Single cell analysis reveals the involvement of the long non-coding RNA Pvt1 in the modulation of muscle atrophy and mitochondrial network

Long non-coding RNAs (lncRNAs) are emerging as important players in the regulation of several aspects of cellular biology. For a better comprehension of their function, it is fundamental to determine their tissue or cell specificity and to identify their subcellular localization. In fact, the activity of lncRNAs may vary according to cell and tissue specificity and subcellular compartmentalization. Myofibers are the smallest complete contractile system of skeletal muscle influencing its contraction velocity and metabolism. How lncRNAs are expressed in different myofibers, participate in metabolism regulation and muscle atrophy or how they are compartmentalized within a single myofiber is still unknown. We compiled a comprehensive catalog of lncRNAs expressed in skeletal muscle, associating the fiber-type specificity and subcellular location to each of them, and demonstrating that many lncRNAs can be involved in the biological processes de-regulated during muscle atrophy. We demonstrated that the lncRNA Pvt1, activated early during muscle atrophy, impacts mitochondrial respiration and morphology and affects mito/autophagy, apoptosis and myofiber size in vivo. This work corroborates the importance of lncRNAs in the regulation of metabolism and neuromuscular pathologies and offers a valuable resource to study the metabolism in single cells characterized by pronounced plasticity

Carnosol controls the human glioblastoma stemness features through the epithelial-mesenchymal transition modulation and the induction of cancer stem cell apoptosis

A high cell proliferation rate, invasiveness and resistance to chemotherapy are the main features of glioblastoma (GBM). GBM aggressiveness has been widely associated both with a minor population of cells presenting stem-like properties (cancer stem-like cells, CSCs) and with the ability of tumor cells to acquire a mesenchymal phenotype (epithelial-mesenchymal transition, EMT). Carnosol (CAR), a natural inhibitor of MDM2/p53 complex, has been attracted attention for its anti-cancer effects on several tumor types, including GBM. Herein, the effects of CAR on U87MG-derived CSC viability and stemness features were evaluated. CAR decreased the rate of CSC formation and promoted the CSC apoptotic cell death through p53 functional reactivation. Moreover, CAR was able to control the TNF-α/TGF-β-induced EMT, counteracting the effects of the cytokine on EMT master regulator genes (Slug, Snail, Twist and ZEB1) and modulating the activation of miR-200c, a key player in the EMT process. Finally, CAR was able to increase the temozolomide (TMZ) anti-proliferative effects. These findings demonstrate that CAR affected the different intracellular mechanism of the complex machinery that regulates GBM stemness. For the first time, the diterpene was highlighted as a promising lead for the development of agents able to decrease the stemness features, thus controlling GBM aggressiveness

Architectural and structural recovery of “mastio” and its courtyard of the new fortress of Volterra

[EN] The recovery of the “mastio” and the surrounding courtyard of the new fortress of Volterra (1472-1474) has as its objective the opening to the public of this fortified work, after 542 years from its construction, with the possibility of being enjoyed without interposing with the prison function of the complex, it also represents the possibility of knowledge and study of a constructive typology in the context of the Renaissance fortified architecture of the Italian school called “transition” with the use of the first artillery. The fortress was born as a military garrison and at the time of Lorenzo the magnificent only a part was used as a prison, it will be definitively transformed into a House of Imprisonment during the Grand Duchy of Lorraine in the middle of the eighteenth century. It is the first work by Francesco di Giovanni di Matteo called the Francione (1428-1495), it has an almost square shape with large cylindrical towers at the corners (rondelle) and at the center of the inner courtyard, a large cylindrical tower like of “mastio” (donjon) and inserted the artillery in the walls. The “mastio” consists of a basement and five floors above ground with a domed roof and connected by a narrow spiral staircase. After the cognitive essays carried out on the internal domes of the “mastio”, placed in the first three floors including the cistern, the presence of “hemispherical domes” emerged, made by workers of the Opera del Duomo in Florence, built entirely in bricks without the carpentry of “centina” (self-supporting), with the system called “alla fiorentina”, as well as the dome of Santa Maria del Fiore in Florence by Filippo Brunelleschi. This construction system is also applied in the fortified structures of Pietrasanta, Poggibonsi, Sarzanello, Castrocaro, Pisa and Terra del Sole.Taddei, D.; Calvani, C.; Pistolesi, R.; Taddei, A.; Martini, A. (2020). Recupero architettonico e strutturale del “mastio” e del suo cortile della fortezza nuova di Volterra. Editorial Universitat Politècnica de València. 1425-1432. https://doi.org/10.4995/FORTMED2020.2020.11361OCS1425143

