77 results on '"Simonelli V"'
Search Results
2. Chapter 15. DNA Repair in the Development of Human Diseases and Therapy
- Author
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D'Errico, M., primary, Pascucci, B., additional, Parlanti, E., additional, Simonelli, V., additional, and Dogliotti, E., additional
- Published
- 2020
- Full Text
- View/download PDF
3. Cardiovascular Involvement in mtDNA Disease: Diagnosis, Management, and Therapeutic Options
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Lioncino M., Monda E., Caiazza M., Fusco A., Cirillo A., Dongiglio F., Simonelli V., Sampaolo S., Ruggiero L., Scarano G., Pota V., Frisso G., Mazzaccara C., D'Amati G., Nigro G., Russo M. G., Wahbi K., Limongelli G., Lioncino, M., Monda, E., Caiazza, M., Fusco, A., Cirillo, A., Dongiglio, F., Simonelli, V., Sampaolo, S., Ruggiero, L., Scarano, G., Pota, V., Frisso, G., Mazzaccara, C., D'Amati, G., Nigro, G., Russo, M. G., Wahbi, K., and Limongelli, G.
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Cardiomyopathy, Dilated ,Mitochondrial Diseases ,mtDNA ,hypertrophic ,DNA ,hypertrophic cardiomyopathy ,MELAS syndrome ,mitochondrial diseases ,DNA, mitochondrial ,humans ,cardiomyopathies ,cardiomyopathy, dilated ,cardiomyopathy, hypertrophic ,Cardiomyopathy, Hypertrophic ,mitochondrial ,DNA, Mitochondrial ,Mitochondrial disease ,Hypertrophic cardiomyopathy ,Humans ,Cardiomyopathies ,cardiomyopathy ,dilated ,Human ,Cardiomyopathie - Abstract
Mitochondrial diseases (MD) include an heterogenous group of systemic disorders caused by sporadic or inherited mutations in nuclear or mitochondrial DNA (mtDNA), causing impairment of oxidative phosphorylation system. Hypertrophic cardiomyopathy is the dominant pattern of cardiomyopathy in all forms of mtDNA disease, being observed in almost 40% of the patients. Dilated cardiomyopathy, left ventricular noncompaction, and conduction system disturbances have been also reported. In this article, the authors discuss the current clinical knowledge on MD, focusing on diagnosis and management of mitochondrial diseases caused by mtDNA mutations.
- Published
- 2021
4. Restless legs syndrome and post polio syndrome: a case−control study
- Author
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Romigi, A., Pierantozzi, M., Placidi, F., Evangelista, E., Albanese, M., Liguori, C., Nazzaro, M., Risina, B. U., Simonelli, V., Izzi, F., Mercuri, N. B., and Desiato, M. T.
- Published
- 2015
- Full Text
- View/download PDF
5. O016 - « Best-track » en chirurgie bariatrique et métabolique : analyse de la faisabilité et de l’efficacité en termes de coûts-bénéfice, obtenue par une étude de cohorte appariée monocentrique
- Author
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Goergen, M., Simonelli, V., Azagra, J.S., Poulain, V., Arendt, C., Pascotto, B., and Zolotas, C.
- Published
- 2016
- Full Text
- View/download PDF
6. Restless legs syndrome and post polio syndrome: a casecontrol study: P711
- Author
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Romigi, A., Desiato, M. T., Izzi, F., Pierantozzi, M., Evangelista, E., Albanese, M., Liguori, C., Mercuri, N., Nazzaro, M., Risina, B., Simonelli, V., and Placidi, F.
- Published
- 2014
7. DNA Repair in the development of human diseases and therapy
- Author
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D'Errico M., Pascucci B., Parlanti E., Simonelli V., and Dogliotti E
- Subjects
DNA damage ,DNA repair ,Human diseases - Abstract
In 1968 James Cleaver reported the first evidence of a link between a skin cancer-prone human syndrome, xeroderma pigmentosum, and a defect in DNA repair. This pivotal study paved the way for a large number of investigations that have clarified the importance of a functioning DNA repair system to the protection not only from skin cancer but also to the maintenance of neurologic, metabolic and immunologic health in the general population. The main focus of this chapter is to use the genetic disorders linked to DNA repair defects to unravel the correlation, often unexpected, between accumulation of different types of DNA damage and pathological endpoints. Moreover, we provide examples of how a better knowledge of DNA damage and repair mechanism may provide insights and opportunities for disease prevention and treatment.
- Published
- 2020
8. Diagnostic and operative fertiloscopy
- Author
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PELLICANO, MASSIMILIANO, CIRILLO, DOMENICO, NAPPI, CARMINE, CATENA U., DI IORIO P., SIMONELLI V., SORRENTINO F., STELLA N., BONIFACIO M., Pellicano, Massimiliano, Catena, U., DI IORIO, P., Simonelli, V., Sorrentino, F., Stella, N., Bonifacio, M., Cirillo, Domenico, and Nappi, Carmine
- Published
- 2007
9. « Best-track » en chirurgie bariatrique et métabolique : analyse de la faisabilité et de l’efficacité en termes de coûts-bénéfice, obtenue par une étude de cohorte appariée monocentrique
- Author
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Goergen, M., primary, Simonelli, V., additional, Azagra, J.S., additional, Poulain, V., additional, Arendt, C., additional, Pascotto, B., additional, and Zolotas, C., additional
- Published
- 2016
- Full Text
- View/download PDF
10. Hand-Sewn Running Barbed Suture versus Endoscopic Stapler Closure of the Mesenteric Defects in Retrocolic and Retrogastric RYGB: A Comparative Case-Matched Study
- Author
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Simonelli, V., primary, Orlando, G., additional, Zolotas, A., additional, Arendt, C., additional, Arru, L., additional, Poulain, V., additional, Azagra, J. S., additional, and Goergen, M., additional
- Published
- 2015
- Full Text
- View/download PDF
11. Restless legs syndrome and post polio syndrome: a case−control study
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Romigi, A., primary, Pierantozzi, M., additional, Placidi, F., additional, Evangelista, E., additional, Albanese, M., additional, Liguori, C., additional, Nazzaro, M., additional, Risina, B. U., additional, Simonelli, V., additional, Izzi, F., additional, Mercuri, N. B., additional, and Desiato, M. T., additional
- Published
- 2014
- Full Text
- View/download PDF
12. Validation of lymphoblastoid cell lines for the identification of at risk DNA repair genotypes
- Author
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Allione, A, Giachino, Claudia, Zijno, A, Porcedda, P, Guarrera, S, Polidoro, S, Di Gregorio, A, Vineis, Pl, Saini, F, Marcon, F, Garofalo, B, Simonelli, V, Barone, F, Minoprio, A, Narciso, L, Loft, S, Moller, P, Vogel, U, Munnia, A, Peluso, M, D'Errico, M, Mazzei, F, Dogliotti, E, and Matullo, Giuseppe
- Published
- 2008
13. Famiglie multiproblematiche: teoria e operatività di un Servizio per la Genitorialità realizzato nel Comune di La Spezia
- Author
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Simonelli, Alessandra, Versi, C., Simonelli, V., and Pistelli, S.
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psyco-social intervention ,Risk Factors ,Parenthood - Published
- 2008
14. The base excsion repair: mechnism and its relevance for cancer susceptibility
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Fortini P., Pascucci B., Parlanti E., D'Errico M., Simonelli V., and Dogliotti E.
