Project description:The Journal Impact Factor dominates research assessment in many disciplines and in many countries. While research assessment will always have to rely to some extent on quantitative, standardized metrics, the focus on this single measure has gone so far as to hamper and distort scientific research. The Declaration on Research Assessment (DORA), signed by influential journals, funders, academic institutions and individuals across the natural sciences, aims to raise awareness and to redress the use of non-objective research assessment practices.
Project description:Onychomycosis is a common fungal infection, afflicting some 10% of the adult population in industrialized countries. Aside from cosmetic concerns, onychomycosis can be the cause of toe and foot pain, as well as the underlying etiology for serious secondary bacterial infections and traumatic ulcerations. In select populations, such as diabetics, the latter conditions may even result in loss of all or part of the lower extremity. Thus, a simple, cost-effective and safe treatment for onychomycosis is highly desirable. Although both topical and oral systemic antifungal agents are available for this purpose, they are not always effective, carry some medical risks, are associated with potentially significant drug-drug interactions, and may be unacceptable to patient and healthcare provider alike. Physical modalities, such as laser therapy, therefore appear appealing. The question is whether laser treatment is sufficiently efficacious and safe to warrant the current high cost per treatment. The readily available literature on this controversy will be reviewed herein.
Project description:Thymidylate synthase is an attractive target for antibiotic and anticancer drugs due to its essential role in the de novo biosynthesis of the DNA nucleotide thymine. The enzymatic reaction is initiated by a nucleophilic activation of the substrate via formation of a covalent bond to an active site cysteine. The traditionally accepted mechanism is then followed by a series of covalently bound intermediates, where that bond is only cleaved upon product release. Recent computational and experimental studies suggest that the covalent bond between the protein and substrate is actually quite labile. Importantly, these findings predict the existence of a noncovalently bound bisubstrate intermediate, not previously anticipated, which could be the target of a novel class of drugs inhibiting DNA biosynthesis. Here we report the synthesis of the proposed intermediate and findings supporting its chemical and kinetic competence. These findings substantiate the predicted nontraditional mechanism and the potential of this intermediate as a new drug lead.
Project description:Intestinal fibrosis is a common feature of Crohn's disease and may appear as a stricture, stenosis, or intestinal obstruction. Fibrostenosing Crohn's disease leads to a significantly impaired quality of life in affected patients and constitutes a challenging treatment situation. In the absence of specific medical antifibrotic treatment options, endoscopic or surgical therapy approaches with their potential harmful side effects are frequently used. However, our understanding of mechanisms of fibrogenesis in general and specifically intestinal fibrosis has emerged. Progression of fibrosis in the liver, lung, or skin can be halted or even reversed, and possible treatment targets have been identified. In face of this observation and given the fact that fibrotic alterations in various organs of the human body share distinct core characteristics, this article aims to address whether reversibility of intestinal fibrosis may be conceivable and to highlight promising research avenues and therapies.
Project description:BACKGROUND:Interest in human factors has increased across healthcare communities and institutions as the value of human centred design in healthcare becomes increasingly clear. However, as human factors is becoming more prominent, there is growing evidence of confusion about human factors science, both anecdotally and in scientific literature. Some of the misconceptions about human factors may inadvertently create missed opportunities for healthcare improvement. METHODS:The objective of this article is to describe the scientific discipline of human factors and provide common ground for partnerships between healthcare and human factors communities. RESULTS:The primary goal of human factors science is to promote efficiency, safety and effectiveness by improving the design of technologies, processes and work systems. As described in this article, human factors also provides insight on when training is likely (or unlikely) to be effective for improving patient safety. Finally, we outline human factors specialty areas that may be particularly relevant for improving healthcare delivery and provide examples to demonstrate their value. CONCLUSIONS:The human factors concepts presented in this article may foster interdisciplinary collaborations to yield new, sustainable solutions for healthcare quality and patient safety.
