingly little is known about the structure/function relationships of amylin. This is largely due to the unfavourable aggregative and solubility properties of the native peptide sequence, which are further complicated by the composition of amylin receptors. These are complexes of the calcitonin receptor with receptor activity‐modifying proteins. This review explores what is known of the structure–function relationships of amylin and provides insights that can be drawn from the closely related peptide, CGRP. We also describe how this information is aiding the development of more potent and stable amylin mimetics, including peptide hybrids.
Organizational Learning Mechanisms and Creative Climate: Insights from an Italian Fashion Design Company
Authors: Cirella Stefano , Canterino Filomena , Guerci Marco , Shani Abraham B. (Rami)
Published: April 2016

This paper investigates the relationship between different types of organizational learning mechanisms and creative climate. In the context of an action research study, this paper focuses on insights from a survey that was administered to all the employees of the Product Design and Development unit of the company. The results demonstrate that the three different types of organizational learning mechanisms considered in the study (cognitive, structural and procedural mechanisms) are associated with creative climate. The study generates new scientific knowledge about the role of organizational learning mechanisms and provides specific recommendations for organizations that aim to enhance creative climate.
Discovery of 7‐Methyl‐10‐Hydroxyhomocamptothecins with 1,2,3‐Triazole Moiety as Potent Topoisomerase I Inhibitors
Authors: Xu Xiguo , Wu Yuelin , Liu Wenfeng , Sheng Chuanquan , Yao Jianzhong , Dong Guoqiang , Fang Kun , Li Jin , Yu Zhiliang , Min Xiao , Zhang Huojun , Miao Zhenyuan , Zhang Wannian
Published: April 2016

Homocamptothecin is emerging as an important topoisomerase I inhibitor originating in natural product camptothecin. We report the modifications and SAR of homocamptothecin on position C10 to develop potent topoisomerase I inhibitors for anticancer drug discovery. Based on click chemistry, twenty‐one 1,2,3‐triazole‐substituted homocamptothecin derivatives were readily synthesized in two steps. For A549, cycloalkyl‐ and alkyl‐substituted compounds 6j, 6l, and 6o revealed highly antiproliferative inhibitory activities with IC50 value of 30, 30, and 50 nm, respectively. In addition, cyclopropyl 6j exhibited greater Topo I inhibitory activity than 20(S)‐Camptothecin, which indicated suitability for further drug development.
Synthesis of Pyrazine‐1,3‐thiazine Hybrid Analogues as Antiviral Agent Against HIV‐1, Influenza A (H1N1), Enterovirus 71 (EV71), and Coxsackievirus B3 (CVB3)
Authors: Wu Hong‐Min , Zhou Kuo , Wu Tao , Cao Yin‐Guang
Published: April 2016

A novel series of pyrazine‐1,3‐thiazine hybrid conjugates were synthesized in excellent yield. These derivatives were subsequently tested against human immunodeficiency virus (HIV‐1); hemagglutinin type 1 and neuraminidase type 1—'influenza' A (H1N1) virus; enterovirus 71 (EV71); and coxsackievirus B3. The effect of these conjugates on the key enzymes responsible for the progression of these viral infections was also illustrated via enzyme‐based assay, such as HIV‐1 reverse transcriptase (RT) and neuraminidase, where entire tested molecules showed considerable inhibition. Particularly, among the tested derivatives, compound 3k was identified as most promising inhibitor of HIV‐1 with 94% of inhibition (IC50 3.26 ± 0.2 μm). Moreover, the compound 3d was found to be the most potent analogue to inhibit the H1N1 virus with IC50 of 5.32 ± 0.4 μm together with inhibition of the neuraminidase enzyme (IC50 11.24 ± 1.1 μm). In regard to inhibitory activity against enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), the tested derivatives showed considerable inhibition of infection. Molecular docking studies were also performed for the most promising inhibitors with their corresponding target protein to exemplify the structural requirement for better inhibitory activity. The results of inhibitory assay showed that designed molecules possess considerable inhibitory activity against the virus tested.
Rates of detection of developmental problems at the 18‐month well‐baby visit by family physicians' using four evidence‐based screening tools compared to usual care: a randomized controlled trial
Authors: Thomas R. E. , Spragins W. , Mazloum G. , Cronkhite M. , Maru G.
Published: April 2016

