bluuebunny/crossref_metadata_2025 huggingface dataset:
A method for selecting suitable technical solutions to support sustainable riverbank stabilisation
Authors: Pinto António Augusto Sampaio , Fernandes Luís Filipe Sanches , de Oliveira Maia Rodrigo Jorge Fonseca
Published: August 2018

The interventions for riverbank stabilisation are among the most common river rehabilitation actions performed in watercourses. However, most of the interventions focus on traditional methods that, although effective at the structural level (i.e., at meeting riverbank stabilisation goals), usually produce negative effects on the ecological status of the river. Thus, due to the increased requirement for sustainable river management solutions, this paper proposes a methodology for selecting suitable technical solutions for riverbank stabilisation. This has two components: (1) characterising, diagnosing and identifying the condition and potential erosion of a riverbank by collecting information at spatial multi‐scale and (2) selecting suitable technical solutions to support sustainable riverbank stabilisation through using evaluation matrices and analysis of the adequacy of each technical solution to the intervention site's conditions and stream flow characteristics. This approach allows a holistic and integrated analysis of the bank erosion problems and the selection of stabilising technical solutions that are best suited from a structural viewpoint. In order to comply with the WFD (Water Framework Directive) on river environment issues, complementary criteria are proposed that help select from the chosen technical solutions those that improve the diversity of habitats as well as mitigate the aesthetic impact with the lowest cost. The methodology was applied to a reach of the Cértima River (located in the Centro region of Portugal), where field visits were performed to help assess the riverbanks’ condition as well as to select technical solutions for riverbank stabilisation. As a result, it was possible to select a set of the most suitable technical solutions to ensure physical and hydraulic required functions, to minimise morphological and landscape changes in the banks, and to promote habitat diversity.
Evaluation of clarity of presentation and applicability of monitoring instructions for patients using lithium in clinical practice guidelines for treatment of bipolar disorder
Authors: Nederlof M , Kupka RW , Braam AM , Egberts ACG , Heerdink ER
Published: August 2018

Objectives

Clinical practice guidelines (CPGs) for treatment of bipolar disorder (BD) aim to provide guidance to health care professionals on monitoring of patients using lithium. The aim was to assess the clarity of presentation and applicability of monitoring instructions for patients using lithium in CPGs for treatment of BD.

Methods

CPGs for treatment of BD were selected from acknowledged professional organizations from multiple continents. CPGs were rated on the clarity of presentation and applicability of lithium monitoring instructions using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The applicability of monitoring instructions was assessed according to the Systematic Information for Monitoring (SIM) score. Monitoring instructions were considered applicable when a SIM score of ≥3 was found.

Results

The clarity of presentation for six out of the nine CPGs was good (>70%) using the AGREE II tool. Only one CPG scored >70% on applicability. Descriptions of the resource implications and facilitators of and barriers to monitoring were most often missing. All CPGs contained instructions for monitoring of lithium serum levels and renal and thyroid function. Information provided in monitoring instructions (n = 247) was in general applicable to clinical practice (77%) based on the SIM score. Overall, a median SIM score of 3 (interquartile range 3‐4) was found.

Conclusions

Improvement of the applicability of CPGs is recommended, and can be achieved by describing the resource implications and facilitators of and barriers to monitoring. In addition, information on critical values and instructions on how to respond to aberrant monitoring parameters are needed. With such improvements, CPGs may better aid health care professionals to monitor patients using lithium.
Return to childhood? Against the infantilization of people with dementia
Authors: Jongsma Karin , Schweda Mark
Published: August 2018

The idea that dementia is essentially a return to childhood and those affected must somehow be similar to children constitutes a deeply rooted and pervasive cultural trope. While such tropes may be helpful in making sense of an otherwise elusive and inscrutable state, they can at the same time promote inadequate understandings of dementia and hence also influence our attitudes and behaviour towards those affected in several problematic ways. In the present work, we provide a detailed account of the origins and implications of the idea that people with dementia are somehow similar to children. In order to spell out the normative significance of this trope and to analyse its shortcomings, we will rely on a life‐course perspective. We will point out that the second‐childhood trope does not do justice to the particularities of the life phases of both children and people with dementia. This lack of biographical sensitivity brings about undignified treatment of and harm to those who have previously lived more autonomous lives. In conclusion, we will argue that people with dementia should not be equated with children as they are at a different point in their lives. This critical analysis of the second‐childhood trope shows the usefulness of a culturally and biographically sensitive theoretical framework for bioethical reflection. In particular, it provides reasons to reject infantilizing attitudes and behaviours and instead take seriously the personality, values and preferences shaped throughout the course of an individual's life.
Mechanistic reasoning and informed consent
Authors: Kennedy Ashley , Malanowski Sarah
Published: August 2018

Evidence‐based medicine (EBM) proponents have argued that mechanistic evidence concerning medical treatments should be considered secondary to evidence derived from randomized controlled trials (RCTs). One common criticism of RCTs is that they often do not yield results that are generalizable to clinical practice, and that for clinical practice application, mechanistic evidence is needed. However, proponents of EBM have argued that mechanistic reasoning is often unreliable and thus not very useful. Here we suggest an important role of mechanistic explanation that has been left out of this discussion entirely, namely, its importance in a patient’s decision of whether or not to take certain drugs. We argue that in certain cases, knowing how a treatment works is just as important for the patient as knowing whether it does. In this paper, we explore how and why giving patients mechanistic information can be an important factor in obtaining informed consent for medical treatment, focusing on the example case of hormonal contraceptives.
Mesenchymal COX2‐PG secretome engages NR4A‐WNT signalling axis in haematopoietic progenitors to suppress anti‐leukaemia immunity
Authors: Wu Limei , Amarachintha Surya , Xu Jian , Oley Frank , Du Wei
Published: August 2018

