Cyclic (amino)(barrelene)carbene Ru-complexes: synthesis and reactivity in olefin metathesis.

The synthesis of ruthenium-complexes with cyclic (amino)(barrelene)carbenes (namely CABCs) as ligands is reported. Isolated in moderate to good yields, these new complexes showed impressive thermal stability at 110 °C over several days. Good catalytic performances were demonstrated in various ring-closing metathesis (RCM), macrocyclic-RCM, ring-closing enyne metathesis (RCEYM), cross-metathesis (CM), and ring-opening cross metathesis (ROCM) reactions.

Investigating employers' attitudes and knowledge about employing someone with a spinal cord injury.

PURPOSE: The aim of this study was to gain an understanding of employers' attitudes to, knowledge about, and policies relating to employing someone with a spinal cord injury (SCI). METHODS: Semi-structured interviews were conducted with nine employers located in Australia from a range of backgrounds and different sized businesses. The interviews were thematically analysed. RESULTS: Three themes were identified: Organisational policies (sub-themes: Recruitment - inherent requirements of the role vs risk mitigation; Recruitment strategies and targets; Disclosure; Accommodations needed or offered); Barriers & facilitators (sub-themes: Lack of knowledge about SCI; Physical accessibility; Workplace culture); Personal attitudes (sub-themes: Personal attitudes don't align with organisational policy; Personal experiences informed understanding). CONCLUSIONS: Organisational policies and practices of the employers' organisations, and workplace culture impact the likelihood of someone with a SCI being employed, particularly in relation to recruitment, employment targets, and available accommodations. Individual staff attitudes and knowledge also influence this process. Multi-faceted approaches are needed to increase the employment of people with SCI.

Barriers to employing someone with spinal cord injury (SCI) include lack of knowledge about SCI, and lack of knowledge about workplace lawsOrganisational policies and practices of organisations impact the likelihood of someone with an SCI being employedIndividual staff attitudes influence employment of people with SCIEmployers' knowledge about and confidence in employing people with SCI, is an important area to target interventions.

Direct Decarboxylative C-2 Alkylation of Azoles through Minisci-Type Coupling.

This note discusses the application of a Minisci-type reaction for the direct alkylation of azoles with carboxylic acids as radical precursors. Different reaction conditions were investigated to achieve high yield of the desired products, focusing on acid strength and solvent screening. Moreover, the reactivity of imidazoles with various carboxylic acids was investigated, showing good yield for most cases. The study reveals the potential of this approach for late-stage functionalization in drug discovery.

Unlocking full and fast conversion in photocatalytic carbon dioxide reduction for applications in radio-carbonylation.

Harvesting sunlight to drive carbon dioxide (CO2) valorisation represents an ideal concept to support a sustainable and carbon-neutral economy. While the photochemical reduction of CO2 to carbon monoxide (CO) has emerged as a hot research topic, the full CO2-to-CO conversion remains an often-overlooked criterion that prevents a productive and direct valorisation of CO into high-value-added chemicals. Herein, we report a photocatalytic process that unlocks full and fast CO2-to-CO conversion (<10 min) and its straightforward valorisation into human health related field of radiochemistry with carbon isotopes. Guided by reaction-model-based kinetic simulations to rationalize reaction optimisations, this manifold opens new opportunities for the direct access to 11C- and 14C-labeled pharmaceuticals from their primary isotopic sources [11C]CO2 and [14C]CO2.

[Acute Kidney Injury Caused by Orellanic Syndrome: Case Report].

Orellanic syndrome is caused by fungi of the Cortinarius orellanus and speciosissimus (Europe) species, Cortinarius fluorescens (South America), and Cortinarius rainierensis (North America). Orellanic syndrome is characterized by initially nonspecific symptoms such as muscle and abdominal pain, and a metallic taste sensation in the mouth. After a few days, more specific symptoms appear, such as intense thirst, headache, chills without fever, and anorexia, followed by a phase of polyuria and then of oligoanuria. Renal failure occurs in 70% of cases and is often irreversible. The clinical case involves a 52-year-old man who developed acute renal failure from Orellanic syndrome, necessitating hemodialysis.

Dynamical diagnostic of extreme events in Venice lagoon and their mitigation with the MoSE.