Background

Early and regular developmental screening can improve children's development through early intervention but is insufficiently used. Most developmental problems are readily evident at the 18‐month well‐baby visit. This trial's purpose is to: (1) compare identification rates of developmental problems by GPs/family physicians using four evidence‐based tools with non‐evidence based screening, and (2) ascertain whether the four tools can be completed in 10‐min pre‐visit on a computer.

Methods

We compared two approaches to early identification via random assignment of 54 families to either: ‘usual care’ (informal judgment including ad‐hoc milestones, n = 25); or (2) ‘Evidence‐based’ care (use of four validated, accurate screening tools, n = 29), including: the Parents' Evaluation of Developmental Status (PEDS), the PEDS‐Developmental Milestones (PEDS‐DM), the Modified Checklist for Autism in Toddlers (M‐CHAT) and PHQ9 (maternal depression).

Results

In the ‘usual care’ group four (16%) and in the evidence‐based tools group 18 (62%) were identified as having a possible developmental problem. In the evidence‐based tools group three infants were to be recalled at 24 months for language checks (no specialist referrals made). In the ‘usual care’ group four problems were identified: one child was referred for speech therapy, two to return to check language at 24 months and a mother to discuss depression. All forms were completed on‐line within 10 min.

Conclusions

Despite higher early detection rates in the evidence‐based care group, there were no differences in referral rates between evidence‐based and usual‐care groups. This suggests that clinicians: (1) override evidence‐based screening results with informal judgment; and/or (2) need assistance understanding test results and making referrals. Possible solutions are improve the quality of information obtained from the screening process, improved training of physicians, improved support for individual practices and acceptance by the regional health authority for overall responsibility for screening and creation of a comprehensive network.
RecombinantSalmonella typhimuriumouter membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)-17/IL-23 in patients with reactive arthritis and undifferentiated spondyloarthropathy
Authors: Chaurasia S , Shasany A K , Aggarwal A , Misra R
Published: April 2016

In developing countries, one-third of patients with reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) are triggered by Salmonella typhimurium. Synovial fluid mononuclear cells (SFMCs) of patients with ReA and uSpA proliferate to low molecular weight fractions (lmwf) of outer membrane proteins (Omp) of S. typhimurium. To characterize further the immunity of Omp of Salmonella, cellular immune response to two recombinant proteins of lmwf, OmpA and OmpD of S. typhimurium (rOmpA/D-sal) was assessed in 30 patients with ReA/uSpA. Using flow cytometry, 17 of 30 patients' SF CD8+ T cells showed significant intracellular interferon (IFN)-γ to Omp crude lysate of S. typhimurium. Of these 17, 11 showed significantly more CD8+CD69+ IFN-γ T cells to rOmpA-sal, whereas only four showed reactivity to rOmpD-sal. The mean stimulation index was significantly greater in rOmpA-sal than rOmpD-sal [3·0 (1·5–6·5) versus 1·5 (1·0–2·75), P < 0·005]. Similarly, using enzyme-linked immunospot (ELISPOT) in these 17 patients, the mean spots of IFN-γ-producing SFMCs were significantly greater in rOmpA-sal than rOmpD-sal [44·9 (3·5–130·7) versus 19·25 (6–41), P < 0·05]. SFMCs stimulated by rOmpA-sal produced significantly more proinflammatory cytokines than rOmpD-sal: IFN-γ [1·44 (0·39–20·42) versus 0·72 (0·048–9·15) ng/ml, P < 0·05], interleukin (IL)−17 [28·60 (6·15–510·86) versus 11·84 (6·83–252·62) pg/ml, P < 0·05], IL-23 [70·19 (15–1161·16) versus 28·25 (> 15–241·52) pg/ml, P < 0·05] and IL-6 [59·78 (2·03–273·36) versus 10·17 (0·004–190·19) ng/ml, P < 0·05]. The rOmpA-sal-specific CD8+ T cell response correlated with duration of current synovitis (r = 0·53, P < 0·05). Thus, OmpA of S. typhimurium is a target of SF CD8+ T cells and drives SFMC to produce increased cytokines of the IL-17/IL-23 axis which contribute to the pathogenesis of Salmonella-triggered ReA.
Differential regulation of miR-146a/FAS and miR-21/FASLG axes in autoimmune lymphoproliferative syndrome due to FAS mutation (ALPS-FAS)
Authors: Marega Lia Furlaneto , Teocchi Marcelo Ananias , dos Santos Vilela Maria Marluce
Published: April 2016

