EAN consensus statement for management of patients with neurological diseases during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.

The international European Academy of Neurology survey on neurological symptoms in patients with COVID-19 infection.

BACKGROUND AND PURPOSE: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. METHODS: A 17-question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020. RESULTS: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.

Does SARS-Cov-2 invade the brain? Translational lessons from animal models.

The current coronavirus disease (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS-CoV-2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS-CoV-2. One key finding that may unify these pathogens is that all require angiotensin-converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS-CoV-2 binds to cell membranes, binds angiotensin-converting enzyme 2 with a higher affinity compared with SARS-CoV. The expression of this receptor in neurons and endothelial cells hints that SARS-CoV-2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune-mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune-mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID-19.

Herbivore, parasitoid and hyperparasitoid insects associated with fruits and seeds of Enterolobium contortisiliquum (Vell) Morong (Fabaceae) / Insetos herbívoros, parasitoides e hiperparasitoides associados a frutos e sementes de Enterolobium contortisiliquum (Vell) Morong (Fabaceae)

Abstract This study aimed to inventory the herbivore insects associated with Enterolobium contortisiliquum (Vell.) Morong (Fabaceae) fruits and seeds and their primary and secondary parasitoids. Six samples collected between May and October 2013 yielded 210 fruits, from which 326 insects of six orders emerged: Coleoptera, Hymenoptera, Lepidoptera, Diptera, Thysanoptera and Psocoptera. Coleoptera (five families) was represented by the seed consumers Merobruchus bicoloripes Pic, Stator sp. Bridwell (Chrysomelidae, Bruchinae), two species of Silvanidae, one species of Scolytinae (Curculionidae), one species of Nitidulidae and one species of Cerambycidae. The cerambycid was also observed forming galleries on fruit mesocarp. Immature individuals of Lepidoptera were observed consuming the fruits and seeds. From the seven Hymenoptera families, only two species were associated with Coleoptera, being Horismenus Walker sp. (Eulophidae) as parasitoid of M. bicoloripes, and Neoheterospilus falcatus (Marsh) (Braconidae) as parasitoid of Scolytinae. The Lepidoptera parasitoids represented four genera: Pseudophanerotoma Zetel, Chelonus Panzer (Braconidae), Orgilus Nees (Braconidae) and Goniozus Forster (Bethylidae). The host associations for the reared parasitoids Bracon Fabricius (Braconidae), Pimplinae sp. (Ichneumonidae) and Perilampus Forster (Perilampidae) were not confirmed. We obtained a single representative of Diptera (Tachinidae) associated with Lepidoptera hosts in this food web.

Resumo Este estudo teve como objetivo inventariar os insetos herbívoros associados a frutos e sementes de Enterolobium contortisiliquum (Vell.) Morong (Fabaceae) e seus parasitoides primários e secundários. De seis amostras coletadas entre maio e outubro de 2013, obteve-se 210 frutos, dos quais emergiram 326 insetos pertencentes a seis ordens: Coleoptera, Hymenoptera, Lepidoptera, Diptera, Thysanoptera e Psocoptera. Coleoptera (cinco famílias) foi representada pelos consumidores de sementes: Merobruchus bicoloripes Pic, Stator sp. Bridwell (Chrysomelidae, Bruchinae), Silvanidae sp. 1 e sp. 2, Scolytinae sp. (Curculionidae), Nitidulidae sp. e Cerambycidae sp. A última espécie também foi observada formando galerias no mesocarpo do fruto. Indivíduos imaturos de Lepidoptera também foram observados consumindo os frutos e sementes. Dos Hymenoptera (sete famílias), duas espécies foram associadas a Coleoptera, sendo Horismenus Walker sp. (Eulophidae) parasitoide de M. bicoloripes e Neoheterospilus falcatus (Marsh) (Braconidae) parasitoide de Scolytinae. Os parasitoides de Lepidoptera foram totalizados em quatro gêneros: Pseudophanerotoma Zetel e Chelonus Panzer (Braconidae), Orgilus Nees (Braconidae) e Goniozus Forster (Bethylidae). As interações para os parasitoides Bracon Fabricius (Braconidae), Pimplinae sp. (Ichneumonidae) e Perilampus Forster (Perilampidae) não foram confirmadas. Nós encontramos apenas um único representante de Diptera (Tachinidae) como parasitoide de Lepidoptera nesta rede trófica.

