bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐life experience in switching to new extended half‐life products at European haemophilia centres
Authors: Peyvandi Flora , Garagiola Isabella , Boscarino Marco , Ryan Aislin , Hermans Cedric , Makris Michael
Published: August 2019

The concept of replacement therapy in haemophilia is changing significantly thanks to the switch from standard products to extended half‐life products. These novel drugs are showing beneficial effects overcoming current prophylaxis limitations by reducing the infusion frequency, maintaining a higher trough level to ensure a lower risk of bleeding, and making treatment significantly less distressing to patients by improving the quality of life. Real‐life data on the efficacy of novel drugs and their impact on routine management of haemophilia A and B patients are still limited. This manuscript reports the results of a European survey conducted by the European Association for Haemophilia and Allied Disorders (EAHAD) at the beginning of 2018 on the clinical management of patients using extended half‐life recombinant FVIII and FIX fusion products, since at the time of the survey none of the PEGylated products were available yet. We report data on the efficacy of these novel drugs by 33 European haemophilia centres that have already switched to extended half‐life fusion products, showing a significant reduction in the number of infusions and a satisfactory trough levels in the clinical care of haemophilia patients, with a greater impact for haemophilia B.
The Paediatric Haemophilia Activities List (pedHAL) in routine assessment: changes over time, child‐parent agreement and informative domains
Authors: Kuijlaars Isolde A. R. , van der Net Janjaap , Schutgens Roger E. G. , Fischer Kathelijn
Published: August 2019

Introduction

The Paediatric Haemophilia Activities List (pedHAL) assesses self‐reported limitations in activities and participation in children with haemophilia.

Aim

To assess longitudinal changes, child‐parent agreement and to identify which pedHAL domains yielded most information in boys with access to early prophylaxis.

Methods

The pedHAL (53 items, 7 domains, optimum 100) was completed annually at the Van Creveldkliniek by boys aged 4‐18 years with moderate/severe haemophilia and their parents. Development of the pedHAL in relation to bleeds, changes per domain over 3‐5 years, child‐parent agreement (% difference child‐parent≤|5|) per domain and domain scores (limitations defined as ≤ 95) were determined.

Results

Seventy‐three patients and their parents (92% severe haemophilia, median age 13.1 years [range 5.4;18.0]) completed ≥1 pedHAL. Median (IQR) pedHAL sum score was 99.5 (95.2;100.0) for children and 99.6 (95.8;100.0) for parents. If patients scored >95 and had no joint and/or muscle bleed, 90.9% of the patients scored >95 at the next assessment. The median change in sum score was 0.0 for both the 3‐ and 5‐year interval. Child‐parent agreement varied between domains from 92% (‘self‐care’) to 71% (‘sitting/kneeling/standing’). Most limitations were reported in the domains ‘sitting/kneeling/standing’, ‘functions of the legs’ and ‘leisure activities and sports.’

Conclusion

In routine clinical practice in Dutch children on prophylaxis, pedHAL scores were high and remained stable in 3‐5 years at group level. In individual patients without joint and/or muscle bleeds, pedHAL scores remained high after 1 year. Child‐parent agreement was not optimal which indicated that both child report and parent proxy should be reported.
Age, lifestyle and self‐perceptions of hair: Is there an association with hair diameter and tensile properties?
Authors: Duvel L. , Herbal A. , Daniels L. , Kong R. , Hillebrand G.G.
Published: August 2019

Objective

To determine the association of age, lifestyle habits and the self‐perception of hair condition with the objectively measured physical properties of hair in Caucasian females with brown hair.

Methods

Hair biophysical properties, lifestyle habits data and self‐perceptions of hair condition were collected on 110 Caucasian females with brown hair ranging in age from 17 to 78. Hair diameter (cross‐sectional area) and tensile properties (elastic modulus, break strength and break extension) were measured at the root end of individual fibres (n = 100/subject) from the crown and frontal regions using objective instrumental methods. Other measures included body mass index (BMI) and Savin female pattern hair loss grades based on judging of standardized front, top and side view head images. Lifestyle habits and practices and self‐perceived hair condition were obtained via a standardized self‐assessment questionnaire.

Results

Hair fibre diameter and break extension decreased significantly with age. Hair fibre elastic modulus and Savin hair loss scores increased significantly with age. No age‐related change in hair fibre break stress was observed. A history of smoking or being overweight was significantly associated with having lower hair fibre cross‐sectional area but was not associated with any of the measured tensile properties. Subjects who perceived their hair as fine, thinning or weak had significantly lower cross‐sectional areas than subjects who did not. Subjects who perceived their hair to be healthy or strong had significantly higher cross‐sectional areas than subjects who did not.