Most cases of autoimmune lymphoproliferative syndrome (ALPS) have an inherited genetic defect involving apoptosis-related genes of the FAS pathway. MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs playing a role in the control of gene expression. This is the first report on miRNAs in ALPS patients. We studied a mother and son carrying the same FAS cell surface death receptor (FAS) mutation, but with only the son manifesting the signs and symptoms of ALPS-FAS. The aim was to analyse, by reverse transcription–quantitative polymerase chain reaction (RT–qPCR), the peripheral blood mononuclear cells (PBMC) relative expression of miR-146a and miR-21, including their passenger strands and respective targets (FAS and FASLG). In comparison with healthy matched control individuals, miR-21-3p was over-expressed significantly (P = 0·0313) in the son, with no significant change in the expression of miR-146a, miR-146a-3p and miR-21. In contrast, the mother had a slight under-expression of the miR-146a pair and miR-21-3p (P = 0·0625). Regarding the miRNA targets, FAS was up-regulated markedly for the mother (P = 0·0078), but down-regulated for the son (P = 0·0625), while FASLG did not have any significant alteration. Taken together, our finding clearly suggests a role of the miR-146a/FAS axis in ALPS-FAS variable expressivity in which FAS haploinsufficiency seems to be compensated only in the mother who had the miR-146a pair down-regulated. As only the son had the major clinical manifestations of ALPS-FAS, miR-21-3p should be investigated as playing a critical role in ALPS physiopathology, including the development of lymphoma.
IL‐1 receptor antagonist levels are associated with glucose tolerance in polycystic ovary syndrome
Authors: Luotola Kari , Piltonen Terhi T. , Puurunen Johanna , Tapanainen Juha S.
Published: April 2016

Objective

To investigate serum interleukin‐1 receptor antagonist (IL‐1Ra) levels in women with polycystic ovary syndrome (PCOS).

Subjects and methods

Serum IL‐1Ra levels were measured at baseline in 73 women with PCOS and 45 control subjects (18–47 years), and in 27 women with PCOS who underwent oral and intravenous glucose tolerance tests (OGTTs and IVGTTs).

Results

IL‐1Ra concentrations predicted OGTT 2‐h glucose levels independently of BMI and insulin resistance (P ≤ 0·001) in women with PCOS. Serum IL‐1Ra concentration was elevated in women with PCOS compared with controls [mean (SD): 309·5 (208·8) vs 199·1 (81·4) ng/l, P < 0·001], but the difference disappeared after adjusting for BMI. An increment of five BMI units raised IL‐1Ra levels by 108·5 ng/l [95% confidence interval (CI): 85·5–131·5, r2 = 0·603] in women with PCOS and only by 77·0 ng/l (95% CI: 50·5–103·5, r2 = 0·512) in controls when adjusted for BMI and age. Levels of IL‐1Ra in obese women with PCOS reflected decreasing OGTT‐derived insulinogenic index (P = 0·032) and disposition index (P = 0·046) independently of BMI. Increased levels of IL‐1Ra correlated with indices showing increasing insulin resistance and AUC insulin (P ≤ 0·002).

