Background. MicroRNAs (miRNAs) are small non-coding RNAs of 20-22 nucleotides, involved in transcriptional and post-transcriptional regulation of gene expression and involved in Parkinson’s disease. Objective. Identification of a suitable gene set to use as normalizers in expression analysis in PBMCs PD study. Assessment of the potential role as PD biomarker of miR-29a-3p, miR-29b-3p, miR-30a-5p, miR-30b-5p, and miR-103a-3p in PBMCs and plasma samples from L-dopa treated PD and drug-naïve PD patients. MiRNAs discovering through deep sequencing analysis and creation of in silico miRNAs target prediction. Methods. Plasma and PBMCs miRNAs from L-dopa treated PD, drug-naïve PD patients, and controls were analyzed (qRT-PCR), data normalized using RNU24/Z30 for PBMCs, and synthetic spike-in for plasma. Statistical significance of miRNA expression differences calculated by computing a two-tailed paired t-test. Illumina MiSeq NGS platform analysis was performed. MiRNA resources were combined to detect putative miRNA targets. Results. RNU24/Z30 as reliable normalizer for expression analysis in PBMCs PD study were identified. An over-expression of miR-103a-3p, miR-29a-3p and miR-30b-5p in PBMCs PD samples were found. Over-expression trend of miR-30a-5p in plasma PD samples and over-expression trend of miR-30b-5p in plasma drug-naїve PD samples were detected. NGS analysis data were not sufficient to generate meaningful biological results. A sophisticated in silico target prediction model were elaborated. Discussion. We showed for the first time an over-expression of miR-103a-3p in PD patients and replicated a documented deregulation in PD, albeit opposite to published data, of miR-29a-3p and miR-30b-5p. The trend of higher expression of miR-30b-5p in plasma drug-naïve PD samples suggested an involvement of the treatment in the plasma miRNA expression. The in silico analysis identified putative candidate target genes, including genes related to neurodegeneration and PD, such as LRRK2 for miR-30b-5p and miR-103a-3p, PARK7/DJ-1 for miR-29a-3p, Bcl-2 as common target for all miRNAs.

Urban airborne particulate matter (PM) is known to increase morbidity and mortality due to cardiopulmonary diseases related to inflammatory processes and genotoxic effects. The aim of this thesis is to highlight the toxic and carcinogenic potential of airborne particulate matters collected during different seasons at a site that is located in the northern area of the city of Bologna by using alternative in vitro tests, such as the cell transformation assay with BALB/c 3T3 A31-1-1 and Bhas 42 cells. The purpose is also to evaluate the lifetime cancer risks associated with air inhalation in different sites (rural and urban), by using the relative potency of compounds belonging to the same chemical class (PAHs and nitro-PAHs) and the specific unit of carcinogenic risk. None of the organic or inorganic extracts of PM2.5 and PM1 induced a significant increase in the average number of transformed foci/plate or in the transformation frequency of BALB/c 3T3 A311-1 cells, whereas the results obtained by Bhas 42 cell transformation showed a significant increase in the average number of transformed foci/plate. All the analyzed organic extracts showed promoting effects in Bhas 42 cells. The application of the UR cancer risk to the transformed value of B(a)P equivalents in the winter– autumn campaigns leads to estimate an increase in the cancer risk similar to that defined in the literature (1 x 10-4 for exposure to 1 ng/m3). The calculated cancer risk was about one order of magnitude lower in the summer campaigns. In conclusion, the proposed approach, based on the integration of the data derived from in vitro testing and cancer risk assessment, could represent a reliable model for investigating environmental mixtures and predicting their effects on toxicological relevant endpoints.

Aim: evaluate the effectiveness of a single session of sub gingival instrumentation with ultrasonic instruments (FMUD) in the treatment of periodontitis in patients with Down syndrome. Materials and Methods: 40 patients (age range between 15 and 35 years) who had at least 8 sites with probing pocket depth (PPD)> 5 mm and presence of bleeding on probing, were randomly assigned to one of the two treatment groups: a single session sub gingival ultrasonic instrumentation (test group), or 4 traditional cause-related therapy sessions with manual instruments (control group). At baseline and at 6 months the following parameters were measured: probing pocket depth (PPD), gingival recession (REC), clinical attachment level (CAL), plaque index (PI) and bleeding on probing (BoP). Results: both techniques at 6 months were effective in improving the clinical parameters of periodontal disease, with a statistically significant reduction in PPD, CAL, PI and BoP. A reduced number of anesthetic cartridges was used in the test group Conclusions: the results demonstrated that a single subgingival ultrasonic instrumentation session represents a valuable therapeutic approach for periodontitis treatment in patients with Down syndrome. From the patient's point of view, this approach offers tangible benefits, in fact, need fewer appointments, less chair time and a reduced use of local anesthetic than the classic four sessions protocol.

Cardiovascular diseases (CVD) comprise the most common chronic disease worldwide. High lipid levels are a strong risk factor, making lipid-lowering statin therapy an important preventive measure. Here we explore the effects of common variants at the KIF6 and HMGCR loci on a range of cardio-metabolic traits and on response to statin therapy. While HMGCR is a well-established lipid-related locus, the role of KIF6 in response to statin therapy is controversial, and its contribution to related phenotype variability has not been clarified. We genotyped a coding KIF6 variant (p.W719R, rs20455) and two intronic ones in high LD to the former (rs9462535,rs9471077), as well as two non-coding variants in HMGCR (rs3761740 and rs3846662). Effects on 14 quantitative and 5 categorical cardiometabolic phenotypes including lipid-lowering therapy response were tested in a sample of 1,645 individuals from the Genetics in Brisighella Health Study (GBHS) from Italy and replicated in 10,662 individuals from the Estonian Genome Center (EGCUT). In GBHS the established HMGCR variant rs3846662 affects LDL cholesterol levels (P=8.5x10-4) while the intronic KIF6 variant rs9471077 modifies APOB levels (P=8.2x10-4). The latter association was confirmed in EGCUT. No significant association between KIF6 variants and response to statin therapy was observed. In the first genetic study involving GBHS we confirm the HMGCR effect on LDL-Cholesterol and demonstrate a novel KIF6 effect on APOB. The latter association needs to be evaluated for its predictive value for overall CVD risk and its potential contribution to stratified patient care.

Alzheimer's disease (AD) is a multifactorial and progressive form of dementia with a senile onset that affects specific areas of the brain. Recent genome wide association (GWA) studies reported that the allele 4 of apolipoprotein E (APOE) and single nucleotide polymorphisms (SNPs) in other genes that regulate inflammatory pathways, such as the gene coding for clusterin (CLU), are associated with AD. The hypothesis is that all of these genes may be involved in different mechanisms mediated by herpes viruses and we argued that the concomitant presence of SNPs in these genes in the same individual may represent a genetic signature predisposing to AD. The present study is focused on SNPs in CLU, interferon (IFN)-λ3/IL-28B, Med23 and the transcription factor IRF7, which are genes involved in antiviral responses and their association with AD and cognitive deterioration. Moreover, the effects of IL-28B, Med23 and IRF7 genotypes upon the presence of epstein-barr virus (EBV) and human herpes virus 6 (HHV-6) in the peripheral blood of AD and controls (CTR) have been also investigated. The activation of the innate immune system has a key role as a promoting factor for AD and in AD patients activated microglia release cytokines that induce neuro-inflammation. In this thesis gene variants and different expression of genes involved in the innate immune response in case-control population studies and in a mouse model of AD were investigated. Results from these experiments suggest that individuals with a particular genetic makeup in defensive mechanisms of the innate immunity may be at risk of defective immune responses. Impaired immunity against persistent viruses such as those of herpes family, might result in chronic and inappropriate activation of microglia, abnormal Aβ production and increased amyloid deposition. Cycles of virus latency and infections may therefore contribute to neurodegeneration associated with AD in genetically predisposed elderly.

Huntington’s disease (HD) is a progressive, fatal, neurodegenerative disorder caused by an abnormal expansion of a CAG repeat sequence in the gene encoding the protein huntingtin (HTT) on chromosome 4. Clinical features of HD include progressive motor dysfunction, cognitive decline, and psychiatric disturbance. Sleep disturbances are frequent in HD patients. However, sleep alterations as well as their association with other symptoms and signs of the disease have not been systematically studied in large groups of HD patients.The aim of the study was to objectively evaluate sleep features in a large, single-center, population of HD patients by means of nocturnal, laboratory based video-polysomnography (V-PSG), and to correlate PSG findings with clinical parameters;evaluate subjective sleep-related symptoms by subjective sleep evaluation and compare the results with those obtained with the gold standard diagnostic tool, namely V-PSG;finally, evaluate the EEG modifications in HD patients during the sleep-wake cycle, by means of the exact LOw REsolution Tomography (eLORETA) software.The results suggest that sleep is severely disrupted in HD patients.Taken together,our data may suggest that the caudate degenerative process observed in HD account for the increased arousability, increased motor activity during wake and sleep (originating periodic limb movements), reduction of REM sleep and, overall, a general sleep disruption.As concerns the subjective sleep evaluation, our data suggest, overall, that the subjective evaluation of sleep in HD patients shows a poor correlation with PSG results. Our EEG data suggest a defined pattern of motor cortex dysfunction during wake and sleep, which correlates with the clinical and polysomnographic evidence of increased motor activity during wake and NREM, and nearly absent motor abnormalities in REM. It could be hypothesized that EEG modifications reflect motor cortex impairment or, conversely, an effort to counterbalance abnormal motor output.

