Rationale and protocol of a double-blind, randomized, placebo-controlled trial to test the efficacy, safety, and tolerability of dimethyl fumarate in Friedreich Ataxia (DMF-FA-201)

IntroductionFriedreich Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder that causes gait and limb ataxia, dysarthria, and impaired vibratory sense, with cardiomyopathy being the predominant cause of death. There is no approved therapy, which results in the use of symptomatic treatments and the chronic support of physiotherapy. Dimethyl fumarate (DMF) is a fumaric acid ester used for the treatment of psoriasis and Multiple Sclerosis (MS). It induces Nrf2 in vitro and in vivo, and it increases frataxin in FRDA patient lymphoblasts, in mouse models, and in MS treated patients.MethodsThe aim of our study is to investigate if DMF can increase the expression of the FXN gene and frataxin protein and ameliorate in-vivo detectable measures of mitochondrial dysfunction in FRDA. The study is composed of a screening visit and two sequential 12-week phases: a core phase and an extension phase. During the first phase (core), patients will be randomly assigned to either the DMF or a placebo group in a 1:1 ratio. During the first week, patients will receive a total daily dose of 240 mg of DMF or placebo; from the second week of treatment, the dose will be increased to two 120 mg tablets BID for a total daily dose of 480 mg. During the second phase (extension), all patients will be treated with DMF. EudraCT number 2021-006274-23.EndpointsThe primary endpoint will be a change in FXN gene expression level after 12 weeks of treatment. Secondary endpoints will be frataxin protein level, cardiopulmonary exercise test outputs, echocardiographic measures, Nrf2 pathway and mitochondrial biogenesis gene expression, safety, clinical scales, and quality of life scales.ConclusionsThis is the first study aimed at exploring the ability of DMF, an already available treatment for MS and psoriasis, to correct the biological deficits of FRDA and potentially improve mitochondrial respiration in-vivo

Parental experiences of homeschooling during the COVID-19 pandemic: differences between seven European countries and between children with and without mental health conditions

The aim of the present study was to examine parental experiences of homeschooling during the COVID-19 pandemic in families with or without a child with a mental health condition across Europe. The study included 6720 parents recruited through schools, patient organizations and social media platforms (2002 parents with a child with a mental health condition and 4718 without) from seven European countries: The United Kingdom (n=508), Sweden (n=1436), Spain (n=1491), Belgium (n=508), the Netherlands (n=324), Germany (n=1662) and Italy (n=794). Many parents reported negative effects of homeschooling for themselves and their child, and many found homeschooling to be of poor quality, with insufficient support from schools. In most countries, contact with teachers was limited, leaving parents with primary responsibility for managing homeschooling. Parents also reported increased levels of stress, worry, social isolation, and domestic conflict. A small number of parents reported increased parental alcohol/drug use. Some differences were found between countries and some negative experiences were more common in families with a child with a mental health condition. However, differences between countries and between families with and without a mental health condition were generally small, indicating that many parents across countries reported negative experiences. Some parents also reported positive experiences of homeschooling. The adverse effects of homeschooling will likely have a long-term impact and contribute to increased inequalities. Given that school closures may be less effective than other interventions, policymakers need to carefully consider the negative consequences of homeschooling during additional waves of the COVID-19 pandemic and future pandemics

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Social functioning and self-perception of social abilities in children and adolescents with Attention Deficit/Hypoeractivity Disorder

