984 resultados para 4-c]pyrrole
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El monitoreo se realizó en agosto 2007, a bordo de la L/P IMARPE IV, desde La Yarada hasta 40 mn frente a Quilca. La temperatura superficial varió de 13,7 a 16,4 °C, menores valores (<14,5 °C) se registraron entre Tancona y Quilca dentro de las 15 mn y mayores (>16 °C) entre Punta Coles y el Dominio Marítimo Sur por fuera de 20 mn. Las anomalías térmicas variaron de -1,4 a -0,8 °C. La gradiente térmica vertical estuvo conformada por 3 isotermas (14 a 16 °C), la isolínea de 15 °C se presentó entre la superficie (zonas costeras) y 35 m. La anchoveta tuvo mayor distribución hasta 40 mn frente a Mollendo, dentro de las 5 mn se ubicó mezclada con múnida, principalmente frente a Playa Tacna y Mollendo.
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En las playas de Atahuanca, Lobiños y Playa Chica de Huacho, del 24 de febrero al 2 de marzo 2003, se desarrolló la pesca con chinchorro manual, la captura total fue 312,77 kg, correspondiendo a lisa el mayor porcentaje (39,55%). La CPUE varió entre 500 kg.h-1 y 8,77 kg.h-1. El rango de tallas varió para lisa entre 22 y 39 cm, mismis entre 11 y 31 cm; la correlación entre longitud y peso fue altamente significativa para lisa con r=0,961 y mismis r=0,997. Las correlaciones de los parámetros de longitud y el perímetro a la marca de la red registraron valores significativos con un r = 0,961 para la lisa y r = 0,973 para el mismis. Las hembras de lisa estuvieron en estadio III (26,32%) y II (21,05%) y los machos en estadio II y IV (15,79%). Las hembras de mismis estuvieron en estadio III (7,41%) y los machos en estadios IV (44,44%) y V (18,52%). Las operaciones de pesca experimental se efectuaron a 6 m de profundidad. La presencia de los recursos costeros est uvo asociada a un rango de 17,1 a 17,4 °C.
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Object Recent years have been marked by efforts to improve the quality and safety of pedicle screw placement in spinal instrumentation. The aim of the present study is to compare the accuracy of the SpineAssist robot system with conventional fluoroscopy-guided pedicle screw placement. Methods Ninety-five patients suffering from degenerative disease and requiring elective lumbar instrumentation were included in the study. The robot cohort (Group I; 55 patients, 244 screws) consisted of an initial open robot-assisted subgroup (Subgroup IA; 17 patients, 83 screws) and a percutaneous cohort (Subgroup IB, 38 patients, 161 screws). In these groups, pedicle screws were placed under robotic guidance and lateral fluoroscopic control. In the fluoroscopy-guided cohort (Group II; 40 patients, 163 screws) screws were inserted using anatomical landmarks and lateral fluoroscopic guidance. The primary outcome measure was accuracy of screw placement on the Gertzbein-Robbins scale (Grade A to E and R [revised]). Secondary parameters were duration of surgery, blood loss, cumulative morphine, and length of stay. Results In the robot group (Group I), a perfect trajectory (A) was observed in 204 screws (83.6%). The remaining screws were graded B (n = 19 [7.8%]), C (n = 9 [3.7%]), D (n = 4 [1.6%]), E (n = 2 [0.8%]), and R (n = 6 [2.5%]). In the fluoroscopy-guided group (Group II), a completely intrapedicular course graded A was found in 79.8% (n = 130). The remaining screws were graded B (n = 12 [7.4%]), C (n = 10 [6.1%]), D (n = 6 [3.7%]), and E (n = 5 [3.1%]). The comparison of "clinically acceptable" (that is, A and B screws) was neither different between groups (I vs II [p = 0.19]) nor subgroups (Subgroup IA vs IB [p = 0.81]; Subgroup IA vs Group II [p = 0.53]; Subgroup IB vs Group II [p = 0.20]). Blood loss was lower in the robot-assisted group than in the fluoroscopy-guided group, while duration of surgery, length of stay, and cumulative morphine dose were not statistically different. Conclusions Robot-guided pedicle screw placement is a safe and useful tool for assisting spine surgeons in degenerative spine cases. Nonetheless, technical difficulties remain and fluoroscopy backup is advocated.