- Subjects
B ER ,Danno al DNA ,Riparazione del DNA ,Suscettibilità genet - Abstract
Base damage or loss occurs at high frequency in the cells (almost 10(4) bases are damaged and hydrolysed per cell per day). DNA repair is fundamental to maintain genomic integrity. Base excision repair (BER) is the main mechanism by which cells correct various types of damaged DNA bases generated either by endogenous or exogenous factors. The widely accepted model for BER mechanism involves five sequential reactions: (i) base removal; (ii) incision of the resulting abasic site; (iii) processing of the generated termini at the strand break; (iv) DNA synthesis, and (v) ligation. In this review, we will briefly summarise the biochemistry of each BER step and will concentrate on the biological relevance of BER as inferred from in vitro and in vivo studies. This information will be the basis for speculation on the potential role of malfunction of BER in human pathology.
- Published
- 2003
15. 8-Oxoguanide DNA damage: at the crossroad of alternative repair pathway
- Author
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Fortini P., Pascucci B., Parlanti E., D'Errico M., Simonelli V., and Dogliotti E.
- Abstract
Radical oxygen species (ROS) generate various modified DNA bases. Among them 8-oxo-7,8-dihydroguanine (8oxoG) is the most abundant and seems to play a major role in mutagenesis and in carcinogenesis. 8oxoG is removed from DNA by the specific glycosylase OGG1. An additional post-replication repair is needed to correct the 8oxoG/A mismatches that are produced by persistent 8oxoG residues. This review is focused on the mechanisms of base excision repair (BER) of this oxidized base. It is shown that, in vitro, efficient and complete repair of 8oxoG/C pairs requires a core of four proteins, namely OGG1, APE1, DNA polymerase (Pol) beta, and DNA ligase I. Repair occurs predominantly by one nucleotide replacement reactions (short-patch BER) and Pol beta is the polymerase of election for the resynthesis step. However, alternative mechanisms can act on 8oxoG residues since Pol beta-null cells are able to repair these lesions. 8oxoG/A mismatches are repaired by human cell extracts via two BER events which occur sequentially on the two strands. The removal of the mismatched adenine is followed by preferential insertion of a cytosine leading to the formation of 8oxoG/C pairs which are then corrected by OGG1-mediated BER. Both repair events are inhibited by aphidicolin, suggesting that a replicative DNA polymerase is involved in the repair synthesis step. We propose that Pol delta/epsilon-mediated BER (long-patch BER) is the mode of repair when lesions persist or are formed at replication. Finally, we address the issues of the relative contribution of the two BER pathways to oxidative damage repair in vivo and the possible role of BER gene variants as cancer susceptibility genes.
- Published
- 2003
16. Diet-related telomere shortening and chromosome stability
- Author
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Marcon, F., primary, Siniscalchi, E., additional, Crebelli, R., additional, Saieva, C., additional, Sera, F., additional, Fortini, P., additional, Simonelli, V., additional, and Palli, D., additional
- Published
- 2011
- Full Text
- View/download PDF
17. The Role of Office and Operative Fertiloscopy in the Infertility Diagnostic Work-Up
- Author
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Pellicano, M., primary, Simonelli, V., additional, Catena, U., additional, and Nappi, C., additional
- Published
- 2008
- Full Text
- View/download PDF
18. Endometriosis and Angiogenic Growth Factors
- Author
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Pellicano, M., primary, Catena, U., additional, Simonelli, V., additional, and Nappi, C., additional
- Published
- 2008
- Full Text
- View/download PDF
19. Base excision repair intermediates are mutagenic in mammalian cells
- Author
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Simonelli, V., primary
- Published
- 2005
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20. Influence of obesity-susceptibility loci (MC4R and INSIG2) on the outcome of weight loss and amelioration of co-morbidity in obese patients treated by a gastric-bypass.
- Author
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Goergen, M., Manzoni, D., De Blasi, V., Fabiano, P., Poulain, V., De Magistris, L., Simonelli, V., Dahan, K., and Azagra, J.-S.
- Published
- 2011
21. 8-Oxoguanine DNA damage: at the crossroad of alternative repair pathways
- Author
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Fortini, P., Pascucci, B., Parlanti, E., D'Errico, M., Simonelli, V., and Dogliotti, E.
- Abstract
Radical oxygen species (ROS) generate various modified DNA bases. Among them 8-oxo-7,8-dihydroguanine (8oxoG) is the most abundant and seems to play a major role in mutagenesis and in carcinogenesis. 8oxoG is removed from DNA by the specific glycosylase OGG1. An additional post-replication repair is needed to correct the 8oxoG/A mismatches that are produced by persistent 8oxoG residues. This review is focused on the mechanisms of base excision repair (BER) of this oxidized base. It is shown that, in vitro, efficient and complete repair of 8oxoG/C pairs requires a core of four proteins, namely OGG1, APE1, DNA polymerase (Pol) β, and DNA ligase I. Repair occurs predominantly by one nucleotide replacement reactions (short-patch BER) and Pol β is the polymerase of election for the resynthesis step. However, alternative mechanisms can act on 8oxoG residues since Pol β-null cells are able to repair these lesions. 8oxoG/A mismatches are repaired by human cell extracts via two BER events which occur sequentially on the two strands. The removal of the mismatched adenine is followed by preferential insertion of a cytosine leading to the formation of 8oxoG/C pairs which are then corrected by OGG1-mediated BER. Both repair events are inhibited by aphidicolin, suggesting that a replicative DNA polymerase is involved in the repair synthesis step. We propose that Pol δ/ɛ-mediated BER (long-patch BER) is the mode of repair when lesions persist or are formed at replication. Finally, we address the issues of the relative contribution of the two BER pathways to oxidative damage repair in vivo and the possible role of BER gene variants as cancer susceptibility genes.
- Published
- 2003
- Full Text
- View/download PDF
22. Bowel Angiodysplasia and Myocardial Infarction secondary to an ischaemic imbalance: a case report
- Author
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Salzano Andrea, Rocca Aldo, Arcopinto Michele, Amato Bruno, Maria Marra Alberto, Simonelli Vincenzo, Mozzillo Pasquale, Giuliani Antonio, Tafuri Domenico, and Cinelli Mariapia
- Subjects
Angiodisplasya ,Miocardial Infarction ,Ischemia ,Bowel ,Medicine - Abstract
Angiodysplasia, defined as a vascular ectasia or arteriovenous malformation, is the most frequent cause of occult bleeding in patients older than 60 years and a significant association with several cardiac condition is described. Patients with anemia and negative findings on upper endoscopy and colonoscopy should be referred for further investigation of the small bowel. The investigation of choice, when available, is wireless capsule endoscopy. Several therapeutic options are available in this cases, as we reviewed in this report. We report a case of 78-year old man admitted to our Intensive Coronary Unit for dyspnea and chest pain. A diagnosis of non-ST-segment elevation acute coronary syndrome was made and a concomintant, significant anemia was found (hemoglobin 8.2 g/dl). No cororary disease was found by an angiography though the past medical history revealed systemic hypertension, chronic kidney disease (KDOQY stage III), and diabetes mellitus type II on insuline therapy. A Wireless Video capsule examination was positive for jejunum angiodysplasia and an argon plasma coagulation was chosen as terapeutic option. No subsequent supportive therapy and interventions were required in subsequent one year of follow-up.
