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Article: DMT1 Expression and Iron Levels at the Crossroads Between Aging and Neurodegeneration.

Ingrassia, Rosaria / Garavaglia, Barbara / Memo, Maurizio

2019 Volume 13, Page(s) 575

Abstract: Iron homeostasis is an essential prerequisite for metabolic and neurological functions throughout the healthy human life, with a dynamic interplay between intracellular and systemic iron metabolism. The development of different neurodegenerative diseases ...

Abstract	Iron homeostasis is an essential prerequisite for metabolic and neurological functions throughout the healthy human life, with a dynamic interplay between intracellular and systemic iron metabolism. The development of different neurodegenerative diseases is associated with alterations of the intracellular transport of iron and heavy metals, principally mediated by Divalent Metal Transporter 1 (DMT1), responsible for Non-Transferrin Bound Iron transport (NTBI). In addition, DMT1 regulation and its compartmentalization in specific brain regions play important roles during aging. This review highlights the contribution of DMT1 to the physiological exchange and distribution of body iron and heavy metals during aging and neurodegenerative diseases. DMT1 also mediates the crosstalk between central nervous system and peripheral tissues, by systemic diffusion through the Blood Brain Barrier (BBB), with the involvement of peripheral iron homeostasis in association with inflammation. In conclusion, a survey about the role of DMT1 and iron will illustrate the complex panel of interrelationship with aging, neurodegeneration and neuroinflammation.
Language	English
Publishing date	2019-06-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2019.00575
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Article: Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).

Ingrassia, Rosaria / Memo, Maurizio / Garavaglia, Barbara

Frontiers in genetics

2017 Volume 8, Page(s) 18

Abstract: Mutations ... ...

Abstract	Mutations in
Language	English
Publishing date	2017-02-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2017.00018
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Article ; Online: Emotional and Behavioural Factors Predisposing to Internet Addiction: The Smartphone Distraction among Italian High School Students.

Benedetto, Loredana / Rollo, Simone / Cafeo, Anna / Di Rosa, Gabriella / Pino, Rossella / Gagliano, Antonella / Germanò, Eva / Ingrassia, Massimo

International journal of environmental research and public health

2024 Volume 21, Issue 4

Abstract: In a digitally oriented society, smartphones provide continual online accessibility to daily life while simultaneously predisposing adolescents to engage in prolonged connections for various purposes, thus escalating the risk of Internet addiction (IA). ... ...

Abstract	In a digitally oriented society, smartphones provide continual online accessibility to daily life while simultaneously predisposing adolescents to engage in prolonged connections for various purposes, thus escalating the risk of Internet addiction (IA). Cognitive processes such as multitasking and attentional shifting are frequently associated with smartphone activities. Additionally, online engagements may serve as emotional strategies for regulating negative states (e.g., boredom and distress), redirecting attention towards more gratifying activities, such as social media contents. This study delves into cognitive-emotional processes (i.e., emotion regulation, attention impulsiveness, online vigilance, and multitasking) and emotional/behavioural factors (i.e., emotional problems, conduct problems, hyperactivity/inattention, peer relationships, and prosocial behaviours) that may be implicated in smartphone activities and technology addiction among adolescents. A community sample of Italian high school students (N = 676; 42.2% females) completed the Smartphone Distraction Scale (SDS), the Strength and Difficulties Questionnaire (SDQ) for internalising/externalising symptoms and the Internet Addiction Test (IAT) to assess the presence and severity of IA. The scores on the SDS were found to be positively associated with IA levels. Furthermore, students exhibiting higher internalising/externalising symptoms, particularly those with traits of attention deficit hyperactivity disorder (ADHD), are more likely to manifest problematic smartphone usage. The implications for screening adolescents more susceptible to developing IA symptoms and for implementing preventive interventions are discussed.
MeSH term(s)	Humans ; Adolescent ; Smartphone ; Female ; Male ; Italy ; Internet Addiction Disorder/psychology ; Internet Addiction Disorder/epidemiology ; Students/psychology ; Emotions ; Behavior, Addictive/psychology ; Surveys and Questionnaires ; Adolescent Behavior/psychology
Language	English
Publishing date	2024-03-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph21040386
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Article ; Online: Transient and Long-Term Improvements in Cognitive Processes following Video Games: An Italian Cross-Sectional Study.

