Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model

Reduced dietary protein intake and intermittent fasting (IF) are both linked to healthy longevity in rodents, and are effective in inhibiting cancer growth. The molecular mechanisms underlying the beneficial effects of chronic protein restriction (PR) and IF are unclear, but may be mediated in part by a down-regulation of the IGF/mTOR pathway. In this study we compared the effects of PR and IF on tumor growth in a xenograft mouse model of breast cancer. We also investigated the effects of PR and IF on the mechanistic Target Of Rapamycin (mTOR) pathway, inhibition of which extends lifespan in model organisms including mice. The mTOR protein kinase is found in two distinct complexes, of which mTOR complex 1 (mTORC1) is responsive to acute treatment with amino acids in cell culture and in vivo. We found that both PR and IF inhibit tumor growth and mTORC1 phosphorylation in tumor xenografts. In somatic tissues, we found that PR, but not IF, selectively inhibits the activity of the amino acid sensitive mTORC1, while the activity of the second mTOR complex, mTORC2, was relatively unaffected by PR. In contrast, IF resulted in increased S6 phosphorylation in multiple metabolic tissues. Our work represents the first finding that PR may reduce mTORC1 activity in tumors and multiple somatic tissues, and suggest that PR may represent a highly translatable option for the treatment not only of cancer, but also other age-related diseases

Standardized Duplex Ultrasound-Based Protocol for Early Diagnosis of Transplant Renal Artery Stenosis: Results of a Single-Institution Retrospective Cohort Study

Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after kidney transplantation (KT) and has been associated with potentially reversible refractory hypertension, graft dysfunction, and reduced patient survival. The aim of the study is to describe the outcomes of a standardized Duplex Ultrasound- (DU-) based screening protocol for early diagnosis of TRAS and for selection of patients potentially requiring endovascular intervention. We retrospectively reviewed our prospectively collected database of KT from January 1998 to select patients diagnosed with TRAS. The follow-up protocol was based on a risk-adapted, dynamic subdivision of eligible KT patients in different risk categories (RC) with different protocol strategies (PS). Of 598 patients included in the study, 52 (9%) patients had hemodynamically significant TRAS and underwent percutaneous angioplasty (PTA) and stent placement. Technical and clinical success rates were 97% and 90%, respectively. 7 cases of restenosis were recorded at follow-up and treated with re-PTA plus stenting. Both DU imaging and clinical parameters improved after stent placement. Prospective high-quality studies are needed to test the efficacy and safety of our protocol in larger series. Accurate trial design and standardized reporting of patient outcomes will be key to address the current clinical needs

Progettazione, realizzazione e caratterizzazione della catena ricevente per il sistema SADino precursore del Sardinia Aperture Array Demonstrator (SAAD)

