LRRK2 and neuroinflammation: Partners in crime in Parkinson's disease?

3noopenopenRusso, Isabella*; Bubacco, Luigi; Greggio, ElisaRusso, Isabella; Bubacco, Luigi; Greggio, Elis

Sirtuins 1–7 expression in human adipose-derived stem cells from subcutaneous and visceral fat depots: influence of obesity and hypoxia

The sirtuin family comprises seven NAD+-dependent deacetylases which control the overall health of organisms through the regulation of pleiotropic metabolic pathways. Sirtuins are important modulators of adipose tissue metabolism and their expression is higher in lean than obese subjects. At present, the role of sirtuins in adipose-derived stem cells has not been investigated yet. Therefore, in this study, we evaluated the expression of the complete panel of sirtuins in adipose-derived stem cells isolated from both subcutaneous and visceral fat of non-obese and obese subjects. We aimed at investigating the influence of obesity on sirtuins' levels, their role in obesity-associated inflammation, and the relationship with the peroxisome proliferator-activated receptor delta, which also plays functions in adipose tissue metabolism. The mRNA levels in the four types of adipose-derived stem cells were evaluated by quantitative polymerase chain reaction, in untreated cells and also after 8 h of hypoxia exposure. Correlations among sirtuins' expression and clinical and molecular parameters were also analyzed. We found that sirtuin1-6 exhibited significant higher mRNA expression in visceral adipose-derived stem cells compared to subcutaneous adipose-derived stem cells of non-obese subjects. Sirtuin1-6 levels were markedly reduced in visceral adipose-derived stem cells of obese patients. Sirtuins' expression in visceral adipose-derived stem cells correlated negatively with body mass index and C-reactive protein and positively with peroxisome proliferator-activated receptor delta. Finally, only in the visceral adipose-derived stem cells of obese patients hypoxia-induced mRNA expression of all of the sirtuins. Our results highlight that sirtuins' levels in adipose-derived stem cells are consistent with protective effects against visceral obesity and inflammation, and suggest a transcriptional mechanism through which acute hypoxia up-regulates sirtuins in the visceral adipose-derived stem cells of obese patients

Candidemia in medicina interna: definizione dei fattori di rischio attraverso uno studio caso-controllo

Negli ultimi vent’anni la candidosi invasiva ha acquisito una crescente importanza nello scenario delle infezioni nosocomiali, mostrando un progressivo aumento della incidenza che cresce parallelamente alla complessità delle procedure invasive, chirurgiche e dei trattamenti. I progressi della ricerca scientifica hanno portato all’allungamento della vita in pazienti ad alto rischio di contrarre infezioni opportunistiche. La candidosi invasiva include uno spettro di patologie determinate da Candida spp., la cui espressione clinica più frequente è la candidemia. Tra le setticemie, quella sostenuta da Candida spp è tra le infezioni a più alta mortalità e con la più alta frequenza di inappropriatezza terapeutica. Il significativo aumento della mortalità può essere determinato da una inadeguata e tempestiva terapia empirica e dal mancato controllo della sorgente di infezione. La diagnosi di una candidemia è inoltre ostacolata dalla aspecificità delle sue manifestazioni cliniche e dalla lunga tempistica che richiede la diagnostica micologica. Lo scopo di questa tesi è quello di analizzare, attraverso uno studio caso-controllo, quali sono i fattori di rischio e le caratteristiche cliniche, associate allo sviluppo di una candidemia in un reparto di medicina interna. In tale modo possiamo gettare le basi per la creazione di uno score clinico che ci guidi nell’individuazione del paziente internistico a rischio di candidemia e nell’inizio tempestivo di una adeguata terapia empirica, nell’attesa degli esami colturali e microbiologici

Citologia tiroidea indeterminata (TIR 3): revisione di casistica e possibile ruolo delle procedure di Medicina Nucleare

