Transmission tree of the highly pathogenic avian influenza (H5N1) epidemic in Israel, 2015

The transmission tree of the Israeli 2015 epidemic of highly pathogenic avian influenza (H5N1) was modelled by combining the spatio-temporal distribution of the outbreaks and the genetic distance between virus isolates. The most likely successions of transmission events were determined and transmission parameters were estimated. It was found that the median infectious pressure exerted at 1 km was 1.59 times (95% CI 1.04, 6.01) and 3.54 times (95% CI 1.09, 131.75) higher than that exerted at 2 and 5 km, respectively, and that three farms were responsible for all seven transmission events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0393-2) contains supplementary material, which is available to authorized users

Characteristics of intracerebral haemorrhage associated with COVID-19: a systematic review and pooled analysis of individual patient and aggregate data

Background and purpose: There are very few studies of the characteristics and causes of ICH in COVID-19, yet such data are essential to guide clinicians in clinical management, including challenging anticoagulation decisions. We aimed to describe the characteristics of spontaneous symptomatic intracerebral haemorrhage (ICH) associated with COVID-19. Methods: We systematically searched PubMed, Embase and the Cochrane Central Database for data from patients with SARS-CoV-2 detected prior to or within 7 days after symptomatic ICH. We did a pooled analysis of individual patient data, then combined data from this pooled analysis with aggregate-level data. Results: We included data from 139 patients (98 with individual data and 41 with aggregate-level data). In our pooled individual data analysis, the median age (IQR) was 60 (53–67) years and 64% (95% CI 54–73.7%) were male; 79% (95% CI 70.0–86.9%) had critically severe COVID-19. The pooled prevalence of lobar ICH was 67% (95% CI 56.3–76.0%), and of multifocal ICH was 36% (95% CI 26.4–47.0%). 71% (95% CI 61.0–80.4%) of patients were treated with anticoagulation (58% (95% CI 48–67.8%) therapeutic). The median NIHSS was 28 (IQR 15–28); mortality was 54% (95% CI 43.7–64.2%). Our combined analysis of individual and aggregate data showed similar findings. The pooled incidence of ICH across 12 cohort studies of inpatients with COVID-19 (n = 63,390) was 0.38% (95% CI 0.22–0.58%). Conclusions: Our data suggest that ICH associated with COVID-19 has different characteristics compared to ICH not associated with COVID-19, including frequent lobar location and multifocality, a high rate of anticoagulation, and high mortality. These observations suggest different underlying mechanisms of ICH in COVID-19 with potential implications for clinical treatment and trials

Clinical and instrumental evaluation of Botulinum Toxin type A safety profile in post stroke spasticity rehabilitation treatment

Post stroke spasticity (PSS) occurs approximately in 30% of stroke survivors. Spasticity varies from a subtle neurological sign to a gross increase in tone causing immobility of joints. PSS is associated with several complications, increasing care needs and utilisation of healthcare resources. Botulinum toxin type A (BoNT-A) has been considered as an effective and safe treatment for focal spasticity in stroke survivors, with low prevalence of complications, reversibility of effect, and efficacy in reducing spastic hypertonia. Recent studies estimated that a significant percentage of patients affected by PSS could benefit from higher doses than those permitted by current country directives. However, at present time, there is no general consensus on the maximum dose of BoNT-A in terms of safety and clinical interchangeability among the three commercially approved products (abobotulinumtoxinA, onabotulinumtoxinA, incobotulinumtoxinA). In light of these considerations, the aim of this thesis is to investigate the safety profile of BoNT-A high doses in the treatment of post stroke spasticity. In our research activity we investigated the clinical effect of this treatment in severely affected patients, focusing on both clinical and instrumental assessment of systemic effects of BoNT-A

Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity.

Recently, we identified a GTPase-activating protein for the ADP ribosylation factor family of small GTP-binding proteins that we call GIT1. This protein initially was identified as an interacting partner for the G protein-coupled receptor kinases, and its overexpression was found to affect signaling and internalization of the prototypical beta(2)-adrenergic receptor. Here, we report that GIT1 overexpression regulates internalization of numerous, but not all, G protein-coupled receptors. The specificity of the GIT1 effect is not related to the type of G protein to which a receptor couples, but rather to the endocytic route it uses. GIT1 only affects the function of G protein-coupled receptors that are internalized through the clathrin-coated pit pathway in a beta-arrestin- and dynamin-sensitive manner. Furthermore, the GIT1 effect is not limited to G protein-coupled receptors because overexpression of this protein also affects internalization of the epidermal growth factor receptor. However, constitutive agonist-independent internalization is not regulated by GIT1, because transferrin uptake is not affected by GIT1 overexpression. Thus, GIT1 is a protein involved in regulating the function of signaling receptors internalized through the clathrin pathway and can be used as a diagnostic tool for defining the endocytic pathway of a receptor

Prediction of specific biomolecule adsorption on silica surfaces as a function of pH and particle size

