Novel transcriptomic panel identifies histologically active eosinophilic oesophagitis.

Eosinophilic oesophagitis (EoE) is characterised by symptoms of esophageal dysfunction and oesinophil tissue infiltration. The EoE Diagnostic Panel (EDP) can distinguish between active and non-active EoE using a set of 77 genes. Recently, the existence of distinct EoE variants featuring symptoms similar to EoE, such as oesophageal dysfunction but lacking eosinophil infiltration, had been determined. We used oesophageal biopsies from patients with histologically active (n=10) and non-active EoE (n=9) as well as from healthy oesophageal controls (n=5) participating in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) and analysed the gene expression profile in these biopsies by total RNA-sequencing (RNA-seq). Moreover, we employed the publicly accessible RNA-seq dataset (series GSE148381) as reported by Greuter et al, encompassing a comprehensive genomic profile of patients presenting with EoE variants. A novel, diagnostic gene expression panel that can effectively distinguish patients with histologically active conventional EoE from patients with EoE in histological remission and control individuals, and from three newly discovered EoE variants was identified. Histologically Active EoE Diagnostic Panel (HAEDP) consists of 53 genes that were identified based on differential expression between histologically active EoE, histological remission and controls (p≤0.05). By combining the HAEDP with EDP, we expanded our knowledge about factors that may contribute to the inflammation in EoE and improved our understanding of the underlying mechanisms of the disease. Conversely, we suggested a compact group of genes common to both HAEDP and EDP to create a reliable diagnostic tool that might enhance the accuracy of EoE diagnosis. We identified a novel set of 53 dysregulated genes that are closely associated with the histological inflammatory activity of EoE. In combination with EDP, our new panel might be a valuable tool for the accurate diagnosis of patients with EoE as well as for monitoring their disease course

Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1) is an immunogenic antigen found in EVs released from pre-acetabular glands of invading cercariae.

Funder: IBERS, Aberystwyth University PhD studentshipFunder: Higher Education Funding Council for Wales (HEFCW) - Global Challenges Research FundExtracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined. Herein, we characterise the most abundant EV-enriched protein in Schistosoma mansoni tissue-migrating schistosomula (Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)). Comparative sequence analysis demonstrates that lev1 orthologs are found in all published Schistosoma genomes, yet homologs are not found outside of the Schistosomatidae. Lifecycle expression analyses collectively reveal that smlev1 transcription peaks in cercariae, is male biased in adults, and is processed by alternative splicing in intra-mammalian lifecycle stages. Immunohistochemistry of cercariae using a polyclonal anti-recombinant SmLEV1 antiserum localises this protein to the pre-acetabular gland, with some disperse localisation to the surface of the parasite. S. mansoni-infected Ugandan fishermen exhibit a strong IgG1 response against SmLEV1 (dropping significantly after praziquantel treatment), with 11% of the cohort exhibiting an IgE response and minimal levels of detectable antigen-specific IgG4. Furthermore, mice vaccinated with rSmLEV1 show a slightly reduced parasite burden upon challenge infection and significantly reduced granuloma volumes, compared with control animals. Collectively, these results describe SmLEV1 as a Schistosomatidae-specific, EV-enriched immunogen. Further investigations are now necessary to uncover the full extent of SmLEV1's role in shaping schistosome EV function and definitive host relationships

Survey of highly non-Keplerian orbits with low-thrust propulsion

Celestial mechanics has traditionally been concerned with orbital motion under the action of a conservative gravitational potential. In particular, the inverse square gravitational force due to the potential of a uniform, spherical mass leads to a family of conic section orbits, as determined by Isaac Newton, who showed that Kepler‟s laws were derivable from his theory of gravitation. While orbital motion under the action of a conservative gravitational potential leads to an array of problems with often complex and interesting solutions, the addition of non-conservative forces offers new avenues of investigation. In particular, non-conservative forces lead to a rich diversity of problems associated with the existence, stability and control of families of highly non-Keplerian orbits generated by a gravitational potential and a non-conservative force. Highly non-Keplerian orbits can potentially have a broad range of practical applications across a number of different disciplines. This review aims to summarize the combined wealth of literature concerned with the dynamics, stability and control of highly non-Keplerian orbits for various low thrust propulsion devices, and to demonstrate some of these potential applications