Il presente rapporto tecnico riassume la progettazione, realizzazione e caratterizzazione della catena di componenti a microonde e a radio frequenza per l’acquisizione del segnale del sistema SADino, precursore del Sardinia Aperture Array Demonstrator (SAAD). Il progetto SAAD prevede la realizzazione di un aperture array composto da 128 antenne Vivaldi a doppia polarizzazione lineare [1-7], installate al sito del Sardinia Radio Telescope (SRT), ciascuna delle quali verrà collegata alla sua catena dedicata di componenti a microonde per l’acquisizione del segnale, che permette di trasportare il segnale analogico rilevato in radio frequenza dall’antenna fino al back-end digitale. Con l’obiettivo di eseguire velocemente i primi test, inizialmente si è deciso di implementare parzialmente l’array SAAD. L’implementazione parziale del sistema SAAD prende appunto il nome di SADino, che prevede la realizzazione di un mini-array di 16 elementi a doppia polarizzazione, con il quale è possibile effettuare le prime osservazioni e i primi test di beam-forming con il back-end digitale dedicato basato sulle schede Italian Tile Processing Module (iTPM) [8]. Con SADino sono state scelte solo 16 antenne (a doppia polarizzazione) dell’intero array SAAD da 128 elementi, disposte in maniera casuale, poiché il back-end digitale iTPM è dotato di soli 32 ingressi. La catena ricevente (una per ogni canale di polarizzazione di ciascuna antenna Vivaldi) è stata progettata basandosi sui risultati di una campagna di misure, effettuata nell’estate del 2020, utile a valutare la presenza in banda di segnali interferenti generati dall’uomo e indesiderati per le attività di ricerca radioastronomica, noti come radio frequency interference (RFI) [6]. Per l’esecuzione di tale campagna di misure, si è utilizzata una delle antenne Vivaldi del SAAD, equipaggiandola con una catena di acquisizione del segnale che ha fatto da precursore (almeno per quanto riguarda la valutazione degli stadi di amplificazione) alla versione finale di catena ricevente da utilizzare sul sistema SADino, precursore dell’intero SAAD. L’obiettivo di questa campagna di misure RFI è stato quello di selezionare una banda di frequenze il più possibile libera da segnali indesiderati e contenuta ovviamente all’interno della banda di lavoro delle antenne che costituiscono l’array. Le antenne Vivaldi del SAAD sono state progettate per lavorare con buona efficienza in un range di frequenze che va da 50 MHz a 500 MHz [4], mentre i componenti a microonde che costituiscono la catena di acquisizione del segnale sono ottimizzati per lavorare nel range di frequenze selezionato in base ai risultati delle misure RFI e all’interno del quale poi opererà il telescopio. In questo rapporto interno vengono presentati i risultati della campagna di misure RFI preliminare, illustrando la catena ricevente utilizzata per queste misure (vedi Sezione 2). Nella Sezione 3 viene descritta la progettazione, realizzazione e caratterizzazione della catena di componenti a microonde per ciascuna antenna del sistema SADino. Nella Sezione 4 viene descritto il sistema di alimentazione che permette di alimentare i componenti attivi inseriti all’interno della catena ricevente e, infine, nella Sezione 5 si riportano le considerazioni conclusive sul lavoro svolto

Solar radiation effects on the Sardinia Radio Telescope performances

The Sardinia Radio Telescope, a 64-metre diameter fully steerable radio telescope operated by INAF, will be upgraded in order to extend its current operating frequency range 0.3-26.5 GHz up to 116 GHz, thanks to a National Operational Program (PON) funding assigned to INAF by the Italian Ministry of University and Research. The PON project is organized in nine Work Packages, one of which is dedicated to the accomplishment of a sophisticated metrology system designed to monitor the cause of the pointing errors and the reflector surface deformations. The entire antenna structure will therefore be equipped with a network of sensors, like thermal sensors, inclinometers, accelerometers, collimators, anemometers, strain gauges and others, to study environmental stresses and how they affect the SRT performances. This work is devoted to the investigation of the thermal stress effects produced by solar radiation. In particular, two analyses are carried out to confirm the relevance of a thorough temperature monitoring system, both conducted using Finite Element Analysis. First, a possible approach for the simulation of realistic thermal scenarios due to insolation is proposed and the effects on the pointing accuracy are analysed. Second, a feasible method to study the impacts that a differential heating of the Back Up Structure (BUS) produces on the radio telescope main reflector surface is presented. Finally, these effects are analysed as optical aberrations and modelled in terms of Zernike polynomials

Status of the High-Frequency Upgrade of the Sardinia Radio Telescope

The Sardinia Radio Telescope is going through a major upgrade aimed at observing the universe at up to 116 GHz. A budget of 18.700.000 E has been awarded to the Italian National Institute of Astrophysics to acquire new state-of-the-art receivers, back-end, and high-performance computing, to develop a sophisticated metrology system and to upgrade the infrastructure and laboratories. This contribution draws the status of the whole project at eight months from the end of the funding scheme planned for August 2022

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome