47 research outputs found

    Autoantibody screening in Guillain-Barré syndrome

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    Background: Guillain-Barré syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation. Although some evidences support the role of autoantibodies in its pathogenesis, the target antigens remain unknown in a substantial proportion of GBS patients. The objective of this study is to screen for autoantibodies targeting peripheral nerve components in Guillain-Barré syndrome. Methods: Autoantibody screening was performed in serum samples from all GBS patients included in the International GBS Outcome study by 11 different Spanish centres. The screening included testing for anti-ganglioside antibodies, anti-nodo/paranodal antibodies, immunocytochemistry on neuroblastoma-derived human motor neurons and murine dorsal root ganglia (DRG) neurons, and immunohistochemistry on monkey peripheral nerve sections. We analysed the staining patterns of patients and controls. The prognostic value of anti-ganglioside antibodies was also analysed. Results: None of the GBS patients (n = 100) reacted against the nodo/paranodal proteins tested, and 61 (61%) were positive for, at least, one anti-ganglioside antibody. GBS sera reacted strongly against DRG neurons more frequently than controls both with IgG (6% vs 0%; p = 0.03) and IgM (11% vs 2.2%; p = 0.02) immunodetection. No differences were observed in the proportion of patients reacting against neuroblastoma-derived human motor neurons. Reactivity against monkey nerve tissue was frequently detected both in patients and controls, but specific patterns were only detected in GBS patients: IgG from 13 (13%) patients reacted strongly against Schwann cells. Finally, we confirmed that IgG anti-GM1 antibodies are associated with poorer outcomes independently of other known prognostic factors. Conclusion: Our study confirms that (1) GBS patients display a heterogeneous repertoire of autoantibodies targeting nerve cells and structures; (2) gangliosides are the most frequent antigens in GBS patients and have a prognostic value; (3) further antigen-discovery experiments may elucidate other potential antigens in GBS

    Veränderungen im Leukozytenprofil der Dupontlerche ( Chersophilus duponti ) in Spanien und Marokko