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We present Very Long Baseline Interferometry (VLBI) observations of the high mass X-ray binary LSI+61303, carried out with the European VLBI Network (EVN). Over the 11 hour observing run, performed 10 days after a radio outburst, the radio source showed a constant flux density, which allowed sensitive imaging of the emission distribution. The structure in the map shows a clear extension to the southeast. Comparing our data with previous VLBI observations we interpret the extension as a collimated radio jet as found in several other X-ray binaries. Assuming that the structure is the result of an expansion that started at the onset of the outburst, we derive an apparent expansion velocity of 0.003 c, which, in the context of Doppler boosting, corresponds to an intrinsic velocity of at least 0.4 c for an ejection close to the line of sight. From the apparent velocity in all available epochs we are able to establish variations in the ejection angle which imply a precessing accretion disk. Finally we point out that LSI+61303, like SS433 and Cygnus X-1, shows evidence for an emission region almost orthogonal to the relativistic jet.
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Erythrocyte concentrates (ECs) are the major labile blood product being transfused worldwide, aiming at curing anemia of diverse origins. In Switzerland, ECs are stored at 4 °C up to 42 days in saline-adenine-glucose-mannitol (SAGM). Such storage induces cellular lesions, altering red blood cells (RBCs) metabolism, protein content and rheological properties. A hot debate exists regarding the impact of the storage lesions, thus the age of ECs on transfusion-related clinical adverse outcomes. Several studies tend to show that poorer outcomes occur in patients receiving older blood products. However, no clear association was demonstrated up to date. While metabolism and early rheological changes are reversible through transfusion of the blood units, oxidized proteins cannot be repaired, and it is likely such irreversible damages would affect the quality of the blood product and the efficiency of the transfusion. In vivo, RBCs are constantly exposed to oxygen fluxes, and are thus well equipped to deal with oxidative challenges. Moreover, functional 20S proteasome complexes allow for recognition and proteolysis of fairly oxidized protein, and some proteins can be eliminated from RBCs by the release of microvesicles. The present PhD thesis is involved in a global research project which goal is to characterize the effect of processing and storage on the quality of ECs. Assessing protein oxidative damages during RBC storage is of major importance to understand the mechanisms of aging of stored RBCs. To this purpose, redox proteomic-based investigations were conducted here. In a first part, cysteine oxidation and protein carbonylation were addressed via 2D-DIGE and derivatization-driven immunodetection approaches, respectively. Then, the oxidized sub- proteomes were characterized through LC-MS/MS identification of proteins in spots of interest (cysteine oxidation) or affinity-purified carbonylated proteins. Gene ontology annotation allowed classifying targets of oxidation according to their molecular functions. In a third part, the P20S activity was evaluated throughout the storage period of ECs, and its susceptibility to highly oxidized environment was investigated. The potential defensive role of microvesiculation was also addressed through the quantification of eliminated carbonylated proteins. We highlighted distinct protein groups differentially affected by cysteine oxidation, either reversibly or irreversibly. In addition, soluble extracts showed a decrease in carbonylation at the beginning of the storage and membrane extracts revealed increasing carbonylation after 4 weeks of storage. Engaged molecular functions revealed that antioxidant (AO) are rather reversibly oxidized at their cysteine residue(s), but are irreversibly oxidized through carbonylation. In the meantime, the 20S proteasome activity is decreased by around 40 % at the end of the storage period. Incubation of fresh RBCs