- Published
- 2015
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23. Long Term Migraine Prophylaxis With Flunarizine: Clinical Evidence
- Author
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Marmo, E., primary, Alfano, V., additional, Cassano, D., additional, Giordano, E., additional, Simonelli, V., additional, and Colucci D'amato, C., additional
- Published
- 1987
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- View/download PDF
24. Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways
- Author
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Nicosia Alfredo, La Monica Nicola, Lahm Armin, De Rinaldis Emanuele, Dogliotti Eugenia, Simonelli Valeria, Viti Valentina, Uva Paolo, Marra Emanuele, Ciliberto Gennaro, and Palombo Fabio
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI) anchored protein expressed not only in prostate but also in pancreas and bladder cancer as shown by immunohistochemistry and mRNA analysis. It has been targeted by monoclonal antibodies in preclinical animal models and more recently in a clinical trial in prostate cancer patients. The biological role played in tumor growth is presently unknown. In this report we have characterized the contribution of PSCA expression to tumor growth. Methods A bladder cell line was engineered to express a doxycycline (dox) regulated shRNA against PSCA. To shed light on the PSCA biological role in tumor growth, microarray analysis was carried out as a function of PSCA expression. Expression of gene set of interest was further analyzed by qPCR Results Down regulation of the PSCA expression was associated with reduced cell proliferation in vitro and in vivo. Mice bearing subcutaneous tumors showed a reduced tumor growth upon treatment with dox, which effectively induced shRNA against PSCA as revealed by GFP expression. Pathway analysis of deregulated genes suggests a statistical significant association between PSCA downregulation and activation of genes downstream of the IFNα/β receptor. Conclusions These experiments established for the first time a correlation between the level of PSCA expression and tumor growth and suggest a role of PSCA in counteracting the natural immune response.
- Published
- 2010
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25. The base excision repair: mechanisms and its relevance for cancer susceptibility
- Author
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Fortini, P., Pascucci, B., Parlanti, E., D’Errico, M., Simonelli, V., and Dogliotti, E.
- Subjects
- *
CELLS , *CANCER , *GENOMICS , *SURGICAL excision - Abstract
Base damage or loss occurs at high frequency in the cells (almost 104 bases are damaged and hydrolysed per cell per day). DNA repair is fundamental to maintain genomic integrity. Base excision repair (BER) is the main mechanism by which cells correct various types of damaged DNA bases generated either by endogenous or exogenous factors. The widely accepted model for BER mechanism involves five sequential reactions: (i) base removal; (ii) incision of the resulting abasic site; (iii) processing of the generated termini at the strand break; (iv) DNA synthesis, and (v) ligation. In this review, we will briefly summarise the biochemistry of each BER step and will concentrate on the biological relevance of BER as inferred from in vitro and in vivo studies. This information will be the basis for speculation on the potential role of malfunction of BER in human pathology. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
26. The dual nature of DNA damage response in obesity and bariatric surgery-induced weight loss.
- Author
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Escobar Marcillo DI, Guglielmi V, Privitera GF, Signore M, Simonelli V, Manganello F, Dell'Orso A, Laterza S, Parlanti E, Pulvirenti A, Marcon F, Siniscalchi E, Fertitta V, Iorio E, Varì R, Nisticò L, Valverde M, Sbraccia P, Dogliotti E, and Fortini P
- Subjects
- Humans, Male, Adult, Female, Middle Aged, Leukocytes, Mononuclear metabolism, Intra-Abdominal Fat metabolism, Mitochondria metabolism, Bariatric Surgery methods, DNA Damage, Obesity metabolism, Obesity surgery, Weight Loss
- Abstract
This novel study applies targeted functional proteomics to examine tissues and cells obtained from a cohort of individuals with severe obesity who underwent bariatric surgery (BS), using a Reverse-Phase Protein Array (RPPA). In obese individuals, visceral adipose tissue (VAT), but not subcutaneous adipose tissue (SAT), shows activation of DNA damage response (DDR) markers including ATM, ATR, histone H2AX, KAP1, Chk1, and Chk2, alongside senescence markers p16 and p21. Additionally, stress-responsive metabolic markers, such as survivin, mTOR, and PFKFB3, are specifically elevated in VAT, suggesting both cellular stress and metabolic dysregulation. Conversely, peripheral blood mononuclear cells (PBMCs), while exhibiting elevated mTOR and JNK levels, did not present significant changes in DDR or senescence markers. Following BS, unexpected increases in phosphorylated ATM, ATR, and KAP1 levels, but not in Chk1 and Chk2 nor in senescence markers, were observed. This was accompanied by heightened levels of survivin and mTOR, along with improvement in markers of mitochondrial quality and health. This suggests that, following BS, pro-survival pathways involved in cellular adaptation to various stressors and metabolic alterations are activated in circulating PBMCs. Moreover, our findings demonstrate that the DDR has a dual nature. In the case of VAT from individuals with obesity, chronic DDR proves to be harmful, as it is associated with senescence and chronic inflammation. Conversely, after BS, the activation of DDR proteins in PBMCs is associated with a beneficial survival response. This response is characterized by metabolic redesign and improved mitochondrial biogenesis and functionality. This study reveals physiological changes associated with obesity and BS that may aid theragnostic approaches., (© 2024. The Author(s).)
- Published
- 2024
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27. Clozapine Treatment for Aggressive Behaviors in Youths with Neurodevelopmental Disorders.
- Author
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Berloffa S, Masi G, Falcone F, Simonelli V, Narzisi A, Valente E, Viglione V, Milone A, and Sesso G
- Subjects
- Male, Child, Humans, Adolescent, Aggression, Psychotherapy, Clozapine adverse effects, Autism Spectrum Disorder, Neurodevelopmental Disorders drug therapy, Antipsychotic Agents adverse effects
- Abstract
Objectives: The aim of this study was to assess effectiveness and tolerability of Clozapine in the treatment of aggression in youth with Neurodevelopmental Disorders. Methods: Patients were consecutively admitted at our third-level university hospital with nationwide catchment from June 2018 to October 2022, and followed up to July 2023. Eligibility criteria were as follows: (1) Autism Spectrum Disorder (ASD) and/or Intellectual Disability/Borderline Cognitive Functioning, (2) behavioral dyscontrol with physical aggression; (3) age range between 8 and 18 years; (4) clinical indication for Clozapine treatment after at least two failed trials with other Second-Generation Antipsychotics (SGAs); (5) availability of an at least 6-month-long follow-up. To evaluate the response to Clozapine, we used the Clinical Global Impressions (CGI) rating scales (Clinical Global Impressions-Severity [CGI-S] and Clinical Global Impressions-Improvement [CGI-I]), the Children's Global Assessment Scale (CGAS), and the Aberrant Behavior Checklist (ABC). Results: Twenty-six children and adolescents (21 boys, age 13.47 ± 2.05 years, follow-up duration 9.77 ± 3.50 months) were included in the analysis. Clinical severity (CGI-S) and functional impairment (Clinical Global Assessment Scale) significantly improved, as well as the ABC Total Score and the scores in several subscales. Sixteen patients (61.54%) were responders (CGI-I ≤2), and 13 (50.00%) displayed remission of aberrant behaviors (ΔABC-Total >35), while response/remission condition was not affected by add-on medications and psychotherapy. Most frequent side effects were increased appetite (50.00%), sialorrhea (38.46%), and increased repetitive behaviors (26.92%). Two patients presented epileptic seizures, while no patients presented leucopoenia. Conclusions: Our results suggest that Clozapine may be helpful in ameliorating treatment-resistant aggression in youth with neurodevelopmental conditions. Possible pharmacological strategies for the management of most frequent side effects are also suggested.
- Published
- 2024
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28. Adenocarcinoma arising from a chronic perianal fistula in a Crohn's disease patient: case report and review of the literature.