Silica nanostructures are biologically available and find wide applications for drug delivery, catalysts, separation processes, and composites. However, specific adsorption of biomolecules on silica surfaces and control in biomimetic synthesis remain largely unpredictable. In this contribution, the variability and control of peptide adsorption on silica nanoparticle surfaces is explained as a function of pH, particle diameter, and peptide electrostatic charge using molecular dynamics simulations with the CHARMM-INTERFACE force field. Adsorption free energies and specific binding residues are analyzed in molecular detail, providing experimentally elusive, atomic-level information on the complex dynamics of aqueous electric double layers in contact with biological molecules. Tunable contributions to adsorption are described in the context of specific silica surface chemistry, including ion pairing, hydrogen bonds, hydrophobic interactions, and conformation effects. Remarkable agreement is found for computed peptide binding as a function of pH and particle size versus experimental adsorption isotherms and zeta-potentials. Representative surface models were built using characterization of the silica surfaces by TEM, SEM, BET, TGA, ζ-potential, and surface titration measurements. The results show that the recently introduced interatomic potentials (Emami et al. Chem. Mater. 2014, 26, 2647) enable computational screening of a limitless number of silica interfaces to predict the binding of drugs, cell receptors, polymers, surfactants, and gases under realistic solution conditions at the scale of 1 to 100 nm. The highly specific binding outcomes underline the significance of the surface chemistry, pH, and topography

The Vacuum in Light-Cone Field Theory

This is an overview of the problem of the vacuum in light-cone field theory, stressing its close connection to other puzzles regarding light-cone quantization. I explain the sense in which the light-cone vacuum is ``trivial,'' and describe a way of setting up a quantum field theory on null planes so that it is equivalent to the usual equal-time formulation. This construction is quite helpful in resolving the puzzling aspects of the light-cone formalism. It furthermore allows the extraction of effective Hamiltonians that incorporate vacuum physics, but that act in a Hilbert space in which the vacuum state is simple. The discussion is fairly informal, and focuses mainly on the conceptual issues. [Talk presented at {\sc Orbis Scientiae 1996}, Miami Beach, FL, January 25--28, 1996. To appear in the proceedings.]Comment: 20 pages, RevTeX, 4 Postscript figures. Minor typos correcte

Patient experience of centralised acute stroke care pathways

Background: In 2010, Greater Manchester (GM) and London centralized acute stroke care services into a reduced number of hyperacute stroke units, with local stroke units providing on‐going care nearer patients’ homes. / Objective: To explore the impact of centralized acute stroke care pathways on the experiences of patients. / Design: Qualitative interview study. Thematic analysis was undertaken, using deductive and inductive approaches. Final data analysis explored themes related to five chronological phases of the centralized stroke care pathway. / Setting and participants: Recruitment from 3 hospitals in GM (15 stroke patients/8 family members) and 4 in London (21 stroke patients/9 family members). / Results: Participants were impressed with emergency services and initial reception at hospital: disquiet about travelling further than a local hospital was allayed by clear explanations. Participants knew who was treating them and were involved in decisions. Difficulties for families visiting hospitals a distance from home were raised. Repatriation to local hospitals was not always timely, but no detrimental effects were reported. Discharge to the community was viewed less positively. / Discussion and conclusions: Patients on the centralized acute stroke care pathways reported many positive aspects of care: the centralization of care pathways can offer patients a good experience. Disadvantages of travelling further were perceived to be outweighed by the opportunity to receive the best quality care. This study highlights the necessity for all staff on a centralized care pathway to provide clear and accessible information to patients, in order to maximize their experience of care

Transient ischaemic attacks: mimics and chameleons.

Suspected transient ischaemic attack (TIA) is a common diagnostic challenge for physicians in neurology, stroke, general medicine and primary care. It is essential to identify TIAs promptly because of the very high early risk of ischaemic stroke, requiring urgent investigation and preventive treatment. On the other hand, it is also important to identify TIA 'mimics', to avoid unnecessary and expensive investigations, incorrect diagnostic labelling and inappropriate long-term prevention treatment. Although the pathophysiology of ischaemic stroke and TIA is identical, and both require rapid and accurate diagnosis, the differential diagnosis differs for TIA owing to the transience of symptoms. For TIA the diagnostic challenge is greater, and the 'mimic' rate higher (and more varied), because there is no definitive diagnostic test. TIA heralds a high risk of early ischaemic stroke, and in many cases the stroke can be prevented if the cause is identified, hence the widespread dissemination of guidelines including rapid assessment and risk tools like the ABCD2 score. However, these guidelines do not emphasise the substantial challenges in making the correct diagnosis in patients with transient neurological symptoms. In this article we will mainly consider the common TIA mimics, but also briefly mention the rather less common situations where TIAs can look like something else ('chameleons')

Characteristics of ischaemic stroke associated with COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with coagulopathy causing venous and arterial thrombosis.1 2 Recent data from the pandemic epicentre in Wuhan, China, reported neurological complications in 36% of 214 patients with COVID-19; acute cerebrovascular disease (mainly ischaemic stroke) was more common among 88 patients with severe COVID-19 than those with non-severe disease (5.7% vs 0.8%).3 However, the mechanisms, phenotype and optimal management of ischaemic stroke associated with COVID-19 remain uncertain. We describe the demographic, clinical, radiological and laboratory characteristics of six consecutive patients assessed between 1st and 16th April 2020 at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK, with acute ischaemic stroke and COVID-19 (confirmed by reverse-transcriptase PCR (RT-PCR)) (table 1). All six patients had large vessel occlusion with markedly elevated D-dimer levels (≥1000μg/L). Three patients had multiterritory infarcts, two had concurrent venous thrombosis, and, in two, ischaemic strokes occurred despite therapeutic anticoagulation