Conclusions

Increased IL‐1Ra levels in women with PCOS were largely explained by increasing adiposity. However, serum IL‐1Ra concentrations predicted 2‐h glucose levels independently of BMI suggesting that increased IL‐1Ra may be associated with disturbed glucose metabolism.
Short‐pulse duration retinal lasers: a review
Authors: Chehade Luke , Chidlow Glyn , Wood John , Casson Robert J
Published: April 2016

The development of lasers for biological use was an important medical advance in the 20th century with numerous evidence‐based therapeutic applications to retinal disease, including capillary leakage at the macula. Although the role of photocoagulative laser in the treatment of macular oedema has diminished, there is evidence for a modified role in clinical management, particularly for extrafoveal leakage. Additionally, it may reduce the frequency of required intravitreal injections and assist in visual stabilization when used as an adjunct. The tissue destructive effect of photocoagulative lasers has motivated the development of safer macular lasers and the search for novel therapeutic applications, including treatment of drusen and regeneration of dysfunctional retinal pigment epithelium.
Diabetic retinopathy in pregnancy: a review
Authors: Morrison Julie L , Hodgson Lauren AB , Lim Lyndell L , Al‐Qureshi Salmaan
Published: April 2016

The prevalence of diabetes in pregnancy is increasing. Pre‐existing diabetes is present in 1 in 167 pregnancies in Australia, divided equally between type 1 and type 2 diabetes. Diabetic retinopathy is a leading cause of blindness in women during their childbearing years, and pregnancy increases the short‐term risk of diabetic retinopathy progression. We examine the risk factors for progression of diabetic retinopathy during pregnancy including duration of diabetes, baseline level of retinopathy, level of glycaemic control and hypertension. We also examine current screening and management guidelines and their levels of evidence, current treatment options for diabetic retinopathy and avenues for further research.
Mutations in the IRBIT domain of ITPR1 are a frequent cause of autosomal dominant nonprogressive congenital ataxia
Authors: Barresi S. , Niceta M. , Alfieri P. , Brankovic V. , Piccini G. , Bruselles A. , Barone M.R. , Cusmai R. , Tartaglia M. , Bertini E. , Zanni G.
Published: April 2016

Congenital ataxias are nonprogressive neurological disorders characterized by neonatal hypotonia, developmental delay and ataxia, variably associated with intellectual disability and other neurological or extraneurological features. We performed trio‐based whole‐exome sequencing of 12 families with congenital cerebellar and/or vermis atrophy in parallel with targeted next‐generation sequencing of known ataxia genes (CACNA1A, ITPR1, KCNC3, ATP2B3 and GRM1) in 12 additional patients with a similar phenotype. Novel pathological mutations of ITPR1 (inositol 1,4,5‐trisphosphate receptor, type 1) were found in seven patients from four families (4/24, ∼16.8%) all localized in the IRBIT (inositol triphosphate receptor binding protein) domain which plays an essential role in the regulation of neuronal plasticity and development. Our study expands the mutational spectrum of ITPR1‐related congenital ataxia and indicates that ITPR1 gene screening should be implemented in this subgroup of ataxias.
Autosomal recessive IFT57 hypomorphic mutation cause ciliary transport defect in unclassified oral–facial–digital syndrome with short stature and brachymesophalangia
Authors: Thevenon J. , Duplomb L. , Phadke S. , Eguether T. , Saunier A. , Avila M. , Carmignac V. , Bruel A.‐L. , St‐Onge J. , Duffourd Y. , Pazour G.J. , Franco B. , Attie‐Bitach T. , Masurel‐Paulet A. , Rivière J.‐B. , Cormier‐Daire V. , Philippe C. , Faivre L. , Thauvin‐Robinet C.
Published: April 2016

