The current focus on the use of new technologies and media for teaching-learning purposes has led to an intensifying interest in the properties and peculiarities of educational videogames. Creating a ...learning environment within a video game might be an opportunity to capitalize and use in a constructive way the time that more and more teens spend playing video games. In light of this, it is particularly interesting the continuous evolution of computer videogames known as "exergames", a term derived from the joining of the words "exercise" and "games". Exergames are video games which encourage the emotional involvement and the sense of presence through interactions based on devices that allow a greater involvement of the body respect to typical controllers such as joysticks, joy pads, keyboards and mousses. These games involve the player in some form of exercise and physical activity through video games and specific feedback and data collection devices. The aim of this study, which is currently under development, is therefore to design an active and engaging learning environment in order to assess whether it is suitable to stimulate and facilitate the learning processes, particularly focusing on the functions of coordination and sensorimotor integration, through the typical interaction of exergames and exploiting the properties and peculiarities of the Microsoft Kinect system as a device to acquire data on the body movements of the player.
"So far the school has been structured on the book, on the laborious acquisition of knowledge formulated in verbal language. Nowadays, thanks to the computer and its ability to simulate reality, it ...is possible to learn more naturally and without effort using our faculties of perception" (Antinucci, 2011). The statement by Antinucci, as well as the studies on many scientific domains supporting the idea of the involvement of sensory-motor integration in the development of intelligence and learning (Piaget, 1952; Vereecken, 1961), suggest to investigate in the didactics methodologies and instruments able to foster this integration ability. These studies also justify the current full attention in the field of movement teaching for new technologies, therefore the present research aims at testing a “shapes game” module that uses Microsoft Kinect System as an input device for the acquisition of data related to the movement of the body segments of the user. The possibility to identify the movement of specific body segments allows to develop teaching methodologies designed to foster the achievement of visual-motor abilities useful to the process of learning in school, through immersive modes of interaction, typical of “exergames” based on a full body involvement (Coshott, 2009). The present study shows the results of the pre-test software, built on a sample of pupils (aged 8 to 10) attending the fifth year of Italian primary school.
Key words: edutainment, exergame, kinect, sensory-motor coordination, videogame.
CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental and epileptic encephalopathy characterised by severe global developmental impairment and seizures that can begin in the first few ...months after birth and are often treatment refractory. Ganaxolone, an investigational neuroactive steroid, reduced seizure frequency in an open-label, phase 2 trial that included patients with CDD. We aimed to further assess the efficacy and safety of ganaxolone in patients with CDD-associated refractory epilepsy.
In the double-blind phase of this randomised, placebo-controlled, phase 3 trial, done at 39 outpatient clinics in eight countries (Australia, France, Israel, Italy, Poland, Russia, the UK, and the USA), patients were eligible if they were aged 2–21 years with a pathogenic or probably pathogenic CDKL5 variant and at least 16 major motor seizures (defined as bilateral tonic, generalised tonic-clonic, bilateral clonic, atonic, or focal to bilateral tonic-clonic) per 28 days in each 4-week period of an 8-week historical period. After a 6-week prospective baseline period, patients were randomly assigned (1:1) via an interactive web response system to receive either enteral adjunctive ganaxolone or matching enteral adjunctive placebo (maximum dose 63 mg/kg per day for patients weighing ≤28 kg or 1800 mg/day for patients weighing >28 kg) for 17 weeks. Patients, caregivers, investigators (including those analysing data), trial staff, and the sponsor (other than the investigational product manager) were masked to treatment allocation. The primary efficacy endpoint was percentage change in median 28-day major motor seizure frequency from the baseline period to the 17-week double-blind phase and was analysed (using a Wilcoxon-rank sum test) in all patients who received at least one dose of trial treatment and for whom baseline data were available. Safety (compared descriptively across groups) was analysed in all patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov, NCT03572933, and the open-label extension phase is ongoing.
