64 research outputs found
La Jurisprudencia del Tribunal de Justicia de la Unión Europea en materia laboral y social: del concepto de trabajador al ejercicio de derechos de acción colectiva
The Court of Justice of the European Union case law in labour and social affairs, very abundant after almost half a century, has had a great impact in the formation of the systems of labour relations in Europe. Its first steps were focused on the free movement of workers and the principle of equality and non-discrimination on grounds of sex, but over the years it has dealt with many other dimensions of employment and the labour market. The CJEU has decided on issues such as the transfer of undertakings and the most recent grounds of discrimination (age, disability, ideas or personal convictions). Its doctrine is also very relevant in relation to many other aspects of the employment relationship: working time, annual leave, temporary employment, part-time contracts, reconciliation of work and family life, collective dismissal, workers participation, the role of collective agreements in a context of economic freedoms or trade union action, including the right to strike. On the other hand, the concept of worker has been very present in all this case law. The Court has always sought to combine the powers of the Member States in order to identify the personal scope of Labour law with the search for common criteria contributing to the harmonization of national systems and the effectiveness of EU LawLa jurisprudencia del Tribunal de Justicia de la Unión Europea en materia laboral y social, muy abundante tras casi medio siglo de rodaje, ha tenido gran influencia en la conformación de los sistemas de relaciones de trabajo en el espacio europeo. Sus primeros pasos se dedicaron a la libre circulación de trabajadores y al principio de igualdad y no discriminación por razón de sexo, pero con el transcurso de los años ha llegado a ocuparse de otras muchas dimensiones del empleo y del mercado de trabajo, desde la transmisión de empresa hasta las más recientes líneas de frontera de la no discriminación (edad, discapacidad, ideas o convicciones personales), pasando por la ordenación del tiempo de trabajo, las vacaciones anuales, la contratación temporal, los contratos a tiempo parcial, la conciliación de la vida laboral y familiar, el despido colectivo, la participación de los trabajadores en la empresa, el papel de los convenios colectivos en un contexto de libertades económicas o el ejercicio de acciones de huelga o conflicto colectivo. El concepto de trabajador, por otra parte, ha estado muy presente en toda la labor jurisdiccional e interpretativa de dicho Tribunal, que ha tratado siempre de combinar la competencia que aún mantienen los Estados miembros para identificar el ámbito subjetivo del ordenamiento laboral con la búsqueda de criterios comunes que contribuyan a la armonización de los sistemas nacionales y a la efectividad de las normas comunitaria
Case report: Self-administration of alpha-1 antitrypsin therapy: a report of two cases
Intravenous augmentation therapy with human alpha-1 proteinase inhibitor for the management of respiratory disease is recommended for people with alpha-1 antitrypsin deficiency (AATD) who are nonsmokers or former smokers. Augmentation therapy usually requires weekly administration at the hospital or clinic and poses an additional burden for patients due to interference with daily life, including work and social activities. Self-administration is a useful alternative to overcome this limitation, but there is a lack of published information on clinical outcomes. We report two cases of individuals with AATD at different stages of the disease who were successfully managed with self-administered augmentation therapy, with increased satisfaction because of the independence gained, lack of interference with clinical stability, and no relevant safety issues
Root infection of canker pathogens, Fusarium circinatum and Diplodia sapinea, in asymptomatic trees in Pinus radiata and Pinus pinaster plantations
