40 research outputs found

    Elliptic and hyperelliptic magnetohydrodynamic equilibria

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    The present study is a continuation of a previous one on "hyperelliptic" axisymmetric equilibria started in [Tasso and Throumoulopoulos, Phys. Plasmas 5, 2378 (1998)]. Specifically, some equilibria with incompressible flow nonaligned with the magnetic field and restricted by appropriate side conditions like "isothermal" magnetic surfaces, "isodynamicity" or P + B^2/2 constant on magnetic surfaces are found to be reducible to elliptic integrals. The third class recovers recent equilibria found in [Schief, Phys. Plasmas 10, 2677 (2003)]. In contrast to field aligned flows, all solutions found here have nonzero toroidal magnetic field on and elliptic surfaces near the magnetic axis.Comment: 9 page

    Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics

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    Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that interact and dissociate the tubulin dimer. Here we show how TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO– present in TBCB, which is similar to the EEY/F-COO– element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE–TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated to microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation

    Treatment of Rat Spinal Cord Injury with the Neurotrophic Factor Albumin-Oleic Acid: Translational Application for Paralysis, Spasticity and Pain

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    Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often characterized by the debilitating symptoms of paralysis, spasticity and pain, which require treatment with novel pleiotropic pharmacological agents. Previous in vitro studies suggest that Albumin (Alb) and Oleic Acid (OA) may play a role together as an endogenous neurotrophic factor. Although Alb can promote basic recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on a known translational measure of SCI associated with symptoms of spasticity and change in nociception has not been studied. Following T9 spinal contusion injury in Wistar rats, intrathecal treatment with: i) Saline, ii) Alb (0.4 nanomoles), iii) OA (80 nanomoles), iv) Alb-Elaidic acid (0.4/80 nanomoles), or v) Alb-OA (0.4/80 nanomoles) were evaluated on basic motor function, temporal summation of noxious reflex activity, and with a new test of descending modulation of spinal activity below the SCI up to one month after injury. Albumin, OA and Alb-OA treatment inhibited nociceptive Tibialis Anterior (TA) reflex activity. Moreover Alb-OA synergistically promoted early recovery of locomotor activity to 50±10% of control and promoted de novo phasic descending inhibition of TA noxious reflex activity to 47±5% following non-invasive electrical conditioning stimulation applied above the iSCI. Spinal L4–L5 immunohistochemistry demonstrated a unique increase in serotonin fibre innervation up to 4.2±1.1 and 2.3±0.3 fold within the dorsal and ventral horn respectively with Alb-OA treatment when compared to uninjured tissue, in addition to a reduction in NR1 NMDA receptor phosphorylation and microglia reactivity. Early recovery of voluntary motor function accompanied with tonic and de novo phasic descending inhibition of nociceptive TA flexor reflex activity following Alb-OA treatment, mediated via known endogenous spinal mechanisms of action, suggests a clinical application of this novel neurotrophic factor for the treatment of paralysis, spasticity and pain

    Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

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    Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Albumin-Oleic Acid (Alb-OA) Synergistically Promotes Early Recovery of Motor Function following T9 Spinal Cord Injury.

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    <p>Longitudinal analysis of the mean time spent on the rotarod following contusion (Cont) SCI from 4 to 28 days revealed that intrathecal administration of both Alb (0.4 nanomoles, p<0.05) and Alb-OA (80 nanomoles, p<0.01) promoted better motor recovery, compared to the spinal contusion group treated with saline (Sal) alone (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g001" target="_blank">Fig. 1A</a>). Treatment with OA (80 nanomoles) alone or Alb-Elaidic acid (Alb-EA, 0.4/80 nanomoles) failed to potentiate locomotor recovery (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g001" target="_blank">Fig. 1A</a>). Analysis of voluntary motor function during the early (4–14 day) and subacute (21–28 day) period of contusion SCI demonstrated that Alb-OA (0.4/80 nanomoles) synergistically promoted functional recovery soon after contusion injury when compared to animals treated with saline (Sal) alone, while Alb treatment enhanced the time spent on the rotarod specifically during the late phase (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g001" target="_blank">Fig. 1B</a>). Statistical analysis was performed with a two-way (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g001" target="_blank">Fig. 1A</a>) and one-way ANOVA (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g001" target="_blank">Fig. 1B</a>), supported by a post-hoc Bonferronni test for each experimental group compared with animals with SCI treated with Sal alone (* - p<0.05; ** - p<0.01).</p

    Inhibition of Tibialis Anterior Reflex Activity with Albumin, Oleic Acid and Albumin-Oleic Acid after SCI.

