Teachers as designers of GBL scenarios: Fostering creativity in the educational settings

This paper presents a research started in 2010 with the aim of fostering the creativity of teachers through the design of Game-Based Learning scenarios. The research has been carried out involving teachers and trainers in the co-design and implementation of digital games as educational resources. Based on the results grained from the research, this paper highlights successful factors of GBL, as well as constraints and boundaries that the introduction of innovative teaching and learning practices faces within educational settings

Il furto del futuro. L’esperienza dei Legami Educativi A Distanza (LEAD) nella scuola dell’infanzia durante il COVID-19

The educational dimension has been highly stressed by the challenges that the pandemic has created, and the medium of technology has enabled the continuum of education. In March 2021 (during a short lockdown) the teaching returned exclusively online even for toddlers, through distance educational bonds (LEAD). This paper examines this new educational digital practice, which has required a technological synchronization action by the entire teaching staff. From creating a virtual learning environment for children, the reflection continues about how to keep the bond, through distance, alive and how to rebuild it on set. La dimensione educativa è stata altamente sollecitata dalle sfide che la pandemia ha generato e il medium della tecnologia ha permesso il continuum della formazione. Nel marzo 2021 (durante un breve lockdown) la didattica è tornata esclusivamente online anche per i più piccoli, attraverso i legami educativi a distanza (LEAD). Il presente contributo esamina questa pratica educativa digitale inedita che ha richiesto un’azione di sincronizzazione tecnologica da parte di tutto il corpo docente. Dalla creazione di un ambiente virtuale di apprendimento per l’infanzia, si riflette sulla sfida di come mantenere vivo il legame a distanza per poi ricostruirlo in presenza

High Sclerostin and Dickkopf-1 (DKK-1) serum levels in children and adolescents with type 1 diabetes mellitus

CONTEXT: Childhood type 1 diabetes (T1DM) is associated with decreased bone mass. Sclerostin and dickkopf-1 (DKK-1) are Wnt inhibitors which regulate bone formation. OBJECTIVE: To evaluate sclerostin and DKK-1 levels in TD1M children and to analyze the influence of the glycaemic control on bone health. DESIGN AND SETTING: Cross-sectional study conducted at a clinical research center. Partecipants: One hundred and six T1DM subjects (12.2 ± 4 years), 66 on multiple daily injections (MDI) and 40 on continuous subcutaneous infusion of insulin (CSII), and 80 controls. RESULTS: The average of bone transmission time (BTT) and amplitude-dependent speed of sound (Ad-Sos) Z-scores was lower in diabetics than controls. Significant increased DKK-1 (3593 ± 1172 vs 2652 ± 689 pg/ml, p<0.006) and sclerostin (29.45 ± 12.32 vs 22.53 ± 8.29, p<0.001) levels were found in diabetics respect to controls, particularly in patients on MDI than ones on CSII. Glycaemic control was improved in CSII patients compared to MDI ones (p<0.001) and was also associated to a significant higher BMI-SDS (p<0.002) and BTT-Z-score (p<0.02). With adjustment for age multiple linear regression analysis for DKK-1 and sclerostin as dependent variables showed that levels of HbA1c%, glucose, 25(OH)-Vitamin D, osteocalcin, PTH, years of diabetes, BMI-SDS and AD-SoS-Z-score are the most important predictors (p<0.0001). CONCLUSIONS: Our study highlighted: 1. the high serum levels of DKK-1 and sclerostin in T1DM children, and their relationship with the altered glycaemic control; 2. the effect of CSII on the improvement of glycaemic control and bone health in T1DM children

Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α

In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. Introduction: Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. Methods: Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. Results: DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. Conclusions: Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. These cytokines could represent new pharmacological targets for OI patients

Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement. Objectives: To provide epidemiological data of EPP in Italy. Materials and Methods: Prospective/retrospective data of EPP patients were collected by an Italian network of porphyria specialist centres (Gruppo Italiano Porfiria, GrIP) over a 20-year period (1996-2017). Results: In total, 179 patients (79 females) with a clinical and biochemical diagnosis of EPP were assessed, revealing a prevalence of 3.15 cases per million persons and an incidence of 0.13 cases per million persons/year. Incidence significantly increased after 2009 (due to the availability of alfa-melanotide, which effectively limits skin photosensitivity). Mean age at diagnosis was 28 years, with only 22 patients (12.2%) diagnosed 6410 years old. Gene mutations were assessed in 173 (96.6%) patients; most (164; 91.3%) were FECH mutations on one allele in association with the hypomorphic variant, c.315-48C, on the other (classic EPP), and nine (5.2%) were ALAS2 mutations (X-linked EPP). Only one case of autosomal recessive EPP was observed. Of the 42 different FECH mutations, 15 are novel, three mutations collectively accounted for 45.9% (75/164) of the mutations (c.215dupT [27.2%], c.901_902delTG [11.5%] and c.67\u2009+\u20095G\u2009>\u2009A [7.2%]), and frameshift mutations were prevalent (33.3%). A form of light protection was used by 109/179 (60.8%) patients, and 100 (56%) had at least one \u3b1-melanotide implant. Three cases of severe acute liver involvement, requiring OLT, were observed. Conclusions: These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy

Surveillance of Summer Mortality and Preparedness to Reduce the Health Impact of Heat Waves in Italy

Since 2004, the Italian Department for Civil Protection and the Ministry of Health have implemented a national program for the prevention of heat-health effects during summer, which to-date includes 34 major cities and 93% of the residents aged 65 years and over. The Italian program represents an important example of an integrated approach to prevent the impact of heat on health, comprising Heat Health Watch Warning Systems, a mortality surveillance system and prevention activities targeted to susceptible subgroups. City-specific warning systems are based on the relationship between temperature and mortality and serve as basis for the modulation of prevention measures. Local prevention activities, based on the guidelines defined by the Ministry of Health, are constructed around the infrastructures and services available. A key component of the prevention program is the identification of susceptible individuals and the active surveillance by General Practitioners, medical personnel and social workers. The mortality surveillance system enables the timely estimation of the impact of heat, and heat waves, on mortality during summer as well as to the evaluation of warning systems and prevention programs. Considering future predictions of climate change, the implementation of effective prevention programs, targeted to high risk subjects, become a priority in the public health agenda

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies.TelethonAssociazione Serena Talarico per i giovani nel mondo and Fondazione Giuseppe Tomasello O.N.L.U.S.Mitocon OnlusResearch to Prevent BlindnessInternational Foundation for Optic Nerve Diseases (IFOND)Struggling Within Leber'sPoincenot FamilyEierman FoundationNational Eye InstituteUniv Rome, Dept Radiol Oncol & Pathol, Rome, ItalyUniv Bologna, Dept Biomed & NeuroMotor Sci DIBINEM, Bologna, ItalyUniv Bari, Dept Biosci Biotechnol & Biopharmaceut, Bari, ItalyBellaria Hosp, IRCCS Ist Sci Neurol Bologna, I-40139 Bologna, ItalyUSC, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USAUSC, Keck Sch Med, Dept Neurosurg, Los Angeles, CA USAUniv Trieste, Dept Reprod Sci Dev & Publ Hlth, Trieste, ItalyUniv Trieste, IRCCS Burlo Garofolo Children Hosp, Trieste, ItalyNewcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, EnglandFdn Ist Neurol Carlo Besta IRCCS, Unit Mol Neurogenet, Milan, ItalyMRC Mitochondrial Biol Unit, Cambridge, EnglandFed Univ São Paulo UNIFESP, Dept Ophthalmol, São Paulo, BrazilUniv São Paulo, Inst Psychol, Dept Expt Psychol, São Paulo, BrazilStudio Oculist dAzeglio, Bologna, ItalyOsped San Giovanni Evangelista, Tivoli, ItalyAzienda Osped San Camillo Forlanini, Rome, ItalyUniv Rome, Dipartimento Metodi & Modelli Econ Finanza & Terr, Rome, ItalyUniv Rome, Dept Mol Med, Rome, ItalyFed Univ São Paulo UNIFESP, Dept Ophthalmol, São Paulo, BrazilTelethon: GGP06233Telethon: GGP11182Telethon: GPP10005National Eye Institute: EY03040Web of Scienc

First Results of the 140^{140}Ce(n,γ)141^{141}Ce Cross-Section Measurement at n_TOF

An accurate measurement of the $^{140}$Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the $^{140}$Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in $^{140}$Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the $^{140}$Ce Maxwellian-averaged cross-section

First Results of the 140^{140}Ce(n,γ)141^{141}Ce Cross-Section Measurement at n_TOF

An accurate measurement of the $^{140}$Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the $^{140}$Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in $^{140}$Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the $^{140}$Ce Maxwellian-averaged cross-section

Measurement of the 244^{244}Cm and 246^{246}Cm Neutron-Induced Cross Sections at the n_TOF Facility

The neutron capture reactions of the $^{244}$Cm and $^{246}$Cm isotopes open the path for the formation of heavier Cm isotopes and of heavier elements such as Bk and Cf in a nuclear reactor. In addition, both isotopes belong to the minor actinides with a large contribution to the decay heat and to the neutron emission in irradiated fuels proposed for the transmutation of nuclear waste and fast critical reactors. The available experimental data for both isotopes are very scarce. We measured the neutron capture cross section with isotopically enriched samples of $^{244}$Cm and $^{246}$Cm provided by JAEA. The measurement covers the range from 1 eV to 250 eV in the n_TOF Experimental Area 2 (EAR-2). In addition, a normalization measurement with the $^{244}$Cm sample was performed at Experimental Area 1 (EAR-1) with the Total Absorption Calorimeter (TAC)