Unusual consequences of status epilepticus in Dravet syndrome

AbstractAlthough status epilepticus (SE) affects the course of Dravet syndrome (DS), it rarely alters dramatically psychomotor outcome. We report an unusual pattern in 3 patients who following refractory SE lasting respectively 2, 7 and 12h experienced persistent and severe cognitive and motor deterioration. We compared these patients to published data and to personal experience in Necker hospital, to find links between severe outcome and clinical features such as treatment or duration of refractory SE. The key point was that anoxoischemic-like lesions appeared on MRI although cardiovascular function had remained stable. Therefore, neither hemodynamic failure, nor abnormalities of cardiac rhythm could explain the lesions and neurological worsening. For theoretical reasons the responsibility of therapy common for the 3 patients, e.g., barbiturates was suspected

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

A "hair-raising" history of alopecia areata

YesA 3500‐year‐old papyrus from ancient Egypt provides a list of treatments for many diseases including “bite hair loss,” most likely alopecia areata (AA). The treatment of AA remained largely unchanged for over 1500 years. In 30 CE, Celsus described AA presenting as scalp alopecia in spots or the “windings of a snake” and suggested treatment with caustic compounds and scarification. The first “modern” description of AA came in 1813, though treatment still largely employed caustic agents. From the mid‐19th century onwards, various hypotheses of AA development were put forward including infectious microbes (1843), nerve defects (1858), physical trauma and psychological stress (1881), focal inflammation (1891), diseased teeth (1902), toxins (1912) and endocrine disorders (1913). The 1950s brought new treatment developments with the first use of corticosteroid compounds (1952), and the first suggestion that AA was an autoimmune disease (1958). Research progressively shifted towards identifying hair follicle‐specific autoantibodies (1995). The potential role of lymphocytes in AA was made implicit with immunohistological studies (1980s). However, studies confirming their functional role were not published until the development of rodent models (1990s). Genetic studies, particularly genome‐wide association studies, have now come to the forefront and open up a new era of AA investigation (2000s). Today, AA research is actively focused on genetics, the microbiome, dietary modulators, the role of atopy, immune cell types in AA pathogenesis, primary antigenic targets, mechanisms by which immune cells influence hair growth, and of course the development of new treatments based on these discoveries.Alopecia UK

Atopic dermatitis : a cutaneous or systemic disease? The search for answers in the history of Dermatology

A dermatite atópica é doença inflamatória cutânea associada à atopia, predisposição a produzir resposta IgE a alérgenos ambientais, constituindo uma das manifestações das doenças atópicas, junto com a asma e a rinite alérgica. A dermatite atópica é caracterizada por episódios recorrentes de eczema associado a prurido, acometendo superfície cutânea geneticamente alterada, induzindo, por fenômenos imunológicos, a presença de inflamação. Trata-se de doença multifatorial, com enfoque nas alterações sistêmicas e alérgicas ou nas manifestações cutâneas, de acordo com diferentes visões da doença. A conceituação da dermatite atópica é importante, porque a conduta terapêutica pode variar segundo essas duas formas diferentes de analisá-la. Autores modernos discutem extensivamente esses aspectos sem, contudo, alcançar uma conclusão sobre a dermatite atópica como doença sistêmica ou cutânea. A procura dos conceitos sobre a doença, desde os primeiros relatos, associada à evolução do pensamento na dermatologia, poderia esclarecer a origem dessas dúvidas. Uma análise histórica demonstra que a dermatite atópica tem seus conceitos atuais oriundos dos estudos de diversos pensadores, que, em diferentes momentos históricos, descreveram a doença, e que muito do que acreditamos atualmente tem, nesses escritos, seus fundamentos.Atopic dermatitis is an inflammatory disease associated to atopy, which is a predisposition to produce an IgE response to environmental allergens and considered one of the manifestations of the atopic diseases, including asthma and allergic rhinitis. Atopic dermatitis is characterized by recurrent eczema flares, associated to pruritus, affecting a genetically disrupted skin surface, inducing, by immunological phenomena, the onset of inflammation. It is a multifactorial disease, with an emphasis on systemic and allergic alterations or skin manifestations, according to different concepts. The definition of atopic dermatitis is important, since its management may vary according to these two different points of view. Modern authors have extensively discussed these concepts, though with no conclusion as to its nature - systemic or cutaneous disease. The search for concepts about the disease, since its first descriptions, associated to the evolution of the dermatology rationale through history, may help understand the origin of these doubts. A historical analysis demonstrates that the currently accepted concepts of atopic dermatitis have their background from different researchers, who, at different historical moments, described the disease, and a great part of our beliefs about atopic dermatitis are related to these ancient writings