extracts with exogenous oxidized proteins showed a dose-dependent and protein-dependent inhibitory effect. Finally, we proved that the release of microvesicles allows the elimination of increasing quantities of carbonylated proteins. Taken together, these results revealed an oxidative pathway model of RBCs storage, on which further investigation towards improved storage conditions will be based. -- Les concentrés érythrocytaires (CE) sont le produit sanguin le plus délivré au monde, permettant de traiter différentes formes d'anémies. En Suisse, les CE sont stocké à 4 °C pendant 42 jours dans une solution saline d'adénine, glucose et mannitol (SAGM). Une telle conservation induit des lésions de stockage qui altèrent le métabolisme, les protéines et les propriétés rhéologique du globule rouge (GR). Un débat important concerne l'impact du temps de stockage des CE sur les risques de réaction transfusionnelles, certaines études tentant de démontrer que des transfusions de sang vieux réduiraient l'espérance de vie des patients. Cependant, aucune association concrète n'a été prouvée à ce jour. Alors que les modifications du métabolisme et changement précoces des propriétés rhéologiques sont réversibles suite à la transfusion du CE, les protéines oxydées ne peuvent être réparées, et il est probable que de telles lésions affectent la qualité et l'efficacité des produits sanguins. In vivo, les GR sont constamment exposés à l'oxygène, et sont donc bien équipés pour résister aux lésions oxydatives. De plus, les complexes fonctionnels de proteasome 20S reconnaissent et dégradent les protéines modérément oxydées, et certaines protéines peuvent être éliminées par les microparticules. Cette thèse de doctorat est imbriquée dans un projet de recherche global ayant pour objectif la caractérisation des effets de la préparation et du stockage sur la qualité des GR. Evaluer les dommages oxydatifs du GR pendant le stockage est primordial pour comprendre les mécanismes de vieillissement des produits sanguin. Dans ce but, des recherches orientées redoxomique ont été conduites. Dans une première partie, l'oxydation des cystéines et la carbonylation des protéines sont évaluées par électrophorèse bidimensionnelle différentielle et par immunodétection de protéines dérivatisées. Ensuite, les protéines d'intérêt ainsi que les protéines carbonylées, purifiées par affinité, sont identifiées par spectrométrie de masse en tandem. Les protéines cibles de l'oxydation sont classées selon leur fonction moléculaire. Dans une troisième partie, l'activité protéolytique du protéasome 20S est suivie durant la période de stockage. L'impact du stress oxydant sur cette activité a été évalué en utilisant des protéines exogènes oxydées in vitro. Le potentiel rôle défensif de la microvesiculation a également été étudié par la quantification des protéines carbonylées éliminées. Dans ce travail, nous avons observé que différents groupes de protéines sont affectés par l'oxydation réversible ou irréversible de leurs cystéines. De plus, une diminution de la carbonylation en début de stockage dans les extraits solubles et une augmentation de la carbonylation après 4 semaines dans les extraits membranaires ont été montrées. Les fonctions moléculaires engagées par les protéines altérées montrent que les défenses antioxydantes sont oxydées de façon réversible sur leurs résidus cystéines, mais sont également irréversiblement carbonylées. Pendant ce temps, l'activité protéolytique du protéasome 20S décroit de 40 % en fin de stockage. L'incubation d'extraits de GR en début de stockage avec des protéines oxydées exogènes montre un effet inhibiteur « dose-dépendant » et « protéine-dépendant ». Enfin, les microvésicules s'avèrent éliminer des quantités croissantes de protéines carbonylées. La synthèse de ces résultats permet de modéliser une voie oxydative du stockage des GRs, à partir de laquelle de futures recherches seront menées avec pour but l'amélioration des conditions de stockage.
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We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre(®) YeastOne? test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.
