Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica

Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization patterns

Clinical evaluation of multi-atlas based segmentation of lymph node regions in head and neck and prostate cancer patients

Background: Semi-automated segmentation using deformable registration of selected atlas cases consisting of expert segmented patient images has been proposed to facilitate the delineation of lymph node regions for three-dimensional conformal and intensity-modulated radiotherapy planning of head and neck and prostate tumours. Our aim is to investigate if fusion of multiple atlases will lead to clinical workload reductions and more accurate segmentation proposals compared to the use of a single atlas segmentation, due to a more complete representation of the anatomical variations. Methods: Atlases for lymph node regions were constructed using 11 head and neck patients and 15 prostate patients based on published recommendations for segmentations. A commercial registration software (Velocity AI) was used to create individual segmentations through deformable registration. Ten head and neck patients, and ten prostate patients, all different from the atlas patients, were randomly chosen for the study from retrospective data. Each patient was first delineated three times, (a) manually by a radiation oncologist, (b) automatically using a single atlas segmentation proposal from a chosen atlas and (c) automatically by fusing the atlas proposals from all cases in the database using the probabilistic weighting fusion algorithm. In a subsequent step a radiation oncologist corrected the segmentation proposals achieved from step (b) and (c) without using the result from method (a) as reference. The time spent for editing the segmentations was recorded separately for each method and for each individual structure. Finally, the Dice Similarity Coefficient and the volume of the structures were used to evaluate the similarity between the structures delineated with the different methods. Results: For the single atlas method, the time reduction compared to manual segmentation was 29% and 23% for head and neck and pelvis lymph nodes, respectively, while editing the fused atlas proposal resulted in time reductions of 49% and 34%. The average volume of the fused atlas proposals was only 74% of the manual segmentation for the head and neck cases and 82% for the prostate cases due to a blurring effect from the fusion process. After editing of the proposals the resulting volume differences were no longer statistically significant, although a slight influence by the proposals could be noticed since the average edited volume was still slightly smaller than the manual segmentation, 9% and 5%, respectively. Conclusions: Segmentation based on fusion of multiple atlases reduces the time needed for delineation of lymph node regions compared to the use of a single atlas segmentation. Even though the time saving is large, the quality of the segmentation is maintained compared to manual segmentation

Metagenomic Detection of Viral Pathogens in Spanish Honeybees: Co- Infection by Aphid Lethal Paralysis, Israel Acute Paralysis and Lake Sinai Viruses

The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and "unknown", emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees