Background
Negative‐pressure wound therapy (NPWT) promotes angiogenesis and granulation, in part by strain‐induced production of growth factors and cytokines. As their expression profiles are being ...unravelled, it is pertinent to consider the mode of action of NPWT at the molecular level.
Methods
MEDLINE (January 1997 to present), Embase (January 1997 to present), PubMed (no time limit), the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles that evaluated the influence of NPWT on growth factor expression quantitatively.
Results
Sixteen studies met the inclusion criteria. Tumour necrosis factor expression was reduced in acute and chronic wounds, whereas expression of interleukin (IL) 1β was reduced in acute wounds only. Systemic IL‐10 and local IL‐8 expression were increased by NPWT. Expression of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor β and platelet‐derived growth factor was increased, consistent with mechanoreceptor and chemoreceptor transduction in response to stress and hypoxia. Matrix metalloproteinase‐1, ‐2, ‐9 and ‐13 expression was reduced but there was no effect on their enzymatic inhibitor, tissue inhibitor of metalloproteinase 1.
Conclusion
Cytokine and growth factor expression profiles under NPWT suggest that promotion of wound healing occurs by modulation of cytokines to an anti‐inflammatory profile, and mechanoreceptor and chemoreceptor‐mediated cell signalling, culminating in angiogenesis, extracellular matrix remodelling and deposition of granulation tissue. This provides a molecular basis for understanding NPWT.
How the vacuum works
The recent interest in the use of Immersive Virtual Reality (IVR) in education seems to correspond with the increased affordability, accessibility and functionality of IVR hardware and software. IVR ...has the potential to enhance
immersion, improve spatial capabilities, promote empathy, increase motivation and possibly improve learning outcomes. However, the extent to which teachers capitalise on these potentials in the future depends their perceptions of IVR and
their behavioural intentions to use it. Accordingly, this study aimed to identify relevant factors and influences relating to preservice teachers' behavioural intention to use IVR, using the Unified Theory of Acceptance and Use of
Technology 2 (UTAUT2) model. Confirmatory factor analysis revealed that UTAUT2 provided a suitable model to describe preservice teachers' perceptions of IVR on all dimensions (performance expectancy, effort expectancy, social influence,
facilitating conditions, hedonic motivation, price value, habit and behavioural intention), with hedonic motivation receiving the highest scores and habit scoring the lowest. Interview responses revealed the reasons for the substantial
variation in preservice teacher perceptions, which depended on a range of external- ("first-order"), internal- ("second-order") and design ("third-order")-related issues. Implications for schools, educational leaders and teacher
education are discussed. Author abstract
•Uni-axial behaviour of concrete-filled-steel-tube (CFST) columns with external steel rings confinement from 62 column tests.•Improved interface bonding, strength, stiffness and ductility of CFST ...columns with provision of external confinement.•Theoretical models proposed for evaluating uni-axial capacity of CFST columns with external ring confinement and verified.
Concrete-filled-steel-tube (CFST) columns show superior strength and ductility performance because of composite action. However, this cannot be fully developed at early elastic stage as steel dilates more than concrete and thereby causing imperfect interface bonding, which reduces the elastic strength and stiffness. To resolve the problem, confinement in the form of rings is proposed in this study to restrict the elastic lateral dilation of concrete. For verification, 62 CFST columns of various dimensions cast with normal-(NSC) or high-strength concrete (HSC) installed with rings were tested under uni-axial compression in this study. From the results, it was evident that: (1) Rings could improve the axial load-carrying capacity, stiffness and decrease the strength degradation rate. (2) The critical confinement index (ξcr) was varied with concrete grade. (3) Rings were effective to limit the lateral deformation of concrete and the steel tube. Based on the obtained results, three analytical models taking into account the confining effects provided by the steel tube and rings developed by the authors are proposed to estimate the axial load-carrying capacity of unconfined and ring-confined CFST columns. The validity of the best proposed model is justified by comparing the predicted theoretical strength with the measured strength in the tests and experimental results by other researchers.
Objective
Evidence‐based guidance of clinical decision‐making for the management of Autism Spectrum Disorder (ASD) is lacking, particularly for co‐occurring psychiatric symptoms. This review ...evaluates treatment evidence for six common symptom targets in children/adolescents with ASD and provides a resource to facilitate application of the evidence to clinical practice.
Method
A systematic search identified randomized controlled trials (RCTs) and high‐quality systematic reviews published between 2007 and 2016, focused on: social interaction/communication impairment, stereotypic/repetitive behaviours, irritability/agitation, attention‐deficit/hyperactivity disorder symptoms, mood or anxiety symptoms, and sleep difficulties. We then completed qualitative evaluation of high‐quality systematic reviews/meta‐analyses and quantitative evaluation of recently published RCTs not covered by prior comprehensive systematic reviews.
Results
Recently published RCTs focused on social interaction and communication impairment (trials = 32) using psychosocial interventions. Interventions for irritability/agitation (trials = 16) were mainly pharmacological. Few RCTs focused on other symptom targets (trials = 2–5/target). Integration of these results with our qualitative review indicated that few established treatment modalities exist, and available evidence is limited by small studies with high risk of bias.
Conclusion
Given the current evidence‐base, treatment targets must be clearly defined, and a systematic approach to intervention trials in children/adolescents with ASD must be undertaken with careful consideration of the limitations of safety/efficacy data.
Hard-switching-induced switching loss can contribute significantly to the power loss of an isolated bidirectional dual-active-bridge (DAB) dc-dc converter operating at high frequency. An ...<inline-formula> <tex-math notation="LaTeX">LC</tex-math></inline-formula>-type series resonant DAB converter based on a switch-controlled-inductor (SCI) is proposed to mitigate the loss arising from hard switching under wide-range variations in output voltage and current. Zero-voltage switching is achieved at the primary side (high voltage), while at the secondary side (low voltage), zero-current switching is preferred to reduce excessive ringing due to circulating current and switching loss. In order to achieve reduced conduction loss, a nominal operating point is chosen where the root-mean-square resonant tank current is the minimum. To validate the proposed topology and modulation scheme, an <inline-formula><tex-math notation="LaTeX">LC</tex-math></inline-formula>-type series resonant DAB converter based on SCI operating at 100 kHz is designed to interface a 400-V dc bus to a supercapacitor-based energy storage. Simulation and experimental results validate the effectiveness of the proposed topology for charging/discharging a supercapacitor with an output voltage variation of between 10 and 48 V and a maximum rated power of 480 W. A maximum efficiency of 94.6% is achieved using the proposed topology and modulation scheme.
Mentalizing deficits are a hallmark of the autism spectrum condition (ASC) and a potential endophenotype for atypical social cognition in ASC. Differences in performance and neural activation on the ...'Reading the Mind in the Eyes' task (the Eyes task) have been identified in individuals with ASC in previous studies.
Performance on the Eyes task along with the associated neural activation was examined in adolescents with ASC (n = 50), their unaffected siblings (n = 40) and typically developing controls (n = 40). Based on prior literature that males and females with ASC display different cognitive and associated neural characteristics, analyses were stratified by sex. Three strategies were applied to test for endophenotypes at the level of neural activation: (1) identifying and locating conjunctions of ASC-control and sibling-control differences; (2) examining whether the sibling group is comparable to the ASC or intermediate between the ASC and control groups; and (3) examining spatial overlaps between ASC-control and sibling-control differences across multiple thresholds.
Impaired behavioural performance on the Eyes task was observed in males with ASC compared to controls, but only at trend level in females; and no difference in performance was identified between sibling and same-sex control groups in both sexes. Neural activation showed a substantial endophenotype effect in the female groups but this was only modest in the male groups.
Behavioural impairment on complex emotion recognition associated with mental state attribution is a phenotypic, rather than an endophenotypic, marker of ASC. However, the neural response during the Eyes task is a potential endophenotypic marker for ASC, particularly in females.
Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to ...detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We show that a substantial fraction of the genome exhibits preferential organization relative to these nuclear bodies. Our results generate a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus.
Display omitted
•SPRITE enables genome-wide mapping of higher-order interactions in the nucleus•SPRITE uncovers two major inter-chromosomal hubs arranged around nuclear bodies•3D distance of DNA regions to these hubs is based on their functional properties•This organization constrains the overall 3D packaging of genomic DNA in the nucleus
SPRITE enables genome-wide detection of multiple simultaneously occurring higher-order DNA interactions within the nucleus and provides a global picture of inter-chromosomal spatial arrangement around nuclear bodies.
It has been proposed that autism spectrums condition may represent a form of extreme male brain (EMB), a notion supported by psychometric, behavioral, and endocrine evidence. Yet, limited data are ...presently available evaluating this hypothesis in terms of neuroanatomy. Here, we investigated sex-related anatomic features in adults with AS, a "pure" form of autism not involving major developmental delay.
Males and females with AS and healthy controls (n = 28 and 30, respectively) were recruited. Structural MR imaging was performed to measure overall gray and white matter volume and to assess regional effects by means of VBM. DTI was used to investigate the integrity of the main white matter tracts.
Significant interactions were found between sex and diagnosis in total white matter volume, regional gray matter volume in the right parietal operculum, and fractional anisotropy (FA) in the body of the CC, cingulum, and CR. Post hoc comparisons indicated that the typical sexual dimorphism found in controls, whereby males have larger FA and total white matter volume, was absent or attenuated in participants with AS.
Our results point to a fundamental role of the factors that underlie sex-specific brain differentiation in the etiology of autism.
Azole resistance in Aspergillus fumigatus is increasingly reported. Here, we describe the validation of the AsperGenius, a new multiplex real-time PCR assay consisting of two multiplex real-time ...PCRs, one that identifies the clinically relevant Aspergillus species, and one that detects the TR34, L98H, T289A, and Y121F mutations in CYP51A and differentiates susceptible from resistant A. fumigatus strains. The diagnostic performance of the AsperGenius assay was tested on 37 bronchoalveolar lavage (BAL) fluid samples from hematology patients and 40 BAL fluid samples from intensive care unit (ICU) patients using a BAL fluid galactomannan level of ≥1.0 or positive culture as the gold standard for detecting the presence of Aspergillus. In the hematology and ICU groups combined, there were 22 BAL fluid samples from patients with invasive aspergillosis (IA) (2 proven, 9 probable, and 11 nonclassifiable). Nineteen of the 22 BAL fluid samples were positive, according to the gold standard. The optimal cycle threshold value for the presence of Aspergillus was <36. Sixteen of the 19 BAL fluid samples had a positive PCR (2 Aspergillus species and 14 A. fumigatus samples). This resulted in a sensitivity, specificity, and positive and negative predictive values of 88.9%, 89.3%, 72.7%, and 96.2%, respectively, for the hematology group and 80.0%, 93.3%, 80.0%, and 93.3%, respectively, in the ICU group. The CYP51A real-time PCR confirmed 12 wild-type and 2 resistant strains (1 TR34-L98H and 1 TR46-Y121F-T289A mutant). Voriconazole therapy failed for both patients. The AsperGenius multiplex real-time PCR assay allows for sensitive and fast detection of Aspergillus species directly from BAL fluid samples. More importantly, this assay detects and differentiates wild-type from resistant strains, even if BAL fluid cultures remain negative.
Glioblastoma is the most aggressive primary brain tumor in adults and due to the invasive nature cannot be completely removed. The WNT inhibitory factor 1 (WIF1), a secreted inhibitor of WNTs, is ...systematically downregulated in glioblastoma and acts as strong tumor suppressor. The aim of this study was the dissection of WIF1-associated tumor-suppressing effects mediated by canonical and non-canonical WNT signaling. We found that WIF1 besides inhibiting the canonical WNT pathway selectively downregulates the WNT/calcium pathway associated with significant reduction of p38-MAPK (p38-mitogen-activated protein kinase) phosphorylation. Knockdown of WNT5A, the only WNT ligand overexpressed in glioblastoma, phenocopied this inhibitory effect. WIF1 expression inhibited cell migration in vitro and in an orthotopic brain tumor model, in accordance with the known regulatory function of the WNT/Ca(2+) pathway on migration and invasion. In search of a mediator for this function differential gene expression profiles of WIF1-expressing cells were performed. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA and key positive regulator of invasion, emerged as the top downregulated gene. Indeed, knockdown of MALAT1 reduced migration in glioblastoma cells, without effect on proliferation. Hence, loss of WIF1 enhances the migratory potential of glioblastoma through WNT5A that activates the WNT/Ca(2+) pathway and MALAT1. These data suggest the involvement of canonical and non-canonical WNT pathways in glioblastoma promoting key features associated with this deadly disease, proliferation on one hand and invasion on the other. Successful targeting will require a dual strategy affecting both canonical and non-canonical WNT pathways.
PDF