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    <p>Qualitative analysis of rectified nociceptive Tibialis Anterior (TA) noxious reflex temporal summation at 28 days following spinal contusion (Cont, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g002" target="_blank">Fig. 2A–2F</a>, scale bar 20 ”V/2.5 s) supported the quantification of reflex inhibition (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g002" target="_blank">Fig. 2H</a>) with either albumin (Alb, 0.4 nanomoles, p<0.001), oleic acid (OA, 80 nanomoles, p<0.001) or the complex Alb-OA (0.4/80 nanomoles, p<0.001) when compared to animals with SCI treated with saline alone (Sal). Importantly noxious TA reflex activity following moderate T9 contusion injury was not different for either the averaged response calculated from the second to seventh stimulus (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g002" target="_blank">Fig. 2G</a>) or the first reflex response (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g002" target="_blank">Fig. 2G</a> inset, same format) amongst the experimental treatment groups when compared to the responses observed in naĂŻve animals or with SCI treated with saline alone. Although no increase in temporal summation for the first to the sixteenth reflex response was identified following contusion SCI (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g002" target="_blank">Fig. 2H</a>), significant inhibition of noxious TA temporal summation in animals with contusion SCI was observed with albumin (p<0.001), oleic acid (OA, p<0.001) and albumin-oleic acid (Alb-OA, p<.001) when compared to the group treated with saline alone (Sal, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g002" target="_blank">Fig. 2H</a>). The stereoisomer complex albumin-elaidic acid (Alb-EA, 0.4/80 nanomoles) failed to inhibit flexor reflex activity following contusion SCI (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026107#pone-0026107-g002" target="_blank">Fig. 2H</a>). Statistical analysis was performed with a two-way ANOVA supported by the post-hoc Bonferronni test compared to the SCI group treated with saline alone (*** - p<0.001).</p

    Treatment with albumin-hydroxyoleic acid complex restores sensorimotor function in rats with spinal cord injury: Efficacy and gene expression regulation.

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    Sensorimotor dysfunction following incomplete spinal cord injury (SCI) is often characterized by paralysis, spasticity and pain. Previously, we showed that intrathecal (i.t.) administration of the albumin-oleic acid (A-OA) complex in rats with SCI produced partial improvement of these symptoms and that oral 2-hydroxyoleic acid (HOA, a non-hydrolyzable OA analogue), was efficacious in the modulation and treatment of nociception and pain-related anxiety, respectively. Here we observed that intrathecal treatment with the complex albumin-HOA (A-HOA) every 3 days following T9 spinal contusion injury improved locomotor function assessed with the Rotarod and inhibited TA noxious reflex activity in Wistar rats. To investigate the mechanism of action of A-HOA, microarray analysis was carried out in the spinal cord lesion area. Representative genes involved in pain and neuroregeneration were selected to validate the changes observed in the microarray analysis by quantitative real-time RT-PCR. Comparison of the expression between healthy rats, SCI rats, and SCI treated with A-HOA rats revealed relevant changes in the expression of genes associated with neuronal morphogenesis and growth, neuronal survival, pain and inflammation. Thus, treatment with A-HOA not only induced a significant overexpression of growth and differentiation factor 10 (GDF10), tenascin C (TNC), aspirin (ASPN) and sushi-repeat-containing X-linked 2 (SRPX2), but also a significant reduction in the expression of prostaglandin E synthase (PTGES) and phospholipases A1 and A2 (PLA1/2). Currently, SCI has very important unmet clinical needs. A-HOA downregulated genes involved with inflammation and upregulated genes involved in neuronal growth, and may serve to promote recovery of function after experimental SCI

    Albumin-Oleic Acid Increases Serotonin (5-HT) Innervation to Above Normal Levels after SCI.

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    <p>Immunohistochemical images revealed that 5-HT innervation density was increased within both the dorsal and ventral horn following Albumin-Oleic acid treatment (0.4/80 nanomoles, 5C and 5I, 10x) compared to either naïve animals (A and G, 10x) or those with SCI contusion (Cont) treated with saline alone (Sal, B and H, 10x). Detailed photographs of laminae I-II (D-F, note faint medial signal in D), lamina VII (J–L) and lamina IX (M–O) revealed the normal presence of 5-HT fibres with varicosities (D, J, M), following SCI (E, K, N) and in animals with spinal T9 contusion with albumin-oleic acid treatment (F, L, O). Quantification of the increase in lumbar 5-HT innervation levels below the SCI within the dorsal (P, p<0.001) or ventral horn (Q, p<0.001) following Albumin-OA treatment (Alb-OA, 0.4/80 nanomoles) was observed, but not after saline (Sal), albumin (Alb), oleic acid (OA) or albumin-elaidic acid (Alb-EA) administration. Statistical analysis was performed with a one-way ANOVA for each experimental group (P and Q, *** - p<0.001). Detailed original examples of fluorescent images of 5-HT fibres within laminae I–II (R) and laminae VII (S) are included with Alb-OA treatment 28 days after T9 SCI.</p
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