[EN] The existence of a latent stage within host tissue of the pine pathogens Fusarium circinatum and Diplodia sapinea, the causal agents of pitch canker and shoot blight disease respectively, has previously been cited. However, studies on this cryptic phase in each disease lifecycle has only been focused on the host aerial parts but not on the roots. Therefore, our objective was to analyze the presence of both pathogens in roots of non-symptomatic mature trees in plantations where the pathogens are known to be causing canker symptoms. For that, we sampled roots from ten non-symptomatic and ten symptomatic trees in three Pinus radiata and one Pinus pinaster plantations in Basque Country, Spain. Both pathogens were isolated from roots of non-symptomatic trees in a higher frequency than from roots of symptomatic trees, 23.3% and 6.6% respectively for D. sapinea and 16.6% and 3.3% respectively for F. circinatum. Neither pathogens was detected in the P. pinaster plantation. The two pathogens were never isolated from the same tree. A high molecular variability was observed for D. sapinea isolates with six different haplotypes and two mating types for the eleven characterized isolates, but only one haplotype and mating type was found for F. circinatum, with all isolates of both fungi being proved pathogenic. These results evidence the importance root infection may have in the disease lifecycle and, therefore, disease management.We acknowledge Maria Teresa Morales Clemente for her excellent technical assistance. Laura Hernandez-Escribano was supported by a fellowship from INIA (FPI-INIA). Financial support for this research was provided by project RTA2013-00048-C03-01, RTA2017-00063-C04-01 and C04-03 (National Progamme I + D + I, INIA, Spain) and the Project Healthy Forest LIFE14 ENV/ES/000179. This article is-based upon work from COST Action FP1406, Pine pitch canker-strategies for management of Gibberella circinata in greenhouses and forests (PINESTRENGTH), supported by COST (European Cooperation in Science and Technology).Hernandez-Escribano, L.; Iturritxa, E.; Aragonés, A.; Mesanza, N.; Berbegal Martinez, M.; Raposo, R.; Elvira-Recuenco, M. (2018). Root infection of canker pathogens, Fusarium circinatum and Diplodia sapinea, in asymptomatic trees in Pinus radiata and Pinus pinaster plantations. Forests. 9(3):1-15. https://doi.org/10.3390/f9030128S11593Nirenberg, H. I., & O’Donnell, K. (1998). New Fusarium Species and Combinations within the Gibberella fujikuroi Species Complex. Mycologia, 90(3), 434. doi:10.2307/3761403Phillips, A. J. L., Alves, A., Abdollahzadeh, J., Slippers, B., Wingfield, M. J., Groenewald, J. Z., & Crous, P. W. (2013). The Botryosphaeriaceae: genera and species known from culture. Studies in Mycology, 76, 51-167. doi:10.3114/sim0021Wingfield, M. J., Hammerbacher, A., Ganley, R. J., Steenkamp, E. T., Gordon, T. R., Wingfield, B. D., & Coutinho, T. A. (2008). Pitch canker caused byFusarium circinatum– a growing threat to pine plantations and forests worldwide. Australasian Plant Pathology, 37(4), 319. doi:10.1071/ap08036Burgess, T. I., Wingfield, M. J., & Wingfield, B. D. (2004). Global distribution ofDiplodia pineagenotypes revealed using simple sequence repeat (SSR) markers. Australasian Plant Pathology, 33(4), 513. doi:10.1071/ap04067Bihon, W., Wingfield, M. J., Slippers, B., Duong, T. A., & Wingfield, B. D. (2014). MAT gene idiomorphs suggest a heterothallic sexual cycle in a predominantly asexual and important pine pathogen. Fungal Genetics and Biology, 62, 55-61. doi:10.1016/j.fgb.2013.10.013Swart, W. J. (1991). Biology and Control ofSphaeropsis sapineaonPinusSpecies in South Africa. Plant Disease, 75(8), 761. doi:10.1094/pd-75-0761Blodgett, J. T., Kruger, E. L., & Stanosz, G. R. (1997). 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First Report of Pitch Canker Caused by Fusarium circinatum on Pinus halepensis and P. pinea in Apulia (Southern Italy). Plant Disease, 91(12), 1683-1683. doi:10.1094/pdis-91-12-1683cBihon, W., Slippers, B., Burgess, T., Wingfield, M. J., & Wingfield, B. D. (2012). Diverse sources of infection and cryptic recombination revealed in South African Diplodia pinea populations. Fungal Biology, 116(1), 112-120. doi:10.1016/j.funbio.2011.10.006KAY, S. J., AH CHEE, A., SALE, P. O., TAYLOR, J. T., HADAR, E., HADAR, Y., & FARRELL, R. L. (2002). Variation among New Zealand isolates of Sphaeropsis sapinea. Forest Pathology, 32(2), 109-121. doi:10.1046/j.1439-0329.2002.00273.xSmith, H., Wingfield, M. J., de Wet, J., & Coutinho, T. A. (2000). Genotypic Diversity of Sphaeropsis sapinea from South Africa and Northern Sumatra. Plant Disease, 84(2), 139-142. doi:10.1094/pdis.2000.84.2.139Zwolinski, J. B., Swart, W. J., & Wingfield, M. J. (1990). 