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As far as the eye can see : a history of seeing
From the mastery of fire a million years ago, humans repeatedly invented new ways to see their surroundings, each other and themselves. Artificial light, early art, mirrors, writing, lenses, printing, photography, film, television, smartphones. These tools didn't just add to our visual repertoire, they shaped Western culture and made us who we are. This volume traces the history of seeing using eleven inventions, from the first evolutionary stirrings of sight to the present. It reveals that with each new invention that changed how or what we see, we changed ourselves, and the world around us.
Book
Clinical features and pathophysiology of complex regional pain syndrome
A complex regional pain syndrome (CRPS)—multiple system dysfunction, severe and often chronic pain, and disability—can be triggered by a minor injury, a fact that has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently improved our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Variation in susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS.
Journal Article
Microbiologically influenced corrosion-more than just microorganisms
Microbiologically influenced corrosion (MIC) is a phenomenon of increasing concern that affects various materials and sectors of society. MIC describes the effects, often negative, that a material can experience due to the presence of microorganisms. Unfortunately, although several research groups and industrial actors worldwide have already addressed MIC, discussions are fragmented, while information sharing and willingness to reach out to other disciplines are limited. A truly interdisciplinary approach, which would be logical for this material/biology/chemistry-related challenge, is rarely taken. In this review, we highlight critical non-biological aspects of MIC that can sometimes be overlooked by microbiologists working on MIC but are highly relevant for an overall understanding of this phenomenon. Here, we identify gaps, methods, and approaches to help solve MIC-related challenges, with an emphasis on the MIC of metals. We also discuss the application of existing tools and approaches for managing MIC and propose ideas to promote an improved understanding of MIC. Furthermore, we highlight areas where the insights and expertise of microbiologists are needed to help progress this field.
Journal Article
Endovascular Stroke Therapy
Ischemic stroke is a leading cause of death and disability throughout the world and is both preventable and treatable. This review focuses on the treatment of the most severe form of ischemic stroke, namely large-vessel ischemic stroke, using endovascular techniques. Such therapies were proven effective in 2015. These therapies are among the most beneficial surgical therapies ever subjected to randomized clinical trials. Recent research has explored treating patients up to 24 h following the onset of stroke using advanced imaging techniques to select patients with brain tissue still at risk. These new findings suggest there exists a tissue clock rather than a time clock when selecting patients for therapy. Stroke systems throughout the world are now embracing endovascular stroke therapy. Improving regional stroke systems of care and expanding eligibility for patients are a major focus of current research.
Journal Article
Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial
Present mechanical devices are unable to achieve recanalisation in up to 20–40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever.
In this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18–85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8–29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69–85 years) and NIHSS scores (≤18 vs 19–29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01270867.
Between Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92–9·69; psuperiority<0·0001). Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0·1826).
Patients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever.
Stryker Neurovascular.
Journal Article
Septin 9 methylated DNA is a sensitive and specific blood test for colorectal cancer
Background
About half of Americans 50 to 75 years old do not follow recommended colorectal cancer (CRC) screening guidelines, leaving 40 million individuals unscreened. A simple blood test would increase screening compliance, promoting early detection and better patient outcomes. The objective of this study is to demonstrate the performance of an improved sensitivity blood-based Septin 9 (
SEPT9
) methylated DNA test for colorectal cancer. Study variables include clinical stage, tumor location and histologic grade.
Methods
Plasma samples were collected from 50 untreated CRC patients at 3 institutions; 94 control samples were collected at 4 US institutions; samples were collected from 300 colonoscopy patients at 1 US clinic prior to endoscopy.
SEPT9
methylated DNA concentration was tested in analytical specimens, plasma of known CRC cases, healthy control subjects, and plasma collected from colonoscopy patients.
Results
The improved
SEPT9
methylated DNA test was more sensitive than previously described methods; the test had an overall sensitivity for CRC of 90% (95% CI, 77.4% to 96.3%) and specificity of 88% (95% CI, 79.6% to 93.7%), detecting CRC in patients of all stages. For early stage cancer (I and II) the test was 87% (95% CI, 71.1% to 95.1%) sensitive. The test identified CRC from all regions, including proximal colon (for example, the cecum) and had a 12% false-positive rate. In a small prospective study, the
SEPT9
test detected 12% of adenomas with a false-positive rate of 3%.