The bone marrow (BM) microenvironment (niche) plays important roles in supporting normal/abnormal haematopoiesis. We investigated the interaction between leukaemic mesenchymal niche and haematopoietic stem and progenitor cells (HSPCs) using the model of Fanconi anaemia (FA), a genetic disorder characterized by BM failure and leukaemia. Healthy donor HSPCs co‐cultured on mesenchymal stromal cells (MSCs) derived from FA patients with acute myeloid leukaemia (AML) exhibited higher human engraftment and myeloid expansion in Non‐obese diabetic severe combined immunodeficiency IL‐2γ−/−/SGM3 recipients. Untargeted metabolomics analysis revealed the progressively elevated prostaglandins (PGs) in the MSCs of FA patients with myelodysplastic syndromes (MDS) and AML. Reduced secretion of PGs subsequent to inflammatory cyclooxygenase 2 (COX2) inhibition ameliorated HSPC/myeloid expansion. Transcriptome analysis demonstrated dysregulation of genes involved in the NR4A family of transcription factors (TFs) and WNT/β‐catenin signalling pathway in FA‐AML‐MSC‐co‐cultured‐CD34+ cells. COX2 inhibition led to significantly decreased NR4A TFs and WNT signalling genes expression. Mechanistically, NR4A1 and NR4A2 synergistically activate the CTNNB1 gene promoter . Knocking down CTNNB1 or NR4A1 in AML‐MSC‐co‐cultured‐CD34+ cells increased leukaemia‐reactive T‐effector cells production and rescued anti‐leukaemia immunity. Together, these findings suggest that specific interactions between leukaemic mesenchymal niche and HSPCs orchestrate a novel COX2/PG‐NR4A/WNT signalling axis, connecting inflammation, cellular metabolism and cancer immunity.
Meta‐analysis and Individual Participant Data Synthesis in Child Development: Introduction to the Special Section
Authors: Roisman Glenn I. , van IJzendoorn Marinus H.
Published: August 2018

This paper serves as an Introduction by the co‐editors to a Special Section of Child Development entitled “Meta‐analysis and Individual Participant Data Synthesis in Child Development.” First, the co‐editors emphasize that the work contained in the Special Section was selected to highlight the value of meta‐analysis not only for synthesizing study‐level published and unpublished data but also as regards its ability to support programmatic, replicable, and cumulative developmental science. Second, the co‐editors identify some of the cross‐cutting themes of the papers featured in the Special Section, including the value of meta‐analysis for summarizing and interrogating the full range of developmental science and in potentially transforming conventional wisdom in given domains along with the importance of recent innovations for improving standard meta‐analytic practice–particularly in the context of developmental questions. Emphasized especially are contributions to the Special Section that extend classic meta‐analysis to individual participant data synthesis.
Subjective Well‐Being Decreasing With Age: New Research on Children Over 8
Authors: Casas Ferran , González‐Carrasco Mònica
Published: August 2018

An increasing number of scientific publications have provided data from different countries suggesting subjective well‐being (SWB) continuously decreases during adolescence. A review of these publications reveals authors have used dissimilar scales in diverse countries. Using data from the international Children's Worlds project (N = 48,040), involving 15 countries, a comparative analysis was performed to determine how mean scores evolve with different SWB scales from the age of 8 onwards. The results support the hypothesis that the tendency of SWB to decrease with age starts at around 10 years of age in most countries, while also confirming that different psychometric scales display different levels of sensitivity to diverse sociocultural contexts and more than one should be used in any research on children and adolescents’ SWB.
Effect of two recombinant Trichinella spiralis serine protease inhibitors on TNBS-induced experimental colitis of mice
Authors: Xu J , Wu L , Yu P , Liu M , Lu Y
Published: August 2018

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease (CD), is a chronic autoimmune disease. Parasitic infections and their products have been shown to have protective effects on autoimmune diseases, including IBD. In this experiment, 96 male BALB/c mice aged 6–8 weeks were divided randomly into two large groups: prevention and therapy. The changes in the various indicators of colitis were detected to demonstrate that Trichinella spiralis serine protease inhibitors can relieve the inflammatory severity of 2,4,6-trinitrobenzenesulphonic acid solution (TNBS)-induced colitis and to explore possible immunological mechanisms. Results showed that the disease activity index (DAI) score, myeloperoxidase (MPO) activity, macroscopic and microscopic damage degrees of colon all decreased significantly, interferon (IFN)-γ expression decreased, interleukin (IL)-4 expression increased, nuclear factor kappa B (NF)-κB expression decreased and the percentage of CD4+CD25+forkhead box protein 3 (FoxP3+) regulatory T cells (Treg) cells in the spleen. MLN increased significantly compared to the phosphate-buffered saline (PBS)/2,4,6-trinitrobenzenesulphonic acid solution (TNB) group. We found the same results with the T. spiralis Kazal-type serine protease inhibitors (TsKaSPI)+TNBS and TsAdSPI+TNBS groups in the large prevention group and the large therapy group, compared to the TNBS+PBS group with the TNBS+TsKaSPI and TNBS+TsAdSPI groups. Immunization with TsKaSPI and TsAdSPI on the CD models showed an intervention effect, possibly because TsKaSPI and TsAdSPI induced a T helper type 2 (Th2)-type immune response and balanced the TNBS-induced Th1-type immune response.
Serum exosomes of chronic gastritis patients infected withHelicobacter pylorimediate IL-1α expression via IL-6 trans-signalling in gastric epithelial cells
Authors: Chen Y , Wang X , Yu Y , Xiao Y , Huang J , Yao Z , Chen X , Zhou T , Li P , Xu C
Published: August 2018