Children and adolescents with ADHD encountered several difficulties during their development, not directly linked to the inattention and hyperactivity traits (Barkley, 2014) and mainly linked to their social functioning (Semrud-Clikeman et al., 2010). Despite several authors (see for a review Harpin et al., 2016) focused on the social functioning impairment associated to ADHD, few studies have directly assessed these characteristics with lab-based tasks. Furthermore, the role of additional factors (e.g., Theory of Mind, EFs, communication) which could influence the social functioning of children and adolescents with ADHD is still not clear enough (Beauchamp & Anderson, 2010). Moreover, several studies have suggested that children with ADHD may overestimate their own competences in various areas of functioning (Owens et al., 2007) compared to external criteria. On the other hand some contradictory results have been observed (see for a review Owens et al., 2007) and it is still not clear if this overestimation of abilities affects several areas of functioning and whether it is specific for ADHD population, or different in other neurodevelopmental disorders (McQuade et al., 2011, 2017). The main aim of the present PhD dissertation is to improve our knowledge of two main developmental areas of children with ADHD: social functioning and self-perception of abilities. Four different studies were carried out, enrolling children and adolescents with a clinical diagnosis of ADHD, children and adolescents with autism spectrum disorder and typically developmental children, matched for gender, age and IQ. Firstly, to better understand the specific characteristics of ADHD in the two areas, a cross-disorder comparisons approach was used. Secondly, some aspects of social functioning and self-perception of abilities which emerge as peculiar of ADHD have been deeply examined in this population, considering the role of additional factors (e.g., Theory of Mind, EFs, communication) (Beauchamp & Anderson, 2010; Owens et al., 2007). New tasks and stimuli have been devised in order to assess the previously mentioned abilities. General conclusions derived from the main findings of the four studies, limitations as well as clinical implications have been highlighted in the final chapter of this dissertation.Children and adolescents with ADHD encountered several difficulties during their development, not directly linked to the inattention and hyperactivity traits (Barkley, 2014) and mainly linked to their social functioning (Semrud-Clikeman et al., 2010). Despite several authors (see for a review Harpin et al., 2016) focused on the social functioning impairment associated to ADHD, few studies have directly assessed these characteristics with lab-based tasks. Furthermore, the role of additional factors (e.g., Theory of Mind, EFs, communication) which could influence the social functioning of children and adolescents with ADHD is still not clear enough (Beauchamp & Anderson, 2010). Moreover, several studies have suggested that children with ADHD may overestimate their own competences in various areas of functioning (Owens et al., 2007) compared to external criteria. On the other hand some contradictory results have been observed (see for a review Owens et al., 2007) and it is still not clear if this overestimation of abilities affects several areas of functioning and whether it is specific for ADHD population, or different in other neurodevelopmental disorders (McQuade et al., 2011, 2017). The main aim of the present PhD dissertation is to improve our knowledge of two main developmental areas of children with ADHD: social functioning and self-perception of abilities. Four different studies were carried out, enrolling children and adolescents with a clinical diagnosis of ADHD, children and adolescents with autism spectrum disorder and typically developmental children, matched for gender, age and IQ. Firstly, to better understand the specific characteristics of ADHD in the two areas, a cross-disorder comparisons approach was used. Secondly, some aspects of social functioning and self-perception of abilities which emerge as peculiar of ADHD have been deeply examined in this population, considering the role of additional factors (e.g., Theory of Mind, EFs, communication) (Beauchamp & Anderson, 2010; Owens et al., 2007). New tasks and stimuli have been devised in order to assess the previously mentioned abilities. General conclusions derived from the main findings of the four studies, limitations as well as clinical implications have been highlighted in the final chapter of this dissertation

roots§routes - research on visual culture

Ogni numero di roots§routes ha un filo conduttore in base al quale vengono chiesti dei contributi a diversi ricercatori, teorici e artisti. Come redattore mi sono occupata insieme al resto del team della selezione dei contributi e del loro editing seguendone tutto il processo fino alla pubblicazione. Ho curato la strategia di social media management per la promozione della rivista tramite i canali facebook e twitter sia dal punto di vista progettuale che esecutivo producendo e selezionando i contenuti audiovisivi a corredo degli articoli

Does Positive Illusory Bias Affect Self-Concept and Loneliness in Children With Symptoms of ADHD?

Objective: Positive illusory bias (PIB) has been amply studied in children with ADHD, but its function is still limited understanding. Method: In a sample of 21 children with symptoms of ADHD, this study investigated whether they were more likely to be rejected by peers and examined PIB, and its influence on self-concept and loneliness, comparing the children with symptoms of ADHD with children who had weak social skills, but no ADHD. The children’s and teachers’ perception of social difficulties were compared, and self-concept and loneliness were analyzed in the two groups, which were also compared with typically developing (TD) children. Results: The results showed the presence of PIB on social skills in children with symptoms of ADHD, but this phenomenon did not give them a higher self-concept, which was similar to that of children with weak social skills and lower than in TD children. Conclusion: The implications of these findings are discussed

Bambini con sintomi ADHD: Relazione tra problematiche internalizzanti e abilit\ue0 sociali

Children with attention deficit and hyperactivity disorder (ADHD) have often co-morbidities, such as relational difficulties and internalizing problems. This study aims to analyze the relationship between ADHD symptoms, social abilities and internalizing problems. Children aged between 7 and 10 years and their teachers were presented with some self-report questionnaires. The results show an agreement between teacher and child assessments on classmates\u2019 social skills. It also emerges that relational difficulties mediate between ADHD symptoms and internalizing disorders. Suggestions for the clinical intervention with children with ADHD symptoms that also show social and/or internalizing disorders are discussed