Conclusion

The biophysical properties of hair change significantly with age. A history of smoking or being overweight was significantly associated with having smaller hair cross‐sectional area but was not associated with differences in hair tensile properties. The self‐perception of having strong or healthy hair seems more associated with having a larger cross‐sectional area than any real differences in hair strength.Abstrait
The Sarbanes‐Oxley act and informed trading in the options market: Evidence from share repurchase announcements
Authors: Badshah Ihsan , Koerniadi Hardjo , Kolari James
Published: August 2019

This study examines the informed options trading hypothesis before and after the implementation of the Sarbanes‐Oxley Act (SOX). We find that informed option trading, as measured by implied volatility spreads, occurs only in the period before the enactment of this Act but disappears thereafter. Our results suggest that the SOX had a significant impact on informed trading in U.S. option markets.
The seasonal and monthly distribution of body limbs affected by burns in paediatric patients in southeast Turkey
Authors: Asena Muhammet , Akelma Hakan , Salık Fikret , Karahan Zeki A.
Published: August 2019

Studies on the frequency of burned limbs according to season and months are limited. The burning of some body limbs, especially in some months, shows that the causes of burns are different, and knowing the reasons is important for providing preventive measures. The aims of this study were to determine the distribution rate of child burns by months and seasons and to contribute to preventive measures by determining the distribution of the burning of body limbs by months. We retrospectively evaluated 419 paediatric patients (0‐17 years of age) who were hospitalised in the burn unit between 1 May 2017 and 1 November 2018. The demographic characteristics of the patients were recorded according to age, gender, months, and seasons of the patients admitted; cause of burns; degree of burns; total body surface area; and burning regions. The distribution of burns by months was established as being mainly in May to October. As for the distribution of the patients according to the seasons, it was found that it was most common in summer, 122 (29.1%), and in the autumn season as well, it was 122 (29.1%). While body burns increased in the summer‐autumn seasons (P < .023), genital area burns were the lowest in winter and were the highest in summer and autumn seasons. Genital site burns increased statistically in September, October, and November (P < .010). Burn traumas are observed to be more frequent in some seasons and months. The environments where individuals live, forms of life, forms of warming, areas of interest, and sociocultural and economic levels are the causes of this variability.
Necrotising fasciitis or pyoderma gangrenosum: A fatal dilemma
Authors: Demirdover Cenk , Geyik Alper , Vayvada Haluk
Published: August 2019

Necrotising fasciitis (NF) is mostly a polymicrobial, severe soft tissue infection that progresses rapidly, penetrating through the subcutaneous tissue to the fascial planes and the muscles. The pyoderma gangrenosum (PG), on the other hand, is a rare, rapidly progressive (except for the post‐surgical PG), autoinflammatory ulcerative skin and soft tissue condition. In this study, we tried to emphasise the importance of diagnosing the NF as well as the PG. Although these two clinical presentations have some standard features, awareness of different symptoms in detail affect the outcome. Any surgical discipline can face NF or PG and, therefore, should be aware of them to decrease the mortality rate. Forty‐five patients with NF and PG who were treated between January 2008 and October 2018 were included in the study and evaluated retrospectively for age, sex, localisation, onset of symptoms and diagnosis, predisposing factors, characteristics of tissue defects, laboratory findings, Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) scores, isolated microbiological agents, surgical intervention, and mortality rate. Demographic, laboratory, and clinical data were analysed. Among these 45 patients, 14 patients had PG, and 31 patients had NF. The mean age and SD for the NF and PG groups were 50.80 ± 17.67 and 50.78 ± 12.72, respectively. Five patients had rheumatological disorders; four patients had diabetes mellitus (DM) in the PG group. Males had higher risk than females in NF (odds ratio [OR] = 0.077, 95% confidence interval [CI] 0.017‐0.34), and females had higher risk in PG (relative risk [RR] = 5). We compared the LRINEC score of NF patients with PG patients. The mean value of this score was 4.53 for PG patients, and 6.06 for NF patients. Fifteen patients (33.3%) had a radiological evaluation. MRI, CT, and USI were used as imaging modalities. Necrotising fasciitis and PG are two distinct entities that are in general difficult to distinguish. Therefore, differential diagnosis and rapid treatment are crucial for lowering the mortality rate.
Crystal structure analysis and high‐temperature phase transitions of complex rare‐earth perovskite, La2(Al1/2MgTa1/2)O6
Authors: Sohn Yoo Jung , Mauer Georg , Roth Georg , Guillon Olivier , Vaßen Robert
Published: August 2019

In situ high‐temperature powder X‐ray diffraction analysis (HT‐XRD) was carried out in the temperature range from 25°C‐1430°C to investigate the crystal structure of double perovskites, La2(Al1/2MgTa1/2)O6 (LAMT) and its phase transitions. This complex perovskite is a promising candidate for application in thermal barrier coating systems. Rietveld analysis shows a rock‐salt type ordering of the B‐site cations in the monoclinic space group symmetry, P21/n at room temperature. Upon heating, a structural phase transition occurs at ~855°C, and the crystal structure becomes rhombohedral with the space group symmetry . On further heating, LAMT transforms to the ideal cubic phase at ~1390°C with the space group symmetry . Both of the structural phase transitions are completely reversible, and were confirmed through complementary differential scanning calorimetry and thermogravimetry measurements. With increasing temperature, the degree of the octahedral tilting decreases and the variance of the different B–O bond lengths is reduced, until in the cubic phase, no tilting is present, and almost equal B–O bond lengths are obtained.
Enhanced red photoluminescence in a nanocomposite thin film composed of Bi3.6Eu0.4Ti3O12 and Au‐decorated ZnO nanorods
Authors: Zhang Yu , Su Li , Wang Haojie , Yu Wei
Published: August 2019