Emerging evidence has linked the exosomes to many immunological disorders, including infectious diseases. However, knowledge regarding the role of exosomes in Helicobacter pylori infection is limited. Here, we show that serum exosomes from chronic gastritis patients with H. pylori infection (Hp exosomes) stimulate the expression of the soluble interleukin (IL)-6 receptor (sIL-6R), which is involved in IL-6 trans-signalling in gastric epithelial cells. Interestingly, sIL-6R up-regulates expression of the proinflammatory cytokine IL-1α, and the neutralization of sIL-6R suppresses IL-1α secretion. Thus, Hp exosomes regulate IL-1α expression via sIL-6R-mediated IL-6 trans-signaling. Altogether, this study reveals a novel perspective in which exosomes play a vital role in immunological mechanisms during H. pylori infection.
The benefits of adding metformin to tamoxifen to protect the endometrium—A randomized placebo‐controlled trial
Authors: Davis Susan R. , Robinson Penelope J. , Jane Fiona , White Shane , Brown Kristy A. , Piessens Sofie , Edwards Andrew , McNeilage Jane , Woinarski Jillian , Chipman Mitchell , Bell Robin J.
Published: August 2018

Background

We investigated whether metformin prevents tamoxifen‐induced endometrial changes and insulin resistance (IR) after a diagnosis of breast cancer.

Methods

This was a single‐centre, randomized, double‐blind, placebo‐controlled, parallel group trial. Postmenopausal women with hormone receptor‐positive breast cancer taking tamoxifen were randomly allocated to metformin 850 mg or identical placebo, twice daily, for 52 weeks. Outcome measures included double endometrial thickness (ET) measured by transvaginal ultrasound, fasting insulin, glucose and IR estimated by the homeostasis model of assessment (HOMA‐IR).

Results

A total of 112 women were screened and 102 randomized. Results are presented as median (range). The 101 women who took at least one dose of medication were aged 56 (43‐72) years, with 5(0.5‐28) years postmenopause, and had taken tamoxifen for 28.9 (0‐367.4) weeks. The baseline ET was 2.9 mm (1.4‐21.9) for the placebo group (n = 52) and 2.5 mm (1.3‐14.8) for the metformin group (n = 50). At 52 weeks, the median ET was statistically significantly lower for the metformin (n = 36) than for the placebo group (n = 45) (2.3 mm (1.4‐7.8) vs 3.0 (1.2‐11.3); P = 0.05). 13.3% allocated to placebo had an ET greater than 4 mm vs 5.7% for metformin (P = 0.26). There was no endometrial atypia or cancer. Compared with placebo, metformin resulted in significantly greater baseline‐adjusted reductions in weight (P < 0.001), waist circumference (0.03) and HOMA‐IR (P < 0.001).

Conclusions

Metformin appears to inhibit tamoxifen‐induced endometrial changes and has favourable metabolic effects. Further research into the adjuvant use of metformin after breast cancer and to prevent EH and cancer is warranted.
Identification of novel immune‐relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis
Authors: Han Zhi‐Jie , Xue Wei‐Wei , Tao Lin , Zhu Feng
Published: August 2018

Aims

Alzheimer's disease (AD) is one of the leading causes of death in elderly people. Its pathogenesis is greatly associated with the abnormality of immune system. However, only a few immune‐relevant AD drug target genes have been discovered up to now, and it is speculated that there are still many potential drug target genes of AD (at least immune‐relevant genes) to be discovered. Thus, this study was designed to identify novel AD drug target genes and explore their biological properties.

Methods

A combinatorial approach was adopted for the first time to discover AD drug targets by collectively considering ontology inference and network analysis. Moreover, a novel strategy limiting the distance of reasoning and in turn reducing noise interference was further proposed to improve inference performance. Potential AD drug target genes were discovered by integrating information of multiple popular databases (TTD, DrugBank, PharmGKB, AlzGene, and BioGRID). Then, the enrichment analyses of the identified drug targets genes based on nine well‐known pathway‐related databases were conducted to explore the function of the identified potential drug target genes.

Results

Eighteen potential drug target genes were finally identified, and 13 of them had been reported to be closely associated with AD. Enrichment analyses of these identified drug target genes, based on nine pathway‐related databases, revealed that the enriched terms were primarily focus on immune‐relevant biological processes. Four of those identified drug target genes are involved in the classical complement pathway and process of antigen presenting.

