Xenograft Tumors Vascularized with Murine Blood Vessels May Overestimate the Effect of Anti-Tumor Drugs: A Pilot Study

Recent evidence demonstrated that endothelial cells initiate signaling events that enhance tumor cell survival, proliferation, invasion, and tumor recurrence. Under this new paradigm for cellular crosstalk within the tumor microenvironment, the origin of endothelial cells and tumor cells may have a direct impact on the pathobiology of cancer. The purpose of this pilot study was to evaluate the effect of endothelial cell species (i.e. murine or human) on xenograft tumor growth and response to therapy. Tumor xenografts vascularized either with human or with murine microvascular endothelial cells were engineered, side-by-side, subcutaneously in the dorsum of immunodefficient mice. When tumors reached 200 mm3, mice were treated for 30 days with either 4 mg/kg cisplatin (i.p.) every 5 days or with 40 mg/kg sunitinib (p.o.) daily. Xenograft human tumors vascularized with human endothelial cells grow faster than xenograft tumors vascularized with mouse endothelial cells (P\u3c0.05). Notably, human tumors vascularized with human endothelial cells exhibited nuclear translocation of p65 (indicative of high NF-kB activity), and were more resistant to treatment with cisplatin or sunitinib than the contralateral tumors vascularized with murine endothelial cells (P\u3c0.05). Collectively, these studies suggest that the species of endothelial cells has a direct impact on xenograft tumor growth and response to treatment with the chemotherapeutic drug cisplatin or with the anti-angiogenic drug sunitinib

CME Evolution in the Structured Heliosphere and Effects at Earth and Mars During Solar Minimum

The activity of the Sun alternates between a solar minimum and a solar maximum, the former corresponding to a period of "quieter" status of the heliosphere. During solar minimum, it is in principle more straightforward to follow eruptive events and solar wind structures from their birth at the Sun throughout their interplanetary journey. In this paper, we report analysis of the origin, evolution, and heliospheric impact of a series of solar transient events that took place during the second half of August 2018, i.e. in the midst of the late declining phase of Solar Cycle 24. In particular, we focus on two successive coronal mass ejections (CMEs) and a following high-speed stream (HSS) on their way towards Earth and Mars. We find that the first CME impacted both planets, whilst the second caused a strong magnetic storm at Earth and went on to miss Mars, which nevertheless experienced space weather effects from the stream interacting region (SIR) preceding the HSS. Analysis of remote-sensing and in-situ data supported by heliospheric modelling suggests that CME--HSS interaction resulted in the second CME rotating and deflecting in interplanetary space, highlighting that accurately reproducing the ambient solar wind is crucial even during "simpler" solar minimum periods. Lastly, we discuss the upstream solar wind conditions and transient structures responsible for driving space weather effects at Earth and Mars.Comment: 27 pages, 7 figures, 1 table, accepted for publication in Space Weathe

Convergence Without Hard Criteria: Does EU Soft Law Affect Domestic Unemployment Protection Schemes?

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Banking on teeth – Stem cells and the dental office

Science and commerce advance together and the stem cell field is no exception. With the promise of cures for conditions as diverse as cancer, autism, neural degeneration, organ replacement and addiction, long-term preservation of dental stem cells is a growth market. The discovery nearly twenty years ago, of viable, multipotent, stem cells in dental pulp from both baby and adult teeth initiated, and drives, this market.The dental stem cell preservation services, “tooth banks”, focus on the collection of a child\u27s baby teeth, as they are shed naturally, and storage of the stem cells from within the pulp for therapeutic use in later years should the child require them. This review focuses on the procedures related to these stem cell storage services and may serve as an introduction for many to the practice of “tooth banking”

A flash of inspiration: Enhancing dental student drug recognition

Students preparing for exams often retain the complexities of a subject but instant recognition and recall is something that, for most, takes time and consistent, repeated study to establish. This can happen through well-managed spaced learning (iterative study) prior to examination; given the preponderance of massed study (cramming for a subject),1 however, many students require long-term exposure in the clinic to patients’ medical histories to achieve instant recall. Understanding the applied pharmacology of common drugs is a current American Dental Association accreditation standard. Ideally, dental students should demonstrate a consistent level of basic drug recognition and the ability to retrieve that information prior to encountering patients

