Effects of retro-nasal aroma release on satiation

It is suggested that the brain response of a food odour sensed retro-nasally is related to satiation. The extent of retro-nasal aroma release during consumption depends on the physical structure of a food, i.e. solid foods generate a longer, more pronounced retro-nasal aroma release than liquid foods. The aim of this study was to investigate if a beverage becomes more satiating when the retro-nasal aroma release profile coincides with the profile of a (soft) solid food. In a double-blind placebo-controlled randomised cross-over full factorial design, twenty-seven healthy subjects (fourteen males and thirteen females; aged 16-65 years; BMI 19-37 kg/m(2) were administered aroma profiles by a computer-controlled stimulator based on air dilution olfactometry. Profile A consisted of a profile that is obtained during consumption of normal beverages. Profile B is normally observed during consumption of (soft) solids. The two profiles were produced with strawberry aroma and administered in a retro-nasal fashion, while the subjects consumed a sweetened milk drink. Before, during and after the sensory stimulation, appetite profile measurements were performed. Subjects felt significantly more satiated if they were aroma stimulated with profile B (P = 0.04). After stimulation with sweet strawberry aroma, there was a significant decrease in desire to eat sweet products (P = 0.0001). In conclusion, perceived satiation was increased by altering the extent of retro-nasal aroma release

The potential impact of CT-MRI matching on tumor volume delineation in advanced head and neck cancer

To study the potential impact of the combined use of CT and MRI scans on the Gross Tumor Volume (GTV) estimation and interobserver variation. Four observers outlined the GTV in six patients with advanced head and neck cancer on CT, axial MRI, and coronal or sagittal MRI. The MRI scans were subsequently matched to the CT scan. The interobserver and interscan set variation were assessed in three dimensions. The mean CT derived volume was a factor of 1.3 larger than the mean axial MRI volume. The range in volumes was larger for the CT than for the axial MRI volumes in five of the six cases. The ratio of the scan set common (i.e., the volume common to all GTVs) and the scan set encompassing volume (i.e., the smallest volume encompassing all GTVs) was closer to one in MRI (0.3-0.6) than in CT (0.1-0.5). The rest volumes (i.e., the volume defined by one observer as GTV in one data set but not in the other data set) were never zero for CT vs. MRI nor for MRI vs. CT. In two cases the craniocaudal border was poorly recognized on the axial MRI but could be delineated with a good agreement between the observers in the coronal/sagittal MRI. MRI-derived GTVs are smaller and have less interobserver variation than CT-derived GTVs. CT and MRI are complementary in delineating the GTV. A coronal or sagittal MRI adds to a better GTV definition in the craniocaudal directio

Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Ensemble Place Codes in Hippocampus: CA1, CA3, and Dentate Gyrus Place Cells Have Multiple Place Fields in Large Environments

Previously we reported that the hippocampus place code must be an ensemble code because place cells in the CA1 region of hippocampus have multiple place fields in a more natural, larger-than-standard enclosure with stairs that permitted movements in 3-D. Here, we further investigated the nature of hippocampal place codes by characterizing the spatial firing properties of place cells in the CA1, CA3, and dentate gyrus (DG) hippocampal subdivisions as rats foraged in a standard 76-cm cylinder as well as a larger-than-standard box (1.8 m×1.4 m) that did not have stairs or any internal structure to permit movements in 3-D. The rats were trained to forage continuously for 1 hour using computer-controlled food delivery. We confirmed that most place cells have single place fields in the standard cylinder and that the positional firing pattern remapped between the cylinder and the large enclosure. Importantly, place cells in the CA1, CA3 and DG areas all characteristically had multiple place fields that were irregularly spaced, as we had reported previously for CA1. We conclude that multiple place fields are a fundamental characteristic of hippocampal place cells that simplifies to a single field in sufficiently small spaces. An ensemble place code is compatible with these observations, which contradict any dedicated coding scheme

Using multi-criteria risk ranking methodology to select case studies for a generic risk assessment framework for exotic disease incursion and spread through Europe

We present a novel approach of using the multi-criteria pathogen prioritisation methodology as a basis for selecting the most appropriate case studies for a generic risk assessment framework. The approach uses selective criteria to rank exotic animal health pathogens according to the likelihood of introduction and the impact of an outbreak if it occurred in the European Union (EU). Pathogens were evaluated based on their impact on production at the EU level and international trade. A subsequent analysis included criteria of relevance to quantitative risk assessment case study selection, such as the availability of data for parameterisation, the need for further research and the desire for the case studies to cover different routes of transmission. The framework demonstrated is flexible with the ability to adjust both the criteria and their weightings to the user's requirements. A web based tool has been developed using the RStudio shiny apps software, to facilitate this

Quantitative analysis of powder mixtures by raman spectrometry : the influence of particle size and its correction