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Gosse J, Simonelli V, and Dessily M
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- Humans, Female, Crohn Disease complications, Crohn Disease surgery, Rectal Fistula diagnosis, Rectal Fistula etiology, Rectal Fistula therapy, Adenocarcinoma etiology, Adenocarcinoma surgery, Adenocarcinoma pathology, Adenocarcinoma, Mucinous complications, Adenocarcinoma, Mucinous diagnosis, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell etiology, Carcinoma, Squamous Cell surgery
- Abstract
Crohn's disease patients frequently develop perianal fistulas during their life. They are also at higher risk to develop cancers. Rarely, those cancers appear within a prior chronic fistula. The main types are adenocarcinoma mostly mucinous and squamous cell carcinoma. They are generally discovered at an advanced stage with a poor prognosis because symptoms are generally the same as those of the fistula itself. Regular follow-up of chronic fistulas is then important for an early diagnosis as well as histological analysis of the fistula during surgery. There is no consensus on the ideal treatment but abdominoperineal resection is the corner stone with or without neo or adjuvant chemo-radiotherapy. This paper presents a rare case of mucinous adenocarcinoma in a chronic perianal fistula in a Crohn's disease female and provides a review of the literature.
- Published
- 2024
- Full Text
- View/download PDF
29. Midline non-ictal rhythmic waveforms as possible electroencephalographic biomarkers of Smith-Klingsmore syndrome in children.
- Author
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Simonelli V, Ferrari AR, Battini R, Brovedani P, and Bartolini E
- Abstract
Introduction: Pathogenic variants of the MTOR gene result in the Smith-Kingsmore syndrome, whose phenotypical spectrum includes facial dysmorphisms and neurological features. Expressivity is variable, patients exhibit a combination of intellectual disability, macrocephaly and epilepsy. The diagnosis can be missed, failing to detect the causative pathogenic mutation in patients with somatic mosaicism or even skipping to analyze MTOR when the phenotype is not completely expressed., Case Study: Herein, we report two children harboring the same MTOR recurring mutation (c.5395G>A/p.Glu1799Lys) whose EEG displayed a peculiar combination of midline rhythmic waveforms and asynchronous spike-and-wave discharges with anterior fast activity in sleep and wake. Conclusion : We suggest these features might be considered as possible hallmarks of the syndrome and could aid to expedite the diagnosis when the phenotype is incomplete., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)
- Published
- 2024
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30. Internet Gaming Disorder in Children and Adolescents with Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder.
- Author
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Simonelli V, Narzisi A, Sesso G, Salvati A, Milone A, Viglione V, Tolomei G, Masi G, and Berloffa S
- Abstract
Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have been related to an increased risk for behavioral addictions including online gaming. However, the relationship between these two conditions and Internet gaming disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ASD youth and ADHD youth, compared with a normal control group, and by assessing selected psychopathological and neuropsychological features in ASD and ADHD patients with and without IGD. This study included 77 ASD patients (67 males, mean age 13.58 ± 2.75 years), 94 ADHD patients (79 males, mean age 11.46 ± 2.47 years), and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) that received structured measures for IGD (IAT, IGDS9-SF, and UADI). In the ADHD group, 72.34% of the sample were above the IGD cut-off, compared with 45.45% in the ASD group and 9.5% in the NC group. ASD patients with IGD presented with greater severity and more severe attention problems, with no difference in the ASD core symptoms between patients with and without IGD. In the comparison between the ASD and ADHD groups according to the presence of IGD, ASD patients with IGD were the most severe group according to the CGI (Clinical Global Impression) scale. The follow-up, conducted on 45 patients affected by ASD, showed an improvement in CGI and CGAS (Children's Global Assessment Scale) scores, but not in the IGD symptoms. These findings could place the diagnosis of ASD as a negative prognostic factor in the follow-up of aspects of video game addiction compared with ADHD.
- Published
- 2024
- Full Text
- View/download PDF
31. Combined Clinical, Molecular, and Muscle Biopsy Approach to Unveil Prevalence and Clinical Features of Rare Neuromuscular and Mitochondrial Diseases in Patients With Cardiomyopathies.
- Author
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Lioncino M, Monda E, Caiazza M, Simonelli V, Nesti C, Mauriello A, Budillon A, Di Santo A, Bruno G, Varone A, Nigro V, Santorelli FM, Pacileo G, Russo MG, Frisso G, Sampaolo S, and Limongelli G
- Subjects
- Humans, Prevalence, Biopsy, Muscles, Mitochondrial Diseases epidemiology, Mitochondrial Diseases genetics, Cardiomyopathies epidemiology, Cardiomyopathies genetics, Cardiomyopathies pathology
- Abstract
Competing Interests: Disclosures None.
- Published
- 2023
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32. Clinical, Genetic, and Histological Characterization of Patients with Rare Neuromuscular and Mitochondrial Diseases Presenting with Different Cardiomyopathy Phenotypes.
- Author
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Monda E, Lioncino M, Caiazza M, Simonelli V, Nesti C, Rubino M, Perna A, Mauriello A, Budillon A, Pota V, Bruno G, Varone A, Nigro V, Santorelli FM, Pacileo G, Russo MG, Frisso G, Sampaolo S, and Limongelli G
- Subjects
- Humans, Mutation, Phenotype, Cardiomyopathies genetics, Cardiomyopathies diagnosis, Mitochondrial Diseases diagnosis, Mitochondrial Diseases genetics, Cardiomyopathy, Hypertrophic, Muscular Diseases diagnosis, Muscular Diseases genetics
- Abstract
Cardiomyopathies are mostly determined by genetic mutations affecting either cardiac muscle cell structure or function. Nevertheless, cardiomyopathies may also be part of complex clinical phenotypes in the spectrum of neuromuscular (NMD) or mitochondrial diseases (MD). The aim of this study is to describe the clinical, molecular, and histological characteristics of a consecutive cohort of patients with cardiomyopathy associated with NMDs or MDs referred to a tertiary cardiomyopathy clinic. Consecutive patients with a definitive diagnosis of NMDs and MDs presenting with a cardiomyopathy phenotype were described. Seven patients were identified: two patients with ACAD9 deficiency ( Patient 1 carried the c.1240C>T (p.Arg414Cys) homozygous variant in ACAD9 ; Patient 2 carried the c.1240C>T (p.Arg414Cys) and the c.1646G>A (p.Ar549Gln) variants in ACAD9 ); two patients with MYH7 -related myopathy ( Patient 3 carried the c.1325G>A (p.Arg442His) variant in MYH7 ; Patient 4 carried the c.1357C>T (p.Arg453Cys) variant in MYH7 ); one patient with desminopathy ( Patient 5 carried the c.46C>T (p.Arg16Cys) variant in DES ); two patients with mitochondrial myopathy ( Patient 6 carried the m.3243A>G variant in MT-TL1 ; Patient 7 carried the c.253G>A (p.Gly85Arg) and the c.1055C>T (p.Thr352Met) variants in MTO1 ). All patients underwent a comprehensive cardiovascular and neuromuscular evaluation, including muscle biopsy and genetic testing. This study described the clinical phenotype of rare NMDs and MDs presenting as cardiomyopathies. A multidisciplinary evaluation, combined with genetic testing, plays a main role in the diagnosis of these rare diseases, and provides information about clinical expectations, and guides management.
- Published
- 2023
- Full Text
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33. The Crosstalk between Gut Microbiota and White Adipose Tissue Mitochondria in Obesity.
