Parkinson's disease: Immune System, infections and Alpha-synuclein protein

Parkinson's disease (PD) is a neurodegenerative disorder and its etiology is unknown, but environmental factors are implicated in the development of this disease. In this project we want to analyze different roles played by α-syn, HSV-1 and Immune System in PD. We have investigated autoimmunity in PD through ELISA and a specific immune-stimulation using homologous peptides of HSV-1 and α-syn in PD patients VS HCs. Moreover with in vitro study we have investigated the potential role of α-syn as a antimicrobial peptide and could therefore contribute to α-syn aggregation, neuroinflammation, and widespread dopaminergic neuron death. Lastly we have analyzed the potential of circulating miRNAs as noninvasive diagnostic candidate biomarkers of PD patients and neuroinflammation. The obtained results are in line with the hypothesis of a possible involvement of the immune system, in particular autoimmunity, in the pathogenesis of Parkinson's disease, and that HSV-1 infections may lead to a progression of the disease. Concerning α-syn as a potential antimicrobial peptides further studies are needed to clarify the complexity of the functions of this protein. Regarding identification of miRNA we have highlighted different levels of expression of some miRNA, 155 and 146a, between patients with PD and healthy controls

Serum BAFF levels, methypredsinolone therapy, Epstein-Barr virus and <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> infection in Multiple Sclerosis patients

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease

Type 1 Diabetes at-risk children highly recognize <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> epitopes homologous to human Znt8 and Proinsulin

Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to T1D as a putative environmental agent triggering or accelerating the disease in Sardinian and Italian populations. Our aim was to investigate the role of MAP in T1D development by evaluating levels of antibodies directed against MAP epitopes and their human homologs corresponding to ZnT8 and proinsulin (PI) in 54 T1D at-risk children from mainland Italy and 42 healthy controls (HCs). A higher prevalence was detected for MAP/ZnT8 pairs (62,96% T1D vs. 7,14% HCs; p &lt; 0.0001) compared to MAP/PI epitopes (22,22% T1D vs. 9,52% HCs) and decreasing trends were observed upon time-point analyses for most peptides. Similarly, classical ZnT8 Abs and GADA decreased in a time-dependent manner, whereas IAA titers increased by 12%. Responses in 0–9 year-old children were stronger than in 10–18 age group (75% vs. 69,1%; p &lt; 0.04). Younger age, female sex and concomitant autoimmune disorders contributed to a stronger seroreactivity suggesting a possible implication of MAP in multiple autoimmune syndrome. Cross-reactivity of the homologous epitopes was reflected by a high correlation coefficient (r2 &gt; 0.8) and a pairwise overlap of positivity (&gt;83% for MAP/ZnT8)

Processing and characterization of Ultra High Temperature High‐Entropy (Ti0.2Zr0.2Hf0.2Mo0.2W0.2)B2-based Ceramics: Effect of W granulometry, graphite, and SiC addition

A highly dense and single phase (Ti0.2Zr0.2Hf0.2Mo0.2W0.2)B2 ceramic product is obtained in this work at 1950°C (20 min, 20 MPa) by Spark Plasma Sintering (SPS) from powders prepared by Self-propagating High-temperature Synthesis (SHS). The formation of the (W,Mo)B2 secondary phase is avoided using fine W precursors and adding 1 wt% graphite to the SHS powders before SPS. Kinetic limitations responsible for hindering the synthesis of the high entropy boride are correspondingly eliminated. The resulting 98.5 % dense sample exhibits a homogeneous microstructure, with Vickers hardness of 26.8 GPa. The introduction of 20 vol% SiC produces an increase of the KIC values from 2.32 to 5.11 MPa m1/2. Very relevant is that the volatilization of Mo- and W-oxides occurring during sample oxidation at high temperature, which leads to its rapid degradation with the formation of a very porous oxide scale, can be strongly inhibited by the silicate phases generated in the composite ceramic

Inflammation, Infectious Triggers, and Parkinson's Disease

Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons of the substantia nigra pars compacta with a reduction of dopamine concentration in the striatum. The complex interaction between genetic and environmental factors seems to play a role in determining susceptibility to PD and may explain the heterogeneity observed in clinical presentations. The exact etiology is not yet clear, but different possible causes have been identified. Inflammation has been increasingly studied as part of the pathophysiology of neurodegenerative diseases, corroborating the hypothesis that the immune system may be the nexus between environmental and genetic factors, and the abnormal immune function can lead to disease. In this review we report the different aspects of inflammation and immune system in Parkinson's disease, with particular interest in the possible role played by immune dysfunctions in PD, with focus on autoimmunity and processes involving infectious agents as a trigger and alpha-synuclein protein (α-syn)

