Stroke warning campaigns: delivering better patient outcomes? A systematic review.

Background: Patient delay in presenting to hospital with stroke symptoms remains one of the major barriers to thrombolysis treatment, leading to its suboptimal use internationally. Educational interventions such as mass media campaigns and community initiatives aim to reduce patient delays by promoting the signs and symptoms of a stroke, but no consistent evidence exists to show that such interventions result in appropriate behavioral responses to stroke symptoms. Methods: A systematic literature search and narrative synthesis were conducted to examine whether public educational interventions were successful in the reduction of patient delay to hospital presentation with stroke symptoms. Three databases, MEDLINE, CINAHL, and PsycINFO, were searched to identify quantitative studies with measurable behavioral end points, including time to hospital presentation, thrombolysis rates, ambulance use, and emergency department (ED) presentations with stroke. Results: Fifteen studies met the inclusion criteria: one randomized controlled trial, two time series analyses, three controlled before and after studies, five uncontrolled before and after studies, two retrospective observational studies, and two prospective observational studies. Studies were heterogeneous in quality; thus, meta-analysis was not feasible. Thirteen studies examined prehospital delay, with ten studies reporting a significant reduction in delay times, with a varied magnitude of effect. Eight studies examined thrombolysis rates, with only three studies reporting a statistically significant increase in thrombolysis administration. Five studies examined ambulance usage, and four reported a statistically significant increase in ambulance transports following the intervention. Three studies examining ED presentations reported significantly increased ED presentations following intervention. Public educational interventions varied widely on type, duration, and content, with description of intervention development largely absent from studies, limiting the potential replication of successful interventions. Conclusions: Positive intervention effects were reported in the majority of studies; however, methodological weaknesses evident in a number of studies limited the generalizability of the observed effects. Reporting of specific intervention design was suboptimal and impeded the identification of key intervention components for reducing patient delay. The parallel delivery of public and professional interventions further limited the identification of successful intervention components. A lack of studies of sound methodological quality using, at a minimum, a controlled before and after design was identified in this review, and thus studies incorporating a rigorous study design are required to strengthen the evidence for public interventions to reduce patient delay in stroke. The potential clinical benefits of public interventions are far-reaching, and the challenge remains in translating knowledge improvements and correct behavioral intentions to appropriate behavior when stroke occurs

I Don\u27t Belong with All the Really Smart Kids Here : Student Characterizations of Belonging in Engineering

This research paper is a qualitative study of how students with diverse demographics, mindsets, and identities describe what it means to belong in engineering. Engineering students’ sense of belonging has a significant impact on students’ decisions to leave engineering. Talented students who feel that they do not belong in engineering are more likely to leave than their peers. Previous studies have focused on belonging for underrepresented students in engineering (e.g., women or minorities) or specific factors contributing to student belonging (e.g., classroom performance). However, few have explored how students describe what it means for them to belong in engineering to understand how this attitude may be formed and internalized by diverse students. To address this gap, thirty-five interviews were conducted with first-year engineering students at four universities under a semi-structured interview protocol to learn about students’ experiences and perceptions of engineering. Interview transcripts were analyzed using inductive and deductive thematic coding to develop broader themes about how a diverse set of undergraduate students describe their sense of belonging in engineering. Student responses were compared to one another while being sensitive to potential differences in students’ demographic or latent diversity (i.e., mindsets, beliefs, and values). Emerging results show differences in how students evaluate belonging relative to their peers. This research can inform and influence engineering faculty to serve students holistically by understanding how students describe belongingness and provides actionable implications to develop and support their sense of belonging. These efforts may support student retention of diverse students across engineering

Closed-loop communication during out-of-hospital resuscitation:Are the loops really closed?

Training for effective communication in high-stakes environments actively promotes targeted communicative strategies. One oft-recommended strategy is closed-loop communication (CLC), which emphasises three components – call-out, checkback, and closing of the loop – to signal understanding. Using CLC is suggested to improve clinical outcomes, but research indicates that medical practitioners do not always apply CLC in team communication. Our paper analyses a context in which speakers’ linguistic choices are guided by explicit recommendations during training, namely out-of-hospital cardiac arrest (OHCA) resuscitation. We examined 20 real-life OHCA resuscitations to determine whether paramedics adopt CLC in the critical first five minutes after the arrival of the designated team leader (a paramedic specially trained in handling OHCA resuscitation), and what other related communication strategies may be used. Results revealed that standard form CLC was not consistently present in any of the resuscitations despite opportunities to use it. Instead, we found evidence of non-standard forms of CLC and closed-ended communication (containing the first two components of standard CLC). These findings may be representative of what happens when medical practitioners communicate in time-critical, real-life contexts where responses to directives can be immediately observed, and suggest that CLC may not always be necessary for effective communication in these contexts

Benefits of a Multi-institutional, Hybrid Approach to Teaching Course Design for Graduate Students, Postdoctoral Scholars, and Leaders

In this study, graduate students and postdoctoral scholars participated in a hybrid, multi-institutional workshop series about course design. Trainees developed college courses based on their research expertise, posting works-in-progress to a shared, online drive for peer review and collaboration. Learners also met weekly with local facilitators at their institution. The program led to similar learning outcomes as when the program was previously run in a face-to-face only format at one institution. However, the multi-institutional design led to additional benefits, especially for leaders at each institution, who described a rich learning community in their collaborative work

Myoglobin‐mediated lipid shuttling increases adrenergic activation of brown and white adipocyte metabolism and is as a marker of thermogenic adipocytes in humans

Background: Recruitment and activation of brown adipose tissue (BAT) results in increased energy expenditure (EE) via thermogenesis and represents an intriguing therapeutic approach to combat obesity and treat associated diseases. Thermogenesis requires an increased and efficient supply of energy substrates and oxygen to the BAT. The hemoprotein myoglobin (MB) is primarily expressed in heart and skeletal muscle fibres, where it facilitates oxygen storage and flux to the mitochondria during exercise. In the last years, further contributions of MB have been assigned to the scavenging of reactive oxygen species (ROS), the regulation of cellular nitric oxide (NO) levels and also lipid binding. There is a substantial expression of MB in BAT, which is induced during brown adipocyte differentiation and BAT activation. This suggests MB as a previously unrecognized player in BAT contributing to thermogenesis. Methods and results: This study analyzed the consequences of MB expression in BAT on mitochondrial function and thermogenesis in vitro and in vivo. Using MB overexpressing, knockdown or knockout adipocytes, we show that expression levels of MB control brown adipocyte mitochondrial respiratory capacity and acute response to adrenergic stimulation, signalling and lipolysis. Overexpression in white adipocytes also increases their metabolic activity. Mutation of lipid interacting residues in MB abolished these beneficial effects of MB. In vivo, whole-body MB knockout resulted in impaired thermoregulation and cold- as well as drug-induced BAT activation in mice. In humans, MB is differentially expressed in subcutaneous (SC) and visceral (VIS) adipose tissue (AT) depots, differentially regulated by the state of obesity and higher expressed in AT samples that exhibit higher thermogenic potential. Conclusions: These data demonstrate for the first time a functional relevance of MBs lipid binding properties and establish MB as an important regulatory element of thermogenic capacity in brown and likely beige adipocytes. Keywords: energy expenditure; hemoprotein; metabolism; obesity; oxphos; uncoupling protein

Wnt5b–Ryk pathway provides directional signals to regulate gastrulation movement

The soluble ligand Wnt5b repels cells expressing the Ryk (related to tyrosine kinase) receptor, establishing directional motility during gastrulation

EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation

<p>Abstract</p> <p>Background</p> <p>Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed <it>EFS </it>(<it>embryonal Fyn-associated substrate</it>) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated <it>EFS </it>promoter region CpG island in tumor classification and metastatic progression.</p> <p>Methods</p> <p><it>EFS </it>methylation was determined by direct sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of individual cloned PCR products. The results were associated with clinical features of tumors and tumor-related death of patients.</p> <p>Results</p> <p>Analysis of 16 UM showed full methylation of the <it>EFS </it>CpG island in 8 (50%), no methylation in 5 (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a higher risk of metastatic progression for tumors with <it>EFS </it>methylation (p = 0.02). This correlation was confirmed in an independent set of 24 randomly chosen tumors. Notably, only UM with <it>EFS </it>methylation gave rise to metastases. Real-time quantitative RT-PCR expression analysis revealed a significant inverse correlation of <it>EFS </it>mRNA expression with <it>EFS </it>methylation in UM. We further found that <it>EFS </it>methylation is tissue-specific with full methylation in peripheral blood cells, and no methylation in sperm, cultured primary fibroblasts and fetal muscle, kidney and brain. Adult brain samples, cultured melanocytes from the uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial methylation. <it>EFS </it>methylation always affects both alleles in normal and tumor samples.</p> <p>Conclusions</p> <p>Biallelic <it>EFS </it>methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and unmethylated precursor cells located in the uveal tract. The <it>EFS </it>methylation of a UM may depend on which type of precursor cell the tumor originated from.</p

Oncogenic CagA Promotes Gastric Cancer Risk via Activating ERK Signaling Pathways: A Nested Case-Control Study

Background: CagA cellular interaction via activation of the ERK signaling pathway may be a starting point in the development of gastric cancer. This study aimed to evaluate whether genes involved in ERK downstream signaling pathways activated by CagA are susceptible genetic markers for gastric cancer. Methods: In the discovery phase, a total of 580 SNPs within +/-5 kbp of 30 candidate genes were genotyped to examine an association with gastric cancer risk in the Korean Multi-center Cancer Cohort (100 incident gastric cancer case-control sets). The most significant SNPs (raw or permutated p value??0.02) identified in the discovery analysis were re-evaluated in the extension phase using unconditional logistic regression model (400 gastric cancer case-control sets). Combined analyses including pooled-and meta-analysis were conducted to summarize all the results. Results: 24 SNPs in eight genes (ERK, Dock180, C3G, Rap1, Src, CrkL, Mek and Crk) were significantly associated with gastric cancer risk in the individual SNP analyses in the discovery phase (p??0.05). In the extension analyses, ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 showed marginally significant gene-dose effects for gastric cancer. Consistently, final combined analysis presented the SNPs as significantly associated with gastric cancer risk (OR = 1.56, [95% CI: 1.19-2.06], OR = 0.61, [95% CI: 0.43-0.87], OR = 0.59, [95% CI: 0.54-0.76], respectively). Conclusions: Our findings suggest that ERK rs5999749, Dock180 rs4635002 and C3G rs7853122 are genetic determinants in gastric carcinogenesis