Introduzione: la trombosi del sistema venoso portale (PVT) rappresenta una complicanza frequente nel paziente con cirrosi epatica. La gestione terapeutica del paziente cirrotico con PVT non è chiara. Obiettivi: analizzare retrospettivamente la storia naturale della trombosi portale e gli eventi emorragici in un gruppo di pazienti cirrotici trattati e non trattati con terapia anticoagulante. Metodi: Da Gennaio 2008 a Dicembre 2015 abbiamo retrospettivamente individuato una coorte di 182 pazienti affetti da PVT. 81 pazienti sono stati trattati con terapia anticoagulante e 101 non hanno ricevuto terapia. Abbiamo valutato le caratteristiche demografiche, l’estensione della trombosi, l’eventuale trattamento anticoagulante, l’evoluzione della patologia e gli eventi emorragici. Risultati: La trombosi è andata incontro a ricanalizzazione in 46 (56,8%) pazienti trattati e in 26 (25,7%) pazienti non trattati (p<0,001). La durata del trattamento (p=0,005) e la doppia somministrazione giornaliera (p=0,003) sono risultati essere gli unici fattori predittivi di ricanalizzazione nei pazienti trattati. Dopo la sospensione della terapia, dei 46 pazienti che hanno ottenuto la ricanalizzazione, 17(36%) hanno presentato una recidiva della trombosi. L’analisi di Kaplan-Meier ha mostrato un tasso di sopravvivenza maggiore nel gruppo dei pazienti trattati (p=0,010) e il trattamento anticoagulante è risultato essere l’unico fattore indipendente correlato alla sopravvivenza all’analisi multivariata (p=0,014). Complicanze emorragiche si sono verificate in 22(21,8%) pazienti non trattati e in 16 (19,7%) pazienti trattati, solo in 4 casi dovute al trattamento anticoagulante. Conclusioni: il trattamento anticoagulante è sicuro ed efficace nei pazienti cirrotici con PVT, raggiungendo dei tassi di ricanalizzazione completa e parziale del 56,8%. La durata del trattamento di almeno 12 mesi e la doppia somministrazione giornaliera sembrano associati a più alti tassi di ricanalizzazione. Nei pazienti che hanno raggiunto la ricanalizzazione, l’interruzione della terapia è associata ad un alto rischio di recidiva. Il trattamento anticoagulante sembra migliorare la sopravvivenza dei pazienti cirrotici con PVT. / Introduction: Portal vein thrombosis (PVT) is a frequent event in patients with cirrhosis. It can be treated with anticoagulants, but the optimal management is still unclear. Aim: The aim of this study was to retrospectively analyze the natural history of portal thrombosis in cirrhotic patients and bleeding events in a large cohort of patients with or without anticoagulation therapy. Methods: We analyzed data from 182 patients with cirrhosis and PVT, diagnosed from January 2008 to December 2015. 81 patients were anticoagulated and 101 were untreated. Demographic characteristics, extension of portal vein thrombosis, anticoagulant treatment and hemorrhagic events were evaluated. Results: thrombosis had improved in 46 (56.8%) treated patients and in 26 (25.7%) untreated patients. The anticoagulation group had significantly better recanalization rate than the untreated group (p <0.001). The duration of treatment (p = 0.005) and twice-daily dosing (p = 0.003) were the only predictors of recanalization in treated patients. Of 46 patients who achieved recanalization, 17 (36%) had recurrent thrombosis after stopping anticoagulation therapy. Kaplan–Meier curve analysis revealed a higher survival rate in the treated group than in controls (p=0,010). Anticoagulant treatment was the only independent factor related to survival in multivariate analysis (p=0,014, HR:0,303, CI: 0.101-0.907). Bleeding complications occurred in 22 (21.8%) untreated patients and in 16 (19.7%) treated patients, only in 4 cases related to the anticoagulant treatment. Conclusions: Anticoagulant is a safe and effective treatment that leads to partial or complete recanalization of the portal venous axis in 56% of patients with cirrhosis and PVT. Duration of treatment of at least 12 months and twice-daily dosing seem associated with higher recanalization rates. Discontinuation of therapy is associated with high risk of recurrence of PVT. The anticoagulant treatment seems to improve survival in cirrhotic patients with PVT.

In questo studio è con un grande campione di pazienti con emorragia cerebrale (111 soggetti) in cui è stata verificata una aumentata prevalenza di sospetto disturbo respiratorio del sonno valutat tramite la scala Berlin Questionnaire rispetto ad altrettanti con ischemia cerebrale (111 soggetti) e altrettanti controlli (n111). La metodica di appaiamento per variabili quali età, sesso, BMI e CCI ha permesso di escludere una eventuale influenza da parte di queste variabili. Dallo studio di variabili di outcome funzionale è risultata significativa la correlazione tra positività per disturbo respiratorio del sonno e un peggior outcome funzionale sia in termini di disabilità (mRS ≥ 3) che di mortalità (mRS =6) nei pazienti con BQ positivo, sia ischemici che emorragici. A riprova di questo ruolo prognosticamente negativo della sospetta OSAS nei pazienti con emorragia cerebrale anche un aumento della durata globale del ricovero in giorni dei pazienti nel gruppo dei positivi. Nel tentativo di esplorare il legame tra disturbi respiratori del sonno ed emorragia cerebrale sono state valutate le neuroimmagini e le caratteristiche di ipertensione arteriosa. E’ stato così riscontrato un tasso complessivo di peggioramento delle lesioni al controllo a 10 giorni circa, aumentato significativamente nei pazienti BQ positivi, con associata inoltre una tendenza all’aumento dell’edema perilesionale. L’ipotesi più probabile rimane comunque che il meccanismo principale con cui il disturbo respiratorio del sonno influisce sull’insorgenza e il peggioramento dell’emorragia cerebrale sia legato all’ipertensione arteriosa. Tale legame, facilmente intuibile considerate le discrete conoscenze sui tre fenomeni, è stato qui dimostrato tramite il riscontro di un tasso notevolmente e significativamente aumentato di ipertensione arteriosa, di profilo pressorio notturno alterato con prevalenza di pazienti non dipper e di aumentata pressione arteriosa farmaco resistente nei pazienti emorragici BQ positivi. / Background: Obstructive sleep apnea (OSA) is currently undertaken to impair ischemic stroke risk especially by intracranial pressure, blood flow, glucose metabolism, atherogenesis, blood coagulation, cardiac arrhythmia and arterial hypertension. In OSA patients hypertension is often related to drug resistance and modification in nocturnal blood pressure profile. In stroke patients with OSA has been observed an impairment of functional outcome. About OSA and intra cranial haemorrhage (ICH) few data are available in literature and most of them are anecdotal. We can speculate that OSA can affect on ICH by arterial hypertension. Methods: in this study we sought to test whether suspected OSA is more prevalent in ICH group than in control. In order to limit potential confounding variables associated with acute ICH, we tested by Berlin Questionnaire (BQ) and Epworth Sleepiness Scale (ESS) referring to the previous 3 months before ICH. Secondarily, we tried to assess if OSA in ICH could affect on functional outcome (mRS) like disability or mortality, as described in ischemic stroke. For these purposes we recruited 111 ICH patients matched by sex, age, Body Mass Index (BMI) and Charlson Comorbidity Index (CCI) with 111 ischemic stroke patients and 111 controls. Results: In ICH patients we found BQ positivity in 30,6% vs 25,2% in ischemic stroke patients vs 13,5% in controls (p 0.01). Moreover BQ positive ICH patients had more disability, mortality, length of recovery, arterial hypertension, drug resistance hypertension and nocturnal blood pressure profile alteration, especially non dipper pattern, than BQ negative ICH. Conclusion: The results suggest that OSA can be considered a risk factor and a negative prognostic factor in ICH patients, as described before in ischemic stroke patients. Moreover we can considered this fenomena probably related to blood pressure alteration caused by sleep breathing disorder.