The 13 subtypes of oral–facial–digital syndrome (OFDS) belong to the heterogeneous group of ciliopathies. Disease‐causing genes encode for centrosomal proteins, components of the transition zone or proteins implicated in ciliary signaling. A unique consanguineous family presenting with an unclassified OFDS with skeletal dysplasia and brachymesophalangia was explored. Homozygosity mapping and exome sequencing led to the identification of a homozygous mutation in IFT57, which encodes a protein implicated in ciliary transport. The mutation caused splicing anomalies with reduced expression of the wild‐type transcript and protein. Both anterograde ciliary transport and sonic hedgehog signaling were significantly decreased in subjects' fibroblasts compared with controls. Sanger sequencing of IFT57 in 13 OFDS subjects and 12 subjects with Ellis–Van Creveld syndrome was negative. This report identifies the implication of IFT57 in human pathology and highlights the first description of a ciliary transport defect in OFDS, extending the genetic heterogeneity of this subgroup of ciliopathies.
The Social Construction of Attachment, Attachment Disorders and Attachment Parenting in International Adoption Discourse and Parent Education
Authors: Pylypa Jen
Published: April 2016

This article examines how ideas about forming emotional attachments with internationally adopted children are communicated to parents via adoption agencies, parenting courses, magazines, books and websites. In adoptive parent education, attachment is often presented as an elusive goal that requires concerted effort to achieve, without which the child may suffer from an attachment disorder with lifelong psychological and behavioural consequences. The result is the promotion of intensive parenting practices derived from, but also exceeding, those advocated by the ‘attachment parenting’ philosophy, practices that are often demanding, inflexible and proscriptive, yet only tenuously connected to their supposed evidence base in psychology.
Influence of wound closure on the volume stability of particulate and non‐particulate GBR materials: an in vitro cone‐beam computed tomographic examination. Part II
Authors: Mir‐Mari Javier , Benic Goran I. , Valmaseda‐Castellón Eduard , Hämmerle Christoph H.F. , Jung Ronald E.
Published: April 2016

Objectives

To test whether GBR with an L‐shaped soft‐block bone substitute and particulate bone substitute differs from GBR with particulate bone substitute as regards the volume stability of the augmented region during flap closure.

Materials and methods

Twenty peri‐implant box‐shaped bone defects were created in 10 pig mandibles. Every bone defect was augmented with each of the following two GBR procedures in turn: control group – particulate xenograft applied buccally + collagen membrane + pins; test group – particulate xenograft applied buccally + L‐shaped soft‐block xenograft applied buccally and occlusally + collagen membrane + pins. Cone‐beam computed tomography scans were obtained before and after wound closure. The horizontal thickness (HT) of the augmented region (bone substitute + membrane) was assessed at the implant shoulder (HT0 mm) and at 1 mm to 5 mm apical to the implant shoulder (HT1 mm‐HT5 mm). In the test group, the vertical thickness (VT) and 45° thickness (45‐T) of the augmented region were measured from the implant shoulder. The changes in HT during flap suturing were calculated as absolute (mm) and relative values (%). Repeated‐measures ANOVAs were used for statistical analysis.

Results

The reduction in HT0 mm was 20.5 ± 23.3% (SD) in the control group and 2.4 ± 9.2% (SD) in the test group (P = 0.014). There were no statistically significant differences in changes in HT1–5 mm between the groups (P > 0.05). In the test group, the reduction in VT amounted to 28.0 ± 11.9% (SD) and the reduction in 45‐T amounted to 24.8 ± 10.2% (SD) (P < 0.001).

