Papers by ilaria simonelli
Safety and efficacy of PTH 1‐34 and 1‐84 therapy in chronic hypoparathyroidism: a meta‐analysis of prospective trials
Journal of Bone and Mineral Research
Supplemental material, Spplementary_figure for Interleukin-6 Disrupts Synaptic Plasticity and Imp... more Supplemental material, Spplementary_figure for Interleukin-6 Disrupts Synaptic Plasticity and Impairs Tissue Damage Compensation in Multiple Sclerosis by Mario Stampanoni Bassi, Ennio Iezzi, Francesco Mori, Ilaria Simonelli, Luana Gilio, Fabio Buttari, Francesco Sica, Nicla De Paolis, Georgia Mandolesi, Alessandra Musella, Francesca De Vito, Ettore Dolcetti, Antonio Bruno, Roberto Furlan, Annamaria Finardi, Girolama A. Marfia, Diego Centonze and Francesca Romana Rizzo in Neurorehabilitation and Neural Repair
The detection of IgE to allergenic molecules in nasal secretions: implications for the diagnosis of allergic rhino-conjunctivitis

Evaluation of zinc, copper, and Cu:Zn ratio in serum, and their implications in the course of COVID-19
Journal of Trace Elements in Medicine and Biology, 2022
Background The dynamics of essential metals such as Copper (Cu) and Zinc (Zn) may be associated w... more Background The dynamics of essential metals such as Copper (Cu) and Zinc (Zn) may be associated with the novel coronavirus disease 2019 (COVID-19) that has spread across the globe. Objectives The aim of this study is to investigate the relationship between serum levels of Cu and Zn, as well as the Cu:Zn ratio in the acute phase of COVID-19 along with the assessment of their connection to other laboratory parameters (hematological, biochemical, hemostatic). Methods Serum levels of Cu and Zn were measured by atomic absorption spectrometry in 75 patients in the acute COVID-19 phase and were compared with those of 22 COVID-19 patients evaluated three months after the acute phase of the disease (‘non-acute’ group) and with those of 68 healthy individuals. Results In comparison with both the non-acute patients and the healthy controls, the acute patients had lower levels of hemoglobulin and albumin, and higher levels of glucose, creatinine, liver transaminases, C-reactive protein (CRP), and higher values of the neutrophils to lymphocytes ratio (NLR) at the hospital admission. They also exhibited increased levels of Cu and decreased of Zn, well represented by the Cu:Zn ratio which was higher in the acute patients than in both non-acute patients (p = 0.001) and healthy controls (p <0.001), with no statistical difference between the last two groups. The Cu:Zn ratio (log scale) positively correlated with CRP (log scale; r = 0.581, p <0.001) and NLR (r = 0.436, p = 0.003). Conclusion Current results demonstrate that abnormal dynamics of Cu and Zn levels in serum occur early during the course of COVID-19 disease, and are mainly associated with the inflammation response.

International Journal of Molecular Sciences, 2020
In multiple sclerosis (MS), inflammation alters synaptic transmission and plasticity, negatively ... more In multiple sclerosis (MS), inflammation alters synaptic transmission and plasticity, negatively influencing the disease course. In the present study, we aimed to explore the influence of the proinflammatory cytokine IL-1β on peculiar features of associative Hebbian synaptic plasticity, such as input specificity, using the paired associative stimulation (PAS). In 33 relapsing remitting-MS patients and 15 healthy controls, PAS was performed on the abductor pollicis brevis (APB) muscle. The effects over the motor hot spot of the APB and abductor digiti minimi (ADM) muscles were tested immediately after PAS and 15 and 30 min later. Intracortical excitability was tested with paired-pulse transcranial magnetic stimulation (TMS). The cerebrospinal fluid (CSF) levels of IL-1β were calculated. In MS patients, PAS failed to induce long-term potentiation (LTP)-like effects in the APB muscle and elicited a paradoxical motor-evoked potential (MEP) increase in the ADM. IL-1β levels were negative...

TMS-EEG Biomarkers of Amnestic Mild Cognitive Impairment Due to Alzheimer’s Disease: A Proof-of-Concept Six Years Prospective Study
Frontiers in Aging Neuroscience, 2021
Background: Early and affordable identification of subjects with amnestic mild cognitive impairme... more Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer’s disease (AD) is a major scientific challenge.Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level.Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (...
Effects of pegvisomant on glucose metabolism in acromegaly: A meta-analysis of prospective interventional studies
Endocrine Abstracts, 2018
Effects of somatostatin analogs on glucose metabolism in acromegalic patients: a meta-analysis of prospective interventional studies

The increasing number and quality of randomized controlled trials (RCTs) employing transcranial d... more The increasing number and quality of randomized controlled trials (RCTs) employing transcranial direct current stimulation (tDCS) denote the rising awareness of neuroscientific community about its electroceutical potential and opening to include these treatments in the framework of medical therapies under the indications of the international authorities. The purpose of this quantitative review is to estimate the recommendation strength applying the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and PICO (population, intervention, comparison, outcome) model values for effective tDCS treatments on no-structural diseases, and to provide an estimate of Sham effect for future RCTs. Applying GRADE evaluation pathway, we searched in literature the tDCS-based RCTs in psychophysical diseases displaying a major involvement of brain electrical activity imbalances. Three independent authors agreed on Class 1 RCTs (18 studies) and meta-analyses were carried ...