This paper firstly reports on a series of nanocomposite thin films composed of a ferroelectric Bi3.6Eu0.4Ti3O12 (BET) and Au‐decorated ZnO nanorods (Au‐ZnO), which are prepared by a ultraviolet‐induced hybrid chemical solution method. The effects of Au nanoparticles (NPs) and ZnO nanorods on the significantly red photoluminescence enhancement of Eu3+ ions are investigated. The results indicate that the larger near band edge (NBE) emission of ZnO by the SPR effect of Au NPs can make an energy transfer from ZnO to Eu3+ ions. Simultaneously, the depression of the deep‐level emission of ZnO can improve the monochromaticity in the visible range. Furthermore, the dielectric and ferroelectric properties of the thin films are also enhanced. The findings suggest that the nanocomposite thin films of a ferroelectric BET and Au‐ZnO could be used as a multifunctional material in the ferroelectric optoelectronic devices with bright light emitting.
Identification of rumen microbial biomarkers linked to methane emission in Holstein dairy cows
Authors: Ramayo‐Caldas Yuliaxis , Zingaretti Laura , Popova Milka , Estellé Jordi , Bernard Aurelien , Pons Nicolas , Bellot Pau , Mach Núria , Rau Andrea , Roume Hugo , Perez‐Enciso Miguel , Faverdin Philippe , Edouard Nadège , Ehrlich Dusko , Morgavi Diego P. , Renand Gilles
Published: August 2019

Mitigation of greenhouse gas emissions is relevant for reducing the environmental impact of ruminant production. In this study, the rumen microbiome from Holstein cows was characterized through a combination of 16S rRNA gene and shotgun metagenomic sequencing. Methane production (CH4) and dry matter intake (DMI) were individually measured over 4–6 weeks to calculate the CH4 yield (CH4y = CH4/DMI) per cow. We implemented a combination of clustering, multivariate and mixed model analyses to identify a set of operational taxonomic unit (OTU) jointly associated with CH4y and the structure of ruminal microbial communities. Three ruminotype clusters (R1, R2 and R3) were identified, and R2 was associated with higher CH4y. The taxonomic composition on R2 had lower abundance of Succinivibrionaceae and Methanosphaera, and higher abundance of Ruminococcaceae, Christensenellaceae and Lachnospiraceae. Metagenomic data confirmed the lower abundance of Succinivibrionaceae and Methanosphaera in R2 and identified genera (Fibrobacter and unclassified Bacteroidales) not highlighted by metataxonomic analysis. In addition, the functional metagenomic analysis revealed that samples classified in cluster R2 were overrepresented by genes coding for KEGG modules associated with methanogenesis, including a significant relative abundance of the methyl‐coenzyme M reductase enzyme. Based on the cluster assignment, we applied a sparse partial least‐squares discriminant analysis at the taxonomic and functional levels. In addition, we implemented a sPLS regression model using the phenotypic variation of CH4y. By combining these two approaches, we identified 86 discriminant bacterial OTUs, notably including families linked to CH4 emission such as Succinivibrionaceae, Ruminococcaceae, Christensenellaceae, Lachnospiraceae and Rikenellaceae. These selected OTUs explained 24% of the CH4y phenotypic variance, whereas the host genome contribution was ~14%. In summary, we identified rumen microbial biomarkers associated with the methane production of dairy cows; these biomarkers could be used for targeted methane‐reduction selection programmes in the dairy cattle industry provided they are heritable.
Differential coexpression networks in bronchiolitis and emphysema phenotypes reveal heterogeneous mechanisms of chronic obstructive pulmonary disease
Authors: Qin Jiangyue , Yang Ting , Zeng Ni , Wan Chun , Gao Lijuan , Li Xiaoou , Chen Lei , Shen Yongchun , Wen Fuqiang
Published: August 2019

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with multiple molecular mechanisms. To investigate and contrast the molecular processes differing between bronchiolitis and emphysema phenotypes of COPD, we downloaded the GSE69818 microarray data set from the Gene Expression Omnibus (GEO), which based on lung tissues from 38 patients with emphysema and 32 patients with bronchiolitis. Then, weighted gene coexpression network analysis (WGCNA) and differential coexpression (DiffCoEx) analysis were performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis (KEGG) analysis. Modules and hub genes for bronchiolitis and emphysema were identified, and we found that genes in modules linked to neutrophil degranulation, Rho protein signal transduction and B cell receptor signalling were coexpressed in emphysema. DiffCoEx analysis showed that four hub genes (IFT88, CCDC103, MMP10 and Bik) were consistently expressed in emphysema patients; these hub genes were enriched, respectively, for functions of cilium assembly and movement, proteolysis and apoptotic mitochondrial changes. In our re‐analysis of GSE69818, gene expression networks in relation to emphysema deepen insights into the molecular mechanism of COPD and also identify some promising therapeutic targets.
European survey on criteria of aesthetics for periodontal evaluation: The ESCAPE study
Authors: Le Roch Sarah , Rouche Frédéric , Valet Fabien , Bouchard Philippe ,   the ESCAPE group
Published: August 2019

Objective

The ESCAPE multicentre survey was designed to (a) compare the agreement of three relevant aesthetic scoring systems among different centres, and (b) evaluate the reproducibility of each question of the questionnaires.

Materials and Methods

EFP centres (n = 14) were involved in an e‐survey. Forty‐two participants (28 teachers, 14 postgraduate students) were asked to score the one‐year aesthetic outcomes of photographs using the Before–After Scoring System (BASS), the Pink Esthetic Score (PES) and the Root coverage Esthetic Score (RES). Mean values of kappa statistics performed on each question were provided to resume global agreement of each method.

Results

Between teachers, a difference of kappa ≥ 0.41 (p = .01) was found for BASS (75%) and PES (57%). Similarly, RES (84%) and PES (57%) were different (p < .001). No difference was found between BASS (75%) and RES (84%). No difference was found between students, whatever the scoring system. Questions of each scoring system showed differences in their reproducibility.

Conclusions

The outcomes of this study indicate that BASS and RES scoring systems are reproducible tools to evaluate aesthetic after root coverage therapies between different centres. Among the various variables, lack of scar, degree of root coverage, colour match and gingival margin that follows the CEJ show the best reliability.
Re: ‘Pyemotes ventricosus detection in a baby skin folds’ and ‘Alternative hypothesis for mite identification with reference to Pyemotes ventricosus detection in a baby skin folds’
Authors: Stingeni L. , Tramontana M. , Principato M. , Moretta I. , Principato S. , Bianchi L. , Hansel K.
Published: August 2019

Linked article: L. Tognetti et al. J Eur Acad Dermatol Venereol 2020; 34: e27–e28. https://doi.org/10.1111/jdv.15869.
Key characteristics of basal cell carcinoma with large subclinical extension
Authors: Greywal T. , Goldenberg A. , Eimpunth S. , Jiang S.B.
Published: August 2019

Background

Basal cell carcinoma with large subclinical extension (BCC‐LSE) is a tumour whose extensive spread becomes apparent during Mohs surgery histopathology review. Not recognizing BCC‐LSE preoperatively may result in a greater number of Mohs layers and in larger than anticipated postoperative defects.

Objective

To evaluate the characteristics of BCC‐LSE.

Methods

This retrospective study reviewed BCC treated with Mohs surgery at a single academic surgical centre between March 2007 and February 2012. A total of 2044 cases met the criteria of BCC‐LSE, which was defined as a lesion requiring at least three Mohs stages and a final surgical margin (difference between preoperative and postoperative measurements in either vertical or horizontal dimensions) of ≥1 cm.

Results

In adjusted multivariable analysis, male sex (P = 0.05), Fitzpatrick skin type I (P = 0.002), history of prior BCC (P = 0.003) and subtypes of basosquamous, metatypical, micronodular, infiltrative, morpheaform and sclerosing (P = 0.005) remained significant BCC‐LSE predictors.

Conclusions

Demographic factors, including personal history of BCC, skin type, anatomic location, gender and age, in addition to tumour histologic subtype assessed through incisional biopsy, can help predict occurrence of BCC‐LSE and assist physicians in optimizing preoperative assessment of surgical time and complexity.
Use of the Skin Cancer Quality of Life Impact Tool (SCQOLIT) – a feasibility study in non‐melanoma skin cancer
Authors: Wali G.N. , Gibbons E. , Kelly L. , Reed J.R. , Matin R.N.
Published: August 2019

Background

Incidence of non‐melanoma skin cancers (NMSCs) is increasing and can significantly impact on quality of life (QOL), yet there are few studies evaluating patient‐reported outcome measures (PROMs) in NMSC populations. We undertook a prospective feasibility study to evaluate a skin cancer‐specific PROM, the Skin Cancer Quality of Life Impact Tool (SCQOLIT), in patients with a new diagnosis of NMSC.

Objectives

(i) To establish acceptability of SCQOLIT in dermatology clinics, (ii) a descriptive analysis of SCQOLIT scores in NMSC.

Methods

Patients with histologically confirmed NMSC completed SCQOLIT, EQ‐5D and a transition item. Questionnaires were completed at baseline and 3 months for group 1 (‘low‐risk’ NMSC) and group 2 (‘high‐risk’ NMSC) with additional questionnaires at 6–9 months for group 2. Patients participated in structured interviews. Clinician experience was captured through staff evaluation forms and a focus group. Acceptability and psychometric properties of SCQOLIT were assessed.

Results

Overall, 318 patients consented to participate. Mean SCQOLIT score at baseline was 5.33, with 2.6% of patients scoring ≥20. No ceiling effects were observed, whilst 13.9% scored 0. Validity was demonstrated against EQ‐5D. Cronbach's alpha 0.84 demonstrated internal consistency. Thirteen patients were interviewed and thought SCQOLIT was comprehensive, captured impact on health‐related QOL and helped express their needs to clinicians. Most clinicians found SCQOLIT ‘very useful’ or ‘useful to some extent’ in facilitating discussions.

Conclusions

This feasibility study demonstrates that SCQOLIT is acceptable to patients and staff in dermatology skin cancer clinics. The psychometric properties of SCQOLIT confirm its utility in NMSC populations.
Using a structured, patient‐centred, educational exchange to facilitate a shared conversation about stroke prevention medications
Authors: Coombes Judith A. , Rowett Debra , Whitty Jennifer A. , Cottrell Neil W.
Published: August 2019

Objective

The aim of this study was to investigate the feasibility of a structured patient‐centred educational exchange to facilitate a shared conversation about stroke prevention medications.