Between June 25, 2018, and July 2, 2020, 114 patients were screened for eligibility, of whom 101 (median age 6 years IQR 3 to 10) were randomly assigned to receive either ganaxolone (n=50) or placebo (n=51). All patients received at least one dose of a study drug, but seizure frequency for one patient in the ganaxolone group was not recorded at baseline and so the primary endpoint was analysed in a population of 100 patients. There was a median percentage change in 28-day major motor seizure frequency of –30·7% (IQR –49·5 to –1·9) in the ganaxolone group and of –6·9% (–24·1 to 39·7) in the placebo group (p=0·0036). The Hodges–Lehmann estimate of median difference in responses to ganaxolone versus placebo was –27·1% (95% CI –47·9 to – 9·6). Treatment-emergent adverse events occurred in 43 (86%) of 50 patients in the ganaxolone group and in 45 (88%) of 51 patients in the placebo group. Somnolence, pyrexia, and upper respiratory tract infections occurred in at least 10% of patients in the ganaxolone group and more frequently than in the placebo group. Serious adverse events occurred in six (12%) patients in the ganaxolone group and in five (10%) patients in the placebo group. Two (4%) patients in the ganaxolone group and four (8%) patients in the placebo group discontinued the trial. There were no deaths in the double-blind phase.
Ganaxolone significantly reduced the frequency of CDD-associated seizures compared with placebo and was generally well tolerated. Results from what is, to our knowledge, the first controlled trial in CDD suggest a potential treatment benefit for ganaxolone. Long-term treatment is being assessed in the ongoing open-label extension phase of this trial.
Marinus Pharmaceuticals.
Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to ...the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation.
Goat populations that are characterized within the AdaptMap project cover a large part of the worldwide distribution of this species and provide the opportunity to assess their diversity at a global ...scale. We analysed genome-wide 50 K single nucleotide polymorphism (SNP) data from 144 populations to describe the global patterns of molecular variation, compare them to those observed in other livestock species, and identify the drivers that led to the current distribution of goats.
A high degree of genetic variability exists among the goat populations studied. Our results highlight a strong partitioning of molecular diversity between and within continents. Three major gene pools correspond to goats from Europe, Africa and West Asia. Dissection of sub-structures disclosed regional gene pools, which reflect the main post-domestication migration routes. We also identified several exchanges, mainly in African populations, and which often involve admixed and cosmopolitan breeds. Extensive gene flow has taken place within specific areas (e.g., south Europe, Morocco and Mali-Burkina Faso-Nigeria), whereas elsewhere isolation due to geographical barriers (e.g., seas or mountains) or human management has decreased local gene flows.
After domestication in the Fertile Crescent in the early Neolithic era (ca. 12,000 YBP), domestic goats that already carried differentiated gene pools spread to Europe, Africa and Asia. The spread of these populations determined the major genomic background of the continental populations, which currently have a more marked subdivision than that observed in other ruminant livestock species. Subsequently, further diversification occurred at the regional level due to geographical and reproductive isolation, which was accompanied by additional migrations and/or importations, the traces of which are still detectable today. The effects of breed formation were clearly detected, particularly in Central and North Europe. Overall, our results highlight a remarkable diversity that occurs at the global scale and is locally partitioned and often affected by introgression from cosmopolitan breeds. These findings support the importance of long-term preservation of goat diversity, and provide a useful framework for investigating adaptive introgression, directing genetic improvement and choosing breeding targets.
The outcome of children and adults with acute lymphoblastic leukemia is markedly different. Since there is limited information on the distribution of clinico-biological variables in different age ...cohorts, we analyzed 5202 patients with acute lymphoblastic leukemia enrolled in the Italian multicenter AIEOP and GIMEMA protocols and stratified them in nine age cohorts. The highest prevalence of acute lymphoblastic leukemia was observed in children, although a second peak was recorded from the 4(th) decade onwards. Interestingly, the lowest incidence was found in females between 14-40 years. Immunophenotypic characterization showed a B-lineage in 85.8% of patients: a pro-B stage, associated with MLL/AF4 positivity, was more frequent in patients between 10-50 years. T-lineage leukemia (14.2%) was rare among small children and increased in patients aged 10-40 years. The prevalence of the BCR/ABL1 rearrangement increased progressively with age starting from the cohort of patients 10-14 years old and was present in 52.7% of cases in the 6th decade. Similarly, the MLL/AF4 rearrangement constantly increased up to the 5(th) decade, while the ETV6/RUNX1 rearrangement disappeared from the age of 30 onwards. This study shows that acute lymphoblastic leukemia in adolescents and young adults is characterized by a male prevalence, higher percentage of T-lineage cases, an increase of poor prognostic molecular markers with aging compared to cases in children, and conclusively quantified the progressive increase of BCR/ABL(+) cases with age, which are potentially manageable by targeted therapies.
Abstract Aim We evaluated the prevalence of apical periodontitis (AP) and the oral health status in patients with inflammatory bowel diseases (IBDs) treated with immunomodulators, with particular ...attention to biologic medications (BMs). Methods One hundred ten patients, 49 men and 61 women (average age, 46 ± 13.8 years), from the Gastroenterology Unit of the University Hospital with IBDs who were treated with BMs or corticosteroids were included in the study. One hundred ten patients who registered for a dental check-up at the Dental Clinic were matched for age, sex, and physical characteristics with the study group without systemic diseases and not taking medications who were the control. Patients underwent a complete oral, dental, and radiographic examination. Decayed, missing, and filled teeth and periapical index score indexes were recorded. Student t test, χ2 , and Mann-Whitney U test were used as appropriate. Results The prevalence of AP was 64% in IBD patients and 59% in the control; according to the gender-stratified analysis, the difference was not significant among the male groups, whereas the number of teeth with AP was significantly higher in female patients with IBDs than in the controls ( P ≤ .05). The prevalence of AP in patients treated with BMs was 65%; women showed 69% higher risk for AP and presented a significantly higher number of teeth with AP ( P ≤ .05). Decayed, missing, and filled teeth index was similar in both groups, whereas patients with IBDs had a higher periapical index score than the controls. Conclusions Women with IBDs and taking immunomodulators had a higher prevalence of AP. All patients with IBDs had larger lesions than healthy subjects. These data emphasize the influence of the status of the immune system in the onset of AP and the need for further studies to confirm these findings.
ABSTRACT
A wide-frequency radio study of active galactic nuclei (AGN) is crucial to evaluate the intervening radiative mechanisms responsible for the observed emission and relate them with the ...underlying accretion physics. We present wide-frequency (5–45 GHz), high-sensitivity (few $\mathrm{{\mu }Jy\, beam^{-1}}$), (sub)-kpc Jansky Very Large Array (JVLA) observations of a sample of 30 nearby ($0.003\, \le \, z\, \le \, 0.3$) AGN detected by the International Gamma-Ray Astrophysics Laboratory (INTEGRAL)/Imager on Board the INTEGRAL Satellite (IBIS) at hard X-ray. We find a high detection fraction of radio emission at all frequencies, i.e. ≥95 per cent at 5, 10, and 15 GHz and ≥80 per cent at 22 and 45 GHz. Two sources out of 30 remain undetected at our high sensitivities. The nuclear radio morphology is predominantly compact, sometimes accompanied by extended jet-like structures, or more complex features. The radio spectral energy distributions (SEDs) of the radio cores appear either as single or as a broken power law, a minority of them exhibit a peaked component. The spectral slopes are either flat/inverted or steep, up to a break/peak or over the whole range. The sample mean SED shows a flat slope up to 15 GHz that steepens between 15 and 22 GHz and becomes again flat above 22 GHz. Significant radio–X-ray correlations are observed at all frequencies. About half of the sample features extended emission, clearly resolved by the JVLA, indicating low-power jets or large-scale outflows. The unresolved cores, which often dominate the radio power, may be of jet, outflow, and/or coronal origin, depending on the observed frequency.
N-myristoylation is a common form of co-translational protein fatty acylation resulting from the attachment of myristate to a required N-terminal glycine residue. We show that aberrantly acquired ...N-myristoylation of SHOC2, a leucine-rich repeat-containing protein that positively modulates RAS-MAPK signal flow, underlies a clinically distinctive condition of the neuro-cardio-facial-cutaneous disorders family. Twenty-five subjects with a relatively consistent phenotype previously termed Noonan-like syndrome with loose anagen hair (MIM607721) shared the 4A>G missense change in SHOC2 (producing an S2G amino acid substitution) that introduces an N-myristoylation site, resulting in aberrant targeting of SHOC2 to the plasma membrane and impaired translocation to the nucleus upon growth factor stimulation. Expression of SHOC2S2G in vitro enhanced MAPK activation in a cell type-specific fashion. Induction of SHOC2S2G in Caenorhabditis elegans engendered protruding vulva, a neomorphic phenotype previously associated with aberrant signaling. These results document the first example of an acquired N-terminal lipid modification of a protein causing human disease.
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