P523 Survey to identify patient characteristics, treatment preferences and impact of inflammatory bowel disease (IBD) on quality of life across 7 countries in Europe

Abstract Background The treatment paradigm for inflammatory bowel disease (IBD) is becoming increasingly diverse and complex. It is suggested that engaging patients through shared decision-making optimises treatment selection in line with clinical need and patient preference and expectations. This patient survey aimed to explore patients' preferences towards attributes of currently available advanced therapies for IBD as well as the impact of IBD on patients' quality of life (QoL) across 7 countries in Europe. The demographic profile of the study cohort and findings on the patient-rated impact of IBD on QoL are reported here. Methods An online, cross-sectional survey (October 2020 to January 2021) enrolling adults aged ≥18 years who self-reported having and being previously/currently treated for Crohn's disease (CD) or ulcerative colitis (UC) was conducted across Europe (France, the UK, Spain, Italy, Belgium, Switzerland and the Netherlands). Patient perspectives on IBD care and preferences regarding specific attributes of existing treatment options were explored using the Carenity platform and via partnerships with local organisations. This descriptive analysis evaluated the demographic and clinical profile of respondents, treatment management and impact on QoL. Results Overall, 686 patients (CD: 360; UC: 326) across 7 countries completed the survey. Among CD and UC patients, respectively, 71.9% and 57.7% were females; mean age (range) was 48.0 (19.0–77.0) and 50.0 (19.0–82.0) years; and mean disease duration (range) was 13.6 (0.2–49.1) and 11.0 (0.1–68.7) years. Overall, 37.5% of CD patients reported fistulising CD, and 9.4% (CD) and 10.1% (UC) of patients had a stoma or pouch; 76.7% (CD) and 78.5% (UC) of patients were being treated for IBD. Approximately 50.0% of patients with IBD were full-time or part-time employed at the time of survey. Abdominal pain, fatigue, and stool frequency were ranked by 83%, 79%, and 73% patients with CD, respectively, as the symptoms most impacting QoL; 79%, 71%, and 61% patients ranked energy status, general well-being and daily activities, respectively, as the most impacted aspects. Abdominal pain, stool frequency and fatigue were ranked by 73%, 72% and 67% patients with UC, respectively, as the symptoms most impacting QoL; the most impacted aspects were similar to those of patients with CD. Patients in both groups prioritised general well-being, energy status and daily activities as aspects for improvement through treatment. Conclusion This large European survey highlights the most impactful symptoms and QoL aspects from the patient perspective. These findings can support clinical decision-making and treatment strategies to improve treatment outcomes and patient QoL

Tailoring the specificity of the type C feruloyl esterase FoFaeC from Fusarium oxysporum towards methyl sinapate by rational redesign based on small molecule docking simulations

The type C feruloyl esterase FoFaeC from Fusarium oxysporum is a newly discovered enzyme with high potential for use in the hydrolysis of lignocellulosic biomass but it shows low activity towards sinapates. In this work, small molecule docking simulations were employed in order to identify important residues for the binding of the four model methyl esters of hydroxycinnamic acids, methyl ferulate/caffeate/sinapate/p-coumarate, to the predicted structure of FoFaeC. Subsequently rational redesign was applied to the enzyme’ active site in order to improve its specificity towards methyl sinapate. A double mutation (F230H/T202V) was considered to provide hydrophobic environment for stabilization of the methoxy substitution on sinapate and a larger binding pocket. Five mutant clones and the wild type were produced in Pichia pastoris and biochemically characterized. All clones showed improved activity, substrate affinity, catalytic efficiency and turnover rate compared to the wild type against methyl sinapate, with clone P13 showing a 5-fold improvement in catalytic efficiency. Although the affinity of all mutant clones was improved against the four model substrates, the catalytic efficiency and turnover rate decreased for the substrates containing a hydroxyl substitution

The Vallo di Diano Range-Bounding Fault-System (Southern Italy): New Evidence of Recent Activity From High-Resolution Seismic Profiling

The Vallo di Diano is the largest intermountain basin in the Southern Apennines (Italy). The basin evolution was controlled by the Quaternary activity of a range-bounding, SW-dipping normal fault system located to the east (Vallo di Diano Fault System, VDFS). Geological and oil industry data define the sin-sedimentary activity of the VDFS up to the Middle Pleistocene. However, commercial profiles do not resolve the shallower, eastern portion of the basin, due to strong lateral heterogeneities and unfavourable surface conditions. Therefore, Late Pleistocene-Holocene activity of the VDFS and its seismogenic potential are still uncertain. To better constrain the shallow structure of the basin, we performed four high-resolution seismic surveys, along its eastern side, where slope breccias and fans cover the Mesozoic carbonate bedrock and bury the VDFS. We also investigated some NW-trending flexures affecting Late Pleistocene fans, that we had previously detected and dubitatively ascribed to recent faulting. Seismic data were acquired with a dense wide-aperture geometry. Two high-resolution (HR) NE-trending profiles, about 1.5 km long, were collected using respectively 5 m and 10 m spaced receivers and sources. Two very high-resolution (VHR) NE-trending profiles, 400 and 350 m long, with densely spaced sources (4 m) and receivers (2 m) were also collected. HR profiling was aimed at imaging alluvial fan thickness and morphology of the underlying carbonate bedrock. VHR surveys targeted the flexures and their possible origin. All lines were acquired with a HR vibroseis source, except for the shortest profile, where we used a buffalo-gun, better suited for very near-surface imaging (z < 50 m depth). Seismic imaging consists of reflectivity images obtained by CDP-processing of reflection data complemented by Vp images obtained by multi-scale seismic tomography. The stack sections illuminated the basin down to 0.4-0.5 s TWT and reveal an array of high-angle, generally SW-dipping faults dissecting the bedrock and the alluvial fans. Faulting created accommodation space in the hanging-wall and displaced the different fan generations. Clear reflection truncations in the stack-sections correspond to significant Vp lateral changes in the tomographic images. VHR tomography is well defined along the shortest line down to 40 m depth, where two steps within slope breccias are visible. Moreover, two low-velocity wedges (colluvial packages) are imaged in the near surface (5-20 m depth). These data support recent faulting consistently with surface geomorphic features. We interpret these fault structures as splays of the range bounding master fault. Comparison with commercial reflection profiles nearby reveals a great improvement in seismic imaging achieved by HR surveys, which allow a detailed seismostratigraphic analysis of the basin.UnpublishedSan Francisco (CA), Moscone West, Howard Street3.2. Tettonica attivaope

Research Note: Cecal microbiota harbored by free-range chickens may influence the reduction of Helicobacter pullorum relative abundance

Helicobacter pullorum is recognized as an emerging food-borne pathogen that may colonize the intestinal tract and the liver of avian species and humans causing several gastrointestinal and liver diseases. However, not all strains are reported to be capable of causing clinical disease, thus making poultry as reservoir for the zoonotic transmission of the infection through carcass contamination of broilers at slaughter. In poultry, the prevalence of this bacterium could be underestimated and the available data mainly refer to conventional rearing systems, whereas free-range and organic breedings have been poorly investigated. Therefore, this study was aimed to characterize the caecal microbiota community of free-range grown chickens and determine the presence and the relative abundance of H. pullorum by using NGS-based 16S rDNA sequencing. A total of 18 chickens reared for 56 d on a semi-extensive management system were euthanized at two time points: 9 birds at 28 d of age (before have access to outdoor; I = Indoor) and other 9 birds at 56 d of age (before slaughter; O = Outdoor). Cecal contents were collected for microbiota analyses. H. pullorum was detected in the cecum of 16/18 samples and its proportion in indoor was significantly higher than outdoor chickens (2.46 and 0.52%, respectively; P < 0.05), showing 78.8% of decrease with the outdoor access of the chickens. Therefore, it may be assumed that the potential for zoonotic infection is less likely. Moreover, H. pullorum was negatively correlated with 17 bacterial species as significantly more abundant in Outdoor microbial caecal communities. Among these, we highlighted the presence of Mucispirillium schaedleri and Oscillospira, already previously associated with a healthy gut and thus representing promising gut bacterial markers for host health. Our findings suggest that alternative production systems with outdoor access, may play a crucial role in the establishment of a healthy gut microbiota, which in turn might prevent colonization of harmful bacteria such as Helicobacter pullorum

Reverse engineering of mandible and prosthetic framework: Effect of titanium implants in conjunction with titanium milled full arch bridge prostheses on the biomechanics of the mandible.

This study aimed at investigating the effects of titanium implants and different configurations of full-arch prostheses on the biomechanics of edentulous mandibles. Reverse engineered, composite, anisotropic, edentulous mandibles made of a poly(methylmethacrylate) core and a glass fibre reinforced outer shell were rapid prototyped and instrumented with strain gauges. Brånemark implants RP platforms in conjunction with titanium Procera one-piece or two-piece bridges were used to simulate oral rehabilitations. A lateral load through the gonion regions was used to test the biomechanical effects of the rehabilitations. In addition, strains due to misfit of the one-piece titanium bridge were compared to those produced by one-piece cast gold bridges. Milled titanium bridges had a better fit than cast gold bridges. The stress distribution in mandibular bone rehabilitated with a one-piece bridge was more perturbed than that observed with a two-piece bridge. In particular the former induced a stress concentration and stress shielding in the molar and symphysis regions, while for the latter design these stresses were strongly reduced. In conclusion, prosthetic frameworks changed the biomechanics of the mandible as a result of both their design and manufacturing technology

The Vallo di Diano Range-Bounding Fault-System (Southern Italy): New Evidence of Recent Activity From High-Resolution Seismic Profiling