Methods

Participants (18 years or older) with a principal diagnosis of stroke or transient ischaemic attack were purposively sampled from the stroke unit of a 780‐bed teaching hospital in Australia and consented to participate in the study. A patient‐centred educational exchange was conducted face to face at the bedside before discharge and by telephone post discharge. The structure of these sessions was adapted from academic detailing, an educational strategy, which includes identifying experience, listening to the needs of the audience, and tailoring messages to influence behaviour. To facilitate sharing of needs, three questionnaires, validated as research tools, were used to identify participants' experience, perceptions, and beliefs. The identified perceptions were used to personalize educational messages. The outcomes of the study were to provide descriptions of patients' perceptions necessities and concerns about their condition and medications, provide examples of personalized responses to these, evaluate acceptability by patients, and determine the time taken to share the information.

Results

Sixteen participants completed both the bedside session (average duration 27 minutes) and the telephone follow‐up (average duration 23 minutes). The strongest patient concern identified was having another stroke. Personalized responses included emphasizing long‐term treatment in response to the perception that stroke will last for a short time, reinforcement of necessity for medications, and further exploration of concerns.

Conclusion

The questionnaires engaged the participants, allowing them to share perceptions and beliefs, facilitating a patient‐centred educational exchange in a timely manner.
Transmission of Mycobacterium chelonae and Mycobacterium marinum in laboratory zebrafish through live feeds
Authors: Chang Carolyn T. , Benedict Samuel , Whipps Christopher M.
Published: August 2019

The zebrafish (Danio rerio) is a popular vertebrate model organism used in a wide range of research fields. Mycobacteriosis, caused by Mycobacterium species, is particularly concerning because it is a common disease associated with chronic infections in these fish. Infections are also a source of uncontrolled experimental variance that may influence research results. Live feeds for zebrafish are common and include paramecia (Paramecium caudatum), brine shrimp (Artemia franciscana) and rotifers (Branchionus spp.). Although nutritionally beneficial, live feeds may pose a biosecurity risk. In this study, we investigate transmission of Mycobacterium chelonae and Mycobacterium marinum through these three live feeds. We show that all three live feeds ingest both M. marinum and M. chelonae and can transmit mycobacterial infections to zebrafish. This observation emphasizes the need for live feeds to be included in the consideration of potential biosecurity risks. This study is of importance to other beyond the zebrafish community, including those of additional aquatic models and those using live feeds for other types of aquaculture.
Evidence for the facultative intracellular behaviour of the fish pathogen Vibrio ordalii
Authors: Avendaño‐Herrera Ruben , Arias‐Muñoz Eloisa , Rojas Verónica , Toranzo Alicia E. , Poblete‐Morales Matías , Córdova Claudio , Irgang Rute
Published: August 2019

Vibrio ordalii is an extracellular, Gram‐negative bacterium that produces vibriosis in salmonids. While pathogenesis is not fully understood, this bacterium has numerous likely genes for adhesion, colonization, invasion factors and, as recently suggested, intracellular behaviour. Therefore, this study aimed to clarify possible intracellular behaviour for V. ordalii Vo‐LM‐18 and ATCC 33509T in the fish‐cell lines SHK‐1 and CHSE‐214. Confocal microscopy revealed Vo‐LM‐18 and ATCC 33509T inside cytoplasm in both fish‐cell lines at 4 hr post‐inoculation (hpi). At 8 and 16 hpi, the proportion of fish cells invaded by both strains increased. Moreover, intracellular V. ordalii were observed after 8 hpi inside mouse embryonic fibroblasts (MEF), demonstrating that entry was not due to a cellular phagocytosis process. Flow cytometry confirmed immunocytochemistry results, with both V. ordalii evidencing statistically significant differences in the number of infected cells between 8 and 16 hpi. Interestingly, V. ordalii infection did not significantly damage fish cells, as determined by LDH liberation. Viable counts at 8 hpi detected, on average for both lines, 176 ± 47 CFU/ml of culturable intracellular Vo‐LM‐18 and ATCC 33509T cells. These in vitro findings support the facultative intracellular behaviour of V. ordalii and may be of importance for understanding pathogenicity and survival in aquatic environments.
The Ca2+ channel subunit CaVβ2a‐subunit down‐regulates voltage‐activated ion current densities by disrupting actin‐dependent traffic in chromaffin cells
Authors: Guerra María J. , González‐Jamett Arlek M. , Báez‐Matus Ximena , Navarro‐Quezada Nieves , Martínez Agustín D. , Neely Alan , Cárdenas Ana M.
Published: August 2019

β‐Subunits of the Ca2+ channel have been conventionally regarded as auxiliary subunits that regulate the expression and activity of the pore‐forming α1 subunit. However, they comprise protein–protein interaction domains, such as a SRC homology 3 domain (SH3) domain, which make them potential signaling molecules. Here we evaluated the role of the β2a subunit of the Ca2+ channels (CaVβ2a) and its SH3 domain (β2a‐SH3) in late stages of channel trafficking in bovine adrenal chromaffin cells. Cultured bovine adrenal chromaffin cells were injected with CaVβ2a or β2a‐SH3 under different conditions, in order to acutely interfere with endogenous associations of these proteins. As assayed by whole‐cell patch clamp recordings, Ca2+ currents were reduced by CaVβ2a in the presence of exogenous α1‐interaction domain. β2a‐SH3, but not its dimerization‐deficient mutant, also reduced Ca2+ currents. Na+ currents were also diminished following β2a‐SH3 injection. Furthermore, β2a‐SH3 was still able to reduce Ca2+ currents when dynamin‐2 function was disrupted, but not when SNARE‐dependent exocytosis or actin polymerization was inhibited. Together with the additional finding that both CaVβ2a and β2a‐SH3 diminished the incorporation of new actin monomers to cortical actin filaments, β2a‐SH3 emerges as a signaling module that might down‐regulate forward trafficking of ion channels by modulating actin dynamics.

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The pathobiology of perturbed mutant huntingtin protein–protein interactions in Huntington's disease
Authors: Wanker Erich E. , Ast Anne , Schindler Franziska , Trepte Philipp , Schnoegl Sigrid
Published: August 2019

Mutations are at the root of many human diseases. Still, we largely do not exactly understand how they trigger pathogenesis. One, more recent, hypothesis has been that they comprehensively perturb protein–protein interaction (PPI) networks and significantly alter key biological processes. Under this premise, many rare genetic disorders with Mendelian inheritance, like Huntington's disease and several spinocerebellar ataxias, are likely to be caused by complex genotype–phenotype relationships involving abnormal PPIs. These altered PPI networks and their effects on cellular pathways are poorly understood at the molecular level. In this review, we focus on PPIs that are perturbed by the expanded pathogenic polyglutamine tract in huntingtin (HTT), the protein which, in its mutated form, leads to the autosomal dominant, neurodegenerative Huntington's disease. One aspect of perturbed mutant HTT interactions is the formation of abnormal protein species such as fibrils or large neuronal inclusions as a result of homotypic and heterotypic aberrant molecular interactions. This review focuses on abnormal PPIs that are associated with the assembly of mutant HTT aggregates in cells and their potential relevance in disease. Furthermore, the mechanisms and pathobiological processes that may contribute to phenotype development, neuronal dysfunction and toxicity in Huntington's disease brains are also discussed.

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This article is part of the Special Issue "Proteomics".
G‐protein‐coupled receptor‐based sensors for imaging neurochemicals with high sensitivity and specificity
Authors: Jing Miao , Zhang Yajun , Wang Huan , Li Yulong
Published: August 2019

Neurotransmitters and neuromodulators are key neurochemicals that mediate cell–cell communication, maintain the body's homeostasis, and control a wide range of biological processes. Thus, dysregulation of neurochemical signaling is associated with a range of psychiatric disorders and neurological diseases. Understanding the physiological and pathophysiological functions of neurochemicals, particularly in complex biological systems in vivo, requires tools that can probe their dynamics with high sensitivity and specificity. Recently, genetically encoded fluorescent sensors for visualizing specific neurochemicals were developed by coupling neurochemical‐sensing G‐protein‐coupled receptors (GPCRs) with a circular‐permutated fluorescent protein. These GPCR‐based sensors can monitor the dynamics of neurochemicals in behaving animals with high spatiotemporal resolution. Here, we review recent progress regarding the development and application of GPCR‐based sensors for imaging neurochemicals, and we discuss future perspectives.

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Early stages of development of the alar fascia (human specimens at 6–12 weeks of development)
Authors: López‐Fernández Pedro , Murillo‐González Jorge , Arráez‐Aybar Luis Alfonso , de la Cuadra‐Blanco Crótida , Moreno‐Borreguero Alicia , Mérida‐Velasco José Ramón
Published: August 2019

In recent years, there has been much discussion concerning the cervical fasciae. The aim of this study is to confirm and to describe the development of the alar fascia as well as its relationship with nearby structures. Histological preparations of 25 human embryos (6–8 weeks of development) and 25 human fetuses (9–12 weeks of development) were studied bilaterally using a conventional optical microscope. Our study confirms the existence of the alar fascia and permits three stages to be established during its development. The initial stage (1st), corresponding to the 6th week of development (Carnegie stages 18–19), is characterized by the beginning of the alar fascia primordium in the retroesophageal space at the level of C7‐T1. In the formation stage (2nd), corresponding to the 7th and 8th weeks of development (Carnegie stages 20–23), the alar fascia primordium grows upwards and reaches the level of C2–C3. In the maturation stage (3rd), beginning in the 9th week of development, the visceral, alar and prevertebral fasciae can be identified. The alar fascia divides the retrovisceral space (retropharyngeal and retroesophageal) into two spaces: one anterior (between the alar fascia and the visceral fascia and extending from C1 to T1, named retropharyngeal or retroesophageal space according to the level) and the other posterior (between the alar fascia and the prevertebral fascia, named danger space). We suggest that this latter space be named the retroalar space. This study suggests that alar fascia development is related to mechanical factors and that the alar fascia permits the sliding of the pharynx and the oesophagus during swallowing.
Cesar Chavez and the Ethics of Exemplarity
Authors: Maya Gustavo
Published: August 2019