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(2007). Ips pini (Curculionidae: Scolytinae) Is a Vector of the Fungal Pathogen, Sphaeropsis sapinea (Coelomycetes), to Austrian Pines, Pinus nigra (Pinaceae). Environmental Entomology, 36(1), 114-120. doi:10.1603/0046-225x(2007)36[114:ipcsia]2.0.co;2Stanosz, G. R., Swart, W. J., & Smith, D. R. (1999). RAPD marker and isozyme characterization of Sphaeropsis sapinea from diverse coniferous hosts and locations. Mycological Research, 103(9), 1193-1202. doi:10.1017/s0953756299008382Palmer, M. A. (1985). Shoot Blight and Collar Rot ofPinus resinosaCaused bySphaeropsis sapineain Forest Tree Nurseries. Plant Disease, 69(9), 739. doi:10.1094/pd-69-739Stanosz, G. R., Smith, D. R., & Leisso, R. (2007). Diplodia shoot blight and asymptomatic persistence of Diplodia pinea on or in stems of jack pine nursery seedlings. Forest Pathology, 37(3), 145-154. doi:10.1111/j.1439-0329.2007.00487.xFlowers, J., Nuckles, E., Hartman, J., & Vaillancourt, L. (2001). Latent Infection of Austrian and Scots Pine Tissues by Sphaeropsis sapinea. Plant Disease, 85(10), 1107-1112. doi:10.1094/pdis.2001.85.10.1107Flowers, J., Hartman, J., & Vaillancourt, L. (2003). Detection of Latent Sphaeropsis sapinea Infections in Austrian Pine Tissues Using Nested-Polymerase Chain Reaction. Phytopathology®, 93(12), 1471-1477. doi:10.1094/phyto.2003.93.12.1471Smith, H., Wingfied, M. ., & Coutinho, T. . (2002). The role of latent Sphaeropsis sapinea infections in post-hail associated die-back of Pinus patula. Forest Ecology and Management, 164(1-3), 177-184. doi:10.1016/s0378-1127(01)00610-7Vujanovic, V., St-Arnaud, M., & Neumann, P.-J. (2000). Susceptibility of cones and seeds to fungal infection in a pine (Pinus spp.) collection. Forest Pathology, 30(6), 305-320. doi:10.1046/j.1439-0329.2000.00211.xBihon, W., Slippers, B., Burgess, T., Wingfield, M. J., & Wingfield, B. D. (2010). Sources of Diplodia pinea endophytic infections in Pinus patula and P. radiata seedlings in South Africa. Forest Pathology, 41(5), 370-375. doi:10.1111/j.1439-0329.2010.00691.xFABRE, B., PIOU, D., DESPREZ-LOUSTAU, M.-L., & MARÇAIS, B. (2011). Can the emergence of pine Diplodia shoot blight in France be explained by changes in pathogen pressure linked to climate change? Global Change Biology, 17(10), 3218-3227. doi:10.1111/j.1365-2486.2011.02428.xSwett, C. L., Kirkpatrick, S. C., & Gordon, T. R. (2016). Evidence for a Hemibiotrophic Association of the Pitch Canker Pathogen Fusarium circinatum with Pinus radiata. Plant Disease, 100(1), 79-84. doi:10.1094/pdis-03-15-0270-reMartín-Rodrigues, N., Sanchez-Zabala, J., Salcedo, I., Majada, J., González-Murua, C., & Duñabeitia, M. K. (2015). New insights into radiata pine seedling root infection byFusarium circinatum. Plant Pathology, 64(6), 1336-1348. doi:10.1111/ppa.12376Swett, C. L., & Gordon, T. R. (2016). Exposure to a pine pathogen enhances growth and disease resistance inPinus radiataseedlings. Forest Pathology, 47(1), e12298. doi:10.1111/efp.12298Stanosz, G. R., Blodgett, J. T., Smith, D. R., & Kruger, E. L. (2001). Water stress and Sphaeropsis
sapinea
as a latent pathogen of red pine seedlings. New Phytologist, 149(3), 531-538. doi:10.1046/j.1469-8137.2001.00052.xBihon, W., Burgess, T., Slippers, B., Wingfield, M. J., & Wingfield, B. D. (2011). Distribution of Diplodia pinea and its genotypic diversity within asymptomatic Pinus patula trees. Australasian Plant Pathology, 40(5), 540-548. doi:10.1007/s13313-011-0060-zAegerter, B. J., & Gordon, T. R. (2006). Rates of pitch canker induced seedling mortality among Pinus radiata families varying in levels of genetic resistance to Gibberella circinata (anamorph Fusarium circinatum). Forest Ecology and Management, 235(1-3), 14-17. doi:10.1016/j.foreco.2006.07.011Nirenberg, H. I. (1981). A simplified method for identifying Fusarium spp. occurring on wheat. Canadian Journal of Botany, 59(9), 1599-1609. doi:10.1139/b81-217Slippers, B., Crous, P. W., Denman, S., Coutinho, T. A., Wingfield, B. D., & Wingfield, M. J. (2004). Combined multiple gene genealogies and phenotypic characters differentiate several species previously identified asBotryosphaeria dothidea. Mycologia, 96(1), 