Assessing the quality of the care offer for people with personality disorders in Italy: the QUADIM project. A multicentre research based on the database of use of Mental Health services

Background: Italy can be viewed as a laboratory to assess the quality of mental healthcare delivered in a community-oriented system, especially for severe mental disorders, such as personality disorders. Although initiatives based on clinical indicators for assessing the quality of mental healthcare have been developed by transnational-organisations, there is still no widespread practice of measuring the quality of care pathways delivered to patients with severe mental disorders in a community-oriented system, especially using administrative healthcare databases. The aim of the study is to evaluate the quality of care delivered to patients with personality disorders taken-in-care by mental health services of four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily). Methods: A set of thirty-three clinical indicators, concerning accessibility, appropriateness, continuity, and safety of care, was implemented using regional healthcare utilization databases, containing data on mental health treatments and diagnosis, hospital admissions, outpatient interventions and exams and drug prescriptions. RESULTS: 31,688 prevalent patients with personality disorders treated in 2015 were identified, of whom 2,331 newly taken-in-care. One-in-10 patients received a standardized assessment, the treatment discontinuity affected half of the cases. 12.7% of prevalent patients received at least one hospitalization, 10.6% in the newly taken-in-care cohort. 6-out-of-10 patients had contact with community-services within 14 days from hospital discharge. Access to psychotherapy and psychoeducational treatments was low and delivered with a low intensity. The median of psychosocial interventions per person-year was 19.1 and 9.4, respectively, in prevalent and newly taken-in-care cases. Nearly 50% of patients received pharmacological treatments. Conclusions: Healthcare utilization databases were used to systematically evaluate and assess service delivery across regional mental health systems; suggesting that in Italy the public mental health services provide to individuals with personality disorders suboptimal treatment paths

Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder

A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD)

How is intolerance of uncertainty related to negative affect in individuals with substance use disorders? The role of the inability to control behaviors when experiencing emotional distress

We used structural equation modeling to assess the role of impaired emotional awareness and clarity (Impaired Awareness/Clarity) and inability to control behaviors when experiencing emotional distress (Inability to Control Behaviors) as an account for the relationship between intolerance of uncertainty (IU) and negative affect (NA) in individuals with Substance Use Disorders (SUDs) and healthy controls (HCs) used for comparison. One-hundred and thirty-one individuals with SUDs (42.75% female; mean age = 39.74 \ub1 11.83) and 131 sex-matched HCs (mean age = 40.02 \ub1 12.34) entered the study. Participants completed questionnaires assessing the constructs of interest. Single-group analyses aimed to identify a baseline model for each group and test the hypothesized direct/indirect relations\u2019 overall significance. Then, a multigroup analysis tested the invariance of model parameters between SUD and HC groups. The model in which IU had both direct and indirect relationships with NA through Impaired Awareness/Clarity and Inability to Control Behaviors was a good fit to the data. The indirect relationship of IU with NA through Inability to Control Behaviors was significant and moderate-sized. The relationship involving Impaired Awareness/Clarity and Inability to Control Behaviors was small-sized and significant in single group analysis only. The multigroup analysis supported the association of IU with NA through Inability to Control Behaviors in the SUD group. Overall, our study highlights the crucial role of the Inability to Control Behaviors in SUDs and suggests that its association with IU might fuel NA in this population

Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease

Differential expression of miRNA 155 and miRNA 146a in Parkinson's disease patients

Parkinson's disease is a neurodegenerative disorder and its etiology is unknown, numerous studies show how different environmental factors can influence the development of disease. miRNAs are involved in several pathologies and their dysregulation contribute to different pathologies, also in neurodegenerative such as Parkinson's disease, Alzheimer's disease, Huntington's disease and Amyotrophic lateral sclerosis. In this study, we profiled the expression of different candidate miRNAs: miR-155, miR-26a, miR-146a, and miR132, in PBMCs of L-dopa treated Parkinson patients and unaffected controls (HCs).We investigated the expression of miRNAs by RT-real time PCR, the results were subjected to statistical analysis. miRNA-155-5p was generally up-regulated in PD patients compared to HCs whereas miRNA-146a-5p was down-regulated in PD patients in comparison to HCs. It is interesting to point out that the expression of miR-155-5p was modified by levodopa treatment, in fact a down-regulation of miR-155-5p in PD patients with the highest dosage was observed.In conclusion, miRNA 155 could not only be a promising target for the anti-inflammatory therapy in PD but also a good candidate as a disease progression biomarker. The role of levodopa in modulating the levels of miRNA 155 requires further studies. Keywords: Parkinson's disease, miRNA, Neurodegeneration, Levo-dopa treatmen