The Italian version of the LARS score: cross-cultural adaptation and validation. An Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CCN) collaborative study

Purpose: The LARS score is an internationally well-accepted questionnaire to assess low anterior resection syndrome, but currently there is no formally validated Italian version. The purpose of this study was to test the reliability and validity of the Italian version among Italian patients submitted to sphincter-sparing surgery for rectal cancer. Methods: The English version of the LARS score was translated into Italian following the forward-and-back translation process. A total of 147 patients filled out our version. Among them, 40 patients answered the questionnaire twice for the test-retest reliability phase. The validity of the LARS score was tested using convergent and discriminant validity indicators by correlating the EORTC QLQ-C30 and QLQ-CR29 questionnaires. The LARS score capability to differentiate groups of patients with different demographic or clinical features was also assessed. Results: The test-retest reliability was excellent in 87.5% of patients, remained in the same LARS category in both tests. The convergent validity phase showed a relevant relationship of the LARS score with the EORTC domains, which was significant for 7 of 15 EORTC QLQ-C30 subscales, and for 14 of 29 EORTC QLQ-CR29 subscales. The LARS score was able to discriminate patients who received radiotherapy (p = 0.0026), TME vs. PME (p = 0.0060), tumour site at < 10 cm from the anal verge (p = 0.0030) and history of protective stoma (p < 0.0001). Conclusion: The Italian version of the LARS score is a valid and reliable tool for measuring LARS in Italian patients after SSS for rectal cancer

avian metapneumovirus circulation in italian broiler farms

Abstract With increasing frequency, avian Metapneumovirus (aMPV) is reported to induce respiratory signs in chickens. An adequate knowledge of current aMPV prevalence among Italian broilers is lacking, with little information available on its economical and health impact on the poultry industry. In order to collect preliminary data on the epidemiological context of aMPV in broiler flocks, a survey was performed in areas of Northern Italy with high poultry density from 2014 to 2016. Upper respiratory tract swabs were collected and processed by A and B subtype-specific multiplex real-time reverse transcription PCR (RT-PCR). Samples were also screened for infectious bronchitis virus (IBV) by generic RT-PCR and sequencing. Productive data and respiratory signs were detailed where possible. The high prevalence of aMPV was confirmed in broilers older than 26 d and also attested in IBV-negative farms. All aMPV detections belonged to subtype B. Italian strain genetic variability was evaluated by the partial attachment (G) gene sequencing of selected strains and compared with contemporary turkey strains and previously published aMPV references, revealing no host specificity and the progressive evolution of this virus in Italy

α-Synuclein Aggregates with β-Amyloid or Tau in Human Red Blood Cells: Correlation with Antioxidant Capability and Physical Exercise in Human Healthy Subjects

Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid1–42 (Aβ), and tau, in both brain and peripheral tissue. In addition to homo-oligomers, the role of α-syn interactions with Aβ or tau has gradually emerged. The altered protein accumulation has been related to both oxidative stress and physical activity; nevertheless, no correlation among the presence of peripheral α-syn hetero-aggregates, antioxidant capacity, and physical exercise has been discovered as of yet. Herein, the content of α-syn, Aβ, tau, and of their heterocomplexes was determined in red blood cells (RBCs) of healthy subjects (sedentary and athletes). Such parameters were related to the extent of the antioxidant capability (AOC), a key marker of oxidative stress in aging-related pathologies, and to physical exercise, which is known to play an important preventive role in NDs and to modulate oxidative stress. Tau content and plasma AOC toward hydroxyl radicals were both reduced in older or sedentary subjects; in contrast, α-syn and Aβ accumulated in elderly subjects and showed an inverse correlation with both hydroxyl AOC and the level of physical activity. For the first time, α-syn heterocomplexes with Aβ or tau were quantified and demonstrated to be inversely related to hydroxyl AOC. Furthermore, α-syn/Aβ aggregates were significantly reduced in athletes and inversely correlated with physical activity level, independent of age. The positive correlation between antioxidant capability/physical activity and reduced protein accumulation was confirmed by these data and suggested that peripheral α-syn heterocomplexes may represent new indicators of ND-related protein misfolding

Frailty and post-operative delirium influence on functional status in patients with hip fracture: the GIOG 2.0 study