Herbivore, parasitoid and hyperparasitoid insects associated with fruits and seeds of Enterolobium contortisiliquum (Vell.) Morong (Fabaceae).

This study aimed to inventory the herbivore insects associated with Enterolobium contortisiliquum (Vell.) Morong (Fabaceae) fruits and seeds and their primary and secondary parasitoids. Six samples collected between May and October 2013 yielded 210 fruits, from which 326 insects of six orders emerged: Coleoptera, Hymenoptera, Lepidoptera, Diptera, Thysanoptera and Psocoptera. Coleoptera (five families) was represented by the seed consumers Merobruchus bicoloripes Pic, Stator sp. Bridwell (Chrysomelidae, Bruchinae), two species of Silvanidae, one species of Scolytinae (Curculionidae), one species of Nitidulidae and one species of Cerambycidae. The cerambycid was also observed forming galleries on fruit mesocarp. Immature individuals of Lepidoptera were observed consuming the fruits and seeds. From the seven Hymenoptera families, only two species were associated with Coleoptera, being Horismenus Walker sp. (Eulophidae) as parasitoid of M. bicoloripes, and Neoheterospilus falcatus (Marsh) (Braconidae) as parasitoid of Scolytinae. The Lepidoptera parasitoids represented four genera: Pseudophanerotoma Zetel, Chelonus Panzer (Braconidae), Orgilus Nees (Braconidae) and Goniozus Forster (Bethylidae). The host associations for the reared parasitoids Bracon Fabricius (Braconidae), Pimplinae sp. (Ichneumonidae) and Perilampus Forster (Perilampidae) were not confirmed. We obtained a single representative of Diptera (Tachinidae) associated with Lepidoptera hosts in this food web.

Morphological Traits of Two Seed-Feeding Beetle Species and the Relationship to Resource Traits.

Morphological traits are useful to investigate insect sex-related differences in body size and to reveal differences in resource use. It has been suggested that as the resource increases, so does the body size of organisms interacting with the resource, highlighting the crucial role of resource quality and quantity in determining the morphological traits of organisms interacting with the resource. Here, we describe morphological traits of two species of Bruchinae, Merobruchus terani (Kingsolver 1980) and Stator maculatopygus (Pic 1930), consuming seeds of Senegalia tenuifolia (Fabaceae: Mimosoideae). We evaluated the influence of monthly sample and sampling sites on tibia and femur length and biomass. In addition, we tested two predictions in which body size related to resource amount and body size related to longevity. Males of M. terani were heavier than females, whereas the two sexes of S. maculatopygus did not differ in biomass. Both species had larger body sizes in the late ripe-fruit stage. With respect to sampling sites, biomass of M. terani did not differ, whereas S. maculatopygus did differ in biomass. Merobruchus terani showed a positive relationship with seed traits, whereas S. maculatopygus showed no relationship. At the same time, fruit traits showed a negative effect on morphological traits for both beetle species. The longevity experiment, performed using only M. terani, showed an equal longevity and seed consumption rate for both sexes. Our study indicates that different species, interacting in the same system and performing similar functional behaviors, respond differently to the same resource.

Identification of Shell Colour Pigments in Marine Snails Clanculus pharaonius and C. margaritarius (Trochoidea; Gastropoda).

