A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project “PROPAG-AGEING”, whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naïve and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development

Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

Advanced age represents one of the major risk factors for Parkinson’s Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson’s Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson’s Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson’s Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson’s Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson’s Disease patients, and healthy siblings of Parkinson’s Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson’s Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson’s Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson’s Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson’s Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson’s Disease

EEG Activation Does Not Differ in Simple and Complex Episodes of Disorders of Arousal: A Spectral Analysis Study

Purpose: Disorders of arousal (DoA) are characterized by incomplete awakening from NREM sleep, with the admixture of both deep sleep and wake EEG activity. Previous observations suggested that changes in EEG activity could be detected in the seconds preceding DoA episodes. The aims of this work were to characterize the topography of EEG spectral changes prior to DoA episodes and to investigate whether or not behavioral complexity could be predicted by changes in EEG immediately preceding behavioral onsets. Patients and Methods: We collected 103 consecutive video-polysomnographic recordings of 53 DoA adult patients and classified all episodes as simple, rising and complex arousal movements. For each episode, a 5-second window preceding its motor onset (“pre-event”) and a 60-second window from 2 to 3 minutes before the episodes (“baseline”) were compared. Subsequently, a between-group comparison was performed for the pre-event of simpler versus the more complex episodes. Results: Spectral analysis over 325 DoA episodes showed an absolute significant increase prior to DoA episodes in all frequency bands excluding sigma, which displayed the opposite effect. In normalized maps, the increase was relatively higher over the central/ anterior areas for both slow and fast frequency bands. No significant differences emerged from the comparison between simpler and more complex episodes. Conclusion: Taken together, these results show that deep sleep and wake-like EEG rhythms coexist over overlapping areas before DoA episodes, suggesting an alteration of local sleep mechanisms. Episodes of different complexity are preceded by a similar EEG activation, implying that they possibly share a similar pathophysiology

Performing sleep studies after the COVID-19 outbreak: practical suggestions from Bologna's sleep unit

The Coronavirus Disease 2019 (COVID-19) pandemic required a thorough re-organization of every sector of the healthcare system. Sleep laboratories need to renew protocols in order to guarantee the safety of patients and healthcare staff while providing exams. Polysomnography (PSG) examinations are essential for the diagnosis and treatment management of several sleep disorders, which may constitute a public or personal safety issue such as obstructive sleep apnea syndrome. Here we provide some practical advice on how to perform sleep studies after the COVID-19 outbreak based on our experience, the review of the existing literature and current national and international recommendations by Health Authorities. We believe that with appropriate precautions it is possible to guarantee a safe restart of PSG and other sleep studies

Analyzing Undergraduate Student Graduation Delay: A Longitudinal Perspective

In Italy the number of years in which undergraduate students should complete their education programme is established by law. However, many students obtain their degree after the expected time: a well-known issue affecting numerous Italian universities. In 1999, therefore, the Italian government introduced a reform that, among other aims, intended to reduce the gap between the average number of years in which a student completed the education programme and the official deadline established by the university regulations

Detection of a New Yellow Fever Virus Lineage Within the South American Genotype I in Brazil

Nucleotide sequences of two regions of the genomes of 11 yellow fever virus (YFV) samples isolated from monkeys or humans with symptomatic yellow fever (YF) in Brazil in 2000,2004, and 2008 were determined with the objective of establishing the genotypes and studying the genetic variation. Results of the Bayesian phylogenetic analysis showed that sequences generated from strains from 2004 and 2008 formed a new subclade within the clade 1 of the South American genotype I. The new subgroup is here designated as 1E. Sequences of YFV strains recovered in 2000 belong to the subclade 1D, which comprises previously characterized YFV strains from Brazil. Molecular dating analyses suggested that the new subclade 1E started diversifying from 1D about 1975 and that the most recent 2004-2008 isolates arose about 1985. J. Med. Virol. 82:175-185, 2010. (C) 2009 Wiley-Liss, Inc.Secretaria de Estado da Saude de Sao Paulo/SPFAPESP[05/53973-0