Drug Repurposing: A Systematic Approach to Evaluate Candidate Oral Neuroprotective Interventions for Secondary Progressive Multiple Sclerosis

Objective: To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis. Design: Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action. Results: We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation. Conclusions: We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders

CTCs-derived xenograft development in a Triple Negative breast cancer case

Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and no available molecular targets. CTCs derived xenografts (CDX) have demonstrated to be a promising tool for understanding cancer biology. In our study, a CDX from a TNBC patient was developed for the first time. After CDX characterization, WNT signaling was found as the main mechanism related with this tumor biology and potential CTCs markers were identified and subsequently validated in TNBC patients. In this cohort high levels of MELK expression were associated with poorer survival rates. Overall, our study demonstrates that CTCs from TNBC are tumorigenic and CDXs are a useful model to obtain valuable information about the tumor

Emotion Coregulation in Mother-Child Dyads: A Dynamic Systems Analysis of Children with and without Autism Spectrum Disorder

Few studies have investigated patterns of emotion coregulation in families of children with Autism Spectrum Disorder (ASD) or contrasted the ways in which their emotion coregulation patterns differ from families of typically developing (TD) children. To address this gap, we used a dynamic systems approach to compare flexible structure and emotional content of coregulation between mothers and children (3-7 years) with ASD (n = 47) and TD children (n = 26). Mother-child play interactions in the home were videotaped and emotion-engagement states were coded in micro-level 5-s intervals based on behavioral and affective expressions. Analyses indicated that mother-child dyads in the ASD group spent more time than dyads in the TD group in mismatched emotion-engagement states (e.g., child negative/mother positive), and children with ASD spent more time than TD children engaged exclusively with objects. Mother-child dyads in the TD group stayed longer in mutual positive engagement states. Compared to dyads in the TD group, mother-child dyads in the ASD group exhibited greater flexibility (i.e., a wider range of emotional-engagement states, more frequent changes in states, and less time in each state). These findings suggest that mothers and their children with ASD do not sustain dyadic positive engagement patterns in a low-stress environment. Findings confirmed the preference of children with ASD for objects over social partners, even when they are at home with their mothers, and elucidated a challenging mother-child interactional style. Results have implications for mother-child interventions aimed at regulating negative emotional states and sustaining positive ones in families raising children with ASD

Rules for processing genetic data for research purposes in view of the new EU General Data Protection Regulation

Genetic data contain sensitive health and non-health-related information about the individuals and their family members. Therefore, adopting adequate privacy safeguards is paramount when processing genetic data for research or clinical purposes. One of the major legal instruments for personal data protection in the EU is the new General Data Protection Regulation (GDPR), which has entered into force in May 2016 and repealed the Directive 95/46/EC, with an ultimate goal of enhancing effectiveness and harmonization of personal data protection in the EU. This paper explores the major provisions of the new Regulation with regard to processing genetic data, and assesses the influence of such provisions on reinforcing the legal safeguards when sharing genetic data for research purposes. The new Regulation attempts to elucidate the scope of personal data, by recognizing pseudonymized data as personal (identifiable) data, and including genetic data in the catalog of special categories of data (sensitive data). Moreover, a set of new rules is laid out in the Regulation for processing personal data under the scientific research exemption. For instance, further use of genetic data for scientific research purposes, without obtaining additional consent will be allowed, if the specific conditions is met. The new Regulation has already fueled concerns among various stakeholders, owing to the challenges that may emerge when implementing the Regulation across the countries. Notably, the provided definition for pseudonymized data has been criticized because it leaves too much room for interpretations, and it might undermine the harmonization of the data protection across the countries