Predicting the profile of increasing disability in multiple sclerosis

Background: Effective therapeutic strategies to preserve function and delay progression in multiple sclerosis (MS) require early recognition of individual disease trajectories. Objectives: To determine the profiles of disability evolution, identify their early predictors and develop a risk score of increasing disability. Methods: We analysed demographic, clinical and magnetic resonance imaging (MRI) data from patients with relapsing MS, Expanded Disability Status Scale (EDSS) score of 3.0–4.0 and follow-up≥2years. Attaining EDSS=6.0 defined increasing disability; relapses and/or MRI defined disease activity. Results: In total, 344 out of 542 (63.5%) patients reached EDSS≥6.0; of these, 220 (64.0%) showed disease activity. In patients with activity, the number of relapses before reaching EDSS 3.0–4.0 predicted increasing disability; age>45 at baseline predicted increasing disability without activity. Combining age and number of relapses increased the risk of and shortened the time to EDSS=6.0. Conclusion: Increasing disability is frequently associated with persistent activity. The high number of relapses identifies early those patients worsening in the presence of activity. Age predicts increasing disability in the absence of activity. The presence of both factors increases the risk of developing severe disability. As this study likely describes the transition to progression, our findings contribute to improving patient management and stratification in trials on progressive MS

Functional conservation of the grapevine candidate gene INNER NO OUTER for ovule development and seed formation

Seedlessness represents a highly appreciated trait in table grapes. Based on an interesting case of seedless fruit production described in the crop species Annona squamosa, we focused on the Vitis vinifera INNER NO OUTER (INO) gene as a candidate. This gene encodes a transcription factor belonging to the YABBY family involved in the determination of abaxial identity in several organs. In Arabidopsis thaliana, this gene was shown to be essential for the formation and asymmetric growth of the ovule outer integument and its mutation leads to a phenotypic defect of ovules and failure in seed formation. In this study, we identified in silico the V. vinifera orthologue and investigated its phylogenetic relationship to INO genes from other species and its expression in different organs in seeded and seedless varieties. Applying cross-species complementation, we have tested its functionality in the Arabidopsis ino-1 mutant. We show that the V. vinifera INO successfully rescues the ovule outer integument growth and seeds set and also partially complements the outer integument asymmetric growth in the Arabidopsis mutant, differently from orthologues from other species. These data demonstrate that VviINO retains similar activity and protein targets in grapevine as in Arabidopsis. Potential implications for grapevine breeding are discussed

Effect on cognition of estroprogestins combined with Interferon beta in multiple sclerosis: analysis of secondary outcomes from a randomized controlled trial

Introduction Cognitive impairment is a disabling symptom in multiple sclerosis (MS). While its management remains challenging, beneficial effects on cognition of interferon beta (IFN-β) have been reported and a positive effect from estroprogestins has been hypothesised, suggesting that the combination of the two medications in women with MS could offer a promising treatment strategy. Objectives We investigated whether a combination of estroprogestins and IFN-β can improve cognition in women with MS. Methods Women with relapsing-remitting (RR) MS were randomly assigned (1:1:1) to receive subcutaneous IFN-β-1a (Rebif®, Merck Serono, Geneva, Switzerland) 44 mcg three times a week (tiw) (group 1), subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 20 mcg and desogestrel 150 mcg (Mercilon®, MSD Italia SRL, Rome, Italy) (group 2) or subcutaneous IFN-β-1a 44 mcg tiw plus ethinyl estradiol 40 mcg and desogestrel 125 mcg (Gracial®, Organon Italia S.p.A., Rome, Italy) (group 3) in a randomised controlled trial, for which we report the analysis of secondary outcomes. At baseline and at 24 months, all patients underwent magnetic resonance imaging (MRI) and a comprehensive cognitive assessment, including Rao’s Brief Repeatable Battery (RBRB) and questionnaires for depression, fatigue and quality of life. Failure in at least two of the RBRB tests defined ‘cognitive impairment’. Results At baseline, there was no difference in the proportion of cognitively impaired patients. At month 24, the proportion of patients with cognitive impairment was lower in group 3 (34.8%) than in group 1 (47.6%) (p = 0.03). The risk of developing cognitive impairment over 24 months was lower in group 3 (p = 0.02). Mood and fatigue scores were comparable across the groups over time at both time points. However, at month 24, group 3 showed worsening on the sexual function subscale of the 54-item MS quality-of-life questionnaire (p = 0.03). Conclusions This study suggests that the combination of high-dose estroprogestins and IFN-β may have positive effects on cognition. However, the effect of this treatment on sexual function requires caution to be exercised