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    [EN] Stress in birds has been widely studied through the measurement of heterophil-to-lymphocyte ratio (H/L ratio). In this study we aimed to assess for the first time the potential variation of stress, measured as H/L ratio, associated to geography (between-country variation) and seasonality (between seasons and within the breeding season), as well as the leukocyte profiles, in the threatened Dupont’s Lark (Chersophilus duponti), using samples from Spain and Morocco. Furthermore, we tested whether variation in H/L ratio was associated with variables such as population density, presence of blood parasites and individual body condition. We found that H/L ratio did not vary between countries, but individuals captured during the breeding season showed higher values of H/L compared to non-breeding ones. Neither male density, nor date within the breeding season had an effect on the H/L ratio. In Spain, individuals with higher body condition showed lower H/L ratio regardless of whether they were malaria-infected. In Morocco, malaria-infected individuals showed higher values of H/L ratio than the non-infected birds. Moreover, we found that our average values of H/L ratio in Morocco were within the ranges of other passerines, but not in Spain. Individuals with higher H/L ratios may be more stressed or present higher capability to face stressful situations. Although H/L ratio is a useful and relatively easy way to obtain measure of stress, the impact that the environment might have on stress and the way it is explained by H/L ratio must be addressed carefully. This study provides new insight for this species’ biology and provides useful reference information to test the status and survival of other populations.[DE] Stress bei Vögeln ist durch die Messung des Verhältnisses von Heterophilen zu T-Lymphozyten (H/L-Verhältnis) umfassend untersucht worden. In dieser Studie wollten wir zum ersten Mal die potentiellen Veränderungen des Stresses in Verbindung mit der Geografie (Unterschiede zwischen einzelnen Ländern) und der Saisonalität (zwischen den Jahreszeiten und innerhalb der Brutsaison), gemessen als H/L-Verhältnis, sowie die Leukozytenprofile bei der bedrohten Dupontlerche (Chersophilus duponti) anhand von Proben aus Spanien und Marokko bewerten. Darüber hinaus haben wir untersucht, ob das H/L-Verhältnis mit Variablen wie der Populationsdichte, dem Vorhandensein von Blutparasiten und der individuellen physischen Verfassung zusammenhängt. Wir stellten fest, dass das H/L-Verhältnis zwischen den einzelnen Ländern nicht variierte, aber die während der Brutzeit gefangenen Tiere höhere H/L-Werte aufwiesen als nicht brütende Tiere. Weder die Dichte an Männchen, noch der Zeitpunkt innerhalb der Brutsaison hatten einen Einfluss auf das H/L-Verhältnis. In Spanien wiesen Tiere mit einer besseren physischen Verfassung ein niedrigeres H/L-Verhältnis auf, unabhängig davon, ob sie mit Malaria infiziert waren. In Marokko zeigten malariainfizierte Vögel höhere Werte des H/L-Verhältnisses als nicht infizierte. Außerdem stellten wir fest, dass unsere Durchschnittswerte für das H/L-Verhältnis in Marokko innerhalb der Werte für andere Sperlingsvögel lagen, nicht aber in Spanien. Tiere mit einem höheren H/L-Verhältnis sind möglicherweise gestresster oder besser in der Lage, mit Stresssituationen umzugehen. Obwohl das H/L-Verhältnis ein nützliches und relativ einfach zu beschaffendes Maß für Stress ist, muss der eventuelle Einfluss der Umwelt auf Stress und die Möglichkeiten, diesen durch das H/L-Verhältnis zu erklären, sorgfältig untersucht werden. Diese Untersuchung bietet neue Einblicke in die Biologie dieser Art und liefert nützliche Referenzinformationen für die Bestimmung des aktuellen Status und für das Überleben anderer Populationen.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.This study was partially funded by the authors, the Spanish Ministry of Environment (MMA; J.J. Areces and B. Heredia), the Spanish Agency for International Cooperation (AECI), and the LIFE Ricoti (LIFE15-NAT-ES-000802), supported by the European Comisison. D.B.R. was supported by FPI-UAM fellowship from the Universidad Autónoma de Madrid (UAM), and the collaboration of the Instituto de Investigación en Recursos Cinegéticos (IREC-CSIC-UCLM). We wish to thank the Servicio de Vida Silvestre of Conselleria D’infraestructures, Territori i Medi Ambient (Generalitat Valenciana) and the Moroccan government for ringing permits and supporting our work. We thank V. Garza, A. Ramírez, R. del pozo, E. Juarez, E.L. García de la Morena, F. Suárez, M. Radi, M. Znari and M. Alouí, and the Colectivo Ornitológico Cigüeña Negra for their help during fieldtrips and arrangements. We also thank two anonymous referees whose helpful comments contributed to improve the paper. This work was approved by the Local Ethical Committee for Animal Experiments of the Autónoma University of Madrid (CEI80-1468-A229).Peer reviewe

    Presidential Election Laws and Multipartism in Latin America

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    This article examines the interaction between the rules governing presidential elections and multipartism in Latin America. Data from 16 Latin American systems are examined through the use of a multivariate model to gain an understanding of the independent impact of presidential electoral formula (plurality vs. majority), the timing of presidential and legislative elections (concurrent vs. nonconcurrent) and legislative district magnitude on legislative multipartism, and by extension, on the number of relevant political parties operating in the nation. The findings demonstrate the strong and significant impact which formula and timing have on multipartism. They also point to the importance of examining the interaction between elections for different constituent institutions. Finally, they underscore the applicability of Duverger's law to presidential elections.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68710/2/10.1177_106591299404700103.pd

    The Candida albicans Ku70 Modulates Telomere Length and Structure by Regulating Both Telomerase and Recombination

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    The heterodimeric Ku complex has been shown to participate in DNA repair and telomere regulation in a variety of organisms. Here we report a detailed characterization of the function of Ku70 in the diploid fungal pathogen Candida albicans. Both ku70 heterozygous and homozygous deletion mutants have a wild-type colony and cellular morphology, and are not sensitive to MMS or UV light. Interestingly, we observed complex effects of KU70 gene dosage on telomere lengths, with the KU70/ku70 heterozygotes exhibiting slightly shorter telomeres, and the ku70 null strain exhibiting long and heterogeneous telomeres. Analysis of combination mutants suggests that the telomere elongation in the ku70 null mutant is due mostly to unregulated telomerase action. In addition, elevated levels of extrachromosomal telomeric circles were detected in the null mutant, consistent with activation of aberrant telomeric recombination. Altogether, our observations point to multiple mechanisms of the Ku complex in telomerase regulation and telomere protection in C. albicans, and reveal interesting similarities and differences in the mechanisms of the Ku complex in disparate systems