Colour and pattern are key traits with important roles in camouflage, warning and attraction. Ideally, in order to begin to understand the evolution and ecology of colour in nature, it is important to identify and, where possible, fully characterise pigments using biochemical methods. The phylum Mollusca includes some of the most beautiful exemplars of biological pigmentation, with the vivid colours of sea shells particularly prized by collectors and scientists alike. Biochemical studies of molluscan shell colour were fairly common in the last century, but few of these studies have been confirmed using modern methods and very few shell pigments have been fully characterised. Here, we use modern chemical and multi-modal spectroscopic techniques to identify two porphyrin pigments and eumelanin in the shell of marine snails Clanculus pharaonius and C margaritarius. The same porphyrins were also identified in coloured foot tissue of both species. We use high performance liquid chromatography (HPLC) to show definitively that these porphyrins are uroporphyrin I and uroporphyrin III. Evidence from confocal microscopy analyses shows that the distribution of porphyrin pigments corresponds to the striking pink-red of C. pharaonius shells, as well as pink-red dots and lines on the early whorls of C. margaritarius and yellow-brown colour of later whorls. Additional HPLC results suggest that eumelanin is likely responsible for black spots. We refer to the two differently coloured porphyrin pigments as trochopuniceus (pink-red) and trochoxouthos (yellow-brown) in order to distinguish between them. Trochopuniceus and trochoxouthos were not found in the shell of a third species of the same superfamily, Calliostoma zizyphinum, despite its superficially similar colouration, suggesting that this species has different shell pigments. These findings have important implications for the study of colour and pattern in molluscs specifically, but in other taxa more generally, since this study shows that homology of visible colour cannot be assumed without identification of pigments.

New cytotoxic sterol glycosides from the octocoral Carijoa (Telesto) riisei.

Two new steroidal glycosides, 3beta-O-(3'-O-acetyl-beta-D-arabinopyranosyl)-25xi-choles tan e-3beta, 5alpha,6beta,26-tetrol-26-acetate (riisein A, 2) and 3beta-O-(4'-O-acetyl-beta-D-arabinopyranosyl)-25xi-choles tan e-3beta, 5alpha,6beta,26-tetrol-26-acetate (riisein B, 3), were isolated from extracts of the Brazilian telestacean octocoral Carijoa (Telesto) riisei collected near Rio de Janeiro. The new glycosides co-occur with the polyhydroxy sterol, 25xi-cholestane-3beta,5alpha,6beta, 26-tetrol-26-acetate (1), an inseparable diastereomeric mixture previously reported from Telesto riisei collected in Micronesia. The structures of the new glycosides were assigned by spectroscopic methods and by comparison with spectral data for sterol 1. Riiseins A and B showed in vitro cytotoxicity toward HCT-116 human colon adenocarcinoma with IC(50) values of 2.0 microg/mL.

Limited synergistic effect of antisense oligonucleotides against bcr-abl and transferrin receptor mRNA in leukemic cells in culture.

The synergistic use of antisense oligonucleotides (ASOs) towards the bcr-abl and the transferrin receptor (TfR) mRNA was studied in a chronic myeloid leukemia (CML) cell line, aiming to improve the efficiency of individual ASO treatment. At 20 microM concentration, bcr-abl ASOs reduced cell growth by 40% and was specific for cells that have the translocation: there was a 34% reduction of BCR-ABL protein. The TfR ASO reduced cell growth by 20% and decreased TfR protein by 24%. The ASOs were more potent at reducing cell growth when used in combination (respectively, -20 and -17% than bcr-abl ASO and TfR ASO when used individually at the 10 microM concentration), thus we postulate that there is synergism of action. Cell cycle analysis also revealed that the sub-G1 peak was bigger in the synergistic treatment.

Diltiazem improves left ventricular systolic function following acute myocardial infarction treated with streptokinase. The Calcium Antagonist in Reperfusion Study (CARES) Group.

The role of diltiazem on left ventricular systolic function was analyzed in 101 patients with acute myocardial infarction treated with streptokinase, being obtained, for the total of the population, higher LV global ejection fraction (p = 0.022), LV regional shortening (p = 0.046) and LV global shortening (p = 0.064) for the treated group, relative to the placebo group; the p values were, respectively, 0.005, 0.009, and 0.012, for patients that achieved TIMI-3 antegrade coronary flow. It is concluded that diltiazem is useful as adjuvant to streptokinase, especially when antegrade coronary blood flow TIMI-3 is obtained.