Theranostic Fibers for Simultaneous Imaging and Drug Delivery

New methods for creating theranostic systems with simultaneous encapsulation of therapeutic, diagnostic, and targeting agents are much sought after. This work reports for the first time the use of coaxial electrospinning to prepare such systems in the form of core–shell fibers. Eudragit S100 was used to form the shell of the fibers, while the core comprised poly(ethylene oxide) loaded with the magnetic resonance contrast agent Gd(DTPA) (Gd(III) diethylenetriaminepentaacetate hydrate) and indomethacin as a model therapeutic agent. The fibers had linear cylindrical morphologies with clear core–shell structures, as demonstrated by electron microscopy. X-ray diffraction and differential scanning calorimetry proved that both indomethacin and Gd(DTPA) were present in the fibers in the amorphous physical form. This is thought to be a result of intermolecular interactions between the different components, the presence of which was suggested by infrared spectroscopy. In vitro dissolution tests indicated that the fibers could provide targeted release of the active ingredients through a combined mechanism of erosion and diffusion. The proton relaxivities for Gd(DTPA) released from the fibers into tris buffer increased (r1 = 4.79–9.75 s–1 mM–1; r2 = 7.98–14.22 s–1 mM–1) compared with fresh Gd(DTPA) (r1 = 4.13 s–1 mM–1 and r2 = 4.40 s–1 mM–1), which proved that electrospinning has not diminished the contrast properties of the complex. The new systems reported herein thus offer a new platform for delivering therapeutic and imaging agents simultaneously to the colon

When a leader job resource can be ambivalent or even destructive: Independence at work as a double-edged sword

<div><p>Independence at work is commonly considered a job resource which fosters motivation and employee well-being. Somewhat paradoxically, it is embedded in a relationship, and employees’ independence also hinges on their leaders’ willingness to grant it. Analyzing this resource as part of the leader-follower relationship can be useful in exploring its beneficial, ambivalent, or detrimental reciprocal effects. We present two Actor-Partner Interdependence Models (APIM) which analyze leaders’ and followers’ independence as antecedents, and work engagement and emotional exhaustion as outcomes. We test our models on 112 pairs of UK workers, finding a significant partner effect between leaders’ independence and followers’ exhaustion. Our findings confirm the utility of a dyadic perspective for investigating leadership and well-being at work, and suggest improvements for leadership training and measures fostering job well-being.</p></div

The relationship between maternal placental growth factor levels and intrapartum fetal compromise

Introduction Whilst some cases of intrapartum fetal compromise are the result of unpredictable catastrophic events, the majority arise from an unrecognised reduction in feto-placental reserve in otherwise healthy pregnancies. There is currently no reliable technique prior to labour that identifies the at-risk fetus. We aimed to investigate the relationship between maternal levels of serum placental growth factor (PlGF) and intrapartum fetal compromise in term pregnancies prior to labour. Secondary outcomes were caesarean delivery for intrapartum fetal compromise and adverse neonatal outcomes. Methods A blinded, prospective, cross sectional study set at Mater Mother's Hospital, Brisbane, Australia. Maternal PlGF concentration was assessed fortnightly from 36 weeks until delivery in 378 low-risk pregnant women. Antenatal and intrapartum care was managed according to local protocols and guidelines, and intrapartum and neonatal outcomes were recorded. Results Pregnancies that developed intrapartum fetal compromise had lower PlGF than those that did not. PlGF concentration was also lower amongst pregnancies that developed intrapartum fetal heart rate abnormalities, were delivered with abnormal cord gases or Apgar ≤7 at 5 min. Additionally, PlGF levels were lower in pregnancies with an adverse composite neonatal outcome. Discussion Lower maternal PlGF concentration is associated with intrapartum fetal compromise and poorer condition of the newborn. Maternal PlGF levels may be useful as a component of a risk stratification tool for intrapartum fetal compromise in apparently 'low risk' term pregnancies prior to labour

An inquiry-based learning approach to teaching information retrieval

The study of information retrieval (IR) has increased in interest and importance with the explosive growth of online information in recent years. Learning about IR within formal courses of study enables users of search engines to use them more knowledgeably and effectively, while providing the starting point for the explorations of new researchers into novel search technologies. Although IR can be taught in a traditional manner of formal classroom instruction with students being led through the details of the subject and expected to reproduce this in assessment, the nature of IR as a topic makes it an ideal subject for inquiry-based learning approaches to teaching. In an inquiry-based learning approach students are introduced to the principles of a subject and then encouraged to develop their understanding by solving structured or open problems. Working through solutions in subsequent class discussions enables students to appreciate the availability of alternative solutions as proposed by their classmates. Following this approach students not only learn the details of IR techniques, but significantly, naturally learn to apply them in solution of problems. In doing this they not only gain an appreciation of alternative solutions to a problem, but also how to assess their relative strengths and weaknesses. Developing confidence and skills in problem solving enables student assessment to be structured around solution of problems. Thus students can be assessed on the basis of their understanding and ability to apply techniques, rather simply their skill at reciting facts. This has the additional benefit of encouraging general problem solving skills which can be of benefit in other subjects. This approach to teaching IR was successfully implemented in an undergraduate module where students were assessed in a written examination exploring their knowledge and understanding of the principles of IR and their ability to apply them to solving problems, and a written assignment based on developing an individual research proposal

