Lysophosphatidylcholine Drives Neuroblast Cell Fate

Neuronal differentiation plays a key role during embryogenesis. However, based on the capacity of neuronal stem cells to either generate or regenerate neurons and because differentiation stops aberrant neuroblasts proliferation, neuronal differentiation is crucial during neuropathological conditions. Although phosphatidylcholine (PtdCho) has been proposed as an important molecule for neurite growth and neuronal regeneration, the identity of the molecular target has remained elusive. This study originally describes that lysophosphatidylcholine (LPtdCho), either exogenously supplied or generated by the imbalance of PtdCho metabolism through the enzymatic action of cytosolic phospholipase A2, acts as a neurotrophic-like factor. We demonstrated that LPtdCho induces neuronal differentiation by activation of the small G protein Ras followed by the Raf/MEK/ERK signaling pathway. Accordingly, LPtdCho redirects neuroblasts gene expression leading to the generation of functional mature neurons expressing βIII-tubulin and having increased acetylcholinesterase activity and membrane biosynthesis required for neuritogenesis. These findings provide mechanistic details of the role of cytidine-5-diphosphocholine (CDP-choline) and PtdCho as neuroprotectors. Furthermore, as LPtdCho recapitulates the effect of the therapeutic agent retinoic acid, these results open new avenues for drug discovery for the treatment of neuropathological conditions.Fil: Paoletti, Luciana Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Domizi, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Marcucci, Hebe Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Montaner, Aneley Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Banchio, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentin

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database

: Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083)

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Jahier interventista: il ruolo di Claudel e Proudhon

Piero Jahier’s ‘interventismo’: the role of Claudel and ProudhonThis essay addresses Piero Jahier’s interventionism within the broader context of Italian Modernism. Jahier’s works – from the early articles appeared on La Voce up to Con me e con gli alpini – is investigated through the lens of the religious background of the author. In doing so, the article emphasizes the role played by two French authors, Paul Claudel and Pierre-Joseph Proudhon, in affecting Jahier’s stance on WWI. It argues that Jahier draws on Claudel’s and Proudhon’s work to shape the theoretical foundation of his interventionism. In Con me e con gli alpini, the echo of voices such as Claudel’s and Proudhon’s interacts with Jahier’s religious education, and gives a significant example of the interplay between Italian and French culture at the beginning of 20th century

Enemy and Officers in Emilio Lussu’s <i>Un anno sull’Altipiano</i>

This essay explores the concept of enemy in Emilio Lussu&#8217;s WWI memoir Un anno sull&#8217;Altipiano (A Soldier on the Southern Front, 1938). The memoir portrays the conflict on the oft-forgotten Alpine Front, where Italian and Austro-Hungarian armies clashed from 1915 to 1918 in a series of battles fought at high altitudes. I argue that two crucial dynamics of modern warfare shape the concept of enemy in WWI literature: the impossibility of close-range encounters, which was due to the superiority of defensive firepower, and hatred for one&#8217;s own officers, which stemmed from the corrosive environment of the trenches, where the aggressive attitude of high-ranking officers often led hundreds of thousands to pointless death. I show how, in Lussu&#8217;s memoir, these dynamics subvert the traditional image of the enemy as imposed by military propaganda, and finally elicit feelings of empathy

Extensive characterization of italian accelerometric stations from single station ambient vibration measurements

This paper describes the analyses of the single-station ambient-vibration measurements performed on the Italian accelerometric network to detect site resonance phenomena potentially affecting earthquake recordings. The use of lowcost, high quality microtremor measurement can be helpful to discriminate among soil classes, since several classification schemes based on resonance frequencies were proposed in the last decades. Operatively, in the framework of the Italian Strong Motion Database project (DPC-INGV 2007–2009 S4; http://esse4.mi.ingv.it), soil resonance frequencies have been evaluated from more than 200 ambient vibration measurements in correspondence of accelerometric stations included in ITACA (http://itaca.mi.ingv.it/ItacaNet/). The noise recordings have been analyzed using the same numerical protocol in order to standardize the results. Particular attention has been paid to evaluate the quality of measurements and to develop an on-purpose mathematical tool to automatically estimate the peaks in the horizontal-to-vertical spectral ratio (HVSR) curve. The reliability of the resonance frequencies from HVSR has been tested by comparing estimates provided by independent methods (modeling or earthquake recordings). The test confirmed the reliability of the microtremor HVSR for assessing the resonance frequencies of the examined sites

Children with neurodevelopmental disorders: how do they sleep?

Purpose of review: In this review we summarized the available evidence on sleep disorders in children with neurodevelopmental disorders (NDDs) in particular: intellectual disability (including some genetic conditions such as Prader-Willi Syndrome, Smith-Magenis Syndrome), Autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), Developmental Coordination Disorder, language disorders, and specific learning disorders. Recent findings: Children with NDDs frequently suffer from sleep disturbances, with a higher prevalence than that of the general pediatric population. Summary: These problems tend to be chronic and may cause additional cognitive and behavioral difficulties, often affecting the whole family's well-being. Sleep behaviors are also related to other important developmental skills, such as attention and listening. Investigating sleep disorders in children with NDDs is therefore crucial in clinical practice. For a systematic approach in clinical practice, we propose the use of a short and easy to remember sleep screening tool

Pipe§Net: The Fifth Mode of Transport for a Sustainable Future

In this paper we introduce Pipe§Net, an innovative solution for the transport of goods via depressurised pipes. This technology is often referred to as the “fifth mode of transport” and constitutes a sustainable alternative to existing transport modes. The goal of Pipe§Net is to relieve congested European transportation networks and to provide a fast, reliable and safe way of transport. The pipes can easily be built alongside existing infrastructure (e.g., road, railway) and allow for the transportation of goods in standardised containers with up to 1,500 km/h. Furthermore, 70% of the energy can be recovered during the braking process which creates an energy-efficient solution. This paper introduces the objectives of Pipe§Net, discusses the concept in some detail and illustrates the expected impacts