Background: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF). Methods: Multicenter prospective observational study of older patients with HF admitted to 12 Italian Orthogeriatric centers (July 2019-August 2022). POD was assessed using the 4AT. A 26-item Frailty Index (FI) was created using data collected on admission. The outcome measures were Cumulated Ambulation Score (CAS) ≤ 2 at discharge and a telephone-administered CAS ≤ 2 after 4 months. Poisson regression models were used to assess the effect of frailty and POD on outcomes. Results: 984 patients (median age 84 years, IQR = 79-89) were recruited: 480 (48.7%) were frail at admission, 311 (31.6%) developed POD, and 158 (15.6%) had both frailty and POD. In a robust Poisson regression, frailty alone (Relative Risk, RR = 1.56, 95% Confidence Intervals, CI 1.19-2.04, p = 0.001) and its combination with POD (RR = 2.57, 95% CI 2.02-3.26, p < 0.001) were associated with poor functional status at discharge. At 4-month follow-up, the combination of frailty with POD (RR 3.65, 95% CI 1.85-7.2, p < 0.001) increased the risk of poor outcome more than frailty alone (RR 2.38, 95% CI 1.21-4.66, p < 0.001). Conclusions: POD development exacerbates the negative effect that frailty exerts on functional outcomes in HF patients

L' impatto del COVID-19 sull'economia. 10 proposte per la ripartenza. Un'analisi fondata sullo studio della provincia di Pisa.

Il presente lavoro, ultimato a inizio luglio 2020, e' il frutto della collaborazione di un gruppo di docenti e ricercatori che operano nei Dipartimenti di Economia e Management, Giurisprudenza e Scienze Politiche dell’Universita' di Pisa. Nato sulla base di una richiesta della Prefettura di Pisa all’Ateneo pisano in piena emergenza sanitaria, esso si propone lo scopo di fornire un’analisi degli effetti che l’emergenza COVID-19 ha avuto sul tessuto economico e sociale della provincia di Pisa e, alla luce dei risultati ottenuti, effettuare alcune “proposte per la ripartenza” per i prossimi mesi. Il convincimento degli autori che questo contributo di analisi e proposte, ancorche' riguardante la realta' territoriale della provincia di Pisa, possa avere una qualche utilita' anche per altre realta' provinciali e regionali, nonche' per quella nazionale. La ragione di tale convinzione e' duplice. Da un lato, l’approccio utilizzato, basato sulla multidisciplinarieta' e sul coinvolgimento delle realtà socio-economiche e istituzionali del territorio, rappresenta un metodo essenziale e generale per la piena comprensione di una realta' nuova e assai complessa quale quella derivante dall’emergenza COVID-19. Gli autori, provenienti da settori scientifici diversi quali l’ambito aziendale, economico, statistico, giuridico e sociolopsicologico, sono stati i primi a rendersi conto di quanto tale metodo di “messa a sistema” delle informazioni e degli attori economici e istituzionali della provincia fosse cruciale, ancorche' inusuale rispetto al carattere tipicamente specialistico delle ricerche in ambito accademico. Dall’altro lato, le proposte contenute nel lavoro, e che sono riportate in modo sintetico val termine di questa introduzione, sono il frutto dell’analisi quantitativa e qualitativa contenuta nei primi capitoli e rappresentano un esempio di come le scienze sociali possano fornire una base informativa essenziale per processi decisionali basati sui fatti (quelli che in ambito scientifico vengono definiti “evidenze empiriche”). In altre parole, le proposte hanno valenza generale, in quanto mettono in evidenza problemi e ipotizzano soluzioni che sono comuni a tutto il territorio nazionale. Il lavoro, organizzato come segue. Il primo capitolo presenta un’analisi strutturalee dinamica dell’economia della provincia di Pisa nel periodo precedente alla crisi sanitaria. Il secondo capitolo contiene una lettura dell’impatto economico, sociale e sanitario dell’emergenza COVID-19 e delle misure di contrasto messe in campo dal governo nei mesi iniziali della crisi (marzo-giugno 2020). Il terzo capitolo contiene un approfondimento dell’analisi economico-aziendale svolta. L’impatto del COVID-19 sull’economia alcuni settori emersi come rilevanti per l’economia provinciale. Il quarto capitolo svolge riflessioni e proposte in ambito giuridico, il quinto capitolo chiude il lavoro presentando alcune proposte di policy. Gli autori desiderano ringraziare il Prefetto di Pisa, per l’attivita' di supporto istituzionale, il Rettore dell’Universita' di Pisa, e tutti gli attori istituzionali e socio-economici che hanno collaborato direttamente – mediante incontri e interviste ‒ o indirettamente – attraverso la messa a disposizione dei dati e informazioni ‒ alla stesura del lavoro