Conclusions
A sensitive blood-based CRC screening test using the
SEPT9
biomarker specifically detects a majority of CRCs of all stages and colorectal locations. The test could be offered to individuals of average risk for CRC who are unwilling or unable to undergo colonscopy.
Journal Article
Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis
Introduction
Angiogenesis is an early event in the pathogenesis of both psoriatic arthritis (PsA) and rheumatoid arthritis (RA); however, there are striking differences in blood vessel morphology and activation between the two arthropathies. The aim of this study was to assess if the PsA and RA joint microenvironments differentially regulate endothelial cell function.
Methods
PsA and RA primary synovial fibroblasts (SFC) were isolated from synovial biopsies, grown to confluence, and supernatants harvested and termed ‘conditioned media’ (CM). Human umbilical vein endothelial cells (HUVEC) were cultured with PsA SFC or RA SFC-CM (20%). HUVEC tube formation, migration, and PBMC adhesion were assessed by matrigel tube formation, wound repair, and PBMC adhesion assays. HUVEC cell surface expression of ICAM, VCAM, and E-Selectin was assessed by flow cytometry. Transcriptome analysis of genes promoting angiogenesis was performed by real-time PCR. Finally, a MSD multiplex angiogenic assay was performed on PsA SFC and RA SFC supernatants.
Results
Macroscopic synovitis and vascularity were similar in PsA and RA patients; however, significant differences in vascular morphological pattern were recorded with tortuous, elongated vessels observed in PsA compared to straight regular branching vessels observed in RA. Transcriptome analysis showed strong upregulation of the pro-angiogenic signature in HUVEC primed with PsA SFC-CM compared to RA SFC-CM and basal control. In parallel, paired PsA SFC-CM significantly induced HUVEC tube formation compared to that of RA SFC-CM. Furthermore, PsA SFC-CM induced HUVEC migration was paralleled by a significant induction in VEGFA, PFKFB3, ICAM-1, and MMP3 mRNA expression. A significant increase in PBMC adhesion and cell surface expression of VCAM-1, ICAM-1, and E-Selectin expression was also demonstrated in PsA SFC-CM-primed HUVEC compared to RA SFC-CM. Finally, VEGF, TSLP, Flt-1, and Tie-2 expression was elevated in PsA SFC-CM compared to RA SFC-CM, with no significant difference in other pro-angiogenic mediators including MIP-3, bFGF, PIGF, and MCP-1.
Conclusion
PsA SFC and RA SFC secreted factors differentially regulate endothelial cell function, with soluble mediators in the PsA joint microenvironment inducing a more pro-angiogenic phenotype compared to the RA.
Journal Article
Evaluating Bacillus Calmette–Guérin Polysaccharide Nucleic Acid as an Adjuvant for Influenza Vaccines in Mice
Background To enhance influenza vaccine efficacy, it is essential to investigate new adjuvants that are both safe and effective. In a recent study utilizing a mouse model, Bacillus Calmette–Guérin polysaccharide nucleic acid (BCG‐PSN) emerged as a promising candidate vaccine adjuvant. Methods This study evaluated the immunomodulatory effects of BCG‐PSN on influenza vaccines hemagglutinin antigen and aluminum adjuvant as controls. Mice were immunized with H1N1 antigen and adjuvants, and serum antibody levels were measured using hemagglutination inhibition, enzyme‐linked immunosorbent assay, and microneutralization assays. Flow cytometry and enzyme‐linked immunospot assays assessed T cell phenotypes and cytokine expression. The protective effects were tested through challenge experiments, and the adjuvants were further evaluated in a quadrivalent seasonal influenza vaccine. Results BCG‐PSN adjuvant exhibited favorable safety profiles and demonstrated an ability to elevate total antibody titers, particularly enhancing neutralizing antibody production when co‐administered with the H1N1 antigen. BCG‐PSN increased cytokine levels and the proportion of CD8+ T lymphocytes, indicating its capacity to enhance cellular immunity. Upon viral challenge in mice, BCG‐PSN mitigated the production of inflammatory factors and reduced lung pathology, effectively protecting the mice. Furthermore, BCG‐PSN displayed heightened immunogenicity against a mixture of four antigens. Conclusions BCG‐PSN is a reliable and efficient adjuvant for influenza vaccines, holding promise for enhancing vaccine efficacy and increasing immune responses.
Journal Article