Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

<b>Background</b>: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. <b>Methods/design</b>: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

Gravitational collapse with tachyon field and barotropic fluid

A particular class of space-time, with a tachyon field, \phi, and a barotropic fluid constituting the matter content, is considered herein as a model for gravitational collapse. For simplicity, the tachyon potential is assumed to be of inverse square form i.e., V(\phi) \sim \phi^{-2}. Our purpose, by making use of the specific kinematical features of the tachyon, which are rather different from a standard scalar field, is to establish the several types of asymptotic behavior that our matter content induces. Employing a dynamical system analysis, complemented by a thorough numerical study, we find classical solutions corresponding to a naked singularity or a black hole formation. In particular, there is a subset where the fluid and tachyon participate in an interesting tracking behaviour, depending sensitively on the initial conditions for the energy densities of the tachyon field and barotropic fluid. Two other classes of solutions are present, corresponding respectively, to either a tachyon or a barotropic fluid regime. Which of these emerges as dominant, will depend on the choice of the barotropic parameter, \gamma. Furthermore, these collapsing scenarios both have as final state the formation of a black hole.Comment: 18 pages, 7 figures. v3: minor changes. Final version to appear in GR

Evidence of beta amyloid independent small vessel disease in familial Alzheimer\u27s disease

\ua9 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology. We studied small vessel disease (SVD) pathology in Familial Alzheimer\u27s disease (FAD) subjects carrying the presenilin 1 (PSEN1) p.Glu280Ala mutation in comparison to those with sporadic Alzheimer\u27s disease (SAD) as a positive control for Alzheimer\u27s pathology and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) bearing different NOTCH3 mutations, as positive controls for SVD pathology. Upon magnetic resonance imaging (MRI) in life, some FAD showed mild white matter hyperintensities and no further radiologic evidence of SVD. In post-mortem studies, total SVD pathology in cortical areas and basal ganglia was similar in PSEN1 FAD and CADASIL subjects, except for the feature of arteriosclerosis which was higher in CADASIL subjects than in PSEN1 FAD subjects. Further only a few SAD subjects showed a similar degree of SVD pathology as observed in CADASIL. Furthermore, we found significantly enlarged perivascular spaces in vessels devoid of cerebral amyloid angiopathy in FAD compared with SAD and CADASIL subjects. As expected, there was greater fibrinogen-positive perivascular reactivity in CADASIL but similar reactivity in PSEN1 FAD and SAD groups. Fibrinogen immunoreactivity correlated with onset age in the PSEN1 FAD cases, suggesting increased vascular permeability may contribute to cognitive decline. Additionally, we found reduced perivascular expression of PDGFRβ AQP4 in microvessels with enlarged PVS in PSEN1 FAD cases. We demonstrate that there is Aβ-independent SVD pathology in PSEN1 FAD, that was marginally lower than that in CADASIL subjects although not evident by MRI. These observations suggest presence of covert SVD even in PSEN1, contributing to disease progression. As is the case in SAD, these consequences may be preventable by early recognition and actively controlling vascular disease risk, even in familial forms of dementia

Physical and Antimicrobial Properties of Compression-Molded Cassava Starch-Chitosan Films for Meat Preservation

