Hoffman Mills (coindonald02)

Prion is an infectious protein (PrPSc) that is derived from a cellular glycoprotein (PrPC) through a conformational transition and associated with a group of prion diseases in animals and humans. Characterization of proteinase K (PK)-resistant PrPSc by western blotting has been critical to diagnosis and understanding of prion diseases including Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) disease in humans. However, formation as well as biochemical and biological properties of the glycoform-selective PrPSc in variably protease-sensitive prionopathy (VPSPr) remain poorly understood. Here we reveal that formation of the ladder-like PrPSc in VPSPr is a PK-dependent two-step process, which is enhanced by basic pH. Two sets of PrPSc fragments can be identified with antibodies directed against an intermediate or a C-terminal domain of the protein. Moreover, antibodies directed against specific PrP glycoforms reveal faster electrophoretic migrations of PrP fragments mono-glycosylated at residue 181 and 197 in VPSPr than those in sporadic CJD (sCJD). Finally, RT-QuIC assay indicates that PrPSc-seeding activity is lower and its lag time is longer in VPSPr than in sCJD. Our results suggest that the glycoform-selective PrPSc in VPSPr is associated with altered glycosylation, resulting in different PK-truncation and aggregation seeding activity compared to PrPSc in sCJD.Metabolically healthy obesity (MHO) has been described as BMI ≥ 30 kg/m2, without metabolic disorders traditionally associated with obesity. Beyond this definition, a standardized criterion, for adults and children, has not been established yet to explain the absence of those metabolic disorders. In this context, biomarkers of inflammation have been proposed as suitable candidates to describe MHO. The use of mature red blood cell fatty acid (RBC FA) profile is here proposed since its membrane lipidome includes biomarkers of pro- and anti-inflammatory conditions with a strict relationship with metabolic and nutritional status. An observational study was carried out in 194 children (76 children with obesity and 118 children with normal weight) between 6 and 16 years old. RBC FAs were analyzed by gas chromatography-flame ionization detector (GC-FID). An unsupervised hierarchical clustering method was conducted on children with obesity, based on the RBC FA profile, to isolate the MHO cluster. The MHO cluster showed FA levels similar to children with normal weight, characterized by lower values of arachidonic acid, (total ω-6 FA, ω6/ω3 FA ratios and higher values for EPA, DHA, and total ω-3 FA) (for all of them p ≤ 0.01) compared to the rest of the children with obesity (obese cluster). The MHO cluster also presented lipid indexes for higher desaturase enzymatic activity and lower SFA/MUFA ratio compared to the obese cluster. These differences are relevant for the follow-up of patients, also in view of personalized protocols providing tailored nutritional recommendations for the essential fatty acid intakes.The authors' line of research is within the existing methodological debate around the concepts of quality of services, destinations, and quality measurements methods. The authors consider that the most appropriate way to measure quality is to develop instruments according to the destination and context in question, defining the quality of the tourist destination for practical purposes based on the satisfaction experienced by the tourist or the SERVPERF model, weighted and used to measure the quality of sun and beach tourist destinations. The authors of this work propose the knowledge of spa tourism, its quality and its level of satisfaction as a research gap and consider it as a starting point to validate a questionnaire that would allow the measurement and comparison of parameters with other segments already studied and that can also serve as a measuring instrument for tourist segments with similar characteristics, not as well known in the inte