A Robust DNA Isolation Protocol from Filtered Commercial Olive Oil for PCR-Based Fingerprinting

Extra virgin olive oil (EVOO) has elevated commercial value due to its health appeal, desirable characteristics and quantitatively limited production, and thus it has become an object of intentional adulteration. As EVOOs on the market might consist of a blend of olive varieties or sometimes even of a mixture of oils from different botanical species, an array of DNA-fingerprinting methods have been developed to check the varietal composition of the blend. Starting from a comparison between publicly available DNA extraction protocols, we set up a timely, low-cost, reproducible and effective DNA isolation protocol, which allows an adequate amount of DNA to be recovered even from commercial filtered EVOOs. Then, in order to verify the effectiveness of the DNA extraction protocol herein proposed, we applied PCR-based fingerprinting methods starting from the DNA extracted from three EVOO samples of unknown composition. In particular, genomic regions harboring nine simple sequence repeats (SSRs) and eight genotyping-by-sequencing-derived single nucleotide polymorphism (SNP) markers were amplified for authentication and traceability of the three EVOO samples. The whole investigation strategy herein described might favor producers in terms of higher revenues and consumers in terms of price transparency and food safety

The effect of inflammation and its reduction on brain plasticity in multiple sclerosis: MRI evidence

Brain plasticity is the basis for systems-level functional reorganization that promotes recovery in multiple sclerosis (MS). As inflammation interferes with plasticity, its pharmacological modulation may restore plasticity by promoting desired patterns of functional reorganization. Here, we tested the hypothesis that brain plasticity probed by a visuomotor adaptation task is impaired with MS inflammation and that pharmacological reduction of inflammation facilitates its restoration. MS patients were assessed twice before (sessions 1 and 2) and once after (session 3) the beginning of Interferon beta (IFN-beta), using behavioural and structural MRI measures. During each session, 2 functional MRI runs of a visuomotor task, separated by 25-minutes of task practice, were performed. Within-session between-run change in task-related functional signal was our imaging marker of plasticity. During session 1, patients were compared with healthy controls. Comparison of patients’ sessions 2 and 3 tested the effect of reduced inflammation on our imaging marker of plasticity. The proportion of patients with gadolinium-enhancing lesions reduced significantly during IFN beta. In session 1, patients demonstrated a greater between-run difference in functional MRI activity of secondary visual areas and cerebellum than controls. This abnormally large practice-induced signal change in visual areas, and in functionally connected posterior parietal and motor cortices, was reduced in patients in session 3 compared with 2. Our results suggest that MS inflammation alters short-term plasticity underlying motor practice. Reduction of inflammation with IFN-beta is associated with a restoration of this plasticity, suggesting that modulation of inflammation may enhance recovery-oriented strategies that rely on patients’ brain plasticity

Genetic diversity and signature of divergence in the genome of grapevine clones of Southern Italy varieties

Sexual reproduction has contributed to a significant degree of variability in cultivated grapevine populations. However, the additional influence of spontaneous somatic mutations has played a pivotal role in shaping the diverse landscape of grapevine agrobiodiversity. These naturally occurring selections, termed 'clones,' represent a vast reservoir of potentially valuable traits and alleles that hold promise for enhancing grape quality and bolstering plant resilience against environmental and biotic challenges. Despite their potential, many of these clones remain largely untapped.In light of this context, this study aims to delve into the population structure, genetic diversity, and distinctive genetic loci within a collection of 138 clones derived from six Campanian and Apulian grapevine varieties, known for their desirable attributes in viticulture and winemaking. Employing two reduced representation sequencing methods, we extracted Single-Nucleotide Polymorphism (SNP) markers. Population structure analysis and fixation index (FST) calculations were conducted both between populations and at individual loci. Notably, varieties originating from the same geographical region exhibited pronounced genetic similarity.The resulting SNP dataset facilitated the identification of approximately two hundred loci featuring divergent markers (FST ≥ 0.80) within annotated exons. Several of these loci exhibited associations with essential traits like phenotypic adaptability and environmental responsiveness, offering compelling opportunities for grapevine breeding initiatives. By shedding light on the genetic variability inherent in these treasured traditional grapevines, our study contributes to the broader understanding of their potential. Importantly, it underscores the urgency of preserving and characterizing these valuable genetic resources to safeguard their intra-varietal diversity and foster future advancements in grapevine cultivation