Project description:Traditionally small-molecule crystallographers have not usually observed or recognized significant radiation damage to their samples during diffraction experiments. However, the increased flux densities provided by third-generation synchrotrons have resulted in increasing numbers of observations of this phenomenon. The diversity of types of small-molecule systems means it is not yet possible to propose a general mechanism for their radiation-induced sample decay, however characterization of the effects will permit attempts to understand and mitigate it. Here, systematic experiments are reported on the effects that sample temperature and beam attenuation have on radiation damage progression, allowing qualitative and quantitative assessment of their impact on crystals of a small-molecule test sample. To allow inter-comparison of different measurements, radiation-damage metrics (diffraction-intensity decline, resolution fall-off, scaling B-factor increase) are plotted against the absorbed dose. For ease-of-dose calculations, the software developed for protein crystallography, RADDOSE-3D, has been modified for use in small-molecule crystallography. It is intended that these initial experiments will assist in establishing protocols for small-molecule crystallographers to optimize the diffraction signal from their samples prior to the onset of the deleterious effects of radiation damage.
Project description:In an era where some find fake news around every corner, the use of sensationalism has inevitably found its way into the scientific literature. This is especially the case for host manipulation by parasites, a phenomenon in which a parasite causes remarkable change in the appearance or behaviour of its host. This concept, which has deservedly garnered popular interest throughout the world in recent years, is nearly 50 years old. In the past two decades, the use of scientific metaphors, including anthropomorphisms and science fiction, to describe host manipulation has become more and more prevalent. It is possible that the repeated use of such catchy, yet misleading words in both the popular media and the scientific literature could unintentionally hamper our understanding of the complexity and extent of host manipulation, ultimately shaping its narrative in part or in full. In this commentary, the impacts of exaggerating host manipulation are brought to light by examining trends in the use of embellishing words. By looking at key examples of exaggerated claims from widely reported host-parasite systems found in the recent scientific literature, it would appear that some of the fiction surrounding host manipulation has since become fact.
Project description:Background/aimsIn today's information era, patients often seek information regarding health using the internet. We assessed reliability and validity of internet information regarding 'prostate cancer'.MethodsSearch term 'prostate cancer' used on Google website (June 2017). Critical analysis was performed on first 100 hits using JAMA benchmarks, DISCERN score, Health on the Net.Results33 500 000 hits returned. Top 100 hits were critically analyzed. Ten links [duplicate links (n = 7), book reviews (n = 1), dead sites (n = 2)] were excluded, therefore 90 were analyzed. Subcategories assessed included: commercial (53.33%), university/medical center (24.44%), government (13.33%); non-governmental/ non-profit organizations (8.89%). Sub-type of information content assessed included: factual (74.44%), clinical trials (18.89%); stories (5.56%); question and answer (1.11%). Website rated as HONcode seal positive (14,44%) or seal negative (85,56%). Website content based on JAMA benchmarks: 0 benchmarks (4.44%), 1 benchmark (16.67%), 2 benchmarks (34.44%), 3 benchmarks (27.78%), 4 benchmarks (16.67%). DISCERN score rated: 'low' score (16-32) = 12 websites (13.33%), 'moderate' score (33-64 points) = 68 websites (75.56%), 'high' score (≥ 65 points) = 10 websites (11.11%).ConclusionCritical assessment of 'Prostate Cancer' information on the internet, showed that overall quality was observed to be accurate, however majority of individual websites are unreliable as a source of information by itself for patients. Doctors and patients need to be aware of this 'quality vs quantity' discrepancy when sourcing PCa information on the internet.
Project description:Prolonged pharmacological acid suppression is associated with various histological changes in the gastric mucosa, particularly in Helicobacter pylori infected patients. In a number of subjects these changes include a shift in the gastric inflammation from the antrum to the corpus. This finding has been interpreted as gastric atrophy, and the possibility that acid suppression accelerates the progress of lesions that may lead to gastric cancer has been considered. Two recent studies on the relation between treatment with proton pump inhibitors and atrophic gastritis have yielded apparently contradictory results. These studies are reviewed in detail here and some of the possible reasons for the discrepant conclusions are explored. In particular, the way the terms "gastric atrophy" and "atrophic gastritis" are used is examined critically.