Genes, 2020
In multiple sclerosis (MS), activated T and B lymphocytes and microglial cells release various pr... more In multiple sclerosis (MS), activated T and B lymphocytes and microglial cells release various proinflammatory cytokines, promoting neuroinflammation and negatively affecting the course of the disease. The immune response homeostasis is crucially regulated by the activity of the enzyme adenosine deaminase (ADA), as evidenced in patients with genetic ADA deficiency and in those treated with cladribine tablets. We investigated in a group of patients with MS the associations of a single nucleotide polymorphism (SNP) of ADA gene with disease characteristics and cerebrospinal fluid (CSF) inflammation. The SNP rs244072 of the ADA gene was determined in 561 patients with MS. Disease characteristics were assessed at the time of diagnosis; furthermore, in 258 patients, proinflammatory and anti-inflammatory molecules were measured in the CSF. We found a significant association between rs244072 and both clinical characteristics and central inflammation. In C-carriers, significantly enhanced di...

Clinical and Experimental Obstetrics & Gynecology
Background: One of the most important causes of preterm birth (PTB) is cervical insufficiency, wh... more Background: One of the most important causes of preterm birth (PTB) is cervical insufficiency, which usually it's treated by performing a surgical cervical cerclage (CC). Currently, a valid alternative to surgical treatment is represented by the application of a non-invasive intravaginal silicon device called Arabin® pessary (AP). The aim of the study is to compare these two therapeutic approaches in terms of gestational and neonatal outcomes. Methods: In this observational cohort study, we retrospectively evaluated the pregnant women between 18 and 24 gestational weeks referred to the Department of Obstetrics and Gynecology of San Giovanni Calibita Fatebenefratelli Hospital of Rome from 2015 to 2017 with the diagnosis of threatened preterm birth. The 26 women were divided into groups according to the treatment received: cervical cerclage (Group-1, inpatient) and Arabin® pessary (Group-2, outpatient), both in combination with vaginal progesterone (PG). The primary outcome was the gestational age at delivery, and various secondary maternal and neonatal outcomes were considered. Results: The results do not show a statistically significant difference between the two groups, both in terms of gestational and neonatal outcomes. Considering surgical risks (anesthesia, blood loss), recovery-time and economic costs of CC, AP showed very interesting advantages resulting in more favorable cost-benefits relation. Conclusion: We confirmed once again that outpatient combination of AP and vaginal PG is a safe, noninvasive choice as treatment of PTB. Unfortunately, the small population doesn't allow to define this a noninferiority trial. Further larger randomized controlled studies are needed to reassure clinicians about the efficacy of this combined non-invasive approach.

Frontiers in Neuroscience
Oxidative status may play a role in chronic inflammation and neurodegeneration which are consider... more Oxidative status may play a role in chronic inflammation and neurodegeneration which are considered critical etiopathogenetic factors in Multiple Sclerosis (MS), both in the early phase of the disease and in the progressive one. The aim of this study is to explore oxidative status related to iron metabolism in peripheral blood of stable Relapsing-Remitting MS with low disability. We studied 60 Relapsing-Remitting MS patients (age 37.2 ± 9.06, EDSS median 1.0), and 40 healthy controls (age 40.3 ± 10.86). We measured total hydroperoxides (dROMs test) and Total Antioxidant Status (TAS), along with the iron metabolism biomarkers: Iron (Fe), ferritin (Ferr), transferrin (Tf), transferrin saturation (Tfsat), and ceruloplasmin (Cp) panel biomarkers [concentration (iCp) and enzymatic activity (eCp), copper (Cu), ceruloplasmin specific activity (eCp:iCp), copper to ceruloplasmin ratio (Cu:Cp), non-ceruloplasmin copper (nCp-Cu)]. We computed also the Cp:Tf ratio as an index of oxidative stress related to iron metabolism. We found lower TAS levels in MS patients than in healthy controls (CTRL) and normal reference level and higher dROMs and Cp:Tf ratio in MS than in healthy controls. Cp and Cu were higher in MS while biomarkers of iron metabolism were not different between patients and controls. Both in controls and MS, dROMs correlated with iCp (CTRL r = 0.821, p < 0.001; MS r = 0.775 p < 0.001) and eCp (CTRL r = 0.734, p < 0.001; MS r = 0.820 p < 0.001). Moreover, only in MS group iCp correlated negatively with Tfsat (r =-0.257, p = 0.047). Dividing MS patients in "untreated" group and "treated" group, we found a significant difference in Fe values [F(2, 97) = 10.136, p < 0.001]; in particular "MS untreated" showed higher mean values (mean = 114.5, SD = 39.37 µg/dL) than CTRL (mean 78.6, SD = 27.55 µg/dL p = 0.001) and "MS treated" (mean = 72.4, SD = 38.08 µg/dL; p < 0.001). Moreover, "MS untreated" showed significantly higher values of Cp:Tf (mean = 10.19, SD = 1.77 * 10 −2 ; p = 0.015), than CTRL (mean = 9.03,