The Vallo di Diano is the largest intermountain basin in the Southern Apennines (Italy). The basin evolution was controlled by the Quaternary activity of a range-bounding, SW-dipping normal fault system located to the east (Vallo di Diano Fault System, VDFS). Geological and oil industry data define the sin-sedimentary activity of the VDFS up to the Middle Pleistocene. However, commercial profiles do not resolve the shallower, eastern portion of the basin, due to strong lateral heterogeneities and unfavourable surface conditions. Therefore, Late Pleistocene-Holocene activity of the VDFS and its seismogenic potential are still uncertain. To better constrain the shallow structure of the basin, we performed four high-resolution seismic surveys, along its eastern side, where slope breccias and fans cover the Mesozoic carbonate bedrock and bury the VDFS. We also investigated some NW-trending flexures affecting Late Pleistocene fans, that we had previously detected and dubitatively ascribed to recent faulting. Seismic data were acquired with a dense wide-aperture geometry. Two high-resolution (HR) NE-trending profiles, about 1.5 km long, were collected using respectively 5 m and 10 m spaced receivers and sources. Two very high-resolution (VHR) NE-trending profiles, 400 and 350 m long, with densely spaced sources (4 m) and receivers (2 m) were also collected. HR profiling was aimed at imaging alluvial fan thickness and morphology of the underlying carbonate bedrock. VHR surveys targeted the flexures and their possible origin. All lines were acquired with a HR vibroseis source, except for the shortest profile, where we used a buffalo-gun, better suited for very near-surface imaging (z < 50 m depth). Seismic imaging consists of reflectivity images obtained by CDP-processing of reflection data complemented by Vp images obtained by multi-scale seismic tomography. The stack sections illuminated the basin down to 0.4-0.5 s TWT and reveal an array of high-angle, generally SW-dipping faults dissecting the bedrock and the alluvial fans. Faulting created accommodation space in the hanging-wall and displaced the different fan generations. Clear reflection truncations in the stack-sections correspond to significant Vp lateral changes in the tomographic images. VHR tomography is well defined along the shortest line down to 40 m depth, where two steps within slope breccias are visible. Moreover, two low-velocity wedges (colluvial packages) are imaged in the near surface (5-20 m depth). These data support recent faulting consistently with surface geomorphic features. We interpret these fault structures as splays of the range bounding master fault. Comparison with commercial reflection profiles nearby reveals a great improvement in seismic imaging achieved by HR surveys, which allow a detailed seismostratigraphic analysis of the basin

Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi.

Newly synthesized proteins and lipids are transported across the Golgi complex via different mechanisms whose respective roles are not completely clear. We previously identified a non-vesicular intra-Golgi transport pathway for glucosylceramide (GlcCer)--the common precursor of the different series of glycosphingolipids-that is operated by the cytosolic GlcCer-transfer protein FAPP2 (also known as PLEKHA8) (ref. 1). However, the molecular determinants of the FAPP2-mediated transfer of GlcCer from the cis-Golgi to the trans-Golgi network, as well as the physiological relevance of maintaining two parallel transport pathways of GlcCer--vesicular and non-vesicular--through the Golgi, remain poorly defined. Here, using mouse and cell models, we clarify the molecular mechanisms underlying the intra-Golgi vectorial transfer of GlcCer by FAPP2 and show that GlcCer is channelled by vesicular and non-vesicular transport to two topologically distinct glycosylation tracks in the Golgi cisternae and the trans-Golgi network, respectively. Our results indicate that the transport modality across the Golgi complex is a key determinant for the glycosylation pattern of a cargo and establish a new paradigm for the branching of the glycosphingolipid synthetic pathwa

The Synthetic Potential of Fungal Feruloyl Esterases : A Correlation with Current Classification Systems and Predicted Structural Properties

Twenty-eight fungal feruloyl esterases (FAEs) were evaluated for their synthetic abilities in a ternary system of n-hexane: t-butanol: 100 mM MOPS-NaOH pH 6.0 forming detergentless microemulsions. Five main derivatives were synthesized, namely prenyl ferulate, prenyl caffeate, butyl ferulate, glyceryl ferulate, and l-arabinose ferulate, offering, in general, higher yields when more hydrophilic alcohol substitutions were used. Acetyl xylan esterase-related FAEs belonging to phylogenetic subfamilies (SF) 5 and 6 showed increased synthetic yields among tested enzymes. In particular, it was shown that FAEs belonging to SF6 generally transesterified aliphatic alcohols more efficiently while SF5 members preferred bulkier l-arabinose. Predicted surface properties and structural characteristics were correlated with the synthetic potential of selected tannase-related, acetyl-xylan-related, and lipase-related FAEs (SF1-2, -6, -7 members) based on homology modeling and small molecular docking simulations.Peer reviewe

Demonstrator of Time Services based on European GNSS signals: the H2020 DEMETRA Project

During 2015-2016, a European Consortium of 15 partners from 8 different countries, developed the DEMETRA (DEMonstrator of EGNSS services based on Time Reference Architecture), a project funded by the European Union in the frame of the Horizon 2020 program. This project aims at developing and experimenting time dissemination services dedicated to specific users like traffic control, energy distribution, finance, telecommunication, and scientific institutions. Nine services have been developed. These services provide time dissemination with accuracy levels from millisecond to the sub-ns, and also additional services like certification, calibration, or integrity. Five of these services are based on the European GNSS. After a development phase (see PTTI 2016 presentation) the full DEMETRA system has been working during six months for demonstration. The paper will report about the experimentation results, showing performances and limits of the proposed time dissemination services, aiming to foster the exploitation of the European GNSS for timing applications