- Author
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Colangeli L, Escobar Marcillo DI, Simonelli V, Iorio E, Rinaldi T, Sbraccia P, Fortini P, and Guglielmi V
- Subjects
- Humans, Obesity metabolism, Adipose Tissue, White metabolism, Adipose Tissue, Brown metabolism, Mitochondria metabolism, Thermogenesis physiology, Energy Metabolism, Gastrointestinal Microbiome physiology
- Abstract
Adipose tissue (AT) dysregulation is a key process in the pathophysiology of obesity and its cardiometabolic complications, but even if a growing body of evidence has been collected over recent decades, the underlying molecular basis of adiposopathy remains to be fully understood. In this context, mitochondria, the intracellular organelles that orchestrate energy production and undergo highly dynamic adaptive changes in response to changing environments, have emerged as crucial regulators of both white (WAT) and brown adipose tissue (BAT) metabolism and function. Given that the gut microbiota and its metabolites are able to regulate host metabolism, adipogenesis, WAT inflammation, and thermogenesis, we hypothesize that their frequently observed dysregulation in obesity could affect AT metabolism by exerting direct and indirect effects on AT mitochondria. By collecting and revising the current evidence on the connections between gut microbiota and AT mitochondria in obesity, we gained insights into the molecular biology of their hitherto largely unexplored crosstalk, tracing how gut microbiota may regulate AT mitochondrial function.
- Published
- 2023
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34. Pathophysiology, Functional Assessment and Prognostic Implications of Nutritional Disorders in Systemic Amyloidosis.
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Dongiglio F, Monda E, Palmiero G, Verrillo F, Rubino M, Diana G, Cirillo A, Fusco A, Vetrano E, Lioncino M, Caiazza M, Cerciello G, Capodicasa L, Chiosi F, Simonelli V, De Rimini ML, Natale F, Di Santo A, Moscarella E, Calabrò P, and Limongelli G
- Abstract
Gastrointestinal involvement is a common clinical feature of patients with systemic amyloidosis. This condition is responsible for invalidating gastrointestinal symptoms, a significant macro and micronutrient deficit, and is a marker of disease severity. Gastrointestinal involvement should be actively sought in patients with systemic amyloidosis, while its diagnosis is challenging in patients with isolated gastrointestinal symptoms. The nutritional status in systemic amyloidosis plays an essential role in the clinical course and is considered a significant prognostic factor. However, the definition of nutritional status is still challenging due to the lack of internationally accepted thresholds for anthropometric and biochemical variables, especially in specific populations such as those with systemic amyloidosis. This review aims to elucidate the fundamental steps for nutritional assessment by using clinical and instrumental tools for better prognostic stratification and patient management regarding quality of life and outcomes.
- Published
- 2023
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35. A multi-marker integrative analysis reveals benefits and risks of bariatric surgery.
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Palleschi S, Guglielmi V, Nisticò L, Ferreri C, Tabolacci C, Facchiano F, Iorio E, Giuliani A, Brescianini S, Medda E, Fagnani C, Rossi B, Minoprio A, Chirico M, Pisanu ME, Di Nolfo F, Fortini P, Simonelli V, Baccarini S, Laterza S, Morretti T, Dell'Orso A, Manganello F, Gentileschi P, Sbraccia P, and Dogliotti E
- Subjects
- Humans, Weight Loss physiology, Weight Gain, Risk Assessment, Obesity, Morbid, Bariatric Surgery methods
- Abstract
Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success., (© 2022. The Author(s).)
- Published
- 2022
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36. An Overview of Molecular Mechanisms in Fabry Disease.
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Amodio F, Caiazza M, Monda E, Rubino M, Capodicasa L, Chiosi F, Simonelli V, Dongiglio F, Fimiani F, Pepe N, Chimenti C, Calabrò P, and Limongelli G
- Subjects
- Humans, alpha-Galactosidase genetics, alpha-Galactosidase metabolism, Biomarkers, Endothelial Cells metabolism, Fabry Disease genetics, Fabry Disease therapy
- Abstract
Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is α-galactosidase A (α-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers.
- Published
- 2022
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37. Acute Tolerability of Methylphenidate in Treatment-Naïve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice.
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Masi G, Pfanner C, Liboni F, Lenzi F, Villafranca A, D'Acunto G, Fantozzi P, Falcone F, Simonelli V, Muratori P, Levantini V, Favole I, Amianto F, Davico C, and Vitiello B
- Subjects
- Adolescent, Child, Delayed-Action Preparations, Female, Humans, Male, Retrospective Studies, Treatment Outcome, Attention Deficit Disorder with Hyperactivity drug therapy, Central Nervous System Stimulants adverse effects, Methylphenidate adverse effects
- Abstract
Objectives: The acute tolerability of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD) has been studied mainly in research samples. Taking advantage of the mandatory test-dose procedure required for starting MPH in Italy, this study aimed to assess the incidence of intolerable adverse events after initial exposure to MPH in routine clinical practice., Methods: The medical records of 480 consecutively treated, previously drug-naïve children and adolescents with ADHD (90% male, mean age 10.6 ± 3.0 years) were retrospectively analyzed. All children received an initial single dose of MPH immediate release (5 or 10 mg) followed by a 4-hour direct medical observation. Heart rate and blood pressure were measured at dosing and 1, 2, and 3 hours afterwards. If the first dose was well tolerated, the child continued treatment with MPH 5-20 mg daily, and was reassessed a week later., Results: Eleven patients (2.3%, 95% CI 1.1-4.1) interrupted treatment within a week of initiation because of the following adverse events: irritability (n = 3), tics worsening (n = 3), reduced appetite (n = 1), enuresis (n = 1), hallucinations (n = 1), hyperfocus (n = 1), and 'rebound' behavioral worsening (n = 1). The most common adverse events were reduced appetite (20%), irritability (14.2%), headache (10.6%), sleep problems (9.4%), stomachache (9.4%), and tics (5%). Intellectual disability increased the risk of any adverse event in general and of irritability in particular. No cardiovascular symptom was clinically reported. However, routine assessments of vital signs during the first 3 hours after the first dose of MPH showed that 9% of the children had a 20% increase in heart rate, 8.8% had a 20% increase in diastolic blood pressure and 4.5% had a 20% increase in systolic blood pressure. Of these, 25.2% still had an elevated heart rate 1 week later., Conclusions: Among stimulant-naïve children in clinical practice, the incidence of acute MPH intolerance can be estimated to be between 1.2 and 4.1%. An asymptomatic elevation in cardiovascular parameters can be observed in about 1 out of 10 children and warrants monitoring during ongoing treatment., (© 2022. The Author(s).)
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- 2022
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38. Cardiovascular Involvement in mtDNA Disease: Diagnosis, Management, and Therapeutic Options.
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Lioncino M, Monda E, Caiazza M, Fusco A, Cirillo A, Dongiglio F, Simonelli V, Sampaolo S, Ruggiero L, Scarano G, Pota V, Frisso G, Mazzaccara C, D'Amati G, Nigro G, Russo MG, Wahbi K, and Limongelli G
- Subjects
- DNA, Mitochondrial genetics, Humans, Cardiomyopathies etiology, Cardiomyopathies genetics, Cardiomyopathy, Dilated, Cardiomyopathy, Hypertrophic diagnosis, Cardiomyopathy, Hypertrophic genetics, Cardiomyopathy, Hypertrophic therapy, Mitochondrial Diseases diagnosis, Mitochondrial Diseases genetics, Mitochondrial Diseases therapy
- Abstract
Mitochondrial diseases (MD) include an heterogenous group of systemic disorders caused by sporadic or inherited mutations in nuclear or mitochondrial DNA (mtDNA), causing impairment of oxidative phosphorylation system. Hypertrophic cardiomyopathy is the dominant pattern of cardiomyopathy in all forms of mtDNA disease, being observed in almost 40% of the patients. Dilated cardiomyopathy, left ventricular noncompaction, and conduction system disturbances have been also reported. In this article, the authors discuss the current clinical knowledge on MD, focusing on diagnosis and management of mitochondrial diseases caused by mtDNA mutations., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2022
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39. Measuring the effects of first antiepileptic medication in Temporal Lobe Epilepsy: Predictive value of quantitative-EEG analysis.