Conclusion

The addition of an L‐shaped soft‐block bone substitute to a particulate xenograft, covered by a collagen membrane and fixed with pins, significantly improved the horizontal volume stability of the augmented region during wound closure.
Pulmonary tuberculosis due to Mycobacterium bovis revealed by skin lesion in slaughterhouse worker
Authors: Mertoğlu Aydan , Biçmen Can , Karaarslan Serap , Buğdayci Mehmet Hüsnü
Published: April 2016

A 46‐year‐old male patient who has worked as a butcher was admitted to the hospital with an unhealing wound on the dorsal side of his hand. Incisional biopsy was performed from the lesion and histopathological diagnosis revealed a granulomatous inflammatory process, compatible with tuberculosis. The patient was directed to the department of chest diseases for further investigation in terms of pulmonary Tuberculosis (TB) infection. On the chest X‐ray and thoracic CT scan, a minimal infiltration was observed in the left upper lobe. In two respiratory samples obtained by fiberoptic bronchoscopy, Mycobacterium tuberculosis complex was isolated and identified as M. bovis in subspecies level. After overall clinical evaluation, anti‐TB treatment was initialized and a radiologic/clinical regression was observed during the follow‐up procedure. This case has been reported as a rare and noteworthy pulmonary TB disease due to M. bovis in a slaughterhouse worker with a cutaneous granulomatous inflammatory reaction.
From the Editor Emerita
Authors: Doering Zahava D.
Published: April 2016

Since 1997, Zahava D. Doering has contributed to Curator: The Museum Journal. This is her last issue as Curator editor. The article highlights the key issues for which the journal has provided a platform to its global readership during her editorship. Issues include psychological and physical access, social roles and responsibility, health, museums without walls, crowdsourcing, environmental sustainability, and human rights and diversity. It also extends gratitude to the editorial staff (named), editorial board members, peer reviewers, and authors she has had the honor to have as colleagues in supporting new dialogues for museums and other cultural venues.
From the New Editor
Authors: Fraser John
Published: April 2016

With the passage of ownership of Curator: The Museum Journal from the California Academy of Sciences (CAS) to John Wiley and Sons, Inc., John Fraser has been appointed as the new Editor. His article summarizes the circulation growth of the journal since Wiley first began publishing the title. The expansion is visible in the number of libraries, the global distribution, and access at low or no cost to institutions in developing economies of the journal. The new editor envisions further growth, and plans a vibrant social media presence, enlarged editorial board, and a continuation of his predecessor's legacy.
Do Museums Change Lives?: Ninth Stephen Weil Memorial Lecture
Authors: Fleming David
Published: April 2016

No museum is actually “neutral,” ever.

This article presents the keynote address presented at the annual conference of the International Committee on Museum Management (INTERCOM) and of the Federation of International Human Rights Museums (FIHRM). In it, the author lays out the provocative case that museums not only are not, but should not be “neutral” when it comes to issues of human rights and social justice. Museums need not present both sides of every argument, or retain a lofty academic tone when it comes to the injustices of the present and the past. As an alternative course, the author presents a framework published by the British Museums Association, entitled Museums Change Lives, which offers a vision for museums to engage with challenging topics. He then offers a series of examples where Museums have embraced a new role as a promoter of social good.
The Exhibition on Catholic Culture: Dialogues and Negotiations at the Vietnam Museum of Ethnology
Authors: Van Huy Nguyen , Thi Ha Vu , Thi Thanh Tam Vu
Published: April 2016

The first exhibition in Vietnam to feature Vietnamese Catholics was held from December 10, 2008 to June 10, 2009 at the Vietnam Museum of Ethnology in Hanoi. The theme of this exhibition was “Catholic Culture as an Intrinsic Part of Vietnamese Culture.” The exhibition was organized by a State‐run museum against a background of difficult relations between the State and its Catholic communities. This article explores how the exhibition was conceived, and how the ideas of the curators were implemented by examining negotiations among different stakeholders involved in the exhibition.
In Search of Magic Bullets
Authors: Freudenheim Tom
Published: April 2016

The author suggests that especially in museums, particularly art museums, creating truly visitor‐friendly environments eludes most institutions. The special, sometimes magical, experience of direct contact with original works of art can be encouraged by management decisions that make the museum a more accessible place. This ranges from technological fixes to simply insisting on friendliness from staff. Examples from the author's experience are provided.
“Loving, Knowing Ignorance”: A Problem for the Educational Mission of Museums
Authors: Gilbert Lisa
Published: April 2016