In recent years, Cesar Chavez’s life and legacy have been subjected to increased scrutiny. The ensuing reevaluations of Chavez, wittingly or not, are matters of ethical, as well as historical and biographical, concern. This article has two aims. First, it reconstructs Chavez’s account of exemplarity and uses it to assess his legacy. Second, it provides an account of exemplarity situated within social practices. As I argue, exemplarity operates through social practices, rather than mystically as posited by a contagion model. The end result is an ethically nuanced reassessment of Chavez and an account of exemplarity that includes its social dimension.
Methodological approaches for investigating links between dental and chronic diseases with claims data: A scoping study
Authors: Blaschke Katja , Seitz Max W. , Schubert Ingrid , Listl Stefan
Published: August 2019

Objectives

The purpose of this study was to provide an overview of methodological approaches to assess the relationship between dental diseases and other noncommunicable diseases on the basis of claims data.

Methods

Based on the methodological framework of Arksey and O'Malley, a scoping study was conducted. By searching electronic databases (PubMed, Web of Science, and LILACS), appropriate articles were identified. After extracting relevant information and entering it into a data‐charting form, the study characteristics and the methodological approaches were summarized descriptively.

Results

Fifty‐one articles were identified for inclusion in the analysis. Most of the selected studies (78 percent) originated from Taiwan and employed a cohort design. The majority of studies considered dental diseases, particularly periodontal disease (PD) measures, but no common standard was identified for the definition of PD. Unmeasured confounding, misclassification, and surveillance bias were reported to be the main limitations of the claims data analyses.

Conclusions

Claims data provide a very useful information source to further delineate the relationship between PDs and other noncommunicable diseases. If diagnostic codes are available, they seem to be the most suitable tool to assess PD in claims‐based studies. In databases that do not contain dental diagnostic codes, e.g., databases in Germany and the United States, the identification of PD is a particular challenge. The inclusion of dental diagnostic codes in all claims databases is strongly recommended. Due to the public health relevance of PD, there is a need for more comprehensive documentation of dental parameters within claims data.
Medical school expansion policies: educational access and physician distribution
Authors: Figueiredo Alexandre Medeiros , McKinley Danette Waller , Lima Kenio Costa , Azevedo George Dantas
Published: August 2019

Introduction

Many countries are employing strategies intended to reduce maldistribution of health workers and inequities. The purpose of this study was to analyse the impact of expansion policies of medical schools on regional inequalities in the distribution of undergraduate class sizes, and the capacity to attract and retain doctors and to expand health facilities.

Methods

We conducted a descriptive analysis to compare the distribution of undergraduate places in 2007 and 2016 to determine the impact of targeted expansion policies on inequalities in access to medical education in Brazil. A group of municipalities with new medical schools (n = 54) and a control group without medical schools (n = 408) were compared to analyse impacts of expansion in the health sector. We compared the increase in the number of physicians per 1000 inhabitants and health establishments per inhabitants between 2007 and 2016 based on these two groups. We also analysed the relationship between geographic distance from the state capital and capacity to attract physicians.

Results

There was a decrease in the regional inequalities of undergraduate places in medical schools; the greatest increase in the places per 1000 inhabitants was in municipalities of between 50 000 and 100 000 inhabitants. Municipalities with new medical schools showed an increase in physicians per 1000 inhabitants and in health establishments per inhabitant ratio, demonstrating the potential to attract and retain doctors, as well as strengthening the health infrastructure. Municipalities more distant from state capitals showed a greater increase in physician : inhabitant ratio.

Discussion

Countries with health workforce shortages and inequalities in their distribution might consider public financing and regulation policies for expansion of medical schools as a strategy to attract and retain professionals. Early results in Brazil showed that such strategies could strengthen service networks in deprived areas, supporting implementation of Universal Healthcare Coverage.
Genome‐wide analysis of MIKC‐type MADS‐box genes in wheat: pervasive duplications, functional conservation and putative neofunctionalization
Authors: Schilling Susanne , Kennedy Alice , Pan Sirui , Jermiin Lars S. , Melzer Rainer
Published: August 2019

Wheat (Triticum aestivum) is one of the most important crops worldwide. Given a growing global population coupled with increasingly challenging cultivation conditions, facilitating wheat breeding by fine‐tuning important traits is of great importance. MADS‐box genes are prime candidates for this, as they are involved in virtually all aspects of plant development.

Here, we present a detailed overview of phylogeny and expression of 201 wheat MIKC‐type MADS‐box genes. Homoeolog retention is significantly above the average genome‐wide retention rate for wheat genes, indicating that many MIKC‐type homoeologs are functionally important and not redundant. Gene expression is generally in agreement with the expected subfamily‐specific expression pattern, indicating broad conservation of function of MIKC‐type genes during wheat evolution.

We also found extensive expansion of some MIKC‐type subfamilies, especially those potentially involved in adaptation to different environmental conditions like flowering time genes. Duplications are especially prominent in distal telomeric regions. A number of MIKC‐type genes show novel expression patterns and respond, for example, to biotic stress, pointing towards neofunctionalization.

