Neuronal network model of interictal and recurrent ictal activity

This is the final version of the article. Available from American Physical Society via the DOI in this record.We propose a neuronal network model which undergoes a saddle node on an invariant circle bifurcation as the mechanism of the transition from the interictal to the ictal (seizure) state. In the vicinity of this transition, the model captures important dynamical features of both interictal and ictal states. We study the nature of interictal spikes and early warnings of the transition predicted by this model. We further demonstrate that recurrent seizures emerge due to the interaction between two networks.This work was partially supported by FET IP Project MULTIPLEX 317532. A.V.G. is grateful to LA I3N for Grant No. PEST UID/CTM/50025/2013. M.A.L. acknowledges the financial support of the Medical Research Council (MRC) via Grant No. MR/K013998/01. K.E.L. was supported by the Department of Anesthesiology at the University of Michigan and the National Institutes of Health, Grant No. RO1 GM098578

Transthyretin interacts with actin regulators in a Drosophila model of familial amyloid polyneuropathy

Familial amyloid polyneuropathy (FAP) is a neurodegenerative disorder whose major hallmark is the deposition of mutated transthyretin (TTR) in the form of amyloid fibrils in the peripheral nervous system (PNS). The exposure of PNS axons to extracellular TTR deposits leads to an axonopathy that culminates in neuronal death. However, the molecular mechanisms underlying TTR-induced neurodegeneration are still unclear, despite the extensive studies in vertebrate models. In this work we used a Drosophila FAP model, based on the expression of the amyloidogenic TTR (V30M) in the fly retina, to uncover genetic interactions with cytoskeleton regulators. We show that TTR interacts with actin regulators and induces cytoskeleton alterations, leading to axonal defects. Moreover, our study pinpoints an interaction between TTRV30M and members of Rho GTPase signaling pathways, the major actin regulators. Based on these findings we propose that actin cytoskeleton alterations may mediate the axonopathy observed in FAP patients, and highlight a molecular pathway, mediated by Rho GTPases, underlying TTR-induced neurodegeneration. We expect this work to prompt novel studies and approaches towards FAP therapy.This work was supported by: FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028336 (PTDC/MED-NEU/28336/2017), to MAL; and Norte-01-0145-FEDER-000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through FEDER, to CSL and MAL. MIOS is a FCT fellow (SFRH/ BD/118728/2016). CSL is funded by DL 57/2016/CP1355/CT0022. MAL is an FCT Investigator. Flies expressing wild-type and mutant alleles of TTR were kindly provided by Malgorzata Pokrzywa and Per Hammarström. The DCAD2, PDF and Rho1 monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. We would like to thank the SEM facility at CEMUP (University of Porto) for technical help and Mónica M Sousa and Fernando Casares for comments on the manuscript

Induced liver injury after high-dose methylprednisolone in a patient with multiple sclerosis

A 33-year-old woman with multiple sclerosis, medicated with high doses of methylprednisolone, cyclophosphamide and glatiramer acetate, was referred to our department due to acute liver injury. The laboratory investigation was normal except for weakly positive antinuclear antibodies. Cyclophosphamide and glatiramer acetate were suspended, and intravenous immunoglobulin with maintenance of high doses of methylprednisolone was initiated. The patient developed another episode of acute hepatitis so the immunoglobulin was stopped. After that, she had three more episodes of elevation of liver enzymes with no hepatic insufficiency while medicated only with high doses of methylprednisolone. At this time, liver biopsy showed focal centrilobubar hepatocyte necrosis with minimal interface hepatitis. After the high doses of methylprednisolone were suspended, the patient remained asymptomatic, with normal hepatic enzymes. This case emphasises that, although rare, induced liver injury after high doses of methylprednisolone can occur.info:eu-repo/semantics/publishedVersio

The role that choice of model plays in predictions for epilepsy surgery

This is the final version. Available on open access from Nature Research via the DOI in this recordMathematical modelling has been widely used to predict the effects of perturbations to brain networks. An important example is epilepsy surgery, where the perturbation in question is the removal of brain tissue in order to render the patient free of seizures. Different dynamical models have been proposed to represent transitions to ictal states in this context. However, our choice of which mathematical model to use to address this question relies on making assumptions regarding the mechanism that defines the transition from background to the seizure state. Since these mechanisms are unknown, it is important to understand how predictions from alternative dynamical descriptions compare. Herein we evaluate to what extent three different dynamical models provide consistent predictions for the effect of removing nodes from networks. We show that for small, directed, connected networks the three considered models provide consistent predictions. For larger networks, predictions are shown to be less consistent. However consistency is higher in networks that have sufficiently large differences in ictogenicity between nodes. We further demonstrate that heterogeneity in ictogenicity across nodes correlates with variability in the number of connections for each node.Engineering and Physical Sciences Research Council (EPSRC)Medical Research Council (MRC)Epilepsy Research UKWellcome Trus

Tratar da Doença. Cuidar do Doente. O Serviço Social como Fator de Humanização

info:eu-repo/semantics/publishedVersio

Clinical communication skills and professionalism education are required from the beginning of medical training - a point of view of family physicians

