Cardiovascular Applications of Hyperpolarized MRI

Many applications of MRI are limited by an inherently low sensitivity. Previous attempts to overcome this insensitivity have focused on the use of MRI systems with stronger magnetic fields. However, the gains that can be achieved in this way are relatively small and increasing the magnetic field invariably leads to greater technical challenges. More recently, the development of a range of techniques, which can be gathered under the umbrella term of “hyperpolarization,” has offered potential solutions to the low sensitivity. Hyperpolarization techniques have been demonstrated to temporarily increase the signal available in an MRI experiment by as much as 100,000-fold. This article outlines the main hyperpolarization techniques that have been proposed and explains how they can increase MRI signals. With particular emphasis on the emerging technique of dynamic nuclear polarization, the existing preclinical cardiovascular applications are reviewed and the potential for clinical translation is discussed

SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance

Skin Cancer:Epidemiology, Disease Burden, Pathophysiology, Diagnosis, and Therapeutic Approaches

Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy in the Caucasian population. Firstly, we review the evidence for the observed increase in the incidence of skin cancer over recent decades, and investigate whether this is a true increase or an artefact of greater screening and over-diagnosis. Prevention strategies are also discussed. Secondly, we discuss the complexities and challenges encountered when diagnosing and developing treatment strategies for skin cancer. Key case studies are presented that highlight the practic challenges of choosing the most appropriate treatment for patients with skin cancer. Thirdly, we consider the potential risks and benefits of increased sun exposure. However, this is discussed in terms of the possibility that the avoidance of sun exposure in order to reduce the risk of skin cancer may be less important than the reduction in all-cause mortality as a result of the potential benefits of increased exposure to the sun. Finally, we consider common questions on human papillomavirus infection

Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study

BACKGROUND: Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. METHODOLOGY/PRINCIPAL FINDINGS: We characterized the genes generally involved in human advanced atherosclerotic (AHA type V-VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value <0.05), 235 genes were up-regulated and 68 genes down-regulated in the carotid plaques, 242 genes up-regulated and 116 down-regulated in the femoral plaques and 256 genes up-regulated and 49 genes down-regulated in the aortic plaques. Nine genes were found to be specifically induced predominantly in aortic plaques, e.g., lactoferrin, and three genes in femoral plaques, e.g., chondroadherin, whereas no gene was found to be specific for carotid plaques. In pathway analysis, a total of 28 pathways or gene sets were found to be significantly dysregulated in atherosclerotic plaques (false discovery rate [FDR] <0.25). CONCLUSIONS: This study describes comprehensively the gene expression changes that generally prevail in human atherosclerotic plaques. In addition, site specific genes induced only in femoral or aortic plaques were found, reflecting that atherosclerotic process has unique features in different vascular beds

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Quantum dots as new-generation fluorochromes for FISH: an appraisal

In the field of nanotechnology, quantum dots (QDs) are a novel class of inorganic fluorochromes composed of nanometre-scale crystals made of a semiconductor material. Given the remarkable optical properties that they possess, they have been proposed as an ideal material for use in fluorescent in-situ hybridization (FISH). That is, they are resistant to photobleaching and they excite at a wide range of wavelengths but emit light in a very narrow band that can be controlled by particle size and thus have the potential for multiplexing experiments. The principal aim of this study was to compare the potential of QDs against traditional organic fluorochromes in both indirect (i.e. QD-conjugated streptavidin) and direct (i.e. synthesis of QD-labelled FISH probes) detection methods. In general, the indirect experiments met with a degree of success, with FISH applications demonstrated for chromosome painting, BAC mapping and use of oligonucleotide probes on human and avian chromosomes/nuclei. Many of the reported properties of QDs (e.g. brightness, 'blinking' and resistance to photobleaching) were observed. On the other hand, signals were more frequently observed where the chromatin was less condensed (e.g. around the periphery of the chromosome or in the interphase nucleus) and significant bleed-through to other filters was apparent (despite the reported narrow emission spectra). Most importantly, experimental success was intermittent (sometimes even in identical, parallel experiments) making attempts to improve reliability difficult. Experimentation with direct labelling showed evidence of the generation of QD-DNA constructs but no successful FISH experiments. We conclude that QDs are not, in their current form, suitable materials for FISH because of the lack of reproducibility of the experiments; we speculate why this might be the case and look forward to the possibility of nanotechnology forming the basis of future molecular cytogenetic applications