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Ricci L, Assenza G, Pulitano P, Simonelli V, Vollero L, Lanzone J, Mecarelli O, Di Lazzaro V, and Tombini M
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- Adult, Aged, Alpha Rhythm drug effects, Alpha Rhythm physiology, Analysis of Variance, Area Under Curve, Beta Rhythm drug effects, Brain physiology, Case-Control Studies, Connectome, Delta Rhythm drug effects, Electroencephalography methods, Electroencephalography Phase Synchronization drug effects, Electroencephalography Phase Synchronization physiology, Epilepsy, Temporal Lobe physiopathology, Female, Gamma Rhythm drug effects, Humans, Male, Middle Aged, Prognosis, ROC Curve, Reproducibility of Results, Retrospective Studies, Theta Rhythm drug effects, Theta Rhythm physiology, Young Adult, Anticonvulsants pharmacology, Electroencephalography drug effects, Epilepsy, Temporal Lobe drug therapy, Levetiracetam pharmacology
- Abstract
Objective: To determine the quantitative EEG responses in a population of drug-naïve patients with Temporal Lobe Epilepsy (TLE) after Levetiracetam (LEV) initiation as first antiepileptic drug (AED). We hypothesized that the outcome of AED treatment can be predicted from EEG data in patients with TLE., Methods: Twenty-three patients with TLE and twenty-five healthy controls were examined. Clinical outcome was dichotomized into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG parameters were compared between healthy controls and patients with TLE at baseline (EEG
pre ) and after three months of AED therapy (EEGpre-post ) and between SF and NSF patients. Receiver Operating Characteristic curves models were built to test whether EEG parameters predicted outcome., Results: AED therapy induces an increase in EEG power for Alpha (p = 0.06) and a decrease in Theta (p < 0.05). Connectivity values were lower in SF compared to NSF patients (p < 0.001). Quantitative EEG predicted outcome after LEV treatment with an estimated accuracy varying from 65.2% to 91.3% (area under the curve [AUC] = 0.56-0.93) for EEGpre and from 69.9% to 86.9% (AUC = 0.69-0.94) for EEGpre-post ., Conclusions: AED therapy induces EEG modifications in TLE patients, and such modifications are predictive of clinical outcome., Significance: Quantitative EEG may help understanding the effect of AEDs in the central nervous system and offer new prognostic biomarkers for patients with epilepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)- Published
- 2021
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40. Behavioural and Emotional Changes during COVID-19 Lockdown in an Italian Paediatric Population with Neurologic and Psychiatric Disorders.
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Conti E, Sgandurra G, De Nicola G, Biagioni T, Boldrini S, Bonaventura E, Buchignani B, Della Vecchia S, Falcone F, Fedi C, Gazzillo M, Marinella G, Mazzullo C, Micomonaco J, Pantalone G, Salvati A, Sesso G, Simonelli V, Tolomei G, Troiano I, Cioni G, Masi G, Muratori F, Milone A, and Battini R
- Abstract
On 11 March 2020, a national lockdown was imposed by the Italian government to contain the spread of COVID19 disease. This is an observational longitudinal study conducted at Fondazione Stella Maris (FSM), Italy to investigate lockdown-related emotional and behavioural changes in paediatric neuropsychiatric population. Families having children (1.5-18 years) with neuropsychiatric disorders referred to FSM have been contacted and proposed to fulfil two online questionnaires (General questionnaire and Child Behaviour Check List (CBCL)) to (i) compare (paired two-sample t -tests) the CBCL scores during lockdown with previous ones, and (ii) investigate the influence (multiple linear regression models) of variables such as age, diagnosis grouping (neurological, neurodevelopmental, emotional, and behavioural disorders) and financial hardship. One hundred and forty-one parents fulfilled the questionnaires. Anxiety and somatic problems increased in 1.5-5 years subpopulation, while obsessive-compulsive, post-traumatic and thought problems increased in 6-18 years subpopulation. In the regression models, younger age in the 1.5-5 years subpopulation resulted as "protective" while financial hardship experienced by families during lockdown was related to psychiatric symptoms increasing in the 6-18 years subpopulation. Some considerations, based on first clinical impressions, are provided in text together with comments in relation to previous and emerging literature on the topic.
- Published
- 2020
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41. Single nucleotide polymorphisms in DNA glycosylases: From function to disease.
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D'Errico M, Parlanti E, Pascucci B, Fortini P, Baccarini S, Simonelli V, and Dogliotti E
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- DNA Damage, Genetic Predisposition to Disease, Genotype, Humans, Oxidative Stress, Phenotype, Polymorphism, Single Nucleotide, Cochlear Diseases genetics, DNA Glycosylases genetics, DNA Repair, Eye Diseases genetics, Myocardial Infarction genetics, Neoplasms genetics, Neurodegenerative Diseases genetics
- Abstract
Oxidative stress is associated with a growing number of diseases that span from cancer to neurodegeneration. Most oxidatively induced DNA base lesions are repaired by the base excision repair (BER) pathway which involves the action of various DNA glycosylases. There are numerous genome wide studies attempting to associate single-nucleotide polymorphisms (SNPs) with predispositions to various types of disease; often, these common variants do not have significant alterations in their biochemical function and do not exhibit a convincing phenotype. Nevertheless several lines of evidence indicate that SNPs in DNA repair genes may modulate DNA repair capacity and contribute to risk of disease. This overview provides a convincing picture that SNPs of DNA glycosylases that remove oxidatively generated DNA lesions are susceptibility factors for a wide disease spectrum that includes besides cancer (particularly lung, breast and gastrointestinal tract), cochlear/ocular disorders, myocardial infarction and neurodegenerative disorders which can be all grouped under the umbrella of oxidative stress-related pathologies., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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42. The response to oxidative stress and metallomics analysis in a twin study: The role of the environment.
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Medda E, Minoprio A, Nisticò L, Bocca B, Simonelli V, D'Errico M, Calcagnile A, Giuliani A, Toccaceli V, Minghetti L, Alimonti A, Stazi MA, Mazzei F, and Dogliotti E
- Subjects
- Adult, Antioxidants metabolism, Biomarkers blood, DNA Damage, DNA Glycosylases blood, DNA Repair, Environmental Exposure, Female, Humans, Male, Metals, Heavy blood, Twins, Dizygotic, Twins, Monozygotic, Environmental Pollutants toxicity, Oxidative Stress
- Abstract
Inefficient response to oxidative stress has been associated with ageing and health risk. Metals are known to inhibit DNA repair and may modify the antioxidant response. How genetic variability and lifestyle factors modulate the response to oxidative stress is poorly explored. Our study aims to disentangle the contribution of genetics and environmental exposures to oxidative stress response using data from twin pairs. The non-enzymatic antioxidant capacity (NEAC), the repair capacity of 8-oxo-7,8-dihydroguanine (OGG activity) and the levels of 12 metals were measured in blood of 64 monozygotic and 31 dizygotic twin pairs. The contributions of genetic and environmental effects were assessed using standard univariate twin modelling. NEAC and OGG activity significantly decreased with age. Gender-, age- and body mass index-associated differences were identified for some metals. Principal Component Analysis identified two groups of metals whose levels in blood were highly correlated: As, Hg, Pb, Se, Zn and Al, Co, Cr, Mn, Ni. The environmental influence was predominant on OGG activity and NEAC variance whereas for most metals the best-fitting model incorporated additive genetic and unique environmental sources of variance. NEAC and OGG activity were both inversely correlated with blood levels of various metals. The inhibition of OGG activity by Cd was largely explained by smoking. Our data show a substantial role of environmental factors in NEAC and OGG activity variance that is not explained by twins' age. Exogenous environmental factors such as metals contribute to oxidative stress by decreasing NEAC and inhibiting repair of oxidatively-induced DNA damage., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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43. Fast-Track in Bariatric and Metabolic Surgery: Feasibility and Cost Analysis Through a Matched-Cohort Study in a Single Centre.