Conclusion

The well‐reproducible results showed the good performance of the combinatorial approach, and the remaining five new targets could be a good starting point for our understanding of the pathogenesis and drug discovery of AD. Moreover, this study supported validity of the combinatorial approach integrating ontology inference with network analysis in the discovery of novel drug target for neurological diseases.
Long noncoding RNA HOTAIR promotes renal cell carcinoma malignancy through alpha‐2, 8‐sialyltransferase 4 by sponging microRNA‐124
Authors: Pan Yue , Wu Yongjin , Hu Jialei , Shan Yujia , Ma Jia , Ma Huipeng , Qi Xia , Jia Li
Published: August 2018

Objectives

Accumulating evidence demonstrated that the long noncoding RNA (lncRNA) HOTAIR (Hox transcript antisense intergenic RNA) plays key role in renal cell carcinoma (RCC) malignancy, while microRNA‐124 (miR‐124) is a tumour suppressor in RCC. The aim of this work was to assess the biological function of HOTAIR and to explore underlying mechanism involved in HOTAIR/miR‐124/alpha‐2, 8‐sialyltransferase 4 (ST8SIA4) axis‐regulated progression in RCC.

Materials and methods

Real‐time PCR analyses and western blots were performed to the levels of HOTAIR, miR‐124 and ST8SIA4 expression in human RCC tissues and RCC cell lines (ACHN and 786‐O). Bioinformatics analysis and dual‐luciferase reporter assay were used to illustrate relationship between HOTAIR and miR‐124 in RCC. Colony formation assays, EdU assays, Ki67 assays and apoptosis assays were taken to evaluate cell proliferation. Tumour xenograft was created to explore the functions of HOTAIR and ST8SIA4 in tumorigenesis in vivo. Migration assays, invasion assays and cell adhesion assays and were also taken to analyse the carcinoma progression.

Results

In this study, HOTAIR level was confirmed to be significantly upregulated in RCC samples and RCC cell lines compared with those in the paired adjacent tissues and normal renal cell line. Overexpression of HOTAIR promoted the capability of proliferation, migration and invasion in RCC cell lines. HOTAIR directly bound to miR‐124, while miR‐124 mediated the expression of ST8SIA4 in RCC cell lines. ST8SIA4 was upregulated in RCC tissues and RCC cell lines. Ectopic expression of ST8SIA4 modulated the proliferation, migration and invasion of RCC cells. Further results indicated that HOTAIR promoted the proliferation and metastasis as a competing endogenous RNA to regulate ST8SIA4 expression by sponging miR‐124 in RCC.

Conclusions

Our results demonstrated that HOTAIR mediated RCC progression in part through miR‐124/ST8SIA4 axis, which functioned as a new prognostic biomarker in RCC.
Diastolic dysfunction in tetralogy of Fallot: Comparison of echocardiography with catheterization
Authors: DiLorenzo Michael , Hwang Wei‐Ting , Goldmuntz Elizabeth , Ky Bonnie , Mercer‐Rosa Laura
Published: August 2018

Background

Right ventricular (RV) systolic dysfunction has been associated with adverse outcomes in tetralogy of Fallot (TOF). However, the role and etiology of diastolic dysfunction remain incompletely defined. We assessed the association between traditional echocardiographic measures of diastolic function with catheter‐based RV end‐diastolic pressure (RVEDP) and identified clinical characteristics independently associated with diastolic dysfunction.

Methods

Single‐center, retrospective cohort study of surgically repaired TOF patients undergoing cardiac catheterization with echocardiograms within 3 months prior to the catheterization. Tricuspid inflow and tissue Doppler measurements (E/A, E/e′, and deceleration time) defined diastolic dysfunction, graded as impaired relaxation, pseudonormal, or restrictive physiology. Regression analyses tested associations between echocardiographic parameters, RVEDP, and clinical characteristics.

Results

Ninety‐four subjects were included. Catheterization age was 8.9 years (interquartile range 4.4, 15.9). RVEDP was 9.5 ± 2.5 mm Hg. Sixty‐one (65%) subjects had echocardiographic evidence of diastolic dysfunction. RVEDP was not associated with echocardiographic parameters of diastolic function (grade of dysfunction, E/e′, or E/A). Higher RVEDP was associated with larger right atrial and RV end‐diastolic area, independently of weight and degree of pulmonary or tricuspid regurgitation, though was not associated with indexed right atrial or RV end‐diastolic area. Greater number of interim procedures was associated with higher RVEDP, E/e′, and the presence of diastolic dysfunction by echocardiography.

Conclusions

Diastolic dysfunction, as determined by echocardiography‐derived and catheter‐based (RVEDP) measures, is prevalent in this TOF population. These measures are not associated with each other; therefore, echocardiographic parameters of diastolic function are not reflective of RVEDP. The development of noninvasive parameters that correlate with filling pressures is required.
Prefrontal cortex modulates firing pattern in the nucleus reuniens of the midline thalamus via distinct corticothalamic pathways
Authors: Zimmerman Eric C. , Grace Anthony A.
Published: August 2018