Particle size distribution and compactness have significant confounding effects on Raman signals of powder mixtures, which cannot be effectively modeled or corrected by traditional multivariate linear calibration methods such as partial least-squares (PLS), and therefore greatly deteriorate the predictive abilities of Raman calibration models for powder mixtures. The ability to obtain directly quantitative information from Raman signals of powder mixtures with varying particle size distribution and compactness is, therefore, of considerable interest In this study, an advanced quantitative Raman calibration model was developed to explicitly account for the confounding effects of particle size distribution and compactness on Raman signals of powder mixtures. Under the theoretical guidance of the proposed Raman calibration model, an advanced dual calibration strategy was adopted to separate the Raman contributions caused by the changes in mass fractions of the constituents in powder mixtures from those induced by the variations in the physical properties of samples, and hence achieve accurate quantitative determination for powder mixture samples. The proposed Raman calibration model was applied to the quantitative analysis of backscatter Raman measurements of a proof-of-concept model system of powder mixtures consisting of barium nitrate and potassium chromate. The average relative prediction error of prediction obtained by the proposed Raman calibration model was less than one-third of the corresponding value of the best performing PLS model for mass fractions of barium nitrate in powder mixtures with variations in particle size distribution, as well as compactness

Cellular and clinical impact of Haploinsufficiency for genes involved in ATR signaling

Ataxia telangiectasia and Rad3-related (ATR) protein, a kinase that regulates a DNA damage-response pathway, is mutated in ATR-Seckel syndrome (ATR-SS), a disorder characterized by severe microcephaly and growth delay. Impaired ATR signaling is also observed in cell lines from additional disorders characterized by microcephaly and growth delay, including non-ATR-SS, Nijmegen breakage syndrome, and MCPH1 (microcephaly, primary autosomal recessive, 1)-dependent primary microcephaly. Here, we examined ATR-pathway function in cell lines from three haploinsufficient contiguous gene-deletion disorders--a subset of blepharophimosis-ptosis-epicanthus inversus syndrome, Miller-Dieker lissencephaly syndrome, and Williams-Beuren syndrome--in which the deleted region encompasses ATR, RPA1, and RFC2, respectively. These three genes function in ATR signaling. Cell lines from these disorders displayed an impaired ATR-dependent DNA damage response. Thus, we describe ATR signaling as a pathway unusually sensitive to haploinsufficiency and identify three further human disorders displaying a defective ATR-dependent DNA damage response. The striking correlation of ATR-pathway dysfunction with the presence of microcephaly and growth delay strongly suggests a causal relationship

Maximising data to optimise animal disease early warning systems and risk assessment tools within Europe

Timely and reliable data and information availability and sharing is essential for early warning, prevention and control of transboundary diseases. While there are a growing number of global datasets capable of providing information for use in early warning systems and risk assessment (RA) tools, there are currently time-consuming data cleansing and harmonisation activities which need to be carried out before they can be reliably used and combined. Thus, using global datasets as they stand can lead to errors in RA parameterisation and results due to inherent biases in the data, e.g. missing disease prevalence data treated as a zero may inadvertently penalise those countries which do report disease outbreaks as opposed to those countries which are affected by a pathogen but do not report outbreak data. It is therefore of great importance that data are clearly provided and easy to understand and that data providers strive for greater harmonisation of database standards. In this paper the datasets utilised in the SPARE (’Spatial risk assessment framework for assessing exotic disease incursion and spread through Europe’) project are described and discussed in terms of key criteria: accessibility, availability, completeness, consistency and quality. It is evident that most databases exist as information portals and not exclusively for RA purposes. Another striking issue from this assessment is the need for enhanced data sharing specifically with regards to data on illegal seizures, arthropod vector/wildlife abundance, intra-country livestock movement and national animal disease surveillance. It is hoped that the outcomes of this work will promote discussion and exchange between data providers, including the development of standardised data exchange protocols. The transformation of datasets to a common format is a considerable challenge but recommendations could and should be made on the standardisation of datasets and reporting in order to achieve a unified approach across Europe

Specificity of Tissue Transglutaminase Explains Cereal Toxicity in Celiac Disease

Celiac disease is caused by a selective lack of T cell tolerance for gluten. It is known that the enzyme tissue transglutaminase (tTG) is involved in the generation of T cell stimulatory gluten peptides through deamidation of glutamine, the most abundant amino acid in gluten. Only particular glutamine residues, however, are modified by tTG. Here we provide evidence that the spacing between glutamine and proline, the second most abundant amino acid in gluten, plays an essential role in the specificity of deamidation. On the basis of this, algorithms were designed and used to successfully predict novel T cell stimulatory peptides in gluten. Strikingly, these algorithms identified many similar peptides in the gluten-like hordeins from barley and secalins from rye but not in the avenins from oats. The avenins contain significantly lower percentages of proline residues, which offers a likely explanation for the lack of toxicity of oats. Thus, the unique amino acid composition of gluten and related proteins in barley and rye favors the generation of toxic T cell stimulatory gluten peptides by tTG. This provides a rationale for the observation that celiac disease patients are intolerant to these cereal proteins but not to other common food proteins