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Simonelli V, Goergen M, Orlando GG, Arru L, Zolotas CA, Geeroms M, Poulain V, and Azagra JS
- Subjects
- Adult, Bariatric Surgery adverse effects, Case-Control Studies, Cost-Benefit Analysis, Critical Pathways economics, Female, Humans, Length of Stay economics, Length of Stay statistics & numerical data, Male, Obesity, Morbid economics, Obesity, Morbid epidemiology, Patient Discharge, Patient Readmission economics, Patient Readmission statistics & numerical data, Postoperative Complications economics, Postoperative Complications epidemiology, Postoperative Period, Retrospective Studies, Bariatric Surgery economics, Bariatric Surgery methods, Obesity, Morbid surgery
- Abstract
Background: Due to the rise in severe obesity in Western countries and the increase in bariatric surgery, enhanced recovery (ER) pathways should be developed and promoted., Methods: A monocentric prospective series of 103 bariatric surgery patients managed with the ER pathway (group ER) was compared with a retrospective and immediately previous series of 103 patients managed with standard care (group CS). The aim of the present study was to assess and compare the differences in terms of mean postoperative length of stay (LOS), costs for surgery and recovery, and the differences in terms of complications, readmission, and reoperation rate in the short term between the ER and CS groups., Results: The mean LOS was 4.18 days in group CS and 1.79 days in group ER (p < 0.0001). The mean operative time (OT) per patient was 190.20 min in the group CS and 133.54 min in the group ER, resulting in an average cost of 7272.57€ per patient in group CS and 5424.09€ per patient in group ER. The average recovery cost was 1809.94€ for the group CS series and 775.07 for the group ER one. Overall complications (Clavien-Dindo up to II) occurred in 6 patients (5.8 %) in group CS and in 2 patients (1.9 %) in group ER (p = 0.149) and specific complications (Clavien-Dindo IIIb) occurred for 9 patients (8.7 %) in Group CS and for 14 patients (13.5 %) in group ER (p = 0.268) after hospital discharge within 1-month of follow-up. Twelve patients (11.5 %) in group CS and 13 (12.5 %) in group ER were readmitted after discharge (p = 0.831) within 1-month of follow-up; 8 patients (7.7 %) in group CS versus 9 patients (8.8 %) in group ER needed to be reoperated (p = 0.800) within 1-month follow-up., Conclusions: Enhanced recovery pathway reduces significantly LOS in bariatric surgical patients and shortens the mean OT of the procedure, with no significant differences in terms of surgical outcomes. Furthermore, recovery charges were lower and operative time was shorter allowing for procedural cost reduction.
- Published
- 2016
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44. Crosstalk between mismatch repair and base excision repair in human gastric cancer.
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Simonelli V, Leuzzi G, Basile G, D'Errico M, Fortini P, Franchitto A, Viti V, Brown AR, Parlanti E, Pascucci B, Palli D, Giuliani A, Palombo F, Sobol RW, and Dogliotti E
- Abstract
DNA repair gene expression in a set of gastric cancers suggested an inverse association between the expression of the mismatch repair (MMR) gene MLH1 and that of the base excision repair (BER) gene DNA polymerase β (Polβ). To gain insight into possible crosstalk of these two repair pathways in cancer, we analysed human gastric adenocarcinoma AGS cells over-expressing Polβ or Polβ active site mutants, alone or in combination with MLH1 silencing. Next, we investigated the cellular response to the alkylating agent methyl methanesulfonate (MMS) and the purine analogue 6-thioguanine (6-TG), agents that induce lesions that are substrates for BER and/or MMR. AGS cells over-expressing Polβ were resistant to 6-TG to a similar extent as when MLH1 was inactivated while inhibition of O
6 -methylguanine-DNA methyltransferase (MGMT) was required to detect resistance to MMS. Upon either treatment, the association with MLH1 down-regulation further amplified the resistant phenotype. Moreover, AGS cells mutated in Polβ were hypersensitive to both 6-TG and MMS killing and their sensitivity was partially rescued by MLH1 silencing. We provide evidence that the critical lethal lesions in this new pathway are double strand breaks that are exacerbated when Polβ is defective and relieved when MLH1 is silenced. In conclusion, we provide evidence of crosstalk between MLH1 and Polβ that modulates the response to alkylation damage. These studies suggest that the Polβ/MLH1 status should be taken into consideration when designing chemotherapeutic approaches for gastric cancer., Competing Interests: CONFLICTS OF INTEREST RWS is a scientific consultant for Trevigen, Inc. The remaining authors state that there is no conflicts of interest.- Published
- 2016
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45. Intraperitoneal mesh prosthesis metastasis from pancreatic cancer, after laparoscopic hernia repair.
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Simonelli V, Boven C, Loi P, El Nakadi I, and Closset J
- Subjects
- Abdominal Pain diagnosis, Abdominal Pain etiology, Aged, Hernia, Inguinal diagnosis, Herniorrhaphy adverse effects, Herniorrhaphy methods, Humans, Laparoscopy methods, Magnetic Resonance Imaging methods, Male, Neoplasm Metastasis, Peritoneal Cavity, Positron-Emission Tomography methods, Rare Diseases, Risk Assessment, Tomography, X-Ray Computed methods, Adenocarcinoma diagnosis, Adenocarcinoma surgery, Hernia, Inguinal surgery, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms surgery, Surgical Mesh adverse effects
- Abstract
Introduction There are very few case reports of metastasis on a mesh prosthesis following laparoscopic hernia repair in the literature and its incidence is completely unknown. Case report A 76-year-old male patient presented in December 2013 with a suspicious malignant lesion of the pancreatic tail on the MRI. He was also complaining of a painful mass in the right para-rectal area. An exploratory laparoscopy performed in December 2013 revealed microscopic whitish peritoneal implants in the left hypochondrium and a massive metastasis involving a mesh prosthesis placed é years before in the right para-rectal area. The pathology report of biopsies of the mesh confirmed a metastasis compatible with a pancreatic tumor. Discussion Possible modes of metastasis and limited published data to date on mesh prosthesis metastasis are presented. This situation can be assimilated to port-site metastasis after laparoscopy. Conclusion A mesh prosthesis metastasis after laparoscopic hernia repair is very rare.
- Published
- 2016
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46. The Response to Oxidative DNA Damage in Neurons: Mechanisms and Disease.
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Narciso L, Parlanti E, Racaniello M, Simonelli V, Cardinale A, Merlo D, and Dogliotti E
- Subjects
- Animals, DNA Breaks, Single-Stranded, Humans, Neurogenesis genetics, Brain metabolism, DNA Damage, DNA Repair, Nervous System Diseases genetics, Neurons metabolism, Oxidative Stress
- Abstract
There is a growing body of evidence indicating that the mechanisms that control genome stability are of key importance in the development and function of the nervous system. The major threat for neurons is oxidative DNA damage, which is repaired by the base excision repair (BER) pathway. Functional mutations of enzymes that are involved in the processing of single-strand breaks (SSB) that are generated during BER have been causally associated with syndromes that present important neurological alterations and cognitive decline. In this review, the plasticity of BER during neurogenesis and the importance of an efficient BER for correct brain function will be specifically addressed paying particular attention to the brain region and neuron-selectivity in SSB repair-associated neurological syndromes and age-related neurodegenerative diseases.