We speculate that conserved, duplicated and neofunctionalized MIKC‐type genes may have played an important role in the adaptation of wheat to a diversity of conditions, hence contributing to the importance of wheat as a global staple food.
Physical activity interventions in early life aimed at reducing later risk of obesity and related non‐communicable diseases: A rapid review of systematic reviews
Authors: Reilly John J. , Hughes Adrienne R. , Gillespie Jennifer , Malden Stephen , Martin Anne
Published: August 2019

To identify useful components of interventions aimed at prevention of childhood obesity and related non‐communicable diseases (NCDs), which included physical activity and which targeted any or all of four life‐course stages: peri‐conception; pregnancy; infancy and toddlerhood (0 to 23 months); and early childhood (24 to 59 months). In May 2016, WHO Geneva searched the Cochrane Library and PubMed for systematic reviews of interventions including physical activity to prevent childhood obesity or risk factors for obesity‐related NCDs. Using a narrative synthesis, the efficacy of randomized controlled trials (RCTs) to alter energy balance outcomes (measures of weight status or body fatness) was characterized by life‐course stage, study characteristics, intervention functions (as defined in the behaviour change wheel), and level of the socio‐ecological model (SEM) targeted. The quality of included systematic reviews was assessed. We retrieved 82 reviews from the World Health Organization (WHO) search, of which 23 were eligible for the present synthesis. The number of eligible studies by life‐course stage was: 0 (peri‐conception); 0 (pregnancy); 8 (infancy and toddlerhood, age 0 to 23 months; seven RCTs; age); and 37 (early childhood, age 24 to 59 months; 30 RCTs;). Thus, there was a lack of evidence for physical activity interventions during peri‐conception and pregnancy. Almost all relevant studies in the 0‐ to 23‐ and 24‐ to 59‐month life‐course stages were multicomponent interventions (ie, targeted physical activity, dietary, and/or sedentary behaviours). Interventions with evidence of efficacy tended to target multiple levels of the SEM, with emphasis on parents, and extend over long periods. Effective intervention elements for early life obesity prevention included classes on parenting skills, alteration of the kindergarten playground, and financial incentives. Evidence from low‐ and middle‐income countries was scarce, and evidence for intervention effect on obesity‐related NCDs was missing. Future physical activity interventions in toddlerhood and early childhood aimed at prevention of obesity should adopt the characteristics typical of effective interventions identified by the present synthesis. There is an urgent need for more evidence on physical activity interventions set in low‐ and middle‐income countries and which target the peri‐conception and pregnancy periods.
Patient motivations and expectations prior to bariatric surgery: A qualitative systematic review
Authors: Cohn Ilana , Raman Jayanthi , Sui Zhixian
Published: August 2019

Bariatric surgery is the most effective treatment for weight loss in individuals with severe and complex obesity. While the extant literature has mostly explored clinical outcomes of surgery, recent research has also examined patients' experiences prior to treatment. This systematic review synthesized findings from qualitative studies investigating patients' motives and expectations prior to undergoing bariatric surgery for weight loss. Twenty‐eight studies published in English involving 580 participants were identified for inclusion. Data extraction and thematic synthesis yielded four global themes: physiological, emotional, cognitive, and interpersonal/environmental. These represented seven subthemes describing patients' presurgery experiences: relationship with food, physical health, activities of living, personal identity, social relations, presurgery information, and beliefs about surgery. In addition to improving physical and medical comorbidities associated with obesity, participants believed that postsurgery weight loss would produce positive psychosocial impacts by strengthening their personal identities, their relationships, and improving their engagement in public and professional life. The complex and widespread nature of the changes patients expected would result from bariatric surgery highlights the importance of providing pretreatment education focused on psychosocial well‐being, as well as concurrent psychological support alongside surgery, to best inform individual treatment selection and clinical practice.
Pregnancy after bariatric surgery: Consensus recommendations for periconception, antenatal and postnatal care
Authors: Shawe Jill , Ceulemans Dries , Akhter Zainab , Neff Karl , Hart Kathryn , Heslehurst Nicola , Štotl Iztok , Agrawal Sanjay , Steegers‐Theunissen Regine , Taheri Shahrad , Greenslade Beth , Rankin Judith , Huda Bobby , Douek Isy , Galjaard Sander , Blumenfeld Orit , Robinson Ann , Whyte Martin , Mathews Elaine , Devlieger Roland
Published: August 2019

The objective of the study is to provide evidence‐based guidance on nutritional management and optimal care for pregnancy after bariatric surgery. A consensus meeting of international and multidisciplinary experts was held to identify relevant research questions in relation to pregnancy after bariatric surgery. A systematic search of available literature was performed, and the ADAPTE protocol for guideline development followed. All available evidence was graded and further discussed during group meetings to formulate recommendations. Where evidence of sufficient quality was lacking, the group made consensus recommendations based on expert clinical experience. The main outcome measures are timing of pregnancy, contraceptive choice, nutritional advice and supplementation, clinical follow‐up of pregnancy, and breastfeeding. We provide recommendations for periconception, antenatal, and postnatal care for women following surgery. These recommendations are summarized in a table and print‐friendly format. Women of reproductive age with a history of bariatric surgery should receive specialized care regarding their reproductive health. Many recommendations are not supported by high‐quality evidence and warrant further research. These areas are highlighted in the paper.