Thixotropic Hydrogels Based on Laponite® and Cucurbituril for Delivery of Lipophilic Drug Molecules

Nowadays the use of hydrogels for biomedical purposes is increasing because of their interesting features that allow the development of targeted drug delivery systems. Herein, hydrogel based on Laponite® (Lap) clay mineral as gelator and cucurbit[6]uril (CB[6]) molecules were synthetized for the delivery of flufenamic acid (FFA) for potential topical application. Firstly, the interaction between CB[6] and FFA was assessed by UV-vis spectroscopic measurements and molecular modeling calculations. Then, the obtained complex was used as filler for Lap hydrogel (Lap/CB[6]/FFA). The properties of the hydrogel in terms of viscosity and, self-repair abilities were investigated; its morphology was imaged by scanning electron and polarized optical microscopies. Furthermore, the changes in the hydrodynamic radii and in the colloidal stability of CB[6]/Lap mixture were investigated in terms of translational diffusion from dynamic light scattering and ζ-potential measurements. Finally, the kinetic in vitro release of FFA, from Lap/CB[6]/FFA hydrogel, was studied in a medium mimicking the pH of skin and the obtained results were discussed both by an experimental point of view and by molecular modeling calculations

Adaptación de las clases prácticas de asignaturas de química a un modelo de semipresencialidad y optimización del tiempo de trabajo en laboratorio

Memoria ID-145 Ayudas de la Universidad de Salamanca para la innovación docente, curso 2020-2021

Beyond group classification: Probabilistic differential diagnosis of frontotemporal dementia and Alzheimer's disease with MRI and CSF biomarkers

Neuroimaging and fluid biomarkers are used to differentiate frontotemporal dementia (FTD) from Alzheimer's disease (AD). We implemented a machine learning algorithm that provides individual probabilistic scores based on magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) data. We investigated whether combining MRI and CSF levels could improve the diagnosis confidence. 215 AD patients, 103 FTD patients, and 173 healthy controls (CTR) were studied. With MRI data, we obtained an accuracy of 82 % for AD vs. FTD. A total of 74 % of FTD and 73 % of AD participants have a high probability of accurate diagnosis. Adding CSF-NfL and 14-3-3 levels improved the accuracy and the number of patients in the confidence group for differentiating FTD from AD. We obtain individual diagnostic probabilities with high precision to address the problem of confidence in the diagnosis. We suggest when MRI, CSF, or the combination are necessary to improve the FTD and AD diagnosis. This algorithm holds promise towards clinical applications as support to clinical findings or in settings with limited access to expert diagnoses

The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5- silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5 -silenced ovarian cancer cells. Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization

Galectin-3 is upregulated in frontotemporal dementia patients with subtype specificity

INTRODUCTIONNeuroinflammation is a major contributor to the progression of frontotemporal dementia (FTD). Galectin-3 (Gal-3), a microglial activation regulator, holds promise as a therapeutic target and potential biomarker. Our study aimed to investigate Gal-3 levels in patients with FTD and assess its diagnostic potential.METHODSWe examined Gal-3 levels in brain, serum, and cerebrospinal fluid (CSF) samples of patients with FTD and controls. Multiple linear regressions between Gal-3 levels and other FTD markers were explored.RESULTSGal-3 levels were increased significantly in patients with FTD, mainly across brain tissue and CSF, compared to controls. Remarkably, Gal-3 levels were higher in cases with tau pathology than TAR-DNA Binding Protein 43 (TDP-43) pathology. Only MAPT mutation carriers displayed increased Gal-3 levels in CSF samples, which correlated with total tau and 14-3-3.DISCUSSIONOur findings underscore the potential of Gal-3 as a diagnostic marker for FTD, particularly in MAPT cases, and highlights the relation of Gal-3 with neuronal injury markers

Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Introduction: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. Results: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. Discussion: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.K.A.T. is supported by the British Academy Postdoctoral Fellowship (PF160048) and the Guarantors of Brain (101149). J.B.R. is supported by the Wellcome Trust (103838), the Medical Research Council (SUAG/051 G101400), and the Cambridge NIHR Biomedical Research Centre. R. S.‐V. is supported by the Instituto de Salud Carlos III and the JPND network PreFrontAls (01ED1512/AC14/0013) and the Fundació Marató de TV3 (20143810). M.M and E.F are supported by the UK Medical Research Council, the Italian Ministry of Health, and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and also a Canadian Institutes of Health Research operating grant (MOP 327387) and funding from the Weston Brain Institute. J.D.R., D.C., and K.M.M. are supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre, and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility. J.D.R. is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH), the MRC UK GENFI grant (MR/ M023664/1), and The Bluefield Project. F.T. is supported by the Italian Ministry of Health (Grant NET‐2011‐02346784). L.C.J. and J.V.S. are supported by the Association for Frontotemporal Dementias Research Grant 2009, ZonMw Memorabel project number 733050103 and 733050813, and the Bluefield project. R.G. is supported by Italian Ministry of Health, Ricerca Corrente. J.L. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145; SyNergy ‐ ID 390857198). The Swedish contributors C.G., L.O., and C.A. were supported by grants from JPND Prefrontals Swedish Research Council (VR) 529‐2014‐7504, JPND GENFI‐PROX Swedish Research Council (VR) 2019‐02248, Swedish Research Council (VR) 2015‐ 02926, Swedish Research Council (VR) 2018‐02754, Swedish FTD Initiative‐Schorling Foundation, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Karolinska Institutet Doctoral Funding, and StratNeuro, Swedish Demensfonden, during the conduct of the study.info:eu-repo/semantics/publishedVersio

The inner fluctuations of the brain in presymptomatic frontotemporal dementia: the chronnectome fingerprint

© 2019 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials.This work was supported in part by grants from the NIH (R01REB020407, P20GM103472), NSF grant 1539067 and the Well- come Trust grant (JBR 103838).info:eu-repo/semantics/publishedVersio

MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia

Introduction: Structural brain imaging is paramount for the diagnosis of behavioural variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis. Methods: A total of 515 subjects from two different bvFTD cohorts (training and independent validation cohorts) were used to perform voxel-wise morphometric analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from deformation-based morphometry differences in isolation and together with semantic fluency. Tenfold cross validation was used to assess the performance of the classifier within the training cohort. A second held-out cohort of genetically confirmed bvFTD cases was used for additional validation. Results: Average 10-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In the separate validation cohort of definite bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added semantic fluency scores. Conclusion: Our results show that structural MRI and semantic fluency can accurately predict bvFTD at the individual subject level within a completely independent validation cohort coming from a different and independent database

Pseudomonas spp. y Staphylococcus spp. de origen alimentario y su conservación en agua destilada Pseudomonas spp. and Staphylococcus spp. of food origin and its conservation in distilled water

INTRODUCCIÓN: El agua destilada ha sido utilizada como medio de soporte para preservar cepas fúngicas, fundamentalmente por existir poca información sobre sus beneficios para mantener otros microorganismos. Con esta premisa, se decidió evaluar su utilidad para conservar bacterias, de origen alimentario, en la colección de cultivos microbianos del Instituto Nacional de Higiene, Epidemiología y Microbiología. MÉTODOS: Un total de 12 cepas (seis pertenecientes a Pseudomonas spp. y seis a Staphylococcus spp.) fueron ensayadas. Los datos de viabilidad obtenidos durante el año de conservación fueron procesados con el paquete estadístico SPSS versión 11.5. El análisis estadístico incluyó el análisis de la varianza para la comparación de las medias del recobrado de viables para las variables tiempo de conservación y dilución, y el test de Scheffé de comparaciones múltiples post hoc para la discriminación de las medias. Fueron controladas las características fisiológicas y la respuesta a la tinción de Gram de las cepas. RESULTADOS: No se encontraron diferencias significativas entre los grupos microbianos conservados en agua destilada. Los factores tiempo de conservación y dilución ejercieron su influencia sobre el recobrado de los cultivos. Se obtuvo estabilidad en la recuperación de viables a partir de los siete días de estudio. Se manifestaron diferencias significativas respecto a las diluciones de mayor valor. Se obtuvo 100 % de estabilidad en las características fisiológicas y en la respuesta a la tinción de Gram para todas las cepas. CONCLUSIONES: La conservación en agua destilada resulta adecuada para preservar las cepas de Pseudomonas spp. y Staphylococcus spp. aisladas de muestras de alimentos durante un año con una buena viabilidad.INTRODUCTION: The distilled water has been used as a support means to preserve fungal strains, mainly due to lack of information on its benefits to maintain other microorganisms. Thus, authors assessed its usefulness to preserve bacteria of food origin in the collection of microbial cultures in the National Institute of Hygiene, Epidemiology and Microbiology. METHODS: A total of 12 strains (six from Pseudomonas spp and six from Staphylococcus spp) were assayed. Data on viability obtained during the year of conservation were processed using the SPSS statistical package version 11.5. The statistical analysis included that of variance to compare the means of recovery of viable for the following variables: time of conservation and dilution, the Scheffé's test of post hoc multiples comparisons for discrimination of means. The physiological characteristics and the response to Gram's tincture of strains were controlled. RESULTS: There were not significant differences among microbial groups conserved in distilled water. The factors time of conservation and dilution had influence on the recovery of the cultures. There was a good stability in vials recovery from the 7 study days. There were significant differences regarding the dilutions of a greater value. It was possible to obtain a 100% of stability in the physiological characteristics and in the response to Gram's tincture for all the strains. CONCLUSIONS: The conservation in distilled water is appropriate to preserve the strains of Pseudomonas spp and of Staphylococcus spp isolated from samples of foods during a year achieving a good viability