Fabio, Rosa Angela / Ingrassia, Massimo / Massa, Marco

International journal of environmental research and public health

2021 Volume 19, Issue 1

Abstract: The aim of the present study is to compare the short- and long-term effects of video-gaming by using the same measurements. More precisely, habitual and occasional video-gamers were compared so as to analyze the long-term effects. An ABABABA design was ... ...

Abstract	The aim of the present study is to compare the short- and long-term effects of video-gaming by using the same measurements. More precisely, habitual and occasional video-gamers were compared so as to analyze the long-term effects. An ABABABA design was used to analyze the short-term effects. The first A refers to baseline measurements: Visual RT, Auditory RT, Aim trainer RT, Go/No-Go RT and N-Back RT. The first B refers to 30 min of gaming, the second A refers to the measurements used in the baseline, the second B refers to 60 min of a video game, the third A refers to the same measurements used in the baseline, the third B refers to a 30-min rest, and finally, the fourth A refers to the measurements used in the baseline. Seventy participants, twenty-nine habitual video-gamers and forty-one occasional video-gamers, participated in the study. The results showed a temporary improvement of cognitive functions (Visual RT, Auditory RT, Aim trainer RT, Go/No-Go RT and N-Back RT) in the short term and a strong enhancement of cognitive functions in the long term. The results are discussed in light of Flow Theory and the automatization process. Contribution of the study: The contribution of this research is to highlight that despite there being a transient enhancement of executive and cognitive functions through the use of mobile video games in the short-term period, with a decrease of performance after a 30-min rest, there is a strong increase of cognitive performance in the long-term period. Flow Theory and the automatization process together can explain this apparent inconsistency between the positive increase of long-term performance and the transient increase of short-term performance. One limitation of the present research is that it is not possible to distinguish whether the long-term enhancements can be attributed either to continued practice in the use of video games compared to non-gamers, or to the possibility that gamers are already predisposed to video game playing. Future research should address this issue.
MeSH term(s)	Cognition ; Cross-Sectional Studies ; Humans ; Video Games
Language	English
Publishing date	2021-12-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19010078
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Article ; Online: Transient and Long-Term Improvements in Cognitive Processes following Video Games

Rosa Angela Fabio / Massimo Ingrassia / Marco Massa

International Journal of Environmental Research and Public Health, Vol 19, Iss 78, p

An Italian Cross-Sectional Study

2022 Volume 78

Abstract	The aim of the present study is to compare the short- and long-term effects of video-gaming by using the same measurements. More precisely, habitual and occasional video-gamers were compared so as to analyze the long-term effects. An ABABABA design was used to analyze the short-term effects. The first A refers to baseline measurements: Visual RT, Auditory RT, Aim trainer RT, Go/No-Go RT and N-Back RT. The first B refers to 30 min of gaming, the second A refers to the measurements used in the baseline, the second B refers to 60 min of a video game, the third A refers to the same measurements used in the baseline, the third B refers to a 30-min rest, and finally, the fourth A refers to the measurements used in the baseline. Seventy participants, twenty-nine habitual video-gamers and forty-one occasional video-gamers, participated in the study. The results showed a temporary improvement of cognitive functions (Visual RT, Auditory RT, Aim trainer RT, Go/No-Go RT and N-Back RT) in the short term and a strong enhancement of cognitive functions in the long term. The results are discussed in light of Flow Theory and the automatization process. Contribution of the study: The contribution of this research is to highlight that despite there being a transient enhancement of executive and cognitive functions through the use of mobile video games in the short-term period, with a decrease of performance after a 30-min rest, there is a strong increase of cognitive performance in the long-term period. Flow Theory and the automatization process together can explain this apparent inconsistency between the positive increase of long-term performance and the transient increase of short-term performance. One limitation of the present research is that it is not possible to distinguish whether the long-term enhancements can be attributed either to continued practice in the use of video games compared to non-gamers, or to the possibility that gamers are already predisposed to video game playing. Future research should address this issue.
Keywords	video-gaming ; cognitive empowerment ; long-term effects ; short-term effects ; flow theory ; automatization theory ; Medicine ; R
Subject code	330
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Serenoa repens + selenium + lycopene vs tadalafil 5 mg for the treatment of lower urinary tract symptoms secondary to benign prostatic obstruction: a Phase IV, non-inferiority, open-label, clinical study (SPRITE study).