83-101. doi:10.1080/15572536.2005.11833000Alves, A., Linaldeddu, B. T., Deidda, A., Scanu, B., & Phillips, A. J. L. (2014). The complex of Diplodia species associated with Fraxinus and some other woody hosts in Italy and Portugal. Fungal Diversity, 67(1), 143-156. doi:10.1007/s13225-014-0282-9Hyde, K. D., Nilsson, R. H., Alias, S. A., Ariyawansa, H. A., Blair, J. E., Cai, L., … Zhou, N. (2014). One stop shop: backbones trees for important phytopathogenic genera: I (2014). Fungal Diversity, 67(1), 21-125. doi:10.1007/s13225-014-0298-1Dissanayake, A. (2016). Botryosphaeriaceae: Current status of genera and species. Mycosphere, 7(7), 1001-1073. doi:10.5943/mycosphere/si/1b/13Linaldeddu, B. (2016). Botryosphaeriaceae species associated with lentisk dieback in Italy and description of Diplodia insularis sp. nov. Mycosphere, 7(7), 962-977. doi:10.5943/mycosphere/si/1b/8Ariyawansa, H. A., Hyde, K. D., Jayasiri, S. C., Buyck, B., Chethana, K. W. T., Dai, D. Q., … Lücking, R. (2015). Fungal diversity notes 111–252—taxonomic and phylogenetic contributions to fungal taxa. Fungal Diversity, 75(1), 27-274. doi:10.1007/s13225-015-0346-5Úrbez-Torres, J. R., Castro-Medina, F., Mohali, S. R., & Gubler, W. D. (2016). Botryosphaeriaceae Species Associated With Cankers and Dieback Symptoms of Acacia mangium and Pinus caribaea var. hondurensis in Venezuela. Plant Disease, 100(12), 2455-2464. doi:10.1094/pdis-05-16-0612-reSmith, D. R., & Stanosz, G. R. (2006). A Species-Specific PCR Assay for Detection of Diplodia pinea and D. scrobiculata in Dead Red and Jack Pines with Collar Rot Symptoms. Plant Disease, 90(3), 307-313. doi:10.1094/pd-90-0307Schweigkofler, W., O’Donnell, K., & Garbelotto, M. (2004). Detection and Quantification of Airborne Conidia of Fusarium circinatum, the Causal Agent of Pine Pitch Canker, from Two California Sites by Using a Real-Time PCR Approach Combined with a Simple Spore Trapping Method. Applied and Environmental Microbiology, 70(6), 3512-3520. doi:10.1128/aem.70.6.3512-3520.2004Wallace, M. M., & Covert, S. F. (2000). Molecular Mating Type Assay forFusarium circinatum. Applied and Environmental Microbiology, 66(12), 5506-5508. doi:10.1128/aem.66.12.5506-5508.2000Berbegal, M., Pérez-Sierra, A., Armengol, J., & Grünwald, N. J. (2013). Evidence for Multiple Introductions and Clonality in Spanish Populations of Fusarium circinatum. Phytopathology®, 103(8), 851-861. doi:10.1094/phyto-11-12-0281-rIturritxa, E., Ganley, R. J., Wright, J., Heppe, E., Steenkamp, E. T., Gordon, T. R., & Wingfield, M. J. (2011). A genetically homogenous population of Fusarium circinatum causes pitch canker of Pinus radiata in the Basque Country, Spain. Fungal Biology, 115(3), 288-295. doi:10.1016/j.funbio.2010.12.014Elvira-Recuenco, M., Iturritxa, E., Majada, J., Alia, R., & Raposo, R. (2014). Adaptive Potential of Maritime Pine (Pinus pinaster) Populations to the Emerging Pitch Canker Pathogen, Fusarium circinatum. PLoS ONE, 9(12), e114971. doi:10.1371/journal.pone.0114971Garbelotto, M., Smith, T., & Schweigkofler, W. (2008). Variation in Rates of Spore Deposition of Fusarium circinatum, the Causal Agent of Pine Pitch Canker, Over a 12-Month-Period at Two Locations in Northern California. Phytopathology®, 98(1), 137-143. doi:10.1094/phyto-98-1-0137Serra-Varela, M. J., Alía, R., Pórtoles, J., Gonzalo, J., Soliño, M., Grivet, D., & Raposo, R. (2017). Incorporating exposure to pitch canker disease to support management decisions of Pinus pinaster Ait. in the face of climate change. PLOS ONE, 12(2), e0171549. doi:10.1371/journal.pone.0171549Hernandez-Escribano, L., Iturritxa, E., Elvira-Recuenco, M., Berbegal, M., Campos, J. A., Renobales, G., … Raposo, R. (2018). Herbaceous plants in the understory of a pitch canker-affected Pinus radiata plantation are endophytically infected with Fusarium circinatum. Fungal Ecology, 32, 65-71. doi:10.1016/j.funeco.2017.12.001Smith, H., Wingfield, M. J., Coutinho, T. A., & Crous, P. W. (1996). Sphaeropsis sapinea and Botryosphaeria dothidea endophytic in Pinus spp. and Eucalyptus spp. in South Africa. South African Journal of Botany, 62(2), 86-88. doi:10.1016/s0254-6299(15)30596-2Santini, A., Pepori, A., Ghelardini, L., & Capretti, P. (2008). Persistence of some pine pathogens in coarse woody debris and cones in a Pinus pinea forest. Forest Ecology and Management, 256(3), 