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Nutrición parenteral domiciliaria en España 2018. Informe del Grupo de Nutrición Artificial Domiciliaria y Ambulatoria NADYA

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    Objetivo: comunicar los datos de nutrición parenteral domiciliaria (NPD) obtenidos del registro del grupo NADYA-SENPE (www.nadya-senpe.com) del año 2018. Material y métodos: análisis descriptivo de los datos recogidos de pacientes adultos y pediátricos con NPD en el registro NADYA-SENPE del 1 de enero al 31 de diciembre de 2018. Resultados: se registraron 278 pacientes (54, 7% mujeres), 23 niños y 255 adultos, procedentes de 45 hospitales españoles, lo que representa una tasa de prevalencia de 5, 95 pacientes/millón de habitantes/año 2018. El diagnóstico más frecuente en adultos fue “oncológico paliativo” (22, 0%), seguido de “otros”. En niños fue la enfermedad de Hirschsprung junto con la enterocolitis necrotizante, con cuatro casos (17, 4%). El primer motivo de indicación fue síndrome de intestino corto tanto en niños (60, 9%) como en adultos (35, 7%). El tipo de catéter más utilizado fue el tunelizado tanto en niños (81, 0%) como en adultos (41, 1%). Finalizaron 75 episodios, la causa más frecuente fue el fallecimiento (52, 0%) y el paso a vía oral (33, 3%). Conclusiones: el número de centros y profesionales colaboradores en el registro de pacientes que reciben NPD se mantiene estable, así como las principales indicaciones y los motivos de finalización de la NPD. Aim: To communicate home parenteral nutrition (HPN) data obtained from the HPN registry of the NADYA-SENPE group (www.nadya-senpe.  com) for the year 2018. Material and methods: Descriptive analysis of the data collected from adult and pediatric patients with HPN in the NADYA-SENPE group registry from January 1st, 2018 to December 31st, 2018.  Results: There were 278 patients from 45 Spanish hospitals (54.7% women), 23 children and 255 adults, which represent a prevalence rate of 5.95 patients/million inhabitants/year 2018. The most frequent diagnosis in adults was “palliative cancer” (22.0%), followed by “others”. In children it was Hirschsprung’s disease together with necrotizing enterocolitis, with four cases (17.4%). The first indication was short bowel syndrome in both children (60.9%) and adults (35.7%). The most frequently used type of catheter was tunneled in both children (81.0%) and adults (41.1%). Ending 75 episodes, the most frequent cause was death (52.0%) and change to oral feeding (33.3%). Conclusions: The number of centers and collaborating professionals in the registry of patients receiving HPN remains stable, as well as the main indications and reasons for termination of HPN

    Comparison of leptin levels, body composition and insulin sensitivity and secretion by OGTT in healthy, early pubertal girls born at either appropriate- or small-for-gestational age

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    Background: Small for gestational age (SGA) has been associated with decreased insulin sensitivity (IS). A possible mechanism is the postnatal development of a metabolically disadvantageous body composition (BC). Aim: To determine whether there are differences between IS and BC in girls in early puberty who were SGA (birth weight < 10th percentile) or appropriate for gestational age (AGA, 10th-90th percentile). Methods: Age-matched (SGA/AGA) early pubertal girls (Tanner II) were recruited from local schools. We determined waist circumference (WC), the sum of four skinfolds (S4S), and per cent fat mass (fat %) by impedanciometry. Leptin and OGTT assays were performed. The insulinogenic index (I-In), HOMA-IR (homeostasis model assessment of insulin resistance) and WBISI (whole body insulin sensitivity) were calculated. Results: Median age (interquartile range) for 30 SGA and 35 AGA girls was 10.2 (1.1) vs. 9.8 (0.9), respectively (P = NS). BMI percentiles were 62.6 (56) vs. 67.4 (39); W
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