Morgia, Giuseppe / Vespasiani, Giuseppe / Pareo, Rosaria M / Voce, Salvatore / Madonia, Massimo / Carini, Marco / Ingrassia, Antonio / Terrone, Carlo / Gentile, Marcello / Carrino, Maurizio / Giannantoni, Antonella / Blefari, Franco / Arnone, Salvatore / Santelli, Giorgio / Russo, Giorgio I

BJU international

2018 Volume 122, Issue 2, Page(s) 317–325

Abstract: Objective: To compare in a randomised, open-label, non-inferiority clinical study, the efficacy and tolerability of Serenoa repens (SeR) + selenium (Se) + lycopene (Ly) (SeR-Se-Ly) therapy vs tadalafil 5 mg in men with lower urinary tract symptoms (LUTS) ...

Abstract	Objective: To compare in a randomised, open-label, non-inferiority clinical study, the efficacy and tolerability of Serenoa repens (SeR) + selenium (Se) + lycopene (Ly) (SeR-Se-Ly) therapy vs tadalafil 5 mg in men with lower urinary tract symptoms (LUTS). Patients and methods: From May 2015 to January 2017, 427 patients were enrolled in 21 different centres (International Standard Randomised Controlled Trial Number Register [ISRCTN] 73316039). Inclusion criteria included: age between 50 and 80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Q Results: In all, 404 patients completed the full protocol. When comparing both therapies, Group A was statistically not inferior to Group B considering the median change in IPSS (-3.0 vs -3.0; P < 0.01), IPSS quality of life (-2.0 vs -2.0; P < 0.05), and Q Conclusion: We have shown that treatment with SeR-Se-Ly was not inferior to tadalafil 5 mg for improving IPSS and Q
MeSH term(s)	Aged ; Aged, 80 and over ; Drug Combinations ; Humans ; Lower Urinary Tract Symptoms/drug therapy ; Lower Urinary Tract Symptoms/etiology ; Lycopene/administration & dosage ; Male ; Middle Aged ; Phosphodiesterase 5 Inhibitors/administration & dosage ; Plant Extracts/administration & dosage ; Prostatic Hyperplasia/complications ; Selenium/administration & dosage ; Tablets ; Tadalafil/administration & dosage ; Treatment Outcome ; Urological Agents/administration & dosage
Chemical Substances	Drug Combinations ; Phosphodiesterase 5 Inhibitors ; Plant Extracts ; Tablets ; Urological Agents ; Tadalafil (742SXX0ICT) ; Selenium (H6241UJ22B) ; saw palmetto extract (J7WWH9M8QS) ; Lycopene (SB0N2N0WV6)
Language	English
Publishing date	2018-04-16
Publishing country	England
Document type	Clinical Trial, Phase IV ; Comparative Study ; Equivalence Trial ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	1462191-5
ISSN	1464-410X ; 1464-4096 ; 1358-8672
ISSN (online)	1464-410X
ISSN	1464-4096 ; 1358-8672
DOI	10.1111/bju.14209
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Article: Ferritins: a family of molecules for iron storage, antioxidation and more.

Arosio, Paolo / Ingrassia, Rosaria / Cavadini, Patrizia

Biochimica et biophysica acta

2008 Volume 1790, Issue 7, Page(s) 589–599

Abstract: Ferritins are characterized by highly conserved three-dimensional structures similar to spherical shells, designed to accommodate large amounts of iron in a safe, soluble and bioavailable form. They can have different architectures with 12 or 24 ... ...

