Neutron imaging and modelling inclined vortex driven thin films.

The vortex fluidic device (VFD) is a thin film microfluidic platform which has a wide range of applications in synthesis and other areas of science, and it is important to understand the nature of the thin film of liquid in its inclined rapidly rotating tube. Neutron imaging has been used to determine the thickness of the film in a quartz tube with its shape modelled mathematically, showing good agreement between the model and experiments. The resultant equations are useful for studying VFD mediated processing in general, for which the optimal tilt angle of the tube is typically 45°. This includes its utility for the intelligent scale-up of organic syntheses, as demonstrated in the present study by the scaling up of an imine and amide synthesis to >1 g/min

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies

Background and purpose: New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions. Methods: A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome. Results: Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case–control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called ‘cryptogenic NORSE’. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described. Conclusions: Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE

Exploring the Susceptibility to Multiple Primary Tumors in Patients with Differentiated Thyroid Cancer

Purpose: It was demonstrated that differentiated thyroid cancer (DTC) patients may develop multiple primary tumors (MPT) during follow-up. Many studies showed an association between reduced telomere length and cancer phenotype; in particular, the short telomeres were associated with the development of a primary tumor. However, the role of altered telomere length in MPT development has not yet been demonstrated. The aim of this study was to evaluate the possible correlation between a short telomere length in blood leukocytes and the risk of developing MPT in DTC patients. Patients and Methods: We retrospectively evaluated 167 DTC patients followed up for a median of 13.6 years. Our control group was represented by 105 healthy subjects without any thyroid disease or present or past history of tumors. Our study groups, age-matched, were evaluated for the relative telomere length measured in leukocytes of peripheral venous blood. Results: The relative telomere length (RTL) was significantly different in healthy subjects compared to the total group of differentiated thyroid cancer patients [p < 0.0001]. Shorter telomeres length was observed in DTC patients with (n = 32) and without (n = 135) MPT compared to healthy subjects (p < 0.0001 and p = 0.0002, respectively). At multivariate analysis, the parameters independently associated with the presence of MPT were RTL [OR: 0.466 (0.226-0.817), p = 0.018] and the familial DTC [OR: 2.949 (1.142-8.466), p = 0.032]. Conclusions: The results of this study suggest a role of the relative telomere length in predicting MPT development in DTC patients. Our results contribute to increasing the knowledge of the genetic mechanisms underlying MPT development in DTC patients, considering relative telomere length as a possible prognostic marker

Revealing the secrets of composite helmets of ancient Japanese tradition

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Unraveling the role of male reproductive tract and haemolymph in cantharidin-exuding Lydus trimaculatus and Mylabris variabilis (Coleoptera: Meloidae): a comparative transcriptomics approach

Background: Meloidae (blister beetles) are known to synthetize cantharidin (CA), a toxic and defensive terpene mainly stored in male accessory glands (MAG) and emitted outward through reflex-bleeding. Recent progresses in understanding CA biosynthesis and production organ(s) in Meloidae have been made, but the way in which self-protection is achieved from the hazardous accumulation and release of CA in blister beetles has been experimentally neglected. To provide hints on this pending question, a comparative de novo assembly transcriptomic approach was performed by targeting two tissues where CA is largely accumulated and regularly circulates in Meloidae: the male reproductive tract (MRT) and the haemolymph. Differential gene expression profiles in these tissues were examined in two blister beetle species, Lydus trimaculatus (Fabricius, 1775) (tribe Lyttini) and Mylabris variabilis (Pallas, 1781) (tribe Mylabrini). Upregulated transcripts were compared between the two species to identify conserved genes possibly involved in CA detoxification and transport. Results: Based on our results, we hypothesize that, to avoid auto-intoxication, ABC, MFS or other solute transporters might sequester purported glycosylated CA precursors into MAG, and lipocalins could bind CA and mitigate its reactivity when released into the haemolymph during the autohaemorrhaging response. We also found an over-representation in haemolymph of protein-domains related to coagulation and integument repairing mechanisms that likely reflects the need to limit fluid loss during reflex-bleeding. Conclusions: The de novo assembled transcriptomes of L. trimaculatus and M. variabilis here provided represent valuable genetic resources to further explore the mechanisms employed to cope with toxicity of CA in blister beetle tissues. These, if revealed, might help conceiving safe and effective drug-delivery approaches to enhance the use of CA in medicine