[EN] Cassava starch-chitosan films were obtained by melt bending and compression molding, using glycerol and polyethylene glycol as plasticizers. Both the starch/chitosan and the polymer/plasticizer ratios were varied in order to analyze their effect on the physical properties of the films. Additionally, the antimicrobial activity of 70:30 polymer:plasticizer films was tested in cold-stored pork meat slices as affected by chitosan content. All film components were thermally stable up to 200 A degrees C, which guaranteed their thermostability during film processing. Starch and chitosan had limited miscibility by melt blending, which resulted in heterogeneous film microstructure. Polyethylene glycol partially crystallized in the films, to a greater extent as the chitosan ratio increased, which limited its plasticizing effect. The films with the highest plasticizer ratio were more permeable to water vapor, less rigid, and less resistant to break. The variation in the chitosan content did not have a significant effect on water vapor permeability. As the chitosan proportion increased, the films became less stretchable, more rigid, and more resistant to break, with a more saturated yellowish color. The incorporation of the highest amount of chitosan in the films led to the reduction in coliforms and total aerobic counts of cold-stored pork meat slices, thus extending their shelf-life.The authors acknowledge the financial support provided by the Spanish Ministerio de Economia y Competividad (Projects AGL2013-42989-R and AGL2016-76699-R). Author Cristina Valencia-Sullca thanks the Peruvian Grant National Program (PRONABEC Grant).Valencia-Sullca, CE.; Atarés Huerta, LM.; Vargas, M.; Chiralt, A. (2018). Physical and Antimicrobial Properties of Compression-Molded Cassava Starch-Chitosan Films for Meat Preservation. Food and Bioprocess Technology. 11(7):1339-1349. https://doi.org/10.1007/s11947-018-2094-5S13391349117Alves, V. D., Mali, S., Beleia, A., & Grossmann, M. V. (2007). Effect of glycerol and amylose enrichment on cassava starch film properties. Journal of Food Engineering, 78(3), 941–946.ASTM (1995). Standard test methods for water vapour transmission of materials. In: Standards designations: E96-95. Annual book of ASTM standards (pp. 406-413). Philadelphia, PA: American Society for Testing and Materials.ASTM (1999). Standard test method for specular gloss. In: Designation (D523). Annual book of ASTM standards, Vol. 06.01. Philadelphia, PA: American Society for Testing and Materials.ASTM (2001). Standard test method for tensile properties of thin plastic sheeting. In: Standard D882 annual book of American standard testing methods. Philadelphia, PA: American Society for Testing and Materials.Atarés, L., Bonilla, J., & Chiralt, A. (2010). Characterization of sodium caseinate-based edible films incorporated with cinnamon or ginger essential oils. Journal of Food Engineering, 100(4), 678–687.Bonilla, J., Atarés, L., Vargas, M., & Chiralt, A. (2013). Properties of wheat starch film-forming dispersions and films as affected by chitosan addition. Journal of Food Engineering, 114(3), 303–312.Bonilla, J., Fortunati, E., Atarés, L., Chiralt, A., & Kenny, J. (2014). Physical, structural and antimicrobial properties of poly vinyl alcohol-chitosan biodegradable films. Food Hydrocolloids, 35, 463–470.Bourtoom, T., & Chinnan, M. S. (2008). Preparation and properties of rice starch–chitosan blend biodegradable film. LWT-Food Science and Technology, 41(9), 1633–1641.Cano, A., Jiménez, A., Cháfer, M., González-Martínez, C., & Chiralt, A. (2014). Effect of amylose: amylopectin ratio and rice bran addition on starch films properties. Carbohydrate Polymers, 111(0), 543–555.Carvalho, A. J. F. (2008). Starch: Major sources, properties and applications as thermoplastic materials. In M. N. Belgacem & A. Gandini (Eds.), Monomers, polymers and composites from renewable resources. Amsterdam: Elsevier.Chillo, S., Flores, S., Mastromatteo, M., Conte, A., Gerschenson, L., & Del Nobile, M. A. (2008). Influence of glycerol and chitosan on tapioca starch-based edible film properties. Journal of Food Engineering, 88(2), 159–168.Commission Regulation, 2005 (EC) No 2073/2005 of 15 November 2005 on microbiological criteria for foodstuffs. In Official Journal of the European Union pp 338/1–338/26.Da Róz, A., Carvalho, A., Gandini, A., & Curvelo, A. (2006). The effect of plasticizers on thermoplastic starch compositions obtained by melt processing. Carbohydrate Polymers, 63(3), 417–424.Dang, K., & Yoksan, R. (2015). Development of thermoplastic starch blown film by incorporating plasticized chitosan. Carbohydrate Polymers, 115, 575–581.Dou, B., Dupont, V., Williams, P. T., Chen, H., & Ding, Y. (2009). Thermogravimetric kinetics of crude glycerol. Bioresource Technology, 100(9), 2613–2620.Fang, J., Fawler, P., Eserig, C., González, R., Costa, J., & Chamudis, L. (2005). Development of biodegradable laminate films derived from naturally occurring carbohydrate polymers. Carbohydrate Polymers, 60(1), 39–42.Hutchings, J. B. (1999). Food color and appearance (2nd ed.). Gaithersburg, Maryland, USA: Aspen Publishers, Inc..Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2012a). Edible and biodegradable starch films: A review. Food Bioprocessing Technology, 5(6), 2058–2076.Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2012b). Effect of re-crystallization on tensile, optical and water vapour barrier properties of corn starch films containing fatty acids. Food Hydrocolloids, 26(1), 302–310.López, O., Garcia, A., Villar, M., Gentili, A., Rodriguez, M., & Albertengo, L. (2014). Thermo-compression of biodegradable thermoplastic corn starch films containing chitin and chitosan. LWT-Food Science and Technology, 57(106), 106–1515.Mali, S., Grossmann, M. V. E., García, M. A., Martino, M. N., & Zaritsky, N. E. (2006). Effects of controlled storage on thermal, mechanical and barrier properties of plasticized films from different starch sources. Journal of Food Engineering, 75(4), 453–460.Mendes, J. F., Paschoalin, R. T., Carmona, V. B., Sena Neto, A. R. A., Marques, C. P., Marconcini, J. M., Mattoso, L. H. C., Medeiros, E. S., & Oliveira, J. E. (2016). Biodegradable polymer blends based on corn starch and thermoplastic chitosan processed by extrusion. Carbohydrate Polymers, 137, 452–458.Ortega-Toro, R., Jiménez, A., Talens, P., & Chiralt, A. (2014). Properties of starch–hydroxypropyl methylcellulose based films obtained by compression molding. Carbohydrate Polymers, 109, 155–165.Ortega-Toro, R., Morey, I., Talens, P., & Chiralt, A. (2015). Active bilayer films of thermoplastic starch and polycaprolactone obtained by compression molding. Carbohydrate Polymers, 127, 282–290.Pelissari, F., Grossmann, M., Yamashita, F., & Pineda, E. (2009). Antimicrobial, mechanical and barrier properties of cassava starch-chitosan films incorporated with oregano essential oil. Journal of Agricultural and Food Chemistry, 57(16), 7499–7504.Pelissari, F. M., Yamashita, F., García, M. A., Martino, M. N., Zaritzky, N. E., & Grossmann, M. V. E. (2012). Constrained mixture design applied to the development of cassava starch-chitosan blown films. Journal of Food Engineering, 108(2), 262–267.Song, R., Xue, R., He, L. H., Liu, Y., & Xiao, Q. L. (2008). The structure and properties of chitosan/polyethylene glycol/silica ternary hybrid organic-inorganic films. Chinese Journal of Polymer Science, 26(05), 621–630.v.Su, J. F., Huang, Z., Yuan, X. Y., Wang, X. Y., & Lim, M. (2010). Structure and properties of carboxymethyl cellulose/soy protein isolate blend edible films crosslinked by Maillard reactions. Carbohydrate Polymers, 79(1), 145–153.Thunwall, M., Boldizar, A., & Rigdahl, M. (2006). Compression molding and tensile properties of thermoplastic potato starch materials. Biomacromolecules, 7(3), 981–986.Tomé, L., Fernandes, S., Sadocco, P., Causio, J., Silvertre, A., Neto, P., & Freire, C. (2012). Antibacterial thermoplastic starch- chitosan based materials prepared by melt-mixing. BioResources, 7(3), 3398–3409.Villalobos, R., Chanona, J., Hernández, P., Gutiérrez, G., & Chiralt, A. (2005). Gloss and transparency of hydroxypropyl methylcellulose films containing surfactants as affected by their microstructure. Food Hydrocolloids, 19(1), 53–61.Xu, Y. X., Kim, K. M., Hanna, M. A., & Nag, D. (2005). Chitosan–starch composite film: Preparation and characterization. Industrial Crops and Products, 21(2), 185–192.Yang, L., & Paulson, A. T. (2000). Mechanical and water vapour barrier properties of edible gellan. Food Research International, 33(7), 563–570

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model