Medicated Janus fibers fabricated using a Teflon-coated side-by-side spinneret

A family of medicated Janus fibers that provides highly tunable biphasic drug release was fabricated using a side-by-side electrospinning process employing a Teflon-coated parallel spinneret. The coated spinneret facilitated the formation of a Janus Taylor cone and in turn high quality integrated Janus structures, which could not be reliably obtained without the Teflon coating. The fibers prepared had one side consisting of polyvinylpyrrolidone (PVP) K60 and ketoprofen, and the other of ethyl cellulose (EC) and ketoprofen. To modulate and tune drug release, PVP K10 was doped into the EC side in some cases. The fibers were linear and had flat morphologies with an indent in the center. They provide biphasic drug release, with the PVP K60 side dissolving very rapidly to deliver a loading dose of the active ingredient, and the EC side resulting in sustained release of the remaining ketoprofen. The addition of PVP K10 to the EC side was able to accelerate the second stage of release; variation in the dopant amount permitted the release rate and extent this phase to be precisely tuned. These results offer the potential to rationally design systems with highly controllable drug release profiles, which can complement natural biological rhythms and deliver maximum therapeutic effects

Medicated Janus fibers fabricated using a Teflon-coated side-by-side spinneret.

A family of medicated Janus fibers that provides highly tunable biphasic drug release was fabricated using a side-by-side electrospinning process employing a Teflon-coated parallel spinneret. The coated spinneret facilitated the formation of a Janus Taylor cone and in turn high quality integrated Janus structures, which could not be reliably obtained without the Teflon coating. The fibers prepared had one side consisting of polyvinylpyrrolidone (PVP) K60 and ketoprofen, and the other of ethyl cellulose (EC) and ketoprofen. To modulate and tune drug release, PVP K10 was doped into the EC side in some cases. The fibers were linear and had flat morphologies with an indent in the center. They provide biphasic drug release, with the PVP K60 side dissolving very rapidly to deliver a loading dose of the active ingredient, and the EC side resulting in sustained release of the remaining ketoprofen. The addition of PVP K10 to the EC side was able to accelerate the second stage of release; variation in the dopant amount permitted the release rate and extent this phase to be precisely tuned. These results offer the potential to rationally design systems with highly controllable drug release profiles, which can complement natural biological rhythms and deliver maximum therapeutic effects

Acetate induces growth arrest in colon cancer cells through modulation of mitochondrial function

Acetate is one of the main short chain fatty acids produced in the colon when fermentable carbohydrates are digested. It has been shown to affect normal metabolism, modulating mitochondrial function and fatty acid oxidation. Currently, there is no clear consensus regarding the effects of acetate on tumorigenesis and cancer metabolism. Here, we investigate the metabolic effects of acetate on colon cancer. HT29 and HCT116 colon cancer cell lines were treated with acetate and its effect on mitochondrial proliferation, reactive oxygen species, density, permeability transition pore, cellular bioenergetics, gene expression of acetyl-CoA synthetase 1 (ACSS1) and 2 (ACSS2) and lipid levels were investigated. Acetate was found to reduce proliferation of both cell lines under normoxia as well as reducing glycolysis; it was also found to increase both oxygen consumption and ROS levels. Cell death observed was independent of ACSS1/2 expression. Under hypoxic conditions, reduced proliferation was maintained in the HT29 cell line but no longer observed in the HCT116 cell line. ACSS2 expression together with cellular lipid levels was increased in both cell lines under hypoxia which may partly protect cells from the anti-proliferative effects of reversed Warburg effect caused by acetate. The findings from this study suggest that effect of acetate on proliferation is a consequence of its impact on mitochondrial metabolism and during normoxia is independent of ACCS1/2 expression

Relativistically rotating dust

Dust configurations play an important role in astrophysics and are the simplest models for rotating bodies. The physical properties of the general--relativistic global solution for the rigidly rotating disk of dust, which has been found recently as the solution of a boundary value problem, are discussed.Comment: 18 pages, 11 figure

Research in Medical Education: Balancing Service and Science*

Since the latter part of the 1990’s, the English-speaking medical education community has been engaged in a debate concerning the types of research that should have priority. To shed light on this debate and to better understand its implications for the practice of research, 23 semi-structured interviews were conducted with “influential figures” from the community. The results were analyzed using the concept of “field” developed by the sociologist Pierre Bourdieu. The results reveal that a large majority of these influential figures believe that research in medical education continues to be of insufficient quality despite the progress that has taken place over the past 2 decades. According to this group, studies tend to be both redundant and opportunistic, and researchers tend to have limited understanding of both theory and methodological practice from the social sciences. Three factors were identified by the participants to explain the current problems in research: the working conditions of researchers, budgetary restraints in financing research in medical education, and the conception of research in the medical environment. Two principal means for improving research are presented: intensifying collaboration between PhD’s and clinicians, and encouraging the diversification of perspectives brought to bear on research in medical education