In this essay, I suggest that Mariana Ortega's concept of “loving, knowing ignorance” (2006) provides a useful conceptual tool for museum practitioners who seek to advance a progressive mission. This form of ignorance assumes authority in describing and acting on behalf of a subject, even as it fails to take seriously the subject's self‐knowledge and agency. While Ortega initially coined this term to describe the stance of white feminists toward women of color, here I extend the concept to describe a wider range of knowers—in this case, the institutional museum. Using a case study at the Museum of Fine Arts, Boston to illustrate this problem, I will suggest that becoming aware of instances of loving, knowing ignorance and learning to avoid it is a key skill for museum professionals who hope for their institutions to fulfill their educational mission in a diverse and democratic society.
Cultural Curating and the Practices of Light: Speculating Diffractively
Authors: Dziekan Vince
Published: April 2016

Drawing inspiration from New Materialist philosopher Karen Barad's challenge to read “diffractively” by experimenting with different patterns of relationality, this article sets out a course of speculative inquiry inspired by the contemporary fascination with digital light‐based installations. Taking the UN's designation of 2015 as the “International Year of Light and Light‐based Technologies” as its point of departure, a subset of mediated environments are identified that transcend the distinction between physical and digital; materiality and immateriality; invisibility and presence. Employing new technologies to create deeply sensorial and highly participatory forms of aesthetic engagement, the selected examples offer a compelling indication of the post‐digital aesthetics that arise from the interrelationship of art, design and computation. Its investigation is structured as a montage of two parts: following an introduction that surveys an illustrative sub‐set of contemporary digital light‐based art works drawn from the 2014 INST‐INT conference, the second half of this text will speculate upon the “dynamic‐constructive” relationship between digital media and the form‐making processes associated with “practices of light” (Cubitt ). The implications of “post‐screen media” for curatorial practice is explored in relation to the mediating function played by modes of exhibition and other program architectures.
Malignant pleural effusion cell blocks are substitutes for tissue in EML4‐ALK rearrangement detection in patients with advanced non‐small‐cell lung cancer
Authors: Zhong J. , Li X. , Bai H. , Zhao J. , Wang Z. , Duan J. , An T. , Wu M. , Wang Y. , Wang S. , Wang J.
Published: April 2016

Objective

To evaluate the feasibility of malignant pleural effusions (MPE) as surrogate samples for the detection of echinoderm microtubule‐associated protein‐like4 (EML4)‐anaplastic lymphoma kinase (ALK) and to investigate the prognostic and predictive value of EML4‐ALK in MPE of non‐small‐cell lung cancer (NSCLC).

Methods

One hundred and nine NSCLC patients were retrospectively analysed. EML4‐ALK was identified using paraffin‐embedded tumour cells in MPE samples by immunohistochemistry (IHC, Ventana) and confirmed by fluorescence using in situ hybridisation (FISH) and qRT‐PCR. The EGFR mutation was determined by MPE, using denaturing high‐performance liquid chromatography (DHPLC).

Results

A total of 5 out of 109 (4.58%) patients were identified as EML4‐ALK rearrangement in MPE by IHC.; In addition to two metachronous samples, the consistency of MPE and tissue for EML4‐ALK detection was 100% (21/21), and the sensitivity and specificity were 100% (2/2) and 100% (19/19), respectively. EML4‐ALK rearrangement cases were confirmed by FISH and qRT‐PCR; the sensitivity were both 100% (2/2) when compared with tissue, and it was 60% (3/5) and 100% (5/5), respectively, when compared with MPE by IHC. The overall response rate (ORR) was 100% (2/2) for patients with EML4‐ALK in MPE. Moreover, the PFS of these patients appeared to be prolonged in chemotherapy (9.27 versus 6.53 and versus 4.67 months, P = 0.122), compared with the EGFR mutation and the EGFR/ALK double negative group, respectively.