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Rats chronically cannulated in the carotid artery and the muscular branch of the femoral vein were subjected to a cold (4 °C) environment for up to 2 h. The changes in blood flow (measured with 46Sc microspheres) and arterio-venous differences in the concentrations of glucose, lactate, triacylglycerols and amino acids allowed the estimation of substrate (and energy) balances across the hindleg. Mean glucose uptake was 0.28mmol min21, mean lactate release was 0.33mmol min21 and the free fatty acid basal release of 0.31mmol min21 was practically zero upon exposure to the cold; the initial uptake of triacylglycerols gave place to a massive release following exposure. The measurement of PO·, PCO· and pH also allowed the estimation of oxygen, CO2 and bicarbonate balances and respiratory quotient changes across the hindleg. The contribution of amino acids to the energy balance of the hindleg was assumed to be low. These data were used to determine the sources of energy used to maintain muscle shivering with time. Three distinct phases were observed in hindleg substrate utilization. (1) The onset of shivering, with the use of glucose/glycogen and an increase in lactate efflux. Lipid oxidation was practically zero (respiratory quotient near 1), but the uptake of triacylglycerols from the blood remained unchanged. (2) A substrate-energy shift, with drastically decreased use of glucose/glycogen, and of lactate efflux; utilization of triacylglycerol as practically the sole source of energy (respiratory quotient approximately 0.7); decreasing uptake of triacylglycerol and increased tissue lipid mobilization. (3) The onset of a new heat-homeostasis setting for prolonged cold-exposure, with maintenance of muscle energy and heat production based on triacylglycerol utilization and efflux from the hindleg (muscle plus skin and subcutaneous adipose masses) contributing energy to help sustain heat production by the core organs and surrounding brown adipose tissue.
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Desenvolupament d'una aplicació amb Microsoft .NET per a la gestió d'un hospital.
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The purpose of this study was to evaluate the efficacy of a Coulomb Controlled Iontophoresis system (CCI) in the local delivery of corticosteroids for the treatment of uveitis. The therapeutic efficacy of Dexamethasone (Dex) administered by CCI was compared to systemic injection and to topical application with the iontophoresis apparatus in the absence of electrical current. The evaluation was done in the treatment of the endotoxin-induced uveitis (EIU) model, and in the effect on TNF gene expression in the iris/ciliary body as well as in the retina and on TNF levels in aqueous humor and vitreous. Dex was administered either at the time of LPS injection or 5 hours later. For iontophoresis, we used a 1 ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera. The applied electrical current was of 400 microA during four minutes with a total surface charge of 0.4 C cm-2. EIU was evaluated by clinical examination, by counts of intraocular inflammatory cells on histological sections, and by measuring the protein levels in the aqueous humor and in the vitreous. The TNF-alpha gene expression in the iris and ciliary body, and in the retina was evaluated by RT-PCR. The systemic effect of Dex delivered by CCI was evaluated on the level of serum TNF-alpha in EIU. Our results demonstrated that local administration of Dex by CCI inhibited anterior and posterior signs of intraocular inflammation as effectively as systemic administration, with no effect on systemic level of TNF. In the anterior and posterior segments of the eye, the protein exudation. TNF levels and the cellular infiltration were inhibited. The TNF-alpha gene expression was inhibited in the anterior as well as the posterior segment of the eye. No clinical nor histological damage were caused by the CCI apparatus. In conclusion, CCI administration of Dex allows for a therapeutic effect on the posterior as well as the anterior segment of the eye, and may present a viable alternative to systemic administration of glucocorticoids in severe ocular inflammations.