The thalamus has long been recognized for its role in relaying sensory information from the periphery, a function accomplished by its “first‐order” nuclei. However, a second category of thalamic nuclei, termed “higher‐order” nuclei, have been shown instead to mediate communication between cortical areas. The nucleus reuniens of the midline thalamus (RE) is a higher‐order nucleus known to act as a conduit of reciprocal communication between the medial prefrontal cortex (mPFC) and hippocampus. While anatomical and behavioural studies of RE are numerous, circuit‐based electrophysiological studies, particularly those examining the impact of cortical input and the thalamic reticular nucleus (TRN) on RE neuron firing, are sparse. To characterize RE neuron firing properties and dissect the circuit dynamics of the infralimbic subdivision of the mPFC (ilPFC), the TRN and RE, we used in vivo, extracellular, single‐unit recordings in male Sprague Dawley rats and manipulated neural activity using targeted pharmacological manipulations, electrical stimulation and a projection‐specific implementation of designer receptors exclusively activated by designer drugs (DREADDs). We show that ilPFC inhibition reduces multiple burst firing parameters in RE, whereas ilPFC stimulation drives burst firing and dampens tonic firing. In addition, TRN inhibition reduces the number of spontaneously active neurons in RE. Finally, inhibition of ilPFC terminals in RE selectively enhances a subset of burst firing parameters. These findings demonstrate that ilPFC input, both via direct projections and via the TRN, can modulate RE neuron firing pattern in nuanced and complex ways. They also highlight the ilPFC‐TRN‐RE circuit as a likely critical component of prefrontal–hippocampal interactions.
Effects of litter source on the dynamics of particulate organic matter fractions and rates of macroaggregate turnover in different soil horizons
Authors: Parwada C. , Van Tol J.
Published: August 2018

Soil texture influences the transformation of soil organic matter (SOM), and depletion and reduction in the number of macroaggregates. However, the extent of changes in SOM in response to its quality and mechanisms of stabilization in different types of soil texture is unclear. We evaluated changes in SOM during a 30‐week incubation experiment using seven soils mixed with two sources of litter; Vachellia karroo (Hayne) Banfi & Galasso leaf and Zea mays L. stover. We hypothesized that changes in intraparticulate organic matter (iPOM) are influenced by litter quality • soil type • time interactions, which affect rates of turnover of macroaggregates. A completely randomized design was used in arranging soil jars in the incubator. Free light fractions and coarse and fine iPOM within macroaggregates (>250 μm) decreased exponentially from week 1 to 30 and were significantly (P < 0.05) affected by litter source • soil horizon • time interactions. Trends of changes in fine iPOM fractions were the same in macroaggregates and microaggregates (P < 0.05). The greatest changes in POM fractions occurred 8 weeks after litter incorporation. Both V. karroo leaf and Z. mays stover stabilized macroaggregates during the first 8 weeks after incubation; thereafter they lost their influence. Therefore, we needed to reapply fresh litter after this period. Changes in iPOM fractions and macroaggregate turnover were specific to a soil type, suggesting that different sources of litter have different stabilizing effects in macroaggregates. Soil macroaggregate stabilization and changes in iPOM could be used as indicators to apply more appropriate management practices for soil protection or productivity.

Highlights

Does the source of organic matter affect transformation rates of different intraparticulate organic matter in the soil?

Degradation of organic matter into very fine particulate matter also increases the rate of turnover of macroaggregates.

Soil type • litter source interactions greatly influenced the rate of transformation from coarse to fine intraparticulate fractions.

Effects of litter quality on dynamics of POM fractions in aggregates and macroaggregate turnover were horizon specific.
Beneficial effects of bilateral subthalamic stimulation on alexithymia in Parkinson's disease
Authors: Dafsari H. S. , Ray‐Chaudhuri K. , Mahlstedt P. , Sachse L. , Steffen J. K. , Petry‐Schmelzer J. N. , Dembek T. A. , Reker P. , Barbe M. T. , Visser‐Vandewalle V. , Fink G. R. , Timmermann L.
Published: August 2018

Background and purpose

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL) and motor and non‐motor symptoms in advanced Parkinson's disease (PD). However, its effect on alexithymia and its relationship to other neuropsychiatric symptoms and QoL in PD is unclear.

Methods

In this prospective, observational study of 39 patients with PD undergoing STN‐DBS, we examined the Parkinson's Disease Questionnaire‐8 (PDQ‐8), 20‐item Toronto Alexithymia Scale (TAS‐20), Hospital Anxiety and Depression Scale (HADS), Self‐Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living, UPDRS motor examination and UPDRS complications (UPDRS‐II/‐III/‐IV) and levodopa‐equivalent daily dose (LEDD) pre‐operatively and at 5‐month follow‐up. Outcome changes were tested with Wilcoxon signed‐rank or paired t‐test when parametric tests were applicable and corrected for multiple comparisons. The relationship between outcome changes was explored with bivariate correlations. Additionally, partial correlations between PDQ‐8 and TAS‐20 were computed controlling for HADS, SRMI and AES change scores. Predictor analyses for PDQ‐8 improvement were calculated for all baseline parameters.

Results

The baseline prevalence of alexithymia was 17.9%. We observed significant beneficial effects of STN‐DBS on PDQ‐8, TAS‐20, HADS, UPDRS‐II, ‐III and ‐IV scores and significant LEDD reduction. The correlation between TAS‐20 and PDQ‐8 improvements remained significant after controlling for all other aforementioned outcomes. Predictor analyses for PDQ‐8 improvement were significant for PDQ‐8 and TAS‐20.