Extreme events are becoming more frequent due to anthropogenic climate change, posing serious concerns on societal and economic impacts and asking for mitigating strategies, as for Venice. Here we proposed a dynamical diagnostic of Extreme Sea Level (ESL) events in the Venice lagoon by using two indicators based on combining extreme value theory and dynamical systems: the instantaneous dimension and the inverse persistence. We show that the latter allows us to localize ESL events with respect to sea level fluctuations around the astronomical tide, while the former informs us on the role of active processes across the lagoon and specifically on the constructive interference of atmospheric contributions with the astronomical tide. We further examined the capability of the MoSE (Experimental Electromechanical Module), a safeguarding system recently put into operation, in mitigating extreme flooding events in relation with the values of the two dynamical indicators. We show that the MoSE acts on the inverse persistence in reducing/controlling the amplitude of sea level fluctuation and provide a valuable support for mitigating ESL events if operating, in a full operational mode, at least several hours before the occurrence an event.

Involving people with lived experience of spinal cord injury in research: a policy for consumer remuneration.

To ensure that research outcomes are relevant and meet the needs of the spinal cord jury (SCI) community, it is essential that people with lived experience of SCI ('consumers') are actively involved in all stages of the research process. One of the goals of the Spinal Research Institute (SRI) ( www.thesri.org ) is to facilitate this active engagement of consumers in research. In order to support consumer involvement, appropriate resources, including remuneration, need to be in place. This paper sets out the process undertaken by the SRI to develop a Policy for Consumer Remuneration. It addresses the rationale for creating a policy, the resources used and shares the model that defines the levels of consumer engagement and associated remuneration. The SRI Policy for Consumer Remuneration sets a standard for the SCI research field, which can serve as a model for Australia and as a template for other countries.

Challenges Arising from Continuous-Flow Olefin Metathesis.

The versatility of olefin metathesis is evident from its successful applications ranging from natural product synthesis to the valorization of renewable feedstocks. On the other side, flow chemistry has recently gained particular interest among the synthetic community, offering valuable alternatives to classic batch chemistry and paving the way to the development of new transformations. The application of continuous-flow methods to olefin metathesis represents one of the most promising evolutions in the field at the interface of industrially relevant synthesis and reactor engineering, significantly improving some of the typical problems such as undesired self-reactions and ethylene-mediated catalyst deactivation. This Minireview aims to provide a brief survey covering the major aspects of those techniques which we hope may be of interest for the chemical community as well as those interested in catalysis, continuous processing, enabling technologies and reactor design.

Comparison of the Blood-Brain Barrier Transport and Vulnerability to P-Glycoprotein-Mediated Drug-Drug Interaction of Domperidone versus Metoclopramide Assessed Using In Vitro Assay and PET Imaging.

Domperidone and metoclopramide are widely prescribed antiemetic drugs with distinct neurological side effects. The impact of P-glycoprotein (P-gp)-mediated efflux at the blood−brain barrier (BBB) on brain exposure and BBB permeation was compared in vitro and in vivo using positron emission tomography (PET) imaging in rats with the radiolabeled analogs [11C]domperidone and [11C]metoclopramide. In P-gp-overexpressing cells, the IC50 of tariquidar, a potent P-gp inhibitor, was drastically different using [11C]domperidone (221 nM [198−248 nM]) or [11C]metoclopramide (4 nM [2−8 nM]) as the substrate. Complete P-gp inhibition led to a 1.8-fold higher increase in the cellular uptake of [11C]domperidone compared with [11C]metoclopramide (p < 0.0001). Brain PET imaging revealed that the baseline brain exposure (AUCbrain) of [11C]metoclopramide was 2.4-fold higher compared with [11C]domperidone (p < 0.001), consistent with a 1.8-fold higher BBB penetration (AUCbrain/AUCplasma). The maximal increase in the brain exposure (2.9-fold, p < 0.0001) and BBB penetration (2.9-fold, p < 0.0001) of [11C]metoclopramide was achieved using 8 mg/kg of tariquidar. In comparison, neither 8 nor 15 mg/kg of tariquidar increased the brain exposure of [11C]domperidone (p > 0.05). Domperidone is an avid P-gp substrate that was in vitro compared with metoclopramide. Domperidone benefits from a lower brain exposure and a limited risk for P-gp-mediated drug−drug interaction involving P-gp inhibition at the BBB.

Synergistic Strategies in Aminocatalysis.

Synergistic catalysis offers the unique possibility of simultaneous activation of both the nucleophile and the electrophile in a reaction. A requirement for this strategy is the stability of the active species towards the reaction conditions and the two concerted catalytic cycles. Since the beginning of the century, aminocatalysis has been established as a platform for the stereoselective activation of carbonyl compounds through HOMO-raising or LUMO-lowering. The burgeoning era of aminocatalysis has been driven by a deep understanding of these activation and stereoinduction modes, thanks to the introduction of versatile and privileged chiral amines. The aim of this review is to cover recent developments in synergistic strategies involving aminocatalysis in combination with organo-, metal-, photo-, and electro-catalysis, focusing on the evolution of privileged aminocatalysts architectures.