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O 1-metilciclopropeno (1-MCP) é um gás que atua inibindo o sítio de ação do etileno, aumentando o tempo de armazenamento de frutos. O objetivo deste trabalho foi avaliar o efeito deste gás na conservação pós-colheita de kiwi 'Monty', à temperatura ambiente. Ele consistiu na exposição dos frutos a concentrações de 0; 0,5 e 1,0 mg dm-3 de 1-MCP, durante 24 horas, e posterior estocagem a 20 ± 4 ºC, por até 20 dias, com avaliações a cada 4 dias. Avaliaram-se: firmeza, translucidez da polpa, sólidos solúveis (SS), pH, acidez titulável (AT), pectina, % de frutos firmes para transporte e consumo. A translucidez da polpa mostrou-se um parâmetro adequado para monitoramento do amadurecimento, visto que houve correlação com a firmeza. A aplicação de 1-MCP preservou a firmeza e preveniu a translucidez da polpa, prolongando a qualidade para transporte e consumo por 4 e 12 dias, respectivamente, e não teve efeito sobre o pH, SS e pectinas. Nos tratamentos com 1-MCP, ocorreu um aumento inicial na acidez, mas com o passar do tempo, ocorreu diminuição da mesma, da firmeza e aumento dos sólidos solúveis e da translucidez da polpa, caracterizando o amadurecimento dos frutos.
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O presente estudo teve por objetivo avaliar o potencial de armazenagem de goiabas serranas em temperaturas de 23 ºC e 4 ºC. Os frutos foram colhidos em pomar comercial, localizado no município de São Joaquim-SC, e armazenados nas temperaturas de 23 ± 1 ºC (75±5% UR, durante quinze dias) e 4 ± 1 ºC (90±5% UR, durante quatro semanas). Durante o armazenamento, foram feitas avaliações de respiração, produção de etileno, teor de sólidos solúveis (SS), acidez titulável (AT), cor da epiderme (ângulo hue; hº) e ocorrência de escurecimento da polpa, manchas escuras na epiderme e podridões. Durante o armazenamento a 23 ºC, os frutos exibiram um padrão climatérico, com pico respiratório entre o 4º e o 5º dia. Nos frutos armazenados a 4 ºC, houve redução na respiração e na produção de etileno. Em frutos a 23 ºC, foi mais acentuada a redução nos valores de SS, AT e h° da epiderme, e aumento na incidência de manchas escuras na epiderme e de podridões, em relação aos frutos armazenados a 4 ºC. O armazenamento a 4 ºC mostrou-se eficiente na redução do metabolismo respiratório e de produção de etileno, na preservação dos atributos de qualidade (SS, AT e hº da epiderme) e na diminuição da severidade das manchas na epiderme e podridões sem, contudo, evitar o desenvolvimento de escurecimento da polpa. O potencial de armazenagem de goiabas serranas a 23 ºC é inferior a uma semana e limitado principalmente pelo desenvolvimento de distúrbios de escurecimento da polpa, manchas na epiderme, bem como podridões.
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A industrialização de frutas permite que os consumidores usufruam seus benefícios funcionais; porém, na maioria das vezes, o processamento produz resíduos industriais que normalmente não são aproveitados. Desta forma, o bagaço do mirtilo é um subproduto da fermentação que geralmente é desprezado na natureza, originando poluição ambiental. Este trabalho objetivou a caracterização físico-química, a determinação da atividade antioxidante, antocianinas e polifenóis do fruto de mirtilo, bagaço de mirtilo proveniente da produção de bebidas fermentadas e da farinha obtida deste bagaço, bem como as propriedades funcionais tecnológicas e a estabilidade microbiológica destas farinhas. As farinhas do fruto e do bagaço foram obtidas a partir da desidratação em estufa a 60 ºC, por 36 h, e moídos em micromoinho refrigerado a 4 ºC. As características físico-químicas foram verificadas a partir das análises de umidade, proteína, lipídeos, cinzas, acidez, pH e sólidos solúveis. A atividade antioxidante foi determinada pelo método DPPH, e os polifenóis totais, pelo método de Folin-Ciocalteu. Os resultados demonstram que tanto o mirtilo quanto o bagaço possuem elevado conteúdo de água. O mirtilo apresentou 61,67 mg/100 g em antocianinas, 431,43 mg EAG/100 g em polifenóis e 3,83 mg/mL de atividade antioxidante, enquanto o bagaço obteve 57,32 mg/100 g; 297,20 mg EAG/100 g; 5,61 mg/mL, respectivamente. As farinhas apresentaram estabilidade microbiológica durante o armazenamento e propriedades funcionais tecnológicas adequadas, possibilitando a geração de novos produtos. Portanto, o aproveitamento de resíduos industriais de mirtilo fermentado apresenta vantagens de agregar valor e minimizar o impacto no meio ambiente.
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RESUMO O morango é uma fruta de alto valor comercial e tem uma rápida deterioração, como a demanda por produtos saudáveis, seguros sob o ponto de vista microbiológico e livre de produtos químicos aumenta cada vez mais, o método de aplicação do gás ozônio em uma atmosfera controlada foi proposto. O objetivo deste trabalho foi verificar a eficiência do gás ozônio produzido por um reator, a fim de que os pequenos produtores de morangos possam usá-lo, contribuindo, assim, para as economias regionais. Morangos (Fragaria ananassa) variedade Oso Grande, colhidasna região de Minas Gerais foram divididas dois grupos: o primeiro recebeu tratamento com ozônio e o segundo não. No primeiro grupo, o ozônio foi aplicado durante 20 minutos a partir de um reator de Corona. Os frutos foram armazenados a 4 ° C, por períodos de 5, 10 e 15 dias. A qualidade dos frutos foi relata a partir dos níveis de sólidos solúveis totais (SS), acidez titulável (AT ), pH, compostos fenólicos (CF), ácido ascórbico (AA), perda de massa fresca (PM%) e análise microbiológica (AM), em diferentes tempos de armazenamento de frutos ozonizados e não ozonizados. O uso de gás ozônio foi eficiente para a pós-colheita de morango. Os níveis de microrganismos estão dentro dos limites aceitáveis e as propriedades físicas e químicas foram mantidas.
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RESUMO Objetivou-se com este estudo avaliar revestimentos comestíveis à base de goma xantana e glicerol, combinada a cloreto de cálcio, ácido oleico e/ou óleo essencial de hortelã-pimenta na conservação de morangos cv. Festival. Os morangos foram selecionados, lavados, sanitizados e, a seguir, submetidos a diferentes tratamentos de revestimentos à base de goma xantana acrescidos de glicerol, cloreto de cálcio, ácido oleico e/ou óleo essencial de hortelã-pimenta. Os frutos foram secos sob ventilação forçada a 4 ºC, por 15 h, e, posteriormente, embalados em bandejas com tampa de Polietileno Tereftalato (PET) e armazenados a 4 ºC, durante 12 dias. Foram realizadas análises de perda de massa, firmeza, luminosidade, tonalidade, pH, acidez, sólidos solúveis totais, antocianinas e a incidência de deterioração fúngica. Os diferentes revestimentos utilizados foram eficientes na conservação dos morangos. O tratamento com goma xantana e glicerol apresentou os melhores resultados, pois a influência do ácido oleico ou do óleo essencial de hortelãpimenta, assim como do cloreto de cálcio, não foi significativa. O revestimento de goma xantana proporcionou redução da perda de massa, manutenção da firmeza, cor, pH, acidez, sólidos solúveis totais, antocianinas e não estimulou o crescimento fúngico. Desta forma, esta goma apresenta potencial para aplicação como revestimento em morangos, visando a maximizar a vida útil deste produto.
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STUDY OBJECTIVES: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. METHODS: HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. RESULTS: HLA-A*11:01 (OR = 1.49 [1.18-1.87] P = 7.0*10(-4)), C*04:01 (OR = 1.34 [1.10-1.63] P = 3.23*10(-3)), and B*35:01 (OR = 1.46 [1.13-1.89] P = 3.64*10(-3)) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr(9) (OR = 1.32 [1.15-1.52] P = 6.95*10(-5)) and HLA-C-Ser(11) (OR = 1.34 [1.15-1.57] P = 2.43*10(-4)). CONCLUSIONS: Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons.