281 research outputs found

    A placeboâ controlled pilot study of a wearable morning bright light treatment for probable PTSD

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    BackgroundEvidenceâ based treatments for postâ traumatic stress disorder (PTSD) have poor uptake and remission rates, suggesting that alternative treatments are needed. Morning bright light may be an effective treatment for PTSD given its established effects on mood and sleep, however, there are no published trials.MethodsWe conducted a placeboâ controlled pilot trial of a wearable light device, the Reâ timer®, for individuals with probable PTSD. Individuals were randomly assigned to the active Reâ timer® (n = 9) or a placebo Reâ timer® dimmed with neutral density filters (n = 6). Participants selfâ administered the treatment at home 1 hr each morning over 4 weeks. PTSD and depression symptoms were assessed at preâ and postâ treatment.ResultsThe Reâ timer® was well tolerated and the perceived benefit was high, though treatment adherence was only moderate. Those in the active group were more likely to achieve a minimal clinically important change in PTSD and depression symptoms and had larger symptom reductions than those in the placebo groupConclusionsA wearable morning light treatment was acceptable and feasible for patients with probable PTSD. This study provides initial proofâ ofâ concept that light treatment can improve PTSD. A larger trial is warranted to establish treatment efficacy. NCT#: 03513848Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149743/1/da22897_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149743/2/da22897.pd

    Fibroblasts derived from oesophageal adenocarcinoma differ in DNA methylation profile from normal oesophageal fibroblasts

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    Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Oesophageal adenocarcinoma (OAC) is increasing in incidence and has a poor prognosis. Tumour derived fibroblasts (TDFs) differ functionally from normal fibroblasts (NDFs), and play a pivotal role in cancer. Many of the differences persist through subculture. We measured the DNA methylation profiles of 10 TDFs from OAC with 12 NDF from normal oesophageal mucosa using Infinium HumanMethylation450 Beadchips and found they differed in multidimensional scaling analysis. We identified 4,856 differentially methylated CpGs (DMCs, adjusted p  0.15), of which 3,243 (66.8%) were hypomethylated in TDFs compared to NDFs. Hypermethylated DMCs were enriched at transcription start sites (TSSs) and in CpG islands, and depleted in transcriptional enhancers. Gene ontology analysis of genes with DMCs at TSSs revealed an enrichment of genes involved in development, morphogenesis, migration, adhesion, regulation of processes and response to stimuli. Alpha-smooth muscle actin (α-SMA) is a marker of activated fibroblasts and a poor prognostic indicator in OAC. Hypomethylated DMCs were observed at the TSS of transcript variant 2 of α-SMA, which correlated with an increase in α-SMA protein expression. These data suggest that DNA methylation may contribute to the maintenance of the TDF phenotype

    Academic Integrity and Artificial Intelligence in Higher Education Contexts: A Rapid Scoping Review Protocol

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    This paper presents a protocol with methodological considerations for a rapid scoping review on academic integrity and artificial intelligence in higher education. This protocol follows Joanna Brigg Institute’s (JBI) updated manual for scoping reviews and the Preferred Reporting Items for Systematic reviews Meta-Analysis (PRISMA) reporting standards. This rapid scoping review aims to identify the breadth of the literature reflecting the intersection of academic integrity and artificial intelligence in higher education institutions. The included studies in the review will be analyzed for insight concerning this emerging area, particularly its ethical implications. Our findings will be relevant for academic staff, administration, and leadership in higher education and academic integrity researchers

    Engineered Knottin Peptide Enables Noninvasive Optical Imaging of Intracranial Medulloblastoma

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    Central nervous system tumors carry grave clinical prognoses due to limited effectiveness of surgical resection, radiation, and chemotherapy. Thus, improved strategies for brain tumor visualization and targeted treatment are critically needed. We demonstrate that mouse cerebellar medulloblastoma (MB) can be targeted and illuminated with a fluorescent, engineered cystine knot (knottin) peptide that binds with high affinity to ι β , ι β , and ι β integrin receptors. This integrin-binding knottin peptide, denoted EETI 2.5F, was evaluated as a molecular imaging probe in both orthotopic and genetic models of MB. Following tail vein injection, fluorescence arising from dye-conjugated EETI 2.5F was localized to the tumor compared with the normal surrounding brain tissue, as measured by optical imaging. The imaging signal intensity correlated with tumor volume. Due to its unique ability to bind to ι β integrin, EETI 2.5F showed superior in vivo and ex vivo brain tumor imaging contrast compared with other engineered integrin-binding knottin peptides and with c(RGDfK), a well-studied integrin-binding peptidomimetic. Next, EETI 2.5F was fused to an antibody fragment crystallizable (Fc) domain (EETI 2.5F-Fc) to determine if a larger integrin-binding protein could also target intracranial brain tumors. EETI 2.5F-Fc, conjugated to a fluorescent dye, illuminated MB following i.v. injection and was able to distribute throughout the tumor parenchyma. In contrast, brain tumor imaging signals were not detected in mice injected with EETI 2.5F proteins containing a scrambled integrin-binding sequence, demonstrating the importance of target specificity. These results highlight the potential of using EETI 2.5F and EETI 2.5-Fc as targeted molecular probes for brain tumor imaging

    A review of clinical practice guidelines found that they were often based on evidence of uncertain relevance to primary care patients

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    Objectives: Primary care patients typically have less severe illness than those in hospital and may be overtreated if clinical guideline evidence is inappropriately generalized. We aimed to assess whether guideline recommendations for primary care were based on relevant research. Study Design and Setting: Literature review of all publications cited in support of National Institute for Health and Care Excellence (NICE) recommendations for primary care. The relevance to primary care of all 45 NICE clinical guidelines published in 2010 and 2011, and their recommendations, was assessed by an expert panel. Results: Twenty-two of 45 NICE clinical guidelines published in 2010 and 2011 were relevant to primary care. These 22 guidelines contained 1,185 recommendations, of which 495 were relevant to primary care, and cited evidence from 1,573 research publications. Of these cited publications, 590 (38%, range by guideline 6–74%) were based on patients typical of primary care. Conclusion: Nearly two-third (62%) of publications cited to support primary care recommendations were of uncertain relevance to patients in primary care. Guideline development groups should more clearly identify which recommendations are intended for primary care and uncertainties about the relevance of the supporting evidence to primary care patients, to avoid potential overtreatment

    A randomised controlled clinical trial comparing the effectiveness of bandaging compared to the JuxtaCures™ device in the management of people with venous ulceration: Feasibility study

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    Introduction: The mainstay of treatment for venous ulceration remains compression therapy. Velcro Wrap devices are being increasingly used in these patients despite limited evidence. This feasibility study aimed to compare standard bandaging to the JuxtaCures™ Velcro wrap device. Methods: A single centre, unblinded RCT compared participants with venous ulceration randomised to either the JuxtaCures™ device or short stretch bandaging. Participants were followed up for 26 weeks. Results: 160 participants were screened with 40 randomised. 3 participants in bandaging and 1 in JuxtaCures™ didn’t complete the study. 60% in JuxtaCures™ healed v 55% in bandaging despite larger ulcers in the JuxtaCures™ arm (9.33 cm2 v 6.97 cm2). There was no significant difference in time to healing (12.17 v 13.64 weeks). JuxtaCures™ showed improved ulcer reduction for those that didn’t heal (14.91–5.00 cm2 v 14.20–8.62 cm2; P = 0.06). JuxtaCures™ had more consistent sub-bandage pressure dropping from 39–36 mmHg versus 41–25 mmHg in bandaging between application and removal (P < 0.001). Quality of life (EQ5D) was improved in JuxtaCures at 3 months (mean difference 0.14, p = 0.04), but not at 1 and 6 months, or in disease specific quality of life. Cost was lower in JuxtaCures™ £842.47 v £1064.68. Duration of appointment was significantly shorter in JuxtaCures™ (41 minutes v 53 minutes; P = 0.003). Conclusion: This study has shown the feasibility and necessity of running a multicentre trial to evaluate the use of Velcro wrap devices for venous ulceration. It highlights the potential benefits of more consistent pressure, increased self-care, and potential with regards to ulcer healing, cost, nursing resource and quality of life
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