Conclusion

EML4‐ALK rearrangement detection in malignant pleural effusions is a complementary method for EML4‐ALK detection. VETANA and qRT‐PCR are more appropriate for MPE detection. EML4‐ALK rearrangement in pleural effusions has a predictive value for treatment.
Role of brush cytology in the diagnosis of neoplastic and non‐neoplastic upper gastrointestinal lesions
Authors: Muniraj F. , Siddaraju N. , Sistla S. C.
Published: April 2016

Objective

To evaluate the utility of brush cytology (BC) in diagnosing non‐neoplastic and neoplastic lesions of the upper gastrointestinal (GI) tract.

Methods

The study comprised 106 brushings from 104 patients with clinically suspected lesions in the upper GI tract. Diagnoses were rendered on correlating brush cytological findings with clinicoradiological findings and compared with endoscopic biopsies (EB). An attempt was made to grade oesophageal squamous cell carcinomas (SCC) and to subcategorise gastric adenocarcinomas (AC). The sensitivity, specificity and predictive values of BC were calculated with respect to clinico‐radiological outcome.

Results

Malignant and benign lesions on BC comprised 74.5% and 25.5%, respectively, and on histology, 64.2% and 28.3%, respectively. Twenty‐one of 32 (65.6%) gastric ACs were accurately sub‐typed (16 intestinal and five diffuse) and 25/36 (69.4%) oesophageal SCCs (7, 15 and three well, moderately and poorly differentiated, respectively) were accurately graded. On correlation with the final clinico‐radiological diagnosis, there was one false‐positive and no false‐negative cases, respectively, on BC; three false‐negative and no false‐positive cases, respectively, on EB; eight EB were non‐representative in which a diagnosis was not rendered, out of which seven were malignant. Thus, BC had a sensitivity and specificity of 100% and 96.4%, respectively, with a positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) of 98.7%, 100% and 99.1% (P ˂ 0.05), respectively. BC was superior to EB in detecting Candida species and EB in detecting Helicobacter pylori.

Conclusions

BC is a useful, routinely applicable and reliable test for diagnosing upper GI lesions.
Usefulness of immunocytochemistry using a Breast Marker antibody cocktail targeting P63/cytokeratin7/18/cytokeratin5/14 for fine needle aspiration of the breast: a retrospective cohort study of 139 cases
Authors: Tanaka S. , Kanomata N. , Teramura K. , Wakita K. , Kunihisa T. , Yano Y. , Moriya T. , Hayashi Y.
Published: April 2016

Objective

The Breast Marker Cocktail from Biocare Medical comprises five antibodies recognising p63, and cytokeratins (CKs) 7, 18, 5 and 14. Immunohistochemistry using this cocktail is useful for diagnosing proliferative intraductal breast lesions. However, cytology using the cocktail has not been reported.

Methods

We report 139 cases of mammary samples collected by fine needle aspiration (FNA) for which histological diagnoses were available. After cell transfer, immunocytochemistry was performed using the cocktail, and clusters of cells were classified. A cluster with no or limited CK5/14 expression (<20% of cells) was classified as a monotonous cluster. One with more than 20% of cells showing CK5/14 expression was defined as a mosaic cluster. When at least one p63‐positive cell was present, we defined it as a cluster with p63. We also evaluated background p63‐positive myoepithelial cell densities.

Results

The diagnostic sensitivity and specificity for carcinomas were 97.8% (89/91) and 91.7% (11/12), respectively, using the criterion of two or more monotonous clusters lacking p63. Two false‐negative cases were triple‐negative cancers; one false‐positive was an apocrine papilloma. The numbers of monotonous clusters with p63 differed significantly between benign lesions, ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS) and invasive carcinomas (P < 0.001). The background myoepithelial cell density was significantly higher in fibroepithelial tumours than in other lesions (P < 0.001).

Conclusions

Immunocytochemistry using this antibody cocktail showed good sensitivity and specificity for diagnosing breast cancers. Thus, this method is useful for mammary cytology using FNA.