A general procedure for carbon isotope labeling of linear urea derivatives with carbon dioxide.

Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. This article reports on a general approach to label urea derivatives with all carbon isotopes, including 14C and 11C, based on a Staudinger aza-Wittig sequence. It provides access to all aliphatic/aromatic urea combinations.

Ductal size indexed to weight and body surface area correlates with morbidities in preterm infants ≤32 weeks.

OBJECTIVES: To assess ductal size correlated to spontaneous closure, pharmacological or surgical treatment; to index ductal diameter to body weight and body surface area; to evaluate the morbidities. STUDY DESIGN: Retrospective study on preterms ≤32 weeks, birth weight ≤1500 g, extremely low birth weight (ELBW) and very low birth weight (VLBW). Inclusion criteria: patent ductus arteriosus (PDA) with a diameter ≥1 millimeter (mm) at 72 h from birth; need for ibuprofen treatment on the basis of a hemodynamically significant ductus arteriosus (HsPDA). RESULTS: One hundred infants with the diagnosis of PDA have been included. We observed a prevalence of spontaneous closure in 34% of newborns (41.3% VLBW versus 26.7% ELBW). The percentage of response to a single course of ibuprofen was of 62% (68.5% ELBW versus 54.3% VLBW). The mean of absolute ductal diameter was of 2.26 ± 0.62 mm in ELBW and 2.18 ± 0.42 mm in VLBW. The indexing of ductus size to body weight demonstrated a higher value in ELBW than VLBW (2.76 ± 0.97 mm/kg versus 1.84 ± 0.40 mm/kg). CONCLUSIONS: Our results confirmed that HsPDA can develop in presence of a ductus >1.5 mm as absolute value or >1.4 mm/kg as indexed to body weight. In ELBW infants the ductal size indexed for body weight and body surface area could be more predictive of spontaneous closure or need for pharmacological treatment compared to the absolute value of ductal size. A strong association between HsPDA and short- or long-term morbidities was confirmed particularly in ELBW.

Red blood cell transfusions and potentially related morbidities in neonates under 32 weeks' gestation.

BACKGROUND: Preterm neonates are likely to require red blood cell (RBC) transfusion, and extremely low birth weight infants almost invariably receive multiple transfusions. Transfusion-reduction strategies can reduce transfusion rates, and might diminish certain adverse outcomes associated with transfusions. MATERIALS AND METHODS: In a single centre, we retrospectively evaluated RBC transfusion rates among preterm infants ≤32 weeks' gestational age (GA), over a 6-year period before and after adopting national transfusion-reduction strategies. We compared demographic data, adverse events, and outcomes between transfused vs not-transfused neonates. Univariate logistic regression was used to evaluate associations between dichotomous outcomes and number of transfusions, and day of first transfusion. Multivariate logistic regression evaluated the correlation between dichotomous outcomes and transfusion as an independent risk factor. RESULTS: During the 6 years studied, 181 infants born at ≤32 weeks' GA were admitted to our Neonatal Intensive Care Unit of whom 80 (44%) received at least one RBC transfusion. The transfusion rate tended downwards after adopting transfusion-reduction strategies, reaching 31% in 2018. The reduction was largely due to a marked fall in transfusions of neonates born at 29-32 weeks' GA (p<0.001). The number of transfusions received correlated with odds of having intraventricular haemorrhage (IVH) (OR=1.9; 95% CI: 1.3-2.7; p=0.0001) and the duration of oxygen supplementation (rho=0.51; 95% CI: 0.33-0.66; p≤0.0001). In multivariate logistic regression analysis, transfusion was an independent risk factor for IVH (adjusted OR=7.38; 95% CI: 2.24-24.30; p=0.0001). DISCUSSION: The application of national, standardised transfusion-reduction strategies was associated with a lower transfusion rate in neonates born at 29-32 weeks' GA, but was less effective among neonates ≤28 weeks, in whom transfusions appeared to be an independent risk factor for severe IVH.

Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial.

BACKGROUND: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). METHODS: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. FINDINGS: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). INTERPRETATION: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy. FUNDING: None.

Carbon isotope labeling of carbamates by late-stage [11C], [13C] and [14C]carbon dioxide incorporation.

A general procedure for the late-stage [11C], [13C] and [14C]carbon isotope labeling of cyclic carbamates is reported. This protocol allows the incorporation of carbon dioxide, the primary source of carbon-14 and carbon-11 radioisotopes, in a direct, cost-effective and sustainable manner. A disconnection/reconnection strategy, involving ring opening/isotopic closure, was also implemented.