- Published
- 2016
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47. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients.
- Author
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Parlanti E, Pietraforte D, Iorio E, Visentin S, De Nuccio C, Zijno A, D'Errico M, Simonelli V, Sanchez M, Fattibene P, Falchi M, and Dogliotti E
- Subjects
- Cells, Cultured, Glutathione metabolism, Humans, Membrane Potential, Mitochondrial, Micronucleus Tests, Mitochondria pathology, Primary Cell Culture, Xeroderma Pigmentosum metabolism, Xeroderma Pigmentosum pathology, Xeroderma Pigmentosum Group A Protein genetics, Fibroblasts metabolism, Micronuclei, Chromosome-Defective, Oxidative Stress genetics, Reactive Oxygen Species metabolism, Xeroderma Pigmentosum genetics, Xeroderma Pigmentosum Group A Protein metabolism
- Abstract
Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O₂₋• and H₂O₂ being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance (¹H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer risk. The increased MN frequency was not affected by inhibition of ROS to normal levels by N-acetyl-L-cysteine., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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48. Restless legs syndrome and post polio syndrome: a case-control study.
- Author
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Romigi A, Pierantozzi M, Placidi F, Evangelista E, Albanese M, Liguori C, Nazzaro M, Risina BU, Simonelli V, Izzi F, Mercuri NB, and Desiato MT
- Subjects
- Adult, Aged, Case-Control Studies, Comorbidity, Female, Humans, Male, Middle Aged, Prevalence, Disorders of Excessive Somnolence epidemiology, Fatigue epidemiology, Postpoliomyelitis Syndrome epidemiology, Quality of Life, Restless Legs Syndrome epidemiology
- Abstract
Background and Purpose: The aim was to investigate the prevalence of restless legs syndrome (RLS), fatigue and daytime sleepiness in a large cohort of patients affected by post polio syndrome (PPS) and their impact on patient health-related quality of life (HRQoL) compared with healthy subjects., Methods: PPS patients were evaluated by means of the Stanford Sleepiness Scale and the Fatigue Severity Scale (FSS). The Short Form Health Survey (SF-36) questionnaire was utilized to assess HRQoL in PPS. RLS was diagnosed when standard criteria were met. Age and sex matched healthy controls were recruited amongst spouses or friends of PPS subjects., Results: A total of 66 PPS patients and 80 healthy controls were enrolled in the study. A significantly higher prevalence of RLS (P < 0.0005; odds ratio 21.5; 95% confidence interval 8.17-57) was found in PPS patients (PPS/RLS+ 63.6%) than in healthy controls (7.5%). The FSS score was higher in PPS/RLS+ than in PPS/RLS- patients (P = 0.03). A significant decrease of SF-36 scores, including the physical function (P = 0.001), physical role (P = 0.0001) and bodily pain (P = 0.03) domains, was found in PPS/RLS+ versus PPS/RLS- patients. Finally, it was found that PPS/RLS+ showed a significant correlation between International Restless Legs Scale score and FSS (P < 0.0001), as well as between International Restless Legs Scale score and most of the SF-36 items (physical role P = 0.0018, general health P = 0.0009, vitality P = 0.0022, social functioning P = 0.002, role emotional P = 0.0019, and mental health P = 0.0003)., Conclusion: Our findings demonstrate a high prevalence of RLS in PPS, and that RLS occurrence may significantly influence the HRQoL and fatigue of PPS patients. A hypothetical link between neuroanatomical and inflammatory mechanisms in RLS and PPS is suggested., (© 2014 EAN.)
- Published
- 2015
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49. Genotype-phenotype analysis of S326C OGG1 polymorphism: a risk factor for oxidative pathologies.
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Simonelli V, Camerini S, Mazzei F, Van Loon B, Allione A, D'Errico M, Barone F, Minoprio A, Ricceri F, Guarrera S, Russo A, Dalhus B, Crescenzi M, Hübscher U, Bjørås M, Matullo G, and Dogliotti E
- Subjects
- Adult, Alleles, DNA Glycosylases metabolism, DNA Repair genetics, Female, Genetic Association Studies, Homozygote, Humans, Male, Middle Aged, Oxidation-Reduction, Polymorphism, Single Nucleotide, Risk Factors, DNA Damage genetics, DNA Glycosylases genetics, Lymphocytes metabolism, Oxidative Stress
- Abstract
8-Oxoguanine DNA glycosylase (OGG) activity was measured by an in vitro assay in lymphocytes of healthy volunteers genotyped for various OGG1 polymorphisms. Only homozygous carriers of the polymorphic C326 allele showed a significantly lower OGG activity compared to the homozygous S326 genotype. The purified S326C OGG1 showed a decreased ability to complete the repair synthesis step in a base excision repair reaction reconstituted in vitro. The propensity of this variant to dimerize as well as its catalytic impairment were shown to be enhanced under oxidizing conditions. Mass spectrometry revealed that the extra cysteine of the variant protein is involved in disulfide bonds compatible with significant conformational changes and/or dimerization. We propose that the S326C OGG1 catalytic impairment and its susceptibility to dimerization and disulfide bond formation in an oxidizing environment all concur to decrease repair capacity. Consequently, the C326 homozygous carriers may be at increased risk of oxidative pathologies., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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50. Effect of blood storage conditions on DNA repair capacity measurements in peripheral blood mononuclear cells.
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Allione A, Porcedda P, Russo A, Ricceri F, Simonelli V, Minoprio A, Guarrera S, Pardini B, Mazzei F, Dogliotti E, Giachino C, and Matullo G
- Subjects
- Adolescent, Adult, Blood Preservation adverse effects, Blood Specimen Collection adverse effects, Blood Specimen Collection methods, Comet Assay, Cryopreservation, Female, Genetic Association Studies standards, Humans, Male, Middle Aged, Temperature, Young Adult, Blood Preservation methods, DNA Repair physiology, Leukocytes, Mononuclear metabolism
- Abstract
Due to the great number of genes involved in DNA repair and the interactions among the pathways responsible for the repair of different types of DNA damage, there is an increasing need for simple and reliable approaches to phenotypically assess DNA repair capacity (DRC). The use of peripheral blood mononuclear cells (PBMCs) in DRC assays is particularly useful for human monitoring studies. However, in such studies it is not always possible to collect and process samples on the same day as the blood is taken. We performed a genotype-phenotype correlation study on DRC on 225 healthy subjects. Due to the large number of blood samples to be processed, PBMCs were either isolated and cryopreserved on the same day of blood collection (day 1) or on the following day after 24h blood storage at room temperature (day 2-RT). Samples processed in different days showed a significant difference in the DRC evaluated as 8-oxoguanine glycosylase activity (OGG assay) in cell extracts (p<0.0001) and as benzo[a]pyrene diol epoxide (BPDE)-induced damage repair by the comet assay (p=0.05). No apparent effect of the blood storage conditions on the outcome of γ-ray induced H2AX phosphorylation assay was reported. These results prompted us to further analyze the effects of blood storage conditions by performing a validation study. Three blood samples were simultaneously taken from ten healthy donors, PBMCs were isolated and cryopreserved as follows: immediately after blood collection (day 1); on the following day, after blood storage at RT (day 2-RT); or after blood storage at 4°C (day 2-4°C). DRC was then evaluated using phenotypic assays. The γ-ray induced H2AX phosphorylation assay has been confirmed as the only assay that showed good reproducibility independently of the blood storage conditions. The measurement of OGG assay was most affected by the blood storage conditions., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2013
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