CPO and quantitative textural analyses within sheath folds

Acknowledgments This has been a multi-national collaboration from authors based in Europe, North America, Australia and India. Erasmus funding to GIA in 2018 enabled a visit to Catania leading to discussion and initiation of this project. The authors are grateful to Amarnath Dandapat for preparation of superpolished rock thin sections at the Department of Geology and Geophysics (IIT Kharagpur, India). Niloy Bhowmik is thanked for assistance with SEM-EBSD data generation in the Central Research Facility (IIT Kharagpur, India). E.F. thanks Sibio Carmelo for thin sections preparation at the University of Turin (Italy). Authors are grateful to ANSTO laboratory personnel for the preparation of specimens (funded proposals: P9835 with the title “Sheath fold texture characterisation”, principal scientist: E.F.; co-proposers: G.I.A. and V.L.; DB6749 with the title “Texture analysis of rocks”, principal scientist: V.L.; co-proposer: E.F.; DB9606 with the title “A pilot experiment for texture characterisation in a sheath fold”, principal scientist: E.F..; co-proposers: G.I.A. and V.L.). L.N. and R.G. report that this publication has been assigned the NRCan contribution number 20230109. Many thanks to Richard D. Law and an anonymous reviewer for their careful revision that substantially improved the original version of the manuscript. We also thanks Dr. T.K. Cawood from the Geological Survey of Canada for her useful comments on the drafted manuscript. The editorial handling by Fabrizio Agosta is greatly appreciated.Peer reviewedPublisher PD

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

Acute visceral pain relief mediated by A(3)AR agonists in rats: involvement of N-type voltage-gated calcium channels

Pharmacological tools for chronic visceral pain management are still limited and inadequate. A(3) adenosine receptor (A(3)AR) agonists are effective in different models of persistent pain. Recently, their activity has been related to the block of N-type voltage-gated Ca(2+) channels (Ca(v)2.2) in dorsal root ganglia (DRG) neurons. The present work aimed to evaluate the efficacy of A(3)AR agonists in reducing postinflammatory visceral hypersensitivity in both male and female rats. Colitis was induced by the intracolonic instillation of 2,4-dinitrobenzenesulfonic acid (DNBS; 30 mg in 0.25 mL 50% EtOH). Visceral hypersensitivity was assessed by measuring the visceromotor response and the abdominal withdrawal reflex to colorectal distension. The effects of A(3)AR agonists (MRS5980 and Cl-IB-MECA) were evaluated over time after DNBS injection and compared to that of the selective Ca(v)2.2 blocker PD173212, and the clinically used drug linaclotide. A(3)AR agonists significantly reduced DNBS-evoked visceral pain both in the postinflammatory (14 and 21 days after DNBS injection) and persistence (28 and 35 days after DNBS) phases. Efficacy was comparable to effects induced by linaclotide. PD173212 fully reduced abdominal hypersensitivity to control values, highlighting the role of Ca(v)2.2. The effects of MRS5980 and Cl-IB-MECA were completely abolished by the selective A(3)AR antagonist MRS1523. Furthermore, patch-clamp recordings showed that A(3)AR agonists inhibited Ca(v)2.2 in dorsal root ganglia neurons isolated from either control or DNBS-treated rats. The effect on Ca(2+) current was PD173212-sensitive and prevented by MRS1523. A(3)AR agonists are effective in relieving visceral hypersensitivity induced by DNBS, suggesting a potential therapeutic role against abdominal pain

Caratterizzazione qualitativa di antiche spade giapponesi attraverso imaging neutronico risolto in energia

La spada giapponese (Katana) è generalmente riconosciuta, nell’ambiente dei beni culturali, come unodegli oggetti più interessanti non solo dal punto di vista stilistico, ma anche per le strabilianti caratteristichemeccaniche. Nel lavoro che segue, sono presentati i risultati delle indagini realizzate, in modo totalmente noninvasivo,su cinque spezzoni di spada giapponese. Le lame, appartenenti ai periodi Koto (987-1596) e Shinto(1596-1781), sono state analizzate attraverso imaging neutronico sia in fascio policromatico sia risolto in energia.La ricostruzione dei volumi e delle slices tomografiche, effettuata a partire dai dati ottenuti dalle proiezionibidimensionali, ha permesso di identificare la distribuzione delle fasi e le caratteristiche distintive che sonocorrelate alle tecniche di forgiatura proprie delle differenti scuole e tradizioni sviluppatesi in Giappone

Foreign Policy and the Ideology of Post-ideology: The Case of Matteo Renzi’s Partito Democratico

The post-communist Italian Left has experienced a long phase of ideational misalignment between ideas placed at different levels, as a qualified discursive institutionalist approach demonstrates. Background public philosophies have often clashed with post-communist political ideology, while foreign policy programmes have often contradicted specific policies. Under the leadership of Matteo Renzi, however, the PD is now experiencing a moment of remarkable ideational consistency. Rather than being founded on entirely new premises, this new consensus folds old elements into new ones and shows all the defining traits of post-ideology. Yet, by espousing post-ideology, Renzi is making an ultimately ideological move whose limitations may soon start to show