Exploring Agreement between MB-CDI Short Forms for Evaluating the Language Skills of Italian Children Aged 18–24 Months
Folia Phoniatrica et Logopaedica
Introduction: The short forms of MacArthur-Bates Communicative Development Inventories (MB-CDI) a... more Introduction: The short forms of MacArthur-Bates Communicative Development Inventories (MB-CDI) are widely used for assessing communicative and linguistic development in infants and toddlers. Italian norms for the Words and Gestures (WG) and Words and Sentences (WS) short forms overlap between 18 and 24 months. Objective: To evaluate the agreement between these two forms. Methods: Parents of 104 children aged 18–24 months filled in both questionnaires. Results: The two questionnaires showed high agreement in measuring expressive vocabulary size and the percentile of lexical production and good agreement in identifying children at-risk for language delay (75% of the cases were accurately identified). Both short forms include a list of 100 words and a set of questions investigating potential risk factors for communication and language disorders. Ten children with an expressive vocabulary <10th percentile were compared to 10 with typical language development. Scores for children <...

Biomolecules
Evidence indicates that patients with Alzheimer’s dementia (AD) show signs of copper (Cu) dyshome... more Evidence indicates that patients with Alzheimer’s dementia (AD) show signs of copper (Cu) dyshomeostasis. This study aimed at evaluating the potential of Cu dysregulation as an AD susceptibility factor. We performed a meta-analysis of 56 studies investigating Cu biomarkers in brain specimens (pooled total of 182 AD and 166 healthy controls, HC) and in serum/plasma (pooled total of 2929 AD and 3547 HC). We also completed a replication study of serum Cu biomarkers in 97 AD patients and 70 HC screened for rs732774 and rs1061472 ATP7B, the gene encoding for the Cu transporter ATPase7B. Our meta-analysis showed decreased Cu in AD brain specimens, increased Cu and nonbound ceruloplasmin (Non-Cp) Cu in serum/plasma samples, and unchanged ceruloplasmin. Serum/plasma Cu excess was associated with a three to fourfold increase in the risk of having AD. Our replication study confirmed meta-analysis results and showed that carriers of the ATP7B AG haplotype were significantly more frequent in th...
Practice-dependent motor cortex plasticity is reduced in non-disabled multiple sclerosis patients
Clinical Neurophysiology
Pediatric Allergy and Immunology
There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis... more There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients.
Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis
CNS Drugs
Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in child-pugh b cirrhosis
Journal of Hepatology

Interleukin-6 Disrupts Synaptic Plasticity and Impairs Tissue Damage Compensation in Multiple Sclerosis
Neurorehabilitation and Neural Repair
Background: Synaptic plasticity helps in reducing the clinical expression of brain damage and rep... more Background: Synaptic plasticity helps in reducing the clinical expression of brain damage and represents a useful mechanism to compensate the negative impact of new brain lesions in multiple sclerosis (MS). Inflammation, altering synaptic plasticity, could negatively influence the disease course in relapsing-remitting MS (RR-MS). Objective: In the present study, we explored whether interleukin (IL)-6, a major proinflammatory cytokine involved in MS pathogenesis, alters synaptic plasticity and affects the ability to compensate for ongoing brain damage. Methods: The effect of IL-6 incubation on long-term potentiation (LTP) induction was explored in vitro, in mice hippocampal slices. We also explored the correlation between the cerebrospinal fluid (CSF) levels of this cytokine and the LTP-like effect induced by the paired associative stimulation (PAS) in a group of RR-MS patients. Finally, we examined the correlation between the CSF levels of IL-6 at the time of diagnosis and the prosp...
Subclinical dysphagia in task-specific mouth tremor triggered by drinking
Clinical Neurophysiology
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Papers by ilaria simonelli