Abstract	Ferritins are characterized by highly conserved three-dimensional structures similar to spherical shells, designed to accommodate large amounts of iron in a safe, soluble and bioavailable form. They can have different architectures with 12 or 24 equivalent or non-equivalent subunits, all surrounding a large cavity. All ferritins readily interact with Fe(II) to induce its oxidation and deposition in the cavity in a mineral form, in a reaction that is catalyzed by a ferroxidase center. This is an anti-oxidant activity that consumes Fe(II) and peroxides, the reagents that produce toxic free radicals in the Fenton reaction. The mechanism of ferritin iron incorporation has been characterized in detail, while that of iron release and recycling has been less thoroughly studied. Generally ferritin expression is regulated by iron and by oxidative damage, and in vertebrates it has a central role in the control of cellular iron homeostasis. Ferritin is mostly cytosolic but is found also in mammalian mitochondria and nuclei, in plant plastids and is secreted in insects. In vertebrates the cytosolic ferritins are composed of H and L subunit types and their assembly in a tissues specific ratio that permits flexibility to adapt to cell needs. The H-ferritin can translocate to the nuclei in some cell types to protect DNA from iron toxicity, or can be actively secreted, accomplishing various functions. The mitochondrial ferritin is found in mammals, it has a restricted tissue distribution and it seems to protect the mitochondria from iron toxicity and oxidative damage. The various functions attributed to the cytosolic, nuclear, secretory and mitochondrial ferritins are discussed.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Ferritins/chemistry ; Ferritins/genetics ; Ferritins/immunology ; Ferritins/physiology ; Humans ; Immunotherapy ; Iron/metabolism ; Neoplasms/drug therapy ; Oxidation-Reduction
Chemical Substances	Antioxidants ; Ferritins (9007-73-2) ; Iron (E1UOL152H7)
Language	English
Publishing date	2008-09-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2008.09.004
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Article: Mutations of ferritin H chain C-terminus produced by nucleotide insertions have altered stability and functional properties.

Ingrassia, Rosaria / Gerardi, Gianmario / Biasiotto, Giorgio / Arosio, Paolo

Journal of biochemistry

2006 Volume 139, Issue 5, Page(s) 881–885

Abstract: Ferritin is an iron storage protein made of 24 subunits. Previous mutational analyses showed that ferritin C-terminal region has a major role in protein stability and assembly but is only marginally involved in the mechanism of iron incorporation. ... ...

Abstract	Ferritin is an iron storage protein made of 24 subunits. Previous mutational analyses showed that ferritin C-terminal region has a major role in protein stability and assembly but is only marginally involved in the mechanism of iron incorporation. However, it has recently been shown that patients who carry alterations of ferritin C-terminal sequence caused by nucleotide insertions show neurological disorders possibly related to altered protein functionality and cellular iron deregulation. To re-evaluate the role of this region, five mutants of mouse H-ferritin were produced by 2-nucleotide insertions that modified the last 6-29 residues and extended the sequence of 14 amino acids. The mutants were expressed in Escherichia coli and analysed for solubility, stability and capacity to incorporate iron. The alteration of the last 6-residue non-helical extension had no evident effect on the properties of ferritin, while solubility and capacity to assemble in ferritin shells decreased progressively with the extension of the modified region. The results also showed that the modification of even a part of the terminal E-helix abolished the capacity of ferritin to incorporate iron during expression in the cells, probably caused by conformational modification of the hydrophobic channels. The data support the hypothesis that the pathogenic mutations alter cellular iron homeostasis.
MeSH term(s)	Animals ; Cloning, Molecular ; Escherichia coli/genetics ; Ferritins/chemistry ; Ferritins/genetics ; Ferritins/metabolism ; Humans ; Iron/metabolism ; Kinetics ; Mice ; Molecular Sequence Data ; Mutagenesis, Insertional/genetics ; Mutation ; Protein Denaturation/genetics ; Recombinant Proteins/metabolism ; Sequence Analysis, DNA ; Sequence Deletion ; Solubility
Chemical Substances	Recombinant Proteins ; Ferritins (9007-73-2) ; Iron (E1UOL152H7)
Language	English
Publishing date	2006-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
DOI	10.1093/jb/mvj101
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Article: Mutations of Ferritin H Chain C-Terminus Produced by Nucleotide Insertions Have Altered Stability and Functional Properties