Background: The Brazilian undergraduate medical course is six years long. As in other countries, a medical residency is not obligatory to practice as a doctor. In this context, this paper aims to clarify what and when competencies in communication and professionalism should be addressed, shedding light on the role of university, residency and post-residency programmes. Methods: Brazilian family physicians with diverse levels of medical training answered a questionnaire designed to seek a consensus on the competencies that should be taught (key competencies) and when students should achieve them during their medical training. The data were analysed using descriptive statistics and correlation tests. Results: A total of seventy-four physicians participated; nearly all participants suggested that the students should achieve communication and professionalism competencies during undergraduate study (twenty out of thirty competencies – 66.7%) or during residency (seven out of thirty competencies – 23.33%). When competencies were analysed in domains, the results were that clinical communication skills and professionalism competencies should be achieved during undergraduate medical education, and interpersonal communication and leadership skills should be reached during postgraduate study. Conclusion: The authors propose that attainment of clinical communication skills and professionalism competencies should be required for undergraduate students. The foundation for Leadership and Interpersonal Abilities should be particularly formed at an undergraduate level and, furthermore, mastered by immersion in the future workplace and medical responsibilities in residency.There was no direct financial support for this research. Financial support for the authors is provided by scholarships from the National Counsel of Technological and Scientific Development (CNPq), Brazil (229753/2013–2) and the Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil (13271/13–0)

Phytoplankton diversity and strategies in regard to physical disturbances in a shallow, oligotrophic, tropical reservoir in Southeast Brazil

The IAG Lake is a small, oligotrophic, and shallow reservoir located in the Parque Estadual das Fontes do Ipiranga Biological Reserve, south of Municipality of Sao Paulo, southeast Brazil. The study of the phytoplankton community dynamics is based on samples collected along the vertical profile of the water column in the pelagic region of the reservoir (Zmax = 4.7 m), 3 times a day (7 h, 13 h, and 19 h) during 7 consecutive days of the dry period (20-26 August 1996) and of the rainy period (22- 28 January 1997), but at 5 depths during the dry period and at 4 depths during the rainy one. The relationships among species richness, diversity, evenness, and dominance were discussed within the Connell's Intermediate Disturbance Hypothesis (IDH). The responses of the descriptive species in the community and C-R-S strategies were studied. The variation of the mixing zone was the main factor responsible for the changes in the community structure as well as for the maintenance of the diversity during both climate periods. The disturbance was considered of high frequency during the dry period and of intermediate frequency during the rainy one. The diversity was higher during the rainy period, confirming the IDH, at least during the present study. Peridinium gatunense Nygaard was dominant in most sample units during the dry period. During the rainy one, Chlamydomonas debaryana Goroschankin and Oocystis lacustris Chodat were the species that contributed the most. Regarding the functional groups, S-strategists dominated the dry period, differing from the rainy one, when the functional diversity was higher. In conclusion, changes in the phytoplankton community structure were well explained by Connell's IDH.El lago IAG es un embalse pequeño, oligotrófico y somero, ubicado en la Reserva Biológica del Parque Estadual das Fontes do Ipiranga, Sur de la Municipalidad de Sao Paulo, sureste del Brasil. El estudio de la dinámica de la comunidad fitoplanctónica está basado en muestras colectadas al largo del perfil vertical de la columna de agua en la región pelágica del embalse (Zmax = 4.7 m), 3 veces al día (7 h, 13 h y 19 h) durante 7 días consecutivos de los períodos seco (20-26 Agosto 1996) y húmedo (22-28 Enero 1997), pero en 5 profundidades durante el período seco y en 4 durante el húmedo. Las relaciones entre riqueza de especies, diversidad, equitabilidad y dominancia fueron discutidos dentro de la Hipótesis de Connell de la Perturbación Intermedia (HPI). Las respuestas de las especies descriptoras de la comunidad y estrategias C-R-S fueron estudiadas. La variación de la zona de mezcla fue el factor más importante en los cambios en la estructura de la comunidad así como para el mantenimiento de la diversidad durante los dos períodos climáticos. La perturbación fue considerada de frecuencia alta durante el período seco y de frecuencia intermedia durante el húmedo. La diversidad fue más alta durante el período de lluvias, confirmando la HPI, por lo menos en este estudio. Peridinium gatunense Nygaard fue dominante en la mayoría de las unidades de muestreo durante el período seco. Durante el período húmedo, Chlamydomonas debaryana Goroschankin y Oocystis lacustris Chodat fueron las especies que más contribuyeron. Considerando los grupos funcionales, los estrategas S dominaron el período seco, a diferencia del período húmedo, cuando la diversidad funcional fue más alta. Concluyendo, los cambios en la estructura de la comunidad del fitoplancton fueron bien explicados por la HPI de Connell

The Role of Excitability and Network Structure in the Emergence of Focal and Generalized Seizures

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The code and synthetic networks generated are available upon request.Epileptic seizures are generally classified as either focal or generalized. It had been traditionally assumed that focal seizures imply localized brain abnormalities, whereas generalized seizures involve widespread brain pathologies. However, recent evidence suggests that large-scale brain networks are involved in the generation of focal seizures, and generalized seizures can originate in localized brain regions. Herein we study how network structure and tissue heterogeneities underpin the emergence of focal and widespread seizure dynamics. Mathematical modeling of seizure emergence in brain networks enables the clarification of the characteristics responsible for focal and generalized seizures. We consider neural mass network dynamics of seizure generation in exemplar synthetic networks and we measure the variance in ictogenicity across the network. Ictogenicity is defined as the involvement of network nodes in seizure activity, and its variance is used to quantify whether seizure patterns are focal or widespread across the network. We address both the influence of network structure and different excitability distributions across the network on the ictogenic variance. We find that this variance depends on both network structure and excitability distribution. High variance, i.e., localized seizure activity, is observed in networks highly heterogeneous with regard to the distribution of connections or excitabilities. However, networks that are both heterogeneous in their structure and excitability can underlie the emergence of generalized seizures, depending on the interplay between structure and excitability. Thus, our results imply that the emergence of focal and generalized seizures is underpinned by an interplay between network structure and excitability distribution.Medical Research Council (MRC)Epilepsy Research UKEngineering and Physical Sciences Research Council (EPSRC)Wellcome TrustInnovate U

Histórias de Vida em Educação: A Construção do Conhecimento a partir de Histórias de Vida

[spa] Esta publicación recoge los trabajos presentados en las III Jornadas de Historias de Vida en Educación – La construcción del conocimiento a partir de las historias de vida, celebradas en la Facultad de Psicología y Ciencias de la Educación de la Universidad de Porto en los días 8 y 9 de noviembre 2012, y organizadas por el Centro de Investigación e Intervención Educativas. En las diferentes contribuciones se profundiza la reflexión sobre el uso de las historias de vida en educación como proceso de investigación y de construcción de conocimiento insustituible, específico y pertinente para la formación y mejora de los docentes y los investigadores y para explorar relaciones y procedimientos particulares derivados de cada ejemplo presentado Esta publicación ofrece un retrato del debate que tuvo lugar en la Universidad de Porto y da muestras de la vitalidad de esa comunidad que integra docentes e investigadores universitarios y estudiantes de master y doctorado de España, Portugal, México, Chile, Suiza, Argentina y Brasil.[por] Esta publicação recolhe os trabalhos apresentados nas III Jornadas de Histórias de Vida em Educação – A construção do conhecimento a partir das histórias de vida, realizadas na Faculdade de Psicologia e de Ciências da Educação da Universidade do Porto nos dias 8 e 9 de novembro de 2012, e organizadas pelo Centro de Investigação e Intervenção Educativas. Nas diferentes comunicações aprofunda-se a reflexão sobre o uso das histórias de vida em educação enquanto processo de investigação e de construção de um conhecimento insubstituível, específico e pertinente para a formação e o desenvolvimento dos docentes e investigadores, assim como para explorar relações e procedimentos particulares derivados de cada exemplo apresentado. Esta publicação oferece um retrato do debate que teve lugar na Universidade do Porto e demonstra a vitalidade dessa comunidade, que integra docentes e investigadores universitários, assim como estudantes de mestrado e de doutoramento, de Espanha, de Portugal, do México, do Chile, da Suíça, da Argentina e do Brasil.[cat] Aquesta publicació recull els treballs presentats a les III Jornades d’Històries de Vida en Educació – La construcció del coneixement a partir de les històries de vida, celebrades a la facultat de Psicologia i Ciències de l’Educació de la Universitat de Porto els dies 8 i 9 de novembre de 2012 i organitzades pel Centre d’Investigació i Intervenció Educatives. A les diferents contribucions es profunditza en la reflexió sobre l’ús de les històries de vida en educació com a procés d’investigació i de construcció de coneixement insubstituïble, específic i pertinent per la formació i millora dels docents i dels investigadors i per explorar relacions i procediments particulars derivats de cada exemple presentat. Aquesta publicació ofereix un retrat del debat que va tenir lloc a la Universitat de Porto i dóna mostres de vitalitat d’aquesta comunitat que integra docents i investigadors universitaris i estudiants de màster i doctorat d’Espanya, Portugal, Mèxic, Xile, Suïssa, Argentina i Brasil.[eng] This publication collects the papers presented at the III Conference on Life Stories in Education - Knowledge construction from life stories, held at the Faculty of Psychology and Educational Sciences of the University of Porto on 8 and 9 of November 2012, and organized by the Centre for Research and Intervention in Education. The various papers expand the reflection on the use of life stories in education as a process of research and of the construction of an irreplaceable, specific and relevant kind of knowledge for professional training and development of teachers and researchers, as well as to explore relationships and procedures coming from each one of the presented examples. This publication provides a picture of the debate that took place at the University of Porto and shows the vitality of that community, which includes university teachers and researchers as well as master and doctoral students from Spain, Portugal, Mexico, Chile, Switzerland, Argentina and Brazil