Conclusions

This is the first report of beneficial effects of STN‐DBS on alexithymia. Alexithymia was significantly associated with QoL outcome independent of anxiety, depression, mania and apathy. Our study highlights the importance of alexithymia for holistic assessments of DBS outcomes.
Patient's perception: shorter and more severe prodromal phase in GBA‐associated PD
Authors: Zimmermann M. , Gaenslen A. , Prahl K. , Srulijes K. , Hauser A.‐K. , Schulte C. , Csoti I. , Berg D. , Brockmann K.
Published: August 2018

Background

Prevalence and time of occurrence of prodromal symptoms of Parkinson's disease (PD) in relation to the onset of classical motor manifestation varies between patients. Possible modifying factors might be different genetic architectures predisposing to varying burden of manifestations.

Objectives

To characterize the prodromal phase in PD patients with heterozygous mutations in the GBA gene compared to PD patients without GBA mutation.

Methods

In a retrospective design, 151 participants [47 PD patients carrying a GBA mutation (PDGBA), 52 idiopathic PD patients (PDidiopathic), 52 healthy elderly (CON)] underwent a validated structured interview designed to assess prevalence and time of occurrence of prodromal symptoms.

Results

PDGBA showed a higher prevalence of prodromal symptoms and almost simultaneous occurrence of non‐motor and early motor symptoms shortly before PD diagnosis whereas PDidiopathic reported a longer prodromal phase starting with non‐motor symptoms.

Conclusion

The short and severe prodromal phase in PDGBA might call for shorter assessment intervals in yet premanifest GBA mutation carriers.
Inactivation of Fam20b in the neural crest‐derived mesenchyme of mouse causes multiple craniofacial defects
Authors: Liu Xuenan , Li Nan , Zhang Hua , Liu Jing , Zhou Nan , Ran Chunxiao , Chen Xiaoyan , Lu Yongbo , Wang Xiaofang , Qin Chunlin , Xiao Jing , Liu Chao
Published: August 2018

The glycosaminoglycan (GAG) chains attached to the core proteins of proteoglycans exert multiple roles, such as enriching signal molecules and regulating the binding of ligands to the corresponding receptors. A newly identified kinase – family with sequence similarity 20 member B (FAM20B) – is essential for the formation of GAG chains. The FAM20B protein phosphorylates the initial xylose on the side chain of a serine residue in the protein. Although the GAG chains of proteoglycans are believed to be indispensable during craniofacial development, there are few reports on their exact functions in craniofacial organogenesis. In this study, by mating Wnt1‐cre mice with Fam20b‐floxed mice (Fam20bflox/flox), we created Wnt1‐Cre;Fam20bflox/flox mice in which Fam20b is ablated in the neural crest‐derived mesenchyme. The Wnt1‐Cre;Fam20bflox/flox mice died immediately after birth because of complete cleft palates. In addition to cleft palate, Wnt1‐Cre;Fam20bflox/flox mice also manifested tongue elevation, micrognathia, microcephaly, suture widening, and reduced mineralization in the calvaria, facial bones, and temporomandibular joint. These findings indicate that the proteoglycans formed through the catalysis of FAM20B are essential for the morphogenesis and mineralization of the craniofacial complex.
Spatial and species‐level predictions of road mortality risk using trait data
Authors: González‐Suárez Manuela , Zanchetta Ferreira Flávio , Grilo Clara
Published: August 2018

Aim

Collisions between wildlife and vehicles are recognized as one of the major causes of mortality for many species. Empirical estimates of road mortality show that some species are more likely to be killed than others, but to what extent this variation can be explained and predicted using intrinsic species characteristics remains poorly understood. This study aims to identify general macroecological patterns associated with road mortality and generate spatial and species‐level predictions of risks.

Location

Brazil.

Time period

2001–2014.

Major taxa

Birds and mammals.

Methods

We fitted trait‐based random forest regression models (controlling for survey characteristics) to explain 783 empirical road mortality rates from Brazil, representing 170 bird and 73 mammalian species. Fitted models were then used to make spatial and species‐level predictions of road mortality risk in Brazil, considering 1,775 birds and 623 mammals that occur within the continental boundaries of the country.

Results

Survey frequency and geographical location were key predictors of observed rates, but mortality was also explained by the body size, reproductive speed and ecological specialization of the species. Spatial predictions revealed a high potential standardized (per kilometre of road) mortality risk in Amazonia for birds and mammals and, additionally, a high risk in Southern Brazil for mammals. Given the existing road network, these predictions mean that >8 million birds and >2 million mammals could be killed per year on Brazilian roads. Furthermore, predicted rates for all Brazilian endotherms uncovered potential vulnerability to road mortality of several understudied species that are currently listed as threatened by the International Union for Conservation of Nature.

Conclusion

With a rapidly expanding global road network, there is an urgent need to develop improved approaches to assess and predict road‐related impacts. This study illustrates the potential of trait‐based models as assessment tools to gain a better understanding of the correlates of vulnerability to road mortality across species, and as predictive tools for difficult‐to‐sample or understudied species and areas.
‘Women, work and family’: Educated women's employment decisions and social policies in Egypt
Authors: Barsoum Ghada
Published: August 2018