Introduzione e Scopo dello Studio L’agenesia completa del corpo calloso (ACC) anche quando isolata può essere espressione di eterogeneità anatomica. Lo scopo dello studio è descrivere la variabilità delle altre strutture commissurali in un’ ampia corte di feti con apparente agenesia completa isolata del corpo calloso con risonanza magnetica (RMN) in epoca pretale Materiale e Metodi In tutti i feti con a ACC riferiti all’ analisi con RM dal 2004 al 2014 presso la Neuroradiologia Pediatrica dell’ Ospedale Buzzi di Milano è stata valutata, da parte di due neuroradiologi esperti con più di 10 anni di esperienza in questo campo, la presenza di altre strutture commissurali: la commissura anteriore (CA) e la commissura ippocampale (CI) Risultati Complessivamente sono stati reclutati 62 casi: 3/62 (4,8%) non presentavano nessuna struttura commissurale cerebrale; 23/62 (37,1%) presentavano solo la CA, 20/62 (32,3%) presentavano sia la CA che la CI in una forma vestigiale, mentre i rimanenti 16/62 casi evidenziavano la presenza di una commissura ibrida (CIB) risultanza della fusione della CI vestigiale con un corpo rudimentale e prematuro del corpo calloso. I reperti prenatali sono stati successivamente confermati dalle immagini ottenute con la RM post-natale quando disponibili. Conclusioni Nella maggioranza dei feti della nostra corte era stata documentata allo studio prenatale con RM la presenza almeno di una commissura (CA); in circa la metà di essi era stata identificata in concomitanza la presenza di una seconda commissura: CI in una forma vestigiale o la CIB composta dalla fusione di due commissure; la CI vestigiale e il prematuro corpo del corpo calloso. Ulteriori studi sono necessari al fine di verificare se tale variabilità commissurale nei feti affetti da ACC isolata possa associarsi a diverse caratteristiche genetiche e avere un impatto sull’ outcome neurologico a lungo termine di questi giovani pazienti. / Background and Purpose Agenesis of corpus callosum (ACC), even when isolated, may be characterized by anatomical variability. The aim of this study was to describe the types of other forebrain commissures, in a large cohort of randomly enrolled fetuses with apparently isolated ACC at prenatal magnetic resonance (MR) imaging. Materials and Methods From 2004 to 2014 in all fetuses with apparently isolated ACC submitted to prenatal MR imaging, the presence of the anterior (AC) or a vestigial hippocampal commissure (HC) was assessed "in consensus" by two pediatric neuroradiologists. Results Overall 62 cases of ACC were retrieved from our database. In 3/62 fetuses (4,8%) no forebrain commissure was visible at prenatal MR imaging, 23/62 cases (37,1%) presented only the AC, 20/62 cases (32,3%) showed both the AC and a residual vestigial HC, whereas in the remaining 16/62 cases (25,8%) a hybrid structure (HS) merging a residual vestigial HC and a rudiment of CC body was detectable. Postnatal MR imaging, when available, confirmed prenatal forebrain commissure findings. Conclusions The vast majority of fetuses with apparently isolated ACC showed at least one forebrain commissure at prenatal MR imaging, and about half of cases also a second commissure: a vestigial HC or a hybrid made of HC and rudiment CC body. It remains to be assessed if such variability is the result of different genotype and if it may have any impact on the long term neurodevelopmental outcome

La chirurgia guidata dalle immagini(IGS) è usata in numerosi settori della chirurgia. Un innovativo sistema di navigazione chiamato Implanav è stato sviluppato dall'Università di Bologna insieme alla ditta BresMedical per consentire al chirurgo di monitorare in tempo reale le strutture anatomiche, durante il posizionamento degli impianti in campo maxillo-facciale. L'obbiettivo dello studio è di valutare in vitro ed in vivo le potenzialità e la precisione di questo sistema. / Image-Guided Surgery (IGS) is used in a variety of medical procedures. An innovative system called ImplaNav has been developed by University of Bologna and BresMedical for oral and maxillofacial surgical navigation, in order to generate three-dimensional volumetric representations of the maxillofacial area, which allow surgeons to evaluate a patient's anatomy before surgery and assist in planning for the placement of implants in appropriate , ideal or preferred positions. The objective of this study is to evaluate the accuracy of the ImplaNavTM software and registration tools by presenting results obtained deploying the system in-vitro and in-vivo cases. The investigation focuses on how the surgical guidance, by way of visualization of a surgeon's instrument via optical tracking offered by the ImplaNavTM system, generates an immediate feedback on the possible misplacement or positioning of a dental implant.