Concept mapping for enhanced comprehension in pharmacology

Concept maps aid comprehension of complex topics. This concept map–based teaching resource comprises a set of documents for instruction and implementation of the learning tool towards increasing student understanding and implementation of course material within a dental pharmacology course. The documents include a teacher\u27s instructional guide, a short presentation and associated document for introduction of the material to students, an instructional overview document, a step-by-step guide for students and instructors, and a grading rubric with additional resource information. The documents, while broadly generic, may be further altered to tailor for any pharmacology course. With implementation of this project, there was high compliance with the suggested map format, although some students submitted highly creative maps with images and hypertext links. In the first year of implementation, the large majority of students created maps above base requirements. Fewer than five percent of the students submitted concept maps that did not follow the format suggested by the instructional document. One student presented the required information in a creative format that did not resemble a concept map but instead comprised boxed lists lined in a linear manner but with no other interconcept relationship links. With implementation of this project, there was high compliance with the suggested map format, although some students submitted highly creative maps with images and hypertext links. In the first year of implementation, the large majority of students created maps above base requirements. Fewer than five percent of the students submitted concept maps that did not follow the format suggested by the instructional document. One student presented the required information in a creative format that did not resemble a concept map but instead comprised boxed lists lined in a linear manner but with no other interconcept relationship links. We are currently applying to our Institutional Review Board to perform a study that would survey the students participating in this assignment. The outcomes data we hope to obtain will relate to the ease of performance, the usefulness of the assignment for study of the chosen assignment topic, and the subsequent use of the concept map tool for both pharmacology and nonpharmacology coursework

Blueberry Fruit Nanovesicles

Nanovesicles have been identified in preparations of edible plants and certain fruit although the exact cellular origin of these vesicles remains unclear. Cross-kingdom biological effects have been demonstrated for nanovesicles isolated from certain fruit - notably lemons and grapes - that are absent from normal, dietary intake of the whole fruit, this suggests a therapeutic potential for isolated fruit vesicles. Anthocyanins and other polyphenolic anti-oxidant compounds are known to accumulate in plant vesicles as are specific proteins, lipids and microRNAs species. Here we investigate the presence of nanovesicles in antioxidant-rich blueberry fruit

Further EU integration will help to stabilise the disruptive forces of nationalism now present in Macedonia

Negotiations towards Macedonia’s accession to the EU have been prolonged and often postponed in recent years, mostly due to an on-going dispute with Greece over the country’s name. Goran Janev argues that these delays, combined with an ‘ethnocratic’ government, have allowed nationalist sentiments to develop and grow in Macedonia. If these nationalist trends are to be reversed it is vital that progress is made towards further European integration

Water Fluoridation in Relationship to the Prevalence of Neurodevelopmental Disorders

Over many years, the prevalence of dental caries has generally declined where the prevalence of neurodevelopmental disorders has increased. Is there a possible connection to water fluoridation? Is this increase in prevalence due to our ability to diagnose these conditions, or a different environmental factor? This study covers fluoride toxicity, caries prevention, and fluoride’s possible correlation to cognitive impairments utilizing a literature review. Fluoride has undeniably been shown to reduce dental caries but is now considered a developmental neurotoxicant according to the United States Department of Health and Human Services. This study found multiple conflicting results for and against fluoride contributing to the prevalence of neurodevelopmental disorders such as Autism and attention-deficit/hyperactivity disorder. There is currently insufficient evidence to conclude whether there is a link between water fluoridation and neurodevelopmental disorders. Fluoride’s classification as a developmental neurotoxicant requires us to further research its systemic effects on the human body to thoroughly identify any connections between the rise in developmental disabilities and water fluoridation. Since we already have many communities with an established fluoridated water supply, and many without added fluoride, this subject may be studied using retrospective data comparing statistics of the prevalence of multiple conditions from fluoridated versus non-fluoridated communities. There has been controversy regarding the use of fluoride basically since its implementation to prevent dental caries. More recently in 2014, the United States Department of Health and Human Services (HHS) published an article that placed fluoride in the same category as lead, as a developmental neurotoxicant. (Grandjean, 2014) It is absolutely crucial that we study this more closely. Thorough research on this topic is vital for the health and safety of our communities which is of the utmost importance. We need to be well informed to make appropriate decisions regarding the use of fluoride, thus confidently easing anxiety regarding the use of fluoride. More data must be collected on this subject to fully understand the implications of fluoridating our public water supplies as this impacts everyone