La patologia nodulare tiroidea è estremamente comune ed il suo riscontro è aumentato negli ultimi anni. Attualmente il 4% della popolazione presenta noduli tiroidei clinicamente palpabili. Dalla revisione della letteratura internazionale si evince che la frequenza della patologia nodulare tiroidea cresce con l’avanzare dell’età con percentuali che si avvicinano al 50% in pazienti con età superiore ai 50 anni e ciò è confermato anche dagli studi autoptici. Scopo del nostro studio è stato quello di revisionare e confrontare con la letteratura i dati di una casistica retrospettiva di pazienti con nodulo tiroideo indeterminato (TIR 3) selezionati nel nostro Centro di Medicina Nucleare

Do patents really foster innovation in the pharmaceutical sector? Results from an evolutionary, agent-based model

The role of the patent system in the pharmaceutical sector is highly debated also due to its strong public health implications. In this paper we develop an evolutionary, agent-based model of the pharmaceutical industry to explore the impact of different configurations of the patent system upon innovation and competition. The model is able to replicate the main stylized facts of the drug industry as emergent properties. We perform policy experiments to assess the impact of different IPR regimes changing the breadth and length of patents. Results suggest that enlarging the extent and duration of patents yields adverse effects in terms of innovation outcomes, as well as of market competition and consumer welfare. Such general conclusions hold even if one takes into account the possible positive effects on R&D intensity and information disclosure triggered by patents

Digitalization, copyright and innovation in the creative industries: an agent-based model

The ambiguity of the empirical results on the relationship between copyright and creativity calls for a better theoretical understanding of the issue, possibly enlarging the analysis to other factors such as technology and copyright enforcement. This paper addresses these complex policy issues by developing an agent-based model (ABM) to study how the interplay between digitization and copyright enforcement affects the production and access to cultural goods. The model includes creators who compete in different submarkets and invest in activities that might lead to the generation of creative outputs in existing submarkets, new (to the creators) submarkets, or in newly “invented†submarkets. Finally, the model features a copyright system that provides creators with the exclusive right to reproduce their original copies and a pirate market responsible for creating and distributing pirated copies

Bone Regeneration Using Mesenchymal Stromal Cells and Biocompatible Scaffolds: A Concise Review of the Current Clinical Trials

: Bone regenerative medicine is a clinical approach combining live osteoblast progenitors, such as mesenchymal stromal cells (MSCs), with a biocompatible scaffold that can integrate into host bone tissue and restore its structural integrity. Over the last few years, many tissue engineering strategies have been developed and thoroughly investigated; however, limited approaches have been translated to clinical application. Consequently, the development and clinical validation of regenerative approaches remain a centerpiece of investigational efforts towards the clinical translation of advanced bioengineered scaffolds. The aim of this review was to identify the latest clinical trials related to the use of scaffolds with or without MSCs to regenerate bone defects. A revision of the literature was performed in PubMed, Embase, and Clinicaltrials.gov from 2018 up to 2023. Nine clinical trials were analyzed according to the inclusion criteria: six presented in the literature and three reported in Clinicaltrials.gov. Data were extracted covering background trial information. Six of the clinical trials added cells to scaffolds, while three used scaffolds alone. The majority of scaffolds were composed of calcium phosphate ceramic alone, such as β-tricalcium phosphate (TCP) (two clinical trials), biphasic calcium phosphate bioceramic granules (three clinical trials), and anorganic bovine bone (two clinical trials), while bone marrow was the primary source of the MSCs (five clinical trials). The MSC expansion was performed in GMP facilities, using human platelet lysate (PL) as a supplement without osteogenic factors. Only one trial reported minor adverse events. Overall, these findings highlight the importance and efficacy of cell-scaffold constructs in regenerative medicine under different conditions. Despite the encouraging clinical results obtained, further studies are needed to assess their clinical efficacy in treating bone diseases to optimize their application

LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate

Background Lrrk2, a gene linked to Parkinson\u2019s disease, encodes a large scaffolding protein with kinase and GTPase activities implicated in vesicle and cytoskeletal-related processes. At the presynaptic site, LRRK2 associates with synaptic vesicles through interaction with a panel of presynaptic proteins. Results Here, we show that LRRK2 kinase activity influences the dynamics of synaptic vesicle fusion. We therefore investigated whether LRRK2 phosphorylates component(s) of the exo/endocytosis machinery. We have previously observed that LRRK2 interacts with NSF, a hexameric AAA+ ATPase that couples ATP hydrolysis to the disassembling of SNARE proteins allowing them to enter another fusion cycle during synaptic exocytosis. Here, we demonstrate that NSF is a substrate of LRRK2 kinase activity. LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling. Substitution of threonine 645 with alanine abrogates LRRK2-mediated increased ATPase activity. Conclusions Given that the most common Parkinson\u2019s disease LRRK2 G2019S mutation displays increased kinase activity, our results suggest that mutant LRRK2 may impair synaptic vesicle dynamics via aberrant phosphorylation of NSF

Actividad insecticida del aceite esencial de Eucalyptus globulus sobre Aphis nerii (Boyer) y Gynaikothrips ficorum (Marchal)

Russo, Serafina. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Yaber Grass, Margarita A. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Fontana, Heidi Cristina. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Leonelli, Elisa. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.63-67Aphids and thrips are very important pest species of many greenhouse and field plants in the world. In recent years, there have been attempts to identify plants for their insecticidal property with a view to find out suitable alternatives to the indiscriminate use of chemical pesticides, which are a risk for human health and the environment. The aim of this work was to evaluate the insecticidal effect of Eucalyptus globulus Labill essential oil (EO) against Aphis nerii Boyer de Fonscolombe (Hemiptera: Aphididae) and Gynaikothrips ficorum Marchal (Thysanoptera: Ploeothridae). The EO was extracted by hydrodistillation and the bioassay was evaluated by toxicity contact method, using solutions at different concentrations and for different time intervals. The EO was more toxic to G. ficorum (LC50 = 0.031µL cm-2) than A. nerii (LC50 = 0.099µL cm-2) on filter discs at 12 h of exposure. These results suggested that EO from E. globulus constitute a good alternative for the control of A. nerii and G. ficorum, considering their insecticidal effects at low applied concentrations and for short periods of time

Hospitalization for pneumonia is associated with decreased 1-year survival in patients with type 2 diabetes results from a prospective cohort study

Diabetes mellitus is a frequent comorbid conditions among patients with pneumonia living in the community. The aim of our study is to evaluate the impact of hospitalization for pneumonia on early (30 day) and late mortality (1 year) in patients with type 2 diabetes mellitus. Prospective comparative cohort study of 203 patients with type 2 diabetes hospitalized for pneumonia versus 206 patients with diabetes hospitalized for other noninfectious causes from January 2012 to December 2013 at Policlinico Umberto I (Rome). Enrolled patients were followed up to discharge and up to 1 year after initial hospital admission or death. Overall, 203 patients with type 2 diabetes admitted to hospital for pneumonia were compared to 206 patients with type 2 diabetes admitted for other causes (39.3% decompensated diabetes, 21.4% cerebrovascular diseases, 9.2% renal failure, 8.3% acute myocardial infarction, and 21.8% other causes). Compared to control patients, those admitted for pneumonia showed a higher 30-day (10.8% vs 1%, P<0.001) and 1-year mortality rate (30.3% vs 16.8%, P<0.001). Compared to survivors, nonsurvivor patients with pneumonia had a higher incidence of moderate to severe chronic kidney disease, hemodialysis, and malnutrition were more likely to present with a mental status deterioration, and had a higher number of cardiovascular events during the follow-up period. Cox regression analysis found age, Charlson comorbidity index, pH<7.35 at admission, hemodialysis, and hospitalization for pneumonia as variables independently associated with mortality. Hospitalization for pneumonia is associated with decreased 1-year survival in patients with type 2 diabetes, and appears to be a major determinant of long-term outcome in these patients