Providing pediatric well-care and sick visits in the COVID-19 pandemic era: the recommendations of the Italian pediatric society.

Pediatricians have observed a significant decrease in in-person child health visits during the COVID-19 pandemic. In the post lockdown period, the coronavirus trend remains positive in Italy but fears of a second wave have recently grown in Italy due to active hotbeds of contagion. The pandemic may negatively affect the care of pediatric patients and overall children welfare as it may present with severe signs and symptoms or it may complicate. The Italian Pediatric Society recommend to separate well visits from sick ones, to educate families and to promote hygienic strategies to provide an adequate pediatric assistance in case of a second pandemic wave.

Facial masks in children: the position statement of the Italian pediatric society.

Facial masks may be one of the most cost-effective strategies to prevent the diffusion of COVID 19 infection. Nevertheless, fake news are spreading, alerting parents on dangerous side effects in children, such as hypercapnia, hypoxia, gut dysbiosis and immune system weakness. Aim of the Italian Pediatric Society statement is to face misconception towards the use of face masks and to spread scientific trustable information.

A model for the geomagnetic field reversal rate and constraints on the heat flux variations at the core-mantle boundary.

A striking feature of many natural magnetic fields generated by dynamo action is the occurrence of polarity reversals. Paleomagnetic measurements revealed that the Earth's magnetic field has been characterised by few hundred stochastic polarity switches during its history. The rate of reversals changes in time, maybe obeying some underlying regular pattern. While chaotic dynamical systems can describe the short-term behaviour of the switches of the Earth's magnetic polarity, modelling the long-term variations of the reversal rate is somewhat problematic, as they occur on timescales of tens to hundreds of millions of years, of the order of mantle convection timescales. By investigating data of geomagnetic reversal rates, we find the presence of cycles with variable frequency and show that the transition towards periods where reversals do not occur for tens of million years (superchrons) can be described by a second-order phase transition that we interpret to be driven by variations of the heat flux at the core-mantle boundary (CMB). The model allows us to extract from the reversal sequence quantitative information on the susceptibility of the reversal rate caused by changes in the CMB heat flux amplitude, thus providing direct information on the deep inner layers of the Earth.

Clinical RoPE (cRoPE) score predicts patent foramen ovale detection among stroke patients: a multicenter observational study.

BACKGROUD: The role of patent foramen ovale (PFO) in cryptogenic stroke (CS) is debated. Tools to predict PFO occurrence and attributable fraction are needed to guide cost-effective diagnostics and treatment. Risk of Paradoxical Embolism (RoPE) score relies on neuroimaging findings, which might be inconclusive in up to 30% of cases. METHODS: We developed a clinical-based easy tool to predict the presence and attributable fraction of PFO in CS patients, without using neuroimaging. The clinical RoPE (cRoPE) score, ranging 1-10, was elaborated through Delphi method from the original RoPE score, replacing cortical infarction with the Oxfordshire Community Stroke Project (OCSP) classification (lacunar stroke = 0 points, other subtypes = 1 point). Then, from the SISIFO (Studio Italiano di prevalenza nello Stroke Ischemico di pervietà del Forame Ovale, or Prevalence of Patent Foramen Ovale in Ischemic Stroke in Italy) study, a multicenter, prospective study on consecutive acute ischemic stroke patients (n = 1130) classified by Trial of Org 10172 in Acute Stroke Treatment (TOAST) and OCSP criteria and undergoing PFO testing, we selected the VV-CDC cohort (Vibo Valentia, Città di Castello, n = 323) to test the accuracy of cRoPE in predicting PFO detection. We compared cRoPE with RoPE to verify cRoPE reliability. Finally, we tested, through ROC analysis, the performance of cRoPE depending on TOAST classification. RESULTS: Overall, PFO was detected in 21% in VV-CDC and in 23.4% in remaining SISIFO cohort (n = 807). cRoPEAUC and RoPEAUC were similar in VV-CDC. cRoPE performance was comparable with RoPE among CS (cRoPEAUC 0.76, 95%CI 0.67-0.85, RoPEAUC 0.75, 95%CI 0.66-0.84). Moving to the remaining SISIFO cohort, cRoPE confirmed satisfactory accuracy in predicting PFO detection in CS patients (cRoPEAUC 0.71, 95%CI 0.66-0.78, p = 0.032). CONCLUSIONS: Conclusions: cRoPE might help in stratification of patients with CS, allowing accurate esteem of the likelihood of PFO to be found, especially in cases when neuroimaging is inconclusive.