Juego educativo basado en realidad virtual e interacción tangible para el aprendizaje de temas de matemática y química

La realidad virtual (RV) posibilita la creación de entornos simulados que pueden ser explorados y en los que el usuario puede interactuar con los objetos que aparecen. La RV presenta diferentes características de interés para el ámbito educativo tales como el sentido de presencia, la inmersión y la interactividad. La inmersión se considera fundamental y determina las diferencias entre los tipos de RV que se pueden implementar, según las tecnologías que se involucren. Cuando se utilizan tecnologías como los Head-Mounted Display (HMD) y las Cave Assisted Virtual Environment (CAVE), la experiencia ofrece a los usuarios un nivel alto de inmersión. Mientras, que en las experiencias basadas en PC, se tienen niveles más bajos de inmersión, ya que se toma conciencia del mundo físico y simulado al mismo tiempo. El escenario educativo no ha sido ajeno a los potenciales beneficios de la RV. Hay una variedad de investigaciones que muestran las posibilidades de esta tecnología en diferentes niveles educativos. Muchas de estas experiencias integran el uso de juegos educativos de RV, que motivan a los estudiantes y docentes al involucrarlos en un tipo de actividad diferente, que complementa el desarrollo de los objetivos educativos. En este trabajo se presenta un juego educativo basado en RV, desarrollado, al momento solo para PC. El juego (denominado Escapados) propone el uso de objetos del entorno físico, vinculado al paradigma de interacción tangible. Escapados tiene por objetivo aplicar conocimientos del área de matemática y de química de los últimos año de la escuela media, y el primer año de facultad. A partir de su historia, que se desarrolla en un mundo 3D, se involucra al jugador (estudiante) a resolver desafíos en los que, por ejemplo, tiene que calcular áreas de superficies, medias aritméticas, reconocer micro y macro nutrientes, y equilibrar reacciones químicas. El juego se propone entretener, motivar y lograr una participación activa de los estudiantes en la aplicación de los conocimientos previamente adquiridos.Red de Universidades con Carreras en Informátic

Deregulation of Ion Channel and Transporter Encoding Genes in Pediatric Gliomas

Brain tumors, including the majority gliomas, are the leading cause of cancer-related death in children. World Health Organization has divided pediatric brain tumors into different grades and, based upon cDNA microarray data identifying gene expression profiles (GEPs), it has become evident in the last decade that the various grades involve different types of genetic alterations. However, it is not known whether ion channel and transporter genes, intimately involved in brain functioning, are associated with such GEPs. We determined the GEPs in an available cohort of 10 pediatric brain tumors initially by comparing the data obtained from four primary tumor samples and corresponding short-term cultures. The correspondence between the two types of samples was statistically significant. We then performed bioinformatic analyses on those samples (a total of nine) which corresponded to tumors of glial origin, either tissues or cell cultures, depending on the best “RNA integrity number.” We used R software to evaluate the genes which were differentially expressed (DE) in gliomas compared with normal brain. Applying a p-value below 0.01 and fold change ≥4, led to identification of 2284 DE genes. Through a Functional Annotation Analysis (FAA) using the NIH-DAVID software, the DE genes turned out to be associated mainly with: immune/inflammatory response, cell proliferation and survival, cell adhesion and motility, neuronal phenotype, and ion transport. We have shown that GEPs of pediatric brain tumors can be studied using either primary tumor samples or short-term cultures with similar results. From FAA, we concluded that, among DE genes, pediatric gliomas show a strong deregulation of genes related to ion channels and transporters