Despite increased access to education, women's conspicuous absence from the labour market in Egypt, and the Arab world in general, has been a key issue. Building on the stock of evidence on women's employment, this study provides a qualitative analysis of the torrent of challenges that educated married and unmarried women face as they venture into the labour market in Egypt. Single women highlight constrained opportunities due to job scarcity and compromised job quality. Issues of low pay, long hours, informality and workplace suitability to gender propriety norms come to the fore in the interview data. Among married working women, the conditions of the work domain are compounded by challenges of time deprivation and weak family and social support. The article highlights women's calculated and aptly negotiated decisions to work or opt out of the labour market in the face of such challenges. The analysis takes issue with the culturalist view that reduces women's employment decisions to ideology. It brings to the context of Arab countries three global arguments pertaining to the inseparability of work and family for women; the role of social policies and labour market conditions in defining women's employment decisions; and the potential disconnect between employment and empowerment. By looking at women as jobseekers and workers, the analysis particularly highlights the intersectionality of different forms of inequality in defining employment opportunities.
Measures of Functioning in Patients With Episodic Migraine: Findings From a Double‐Blind, Randomized, Placebo‐Controlled Phase 2b Trial With Galcanezumab
Authors: Ayer David W. , Skljarevski Vladimir , Ford Janet H. , Nyhuis Allen W. , Lipton Richard B. , Aurora Sheena K.
Published: August 2018

Objective – To evaluate 12‐week changes from baseline of 2 disease‐specific patient‐reported outcome (PRO) measures in adults with migraine treated with galcanezumab, an investigational humanized antibody binding calcitonin gene‐related peptide (CGRP), or placebo.

Background – Preventing headache‐related functional impairment is an important goal of migraine preventive treatment and a measurement target for PROs. Understanding which drugs have the potential to improve patient functioning in addition to preventing migraine headaches is vital to lessening patient burden.

Design/Methods – This Phase 2b double‐blind, randomized, placebo‐controlled study enrolled adults with episodic migraine. Galcanezumab (120 mg subcutaneous injection; n = 60) or placebo (n = 127) was administered every 28 days for 12 weeks. Post hoc secondary analyses were conducted for those who completed 12 weeks of treatment on 2 PROs: The Migraine‐Specific Quality of Life Questionnaire (MSQ) v2.1 and the Headache Impact Test™ (HIT‐6).

Results – Analysis of covariance revealed significant differences in least square mean changes from baseline between galcanezumab and placebo for all MSQ domains including total mean change placebo of 18.63, galcanezumab of 27.36 (95% CI 2.449, 15.008; P‐value of .0067); Role Function‐Restrictive mean change placebo of 22.40, galcanezumab of 31.92 (95% CI 2.636, 16.518; P‐value of .0071); Role Function‐Preventive mean change placebo of 13.43, galcanezumab of 19.76 (95% CI 0.476, 12.185; P‐value of .0342); and Emotional Function mean change placebo of 16.88, galcanezumab of 26.61 (95% CI 2.789, 16.674; P‐value of .0063). At baseline, mean number of migraine headache days (MHDs) did not correlate with MSQ total scores or HIT‐6. At 12 weeks post‐treatment, MHD correlated with MSQ and HIT‐6 scores (all P < .0001). Change in MHD was associated with change in MSQ domains and change in HIT‐6 scores (all P < .0001).

Conclusions – In comparison with placebo, treatment with galcanezumab was associated with significant functional improvements as reflected by changes in MSQ scores. Change in MHD was associated with improvements in MSQ and reductions in HIT‐6 scores, indicating the clinical importance of these changes in relation to PROs that measure function.
Lucretia and the Impossibility of Female Republicanism in Margaret Cavendish'sSociable Letters
Authors: Bergès Sandrine
Published: August 2018

Margaret Cavendish is known for her personal allegiance to monarchy in England. This is reflected in her writings; as Hobbes did, she tended to criticize severely any attempt at rebellion and did not think England could become a republic. Yet it seems that Cavendish did have sympathy with some republican values, in particular, as Lisa Walters has argued, with the republican concept of freedom as nondomination. How can we explain this apparent inconsistency? I believe that the answer lies in a lack of fit between the republican theories that were available to her and the values she accepted and according to which she was expected to live her life.
Mapping, in vivo, the uniformity of two skin properties alongside the human face by a 3D virtual approach
Authors: Pierre J. , Francois G. , Benize A. M. , Rubert V. , Coutet J. , Flament F.
Published: August 2018

Objective

To determine the homogeneity in the distribution of two cutaneous functions (hydration and elasticity) along the entire human face.

Material and Methods

The half faces (right or left, randomly chosen) of two groups of Caucasian women were measured on 24 different small sites (elasticity) and 41 others (hydration), by instruments of small‐sized probes (Cutometer® and Corneometer®, respectively). Hydration of the face was recorded at different times (up to 24 h), post application of a highly hydrating product. The recorded values (left and right half faces) were further gathered and digitally positioned on a virtual feminine face and their intensity was illustrated through a colored white (lower values)‐blue (higher values) scale.

Results

The reconstitution of the mapping of the two measured parameters (from the left and right sides of different subjects), shows a perfect symmetry vis à vis the nose axis. However, both parameters present slightly variable but significant values along the human face. Sites from the temple are less elastic than chin or forehead. The upper and lower parts of the forehead show slight disparities in their elasticity values. Cheeks are significantly less prone at retaining their imparted hydration status (lost 2 h after application of a hydrating product) as compared to sub‐ocular regions or chin that retain their hydration up to 24 h. Attempts to establish a mutual relationship between the two skin properties unsurprisingly failed.

Conclusion

The two studied skin properties show a slight but highly symmetric disparity along the entire human face.
Assessment of artefacts produced by metal posts on CBCT images
Authors: Lira de Farias Freitas A. P. , Cavalcanti Y. W. , Costa F. C. M. , Peixoto L. R. , Maia A. M. A. , Rovaris K. , Bento P. M. , Melo D. P.
Published: August 2018

Aim

To evaluate artefact intensity in cone beam computed tomography (CBCT) images of two alloys used in metal posts scanned using different exposure parameters.

Methodology

The sample consisted of 20 single‐rooted teeth divided into two groups for use with either a NiCr post or AgPd post. All teeth were scanned with and without their corresponding metal posts and with and without the presence of an extra restored tooth in the arch. The samples were scanned using CS 9000 3D scanner with two exposure protocols: 85 kV 6.3 mA and 85 kV 10 mA. Voxel size and FOV were fixed at 0.100 mm and 5 cm × 3.75 cm. The presence of artefacts was assessed qualitatively by two calibrated observers using the CBCT volume and paired 2D images, and quantitatively by one trained observer, using ImageJ software. Wilcoxon's signed rank, Mann–Whitney, kappa and chi‐square tests were used for qualitative analyses. Two‐way anova and Tukey's tests were used for quantitative analyses. All analyses were conducted considering the 95% confidence level (α < 0.05).

Results

For the CBCT volume qualitative analysis, significant differences were observed between the metal alloys in the presence of an extra restored tooth, with higher artefact intensity for AgPd when assessing hypodense halos and lines (P = 0.006). Images with two restored teeth had significantly more hypodense and hyperdense lines (P = 0.033). When evaluating exposure parameters and number of restored teeth, the paired image quality analysis revealed significant disagreement between observers for diagnostic image quality (P = 0.001). Quantitative artefact analysis revealed higher artefact intensity for the AgPd posts in the presence of two restored teeth.

Conclusion

Although the exposure parameters tested did not interfere with artefact intensity, post alloys with a higher atomic number and the presence of another metal structure in the arch increased artefact intensity and impaired the diagnostic quality of CBCT images.
Lymphedema in patients with hidradenitis suppurativa: a systematic review of published literature
Authors: Micieli Robert , Alavi Afsaneh
Published: August 2018

Background

Lymphedema is a debilitating complication of hidradenitis suppurativa (HS) that can be therapeutically challenging. Systematic evaluation of the clinical presentation and management of this condition has yet to be performed.

Methods

OVID MEDLINE and EMBASE databases were searched along with a review of the references of searched articles for all English reports discussing lymphedema secondary to HS.

Results

Two case series and 15 case reports met inclusion criteria, representing 27 patients. On average, these patients had a history of HS for 18 years (range 4–30 years). Lymphedema was found in the following areas in order of frequency: scrotum (16 patients, 59%), penis (12 patients, 44%), labia majora (4 patients, 15%), perineum (3 patients, 11%), groin (3 patients, 11%), buttocks (2 patients, 7%), and abdomen (1 patient, 4%). In six patients (22%), lymphedema occurred in two or more of the aforementioned locations. Lymphedema most commonly presented not only as swelling with induration but also as verrucous papules or nodules. The majority of cases (14 patients, 52%) were treated with radical surgical excision combined with medical therapy and obtained favorable outcomes. Surgical defect was most frequently covered with split thickness skin grafts 7 patients, 54%) followed by skin flaps (3 patients, 11%) and healing by secondary intention (3 patients, 11%).

Conclusions

Lymphedema appears to be a relatively rare complication of chronic HS that most commonly affects the anogenital region. Based on the evidence available, dermatologists should pursue a collaborative approach with surgery in the management of this condition at early stages.
Association among chronotype, dietary behaviours, and caries experience in Brazilian adolescents: Is there a behavioural pattern?
Authors: da Silveira Karen Simon Rezende , Prado Ivana Meyer , Abreu Lucas Guimarães , Serra‐Negra Júnia Maria Cheib , Auad Sheyla Márcia
Published: August 2018

Background

Dental caries (DC) remains a public health issue. Chronotype, diet, and oral hygiene may influence its development.

Objective

To investigate the association of chronotype, diet, oral hygiene, and DC among 12‐year‐olds.

Methods

A cross‐sectional study with 245 adolescents was conducted in public and private schools in southeast Brazil. Sociodemographics, dietary and oral hygiene habits were collected through a self‐reported questionnaire. Chronotype was assessed using the Portuguese version of the Puberty and Phase Preference Scale (PPPS). Subjects were examined for DC (WHO criteria). Bivariate and multivariate analyses were performed (P < 0.05).

Results

DC was present in 42.0% of the sample. In the bivariate analysis, a higher DMFT was associated with living in rural areas (P = 0.006), parents’/caregivers’ lower schooling (P = 0.008), and a not daily intake of vegetables (P = 0.033). Chronotype was not associated with DMFT scores. The Poisson regression model showed that adolescents who did not have breakfast regularly (PR = 1.55; 95% CI = 1.17‐2.08; P = 0.003), lived in rural areas (PR = 2.20; 95% CI = 1.59‐3.04; P < 0.001) and did not consume vegetables daily (PR = 1.55; 95% CI = 1.11‐2.17; P = 0.009) were more likely to present a higher DMFT.

Conclusions

DC is associated to living in rural areas and dietary habits, such as not having breakfast regularly and lack of daily intake of vegetables.