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

Aβ5−xPeptides: N‑Terminal Truncation Yields Tunable Cu(II)Complexes

The Aβ5−x peptides (x = 38, 40, 42) are minor Aβ species in normal brains but elevated upon the application of inhibitors of Aβ processing enzymes. They are interesting from the point of view of coordination chemistry for the presence of an Arg-His metal binding sequence at their N-terminus capable of forming a 3-nitrogen (3N) three-coordinate chelate system. Similar sequences in other bioactive peptides were shown to bind Cu(II) ions in biological systems. Therefore, we investigated Cu(II) complex formation and reactivity of a series of truncated Aβ5−x peptide models comprising the metal binding site: Aβ5−9, Aβ5−12, Aβ5−12Y10F, and Aβ5−16. Using CD and UV−vis spectroscopies and potentiometry, we found that all peptides coordinated the Cu(II) ion with substantial affinities higher than 3 × 1012 M−1 at pH 7.4 for Aβ5−9 and Aβ5−12. This affinity was elevated 3-fold in Aβ5−16 by the formation of the internal macrochelate with the fourth coordination site occupied by the imidazole nitrogen of the His13 or His14 residue. A much higher boost of affinity could be achieved in Aβ5−9 and Aβ5−12 by adding appropriate amounts of the external imidazole ligand. The 3N Cu-Aβ5−x complexes could be irreversibly reduced to Cu(I) at about −0.6 V vs Ag/AgCl and oxidized to Cu(III) at about 1.2 V vs Ag/AgCl. The internal or external imidazole coordination to the 3N core resulted in a slight destabilization of the Cu(I) state and stabilization of the Cu(III) state. Taken together these results indicate that Aβ5−x peptides, which bind Cu(II) ions much more strongly than Aβ1−x peptides and only slightly weaker than Aβ4−x peptides could interfere with Cu(II) handling by these peptides, adding to copper dyshomeostasis in Alzheimer brains

Particle aggregation in large counter-current spray drying towers: Nozzle configuration, vortex momentum and temperature

This work investigates particle growth in a counter-current swirl detergent dryer, operating with a single nozzle, at a range of nozzle heights, air drying temperatures, TA, and superficial air velocities, UA, which were selected to enhance or inhibit particle aggregation in the dryer. The growth kinetics are discussed paying special attention to the impact of the cycle of deposition and re-entrainment of material from the wall deposits. All cases lead to substantial aggregation and mono-modal product size distributions. The operation at low UA and high TA, (i.e. low momentum) does not inhibit growth as one would expect from a lower particle concentration and faster heat and mass transfer, conditions which would lead to less particle collisions resulting in growth. In contrast, generation of aggregated particles > 850 μm is promoted, suggesting that a change in the erosion behavior of particles from the wall due to a reduction in energy of particle impacts. As a result of lower stresses, erosion is suppressed and clusters remain at the wall for longer, what allows them to sinter and be re-entrained at larger sizes. In contrast, increasing the momentum of the continuous phase by operation at low TA and high UA inhibits particle growth, particularly in the production of the largest sizes > 850 μm. In this case the rate and energy of impacts to the wall increases, this leads to higher disruptive stresses on the wall deposits, thus, reducing the size of the clusters re-entrained. In summary, this work describes aggregation mechanisms in swirl detergent dryers operated with single nozzles, suggesting that, contrary to expectations, wearing of deposits rather than air-borne contacts may be a key contributor to the enhancement or inhibition of growth

Influence of wall friction on flow regimes and scale-up of counter-current swirl spray dryers

The structure of the vortex flow in swirl spray dryers is investigated after having fouled the walls with deposits typical of detergent manufacture. The range of Re and swirl intensity Ω characteristic of industry are studied using three counter-current units of varying scale and design. The friction with the deposits increases the flow turbulence kinetic energy and causes a drastic attenuation of the swirl and as a result, the vortex breaks down in the chamber forming recirculation regions (i.e. areas of reverse flow). Three flow regimes (1) no recirculation, (2) central and (3) annular recirculation have been identified depending on the swirl intensity. New control and scale up strategies are proposed for swirl dryers based in predicting the decay and the flow regime using the unit geometry (i.e. initial swirl intensity Ωi) and experimental decay rates function of the coverage and thickness of deposits. The impact in design and numerical modelling must be stressed. Adequate prediction of the swirl is vital to study fouling and recirculation, which surely play an important part in the dispersion and aggregation of the solid phase. Current models have no means to replicate these phenomena, and yet, in this case neglecting the deposits and assuming smooth walls would result in (a) over-prediction of swirl velocity up to 40-186% (b) under-prediction of turbulent kinetic energy up to 67-85% and (c) failure to recognise recirculation areas