Ingrassia, Rosaria / Gerardi, Gianmario / Biasiotto, Giorgio / Arosio, Paolo

Journal of biochemistry. 2006 May, v. 139, no. 5

2006

Abstract	Ferritin is an iron storage protein made of 24 subunits. Previous mutational analyses showed that ferritin C-terminal region has a major role in protein stability and assembly but is only marginally involved in the mechanism of iron incorporation. However, it has recently been shown that patients who carry alterations of ferritin C-terminal sequence caused by nucleotide insertions show neurological disorders possibly related to altered protein functionality and cellular iron deregulation. To re-evaluate the role of this region, five mutants of mouse H-ferritin were produced by 2-nucleotide insertions that modified the last 6-29 residues and extended the sequence of 14 amino acids. The mutants were expressed in Escherichia coli and analysed for solubility, stability and capacity to incorporate iron. The alteration of the last 6-residue non-helical extension had no evident effect on the properties of ferritin, while solubility and capacity to assemble in ferritin shells decreased progressively with the extension of the modified region. The results also showed that the modification of even a part of the terminal E-helix abolished the capacity of ferritin to incorporate iron during expression in the cells, probably caused by conformational modification of the hydrophobic channels. The data support the hypothesis that the pathogenic mutations alter cellular iron homeostasis.
Language	English
Dates of publication	2006-05
Size	p. 881-885.
Publishing place	Oxford University Press
Document type	Article
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
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Article: Impact of Three Kinds of Early Interventions on Developmental Profile in Toddlers with Autism Spectrum Disorder.

Cucinotta, Francesca / Vetri, Luigi / Ruta, Liliana / Turriziani, Laura / Benedetto, Loredana / Ingrassia, Massimo / Maggio, Roberta / Germanò, Eva / Alquino, Ausilia / Siracusano, Rosamaria / Roccella, Michele / Gagliano, Antonella

Journal of clinical medicine

2022 Volume 11, Issue 18

Abstract: Autism spectrum disorder is a neurodevelopmental disorder with a rising prevalence disorder. This high-cost/high-burden condition needs evidence-based behavioral treatments that are able to reduce the impact of symptoms on children’s functioning. This ... ...

Abstract	Autism spectrum disorder is a neurodevelopmental disorder with a rising prevalence disorder. This high-cost/high-burden condition needs evidence-based behavioral treatments that are able to reduce the impact of symptoms on children’s functioning. This retrospective chart review study compared the impact of different types of early interventions on toddlers diagnosed with an autism spectrum disorder developmental profile. Analyses were conducted on 90 subjects (mean = 27.76 months, range 18−44 months; M:F = 4.29:1), of which 36 children underwent the usual treatment, 13 children underwent an intervention based on early intensive behavioral intervention (EIBI) and 41 children received the Early Start Denver Model, for one year, with the same weekly frequency of about 6 h a week. A significant decrease in the severity of autism symptoms was observed for all children when looking at the Ados-2 severity score (average difference = 3.05, SD = 0.71, p = < 0.001) and the Ados-2 social subscale (average difference = 2.87, SD = 0.59, p < 0.001). Otherwise, for most of the Griffiths subscales, we found a significant improvement only for those children who underwent the Early Start Denver Model intervention (General Quotient average difference = 14.47, SD = 3.22, corrected p < 0.001). Analyzing the influence of age on the investigated scores, we found a significant association with the Eye−hand Coordination Quotient (p = 0.003), Performance Quotient (p = 0.042) and General Quotient (p = 0.006). In all these domains, a mild negative correlation with age was observed, as measured by the Pearson’s correlation coefficient (r = −0.32, p = 0.002; r = −0.21, p = 0.044; r = −0.25, p = 0.019, respectively), suggesting less severe developmental skills at the start of treatment for older children. Our results are consistent with the literature that underlines the importance of early intervention, since prompt diagnosis can reduce the severity of autism symptoms; nevertheless, in toddlers, our study demonstrated that an intervention model based on naturalistic developmental behavioral principles such as the Early Start Denver Model is more effective on children’s developmental profile. Further studies are required to assess the extent of effectiveness of different early intervention models in community settings.
Language	English
Publishing date	2022-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11185424
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