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Ischaemia/reperfusion injury (IRI) is a condition that occurs when tissues from different organs undergo reperfusion following an ischaemic event. The mitochondrial permeability transition pore (mPTP), a multiprotein platform including structural components of ATP synthase with putative gate function, is an emerging pharmacological target that could be modulated to facilitate the restoration of organ function after a hypoxic insult. Herein, we reported the synthesis and biological characterisation of new molecules with a 1,4,8-triaza-spiro[4.5]decan-2-one framework of potential interest for the treatment of IRI able to inhibit the opening of mPTP in a cardiac model in vitro. Modelling studies were useful to rationalise the observed structure-activity relationship detecting a binding site for the investigated molecules at the interface between the c -ring and subunit a of ATP synthase. Compound was shown to display high potency as mPTP inhibitor combined with the capability to counteract cardiomyocytes death in an in vitro model of hypoxia/reoxygenation.

IntroductionWe aimed to create standardized protocol for language examination in patients who underwent video-EEG recording and assessed its efficacy in the characterization of ictal language impairment, its ability to differentiate this from impaired awareness, and interobserver reliability in clinical practice.MethodsFrom our database of video-EEG recordings, we selected a representative sample of 63 focal seizures with presumed language impairment. A multidisciplinary team of epileptologists, EEG technicians, and speech therapists analyzed the selected videos to highlight the critical issues of ordinary ictal language evaluation. We subsequently followed a multi-step process to develop the protocol and assess its interobserver reliability.ResultsA protocol based on seven tests in hierarchical succession was created, summed up in the acronym CA-P-S C-A-R-E (Closed Answers, Pro-speak question, Simple orders, Common object denomination, Audio repetition, Reading, Evoke). Following its preliminary administration for 5 months, we assessed the inter-observer reliability of 16 healthcare professionals in distinguishing between language impairment and impaired awareness among a sample of 10 seizures, finding a substantial agreement (kappa 0.61).ConclusionThe proposed protocol, made of simple and easy to memorize tests, is an effective tool that evaluates multiple domains beyond language. Its use could help to recognize ictal aphasia effectively and differentiate it from impaired awareness, minimizing inter-examiner variability.

Ischaemia/reperfusion injury (IRI) is a condition that occurs when tissues from different organs undergo reperfusion following an ischaemic event. The mitochondrial permeability transition pore (mPTP), a multiprotein platform including structural components of ATP synthase with putative gate function, is an emerging pharmacological target that could be modulated to facilitate the restoration of organ function after a hypoxic insult. Herein, we reported the synthesis and biological characterisation of new molecules with a 1,4,8-triaza-spiro[4.5]decan-2-one framework of potential interest for the treatment of IRI able to inhibit the opening of mPTP in a cardiac model in vitro. Modelling studies were useful to rationalise the observed structure-activity relationship detecting a binding site for the investigated molecules at the interface between the c8-ring and subunit a of ATP synthase. Compound 14e was shown to display high potency as mPTP inhibitor combined with the capability to counteract cardiomyocytes death in an in vitro model of hypoxia/reoxygenation.Ischaemia/reperfusion injury (IRI) is a condition that occurs when tissues from different organs undergo reperfusion following an ischaemic event. The mitochondrial permeability transition pore (mPTP), a multiprotein platform including structural components of ATP synthase with putative gate function, is an emerging pharmacological target that could be modulated to facilitate the restoration of organ function after a hypoxic insult. Herein, we reported the synthesis and biological characterisation of new molecules with a 1,4,8-triaza-spiro[4.5]decan-2-one framework of potential interest for the treatment of IRI able to inhibit the opening of mPTP in a cardiac model in vitro. Modelling studies were useful to rationalise the observed structure-activity relationship detecting a binding site for the investigated molecules at the interface between the c8-ring and subunit a of ATP synthase. Compound 14e was shown to display high potency as mPTP inhibitor combined with the capability to counteract cardiomyocytes death in an in vitro model of hypoxia/reoxygenation.

Airport emergencies are rare but potentially catastrophic; therefore, system preparedness is crucial. Airport emergency plans include the organization of emergency drills on a regular basis, including full-scale exercises, to train and test the entire rescue organization. This report describes a full-scale simulation at Bologna International Airport, Italy, in October 2022, involving local EMS resources. A full-scale aeroplane crash was simulated on the airport ground, activating the Airport emergency plan, and requiring the intervention of supplementary resources (ambulances, medical cars, and other emergency vehicles). Twenty-seven simulated patients were evaluated by EMS: START triage assessment was correct for 81.48% of patients; 11.11% were over-triaged and 7.41% were under-triaged. All patients were transported to the hospitals of the area. The simulation ended 2 hours and 28 minutes after the initial alarm. The response time proved a good response. Triage accuracy was correct in more than 80% of simulated patients. The availability of a trauma centre within 6 kilometres allowed the transportation of a quota of patients directly from the event, without affecting transportation times. Areas for improvement were identified in the communication within the different agencies and in moving ambulances within the airport runway without airport personnel guidance.

Plant-derived remedies rich in chalcone-based compounds have been known for centuries in the treatment of specific diseases, and nowadays, the fascinating chalcone framework is considered a useful and, above all, abundant natural chemotype. Velutone F, a new chalconoid from Millettia velutina, exhibits a potent effect as an NLRP3-inflammasome inhibitor; the search for new natural/non-natural lead compounds as NLRP3 inhibitors is a current topical subject in medicinal chemistry. The details of our work toward the synthesis of velutone F and the unknown non-natural regioisomers are herein reported. We used different synthetic strategies both for the construction of the distinctive benzofuran nucleus (BF) and for the key phenylpropenone system (PhP). Importantly, we have disclosed a facile entry to the velutone F via synthetic routes that can also be useful for preparing non-natural analogs, a prerequisite for extensive SAR studies on the new flavonoid class of NLRP3-inhibitors.

Pancreatic fluid collections (PFCs) are well-known complications of acute pancreatitis. The overinfection of these collections leads to a worsening of the prognosis with an increase in the morbidity and mortality rate. The primary strategy for managing infected pancreatic necrosis (IPN) or symptomatic PFCs is a minimally invasive step-up approach, with endosonography-guided (EUS-guided) transmural drainage and debridement as the preferred and less invasive method. Different stents are available to drain PFCs: self-expandable metal stents (SEMSs), double pigtail stents (DPPSs), or lumen-apposing metal stents (LAMSs). In particular, LAMSs are useful when direct endoscopic necrosectomy is needed, as they allow easy access to the necrotic cavity; however, the rate of adverse events is not negligible, and to date, the superiority over DPPSs is still debated. Moreover, the timing for necrosectomy, the drainage technique, and the concurrent medical management are still debated. In this review, we focus attention on indications, timing, techniques, complications, and particularly on aspects that remain under debate concerning the EUS-guided drainage of PFCs.

The undesired interaction of a quantum system with its environment generally leads to a coherence decay of superposition states in time. A precise knowledge of the spectral content of the noise induced by the environment is crucial to protect qubit coherence and optimize its employment in quantum device applications. We experimentally show that the use of neural networks (NNs) can highly increase the accuracy of noise spectroscopy, by reconstructing the power spectral density that characterizes an ensemble of carbon impurities around a nitrogen-vacancy (NV) center in diamond. NNs are trained over spin coherence functions of the NV center subjected to different Carr–Purcell sequences, typically used for dynamical decoupling (DD). As a result, we determine that deep learning models can be more accurate than standard DD noise-spectroscopy techniques, by requiring at the same time a much smaller number of DD sequences.

Diet is the first to affect our intestinal microbiota and therefore the state of eubiosis. Several studies are highlighting the potential benefits of taking certain nutritional supplements, but a dietary regime that can ensure the health of the intestinal microbiota, and the many pathways it governs, is not yet clearly defined. We performed a systematic review of the main studies concerning the impact of an omnivorous diet on the composition of the microbiota and the production of short-chain fatty acids (SCFAs). Some genera and phyla of interest emerged significantly and about half of the studies evaluated consider them to have an equally significant impact on the production of SCFAs, to be a source of nutrition for our colon cells, and many other processes. Although numerous randomized trials are still needed, the Mediterranean diet could play a valuable role in ensuring our health through direct interaction with our microbiota.

Choosing adaptation and mitigation actions, through nature-based solutions, fosters the ecological transition process, which is necessary to face the challenges of climate change. However, these interventions are often discontinuous and disconnected, especially within dense and delicate urban fabrics such as historic centres. The research proposes a multi-scalar methodological approach aimed at defining an integrated design tool to improve the microclimatic well-being, accessibility and aesthetic quality of open spaces located in consolidated urban environments. Through the synergy between natural, technological and social components, the aim is to create replicable minimum intervention units designed to foster democratic and ecosystemic connections.

Acute myeloid leukemia (AML) is an aggressive disease with a high relapse rate. In this study, we map the metabolic profile of CD34 + (CD38 low/- ) AML cells and the extracellular vesicle signatures in circulation from AML patients at diagnosis. CD34 + AML cells display high antioxidant glutathione levels and enhanced mitochondrial functionality, both associated with poor clinical outcomes. Although CD34 + AML cells are highly dependent on glucose oxidation and glycolysis for energy, those from intermediate- and adverse-risk patients reveal increased mitochondrial dependence. Extracellular vesicles from AML are mainly enriched in stem cell markers and express antioxidant GPX3, with their profiles showing potential prognostic value. Extracellular vesicles enhance mitochondrial functionality and dependence on CD34 + AML cells via the glutathione/GPX4 axis. Notably, extracellular vesicles from adverse-risk patients enhance leukemia cell engraftment in vivo. Here, we show a potential noninvasive approach based on liquid ‘cell-extracellular vesicle’ biopsy toward a redefined metabolic stratification in AML. The role of metabolism in acute myeloid leukaemia (AML) onset remains to be explored. Here, the authors explore the metabolic landscape of AML cells and the signature of extracellular vesicles (EVs) in peripheral blood and show that circulating EVs regulate leukaemia (stem) cell metabolic reprogramming.