502-506. doi:10.1016/j.foreco.2008.05.010Oblinger, B. W., Smith, D. R., & Stanosz, G. R. (2011). Red pine harvest debris as a potential source of inoculum of Diplodia shoot blight pathogens. Forest Ecology and Management, 262(4), 663-670. doi:10.1016/j.foreco.2011.04.038Eyles, A., Bonello, P., Ganley, R., & Mohammed, C. (2009). Induced resistance to pests and pathogens in trees. New Phytologist, 185(4), 893-908. doi:10.1111/j.1469-8137.2009.03127.xJunker, C., Draeger, S., & Schulz, B. (2012). A fine line – endophytes or pathogens in Arabidopsis thaliana. Fungal Ecology, 5(6), 657-662. doi:10.1016/j.funeco.2012.05.002Flowers, J. L., Hartman, J. R., & Vaillancourt, L. J. (2006). Histology of Diplodia pinea in diseased and latently infected Pinus nigra shoots. Forest Pathology, 36(6), 447-459. doi:10.1111/j.1439-0329.2006.00473.
Analysis of the average ultrafiltration rate per session of patients in a hemodialysis unit
Introduction: In haemodialysis (HD) patients, the wrong adjustment of the ideal weight can lead to fluid overload, which can cause episodes of heart failure or, conversely, to a low weight situation, generating hypotension that triggers ischemic heart disease. A maximum ultrafiltration (UF) of 10 ml/kg/hr is considered adequate. A higher value is associated with an increase in mortality. Objectives: To analyse the average ultrafiltration rate used in the study centre, and to know what percentage of patients exceeded the maximum recommended ultrafiltration. Material and Method: An observational, prospective study in 58 haemodialysis patients was carried out, analysing the ultrafiltration rate expressed in ml/kg/hr per session for 6 months. A UF rate>10 ml/kg/hr was defined as the cut-off point, according to the current criteria of adequate rate, to determine which patients had a UF greater than 10 ml/kg/hr in more than 25% of the sessions. Results: During the study period, the average UF rate of all patients was 8.78±2.76 ml/kg/hr, although the percentage of sessions per patient with a UF rate greater than 10 ml/kg/hr was 35.9±29.74%. Conclusion: A high percentage of patients present UF rates above the recommended values. Strategies to decrease values must be sought, with health education on diet and individualized adjustment of dialysis sessions being fundamental aspects.Introducción: En los pacientes en hemodiálisis (HD), el ajuste erróneo del peso ideal puede llevarlos a la sobrecarga de líquido que puede desembocar en episodios de insuficiencia cardiaca o a la inversa, a una situación de bajo peso generando hipotensiones que pueden originar cardiopatía isquémica. Se estima como adecuada una ultrafiltración (UF) máxima de 10 mililitro/kilogramo/hora, valor por encima del cual está demostrado el aumento de la mortalidad. Objetivos: Analizar que tasa de ultrafiltración media usamos en nuestra unidad, y conocer qué porcentaje de pacientes sobrepasaban la ultrafiltración máxima recomendada. Material y Método: Realizamos un estudio observacional, prospectivo, en 58 pacientes en hemodiálisis, analizando la tasa de ultrafiltración expresada en ml/kg/hora por sesión durante 6 meses. Se definió una tasa de UF>10 mililitro/kilogramo/hora como punto de corte para, según los criterios actuales de tasa adecuada, deCorrespondencia: Mónica Pereira García. Email: [email protected] terminar que pacientes presentaban una UF superior a 10 ml/Kg/h en más de un 25% de las sesiones. Resultados: Durante el periodo de estudio la tasa media de UF de todos los pacientes fue de 8,78±2,76 ml/kg/h, aunque el porcentaje de sesiones por paciente con tasa de UF superior a 10 ml/kg/h fue de un 35,9±29,74%. Conclusión: Un porcentaje alto de pacientes presentan tasas de UF por encima de los valores recomendados. Se han de buscar estrategias para minimizar esta situación, donde la educación sanitaria sobre alimentación y el ajuste individualizado de las sesiones de diálisis son aspectos fundamentale
Servicio de evaluación y diagnóstico en educación como apoyo a las prácticas de las asignaturas que exigen evaluación y diagnóstico
Depto. de Investigación y Psicología en EducaciónFac. de EducaciónFALSEsubmitte
A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility
Introduction:
A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p>
Methods:
Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays.
Results:
We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p>
Conclusion:
Our results suggest a role of PPARG gene in the development of SSc
The complex HLA-E-nonapeptide in Behçet disease
Introduction: The knowledge of the aetiology of Behçet disease (BD), an immune-mediated vasculitis, is limited. HLA-B, mainly HLA-B51, and HLA-A molecules are associated with disease, but the ultimate cause of this association remains obscure. There is evidence that NK cells participate in the etiopathology of BD. NK cells have activator and inhibitor surface receptors, like the KIR and the NKG2 families. Classical HLA-class I molecules (A, B and C) are keys in the activity control of the NK because they are KIR ligands. Most NKG2 receptors bind HLA-E, which presents only nonapeptides derived from the signal peptide of other class-I molecules.
Objective: This study investigates the contribution of the pair HLA-E and ligand, nonapeptide derived from the 3-11 sequence of the signal peptides of class I classical molecules, to the susceptibility to BD.
Methods: We analyzed the frequency of the HLA-derivated nonapeptide forms in 466 BD patients and 444 controls and an HLA-E functional dimorphism in a subgroup of patients and controls. Results: In B51 negative patients, the frequency of VMAPRTLLL was lower (70.4% versus 80.0% in controls; P=0.006, Pc=0.04, OR=0.60, 95%CI 0.41-0.86), and the frequency of VMAPRTLVL was higher (81.6% versus 71.4% in controls; P=0.004, Pc=0.03, OR=1.78, 95%CI 1.20-2.63). In homozygosity, VMAPRTLLL is protective, and VMAPRTLVL confers risk. The heterozygous condition is neutral. There were no significant differences in the distribution of the HLA-E dimorphism.
Discussion: Our results explain the association of BD with diverse HLA-A molecules, reinforce the hypothesis of the involvement of the NK cells in the disease and do not suggest a significant contribution of the HLA-E polymorphism to disease susceptibility
Association of Functional Polymorphisms of KIR3DL1/DS1 With Behçet's Disease
Behçet's disease (BD) is an immune-mediated vasculitis related to imbalances between the innate and adaptive immune response. Infectious agents or environmental factors may trigger the disease in genetically predisposed individuals. HLA-B51 is the genetic factor stronger associated with the disease, although the bases of this association remain elusive. NK cells have also been implicated in the etiopathogenesis of BD. A family of NK receptors, Killer-cell Immunoglobulin-like Receptor (KIR), with a very complex organization, is very important in the education and control of the NK cells by the union to their ligands, most of them, HLA class I molecules. This study aimed to investigate the contribution of certain KIR functional polymorphisms to the susceptibility to BD. A total of 466 BD patients and 444 healthy individuals were genotyped in HLA class I (A, B, and C). The set of KIR genes and the functional variants of KIR3DL1/DS1 and KIR2DS4 were also determined. Frequency of KIR3DL1004 was lower in patients than in controls (0.15 vs. 0.20, P = 0.005, Pc = 0.015; OR = 0.70; 95% CI 0.54-0.90) in both B51 positive and negative individuals. KIR3DL1004, which encodes a misfolded protein, is included in a common telomeric haplotype with only one functional KIR gene, KIR3DL2. Both, KIR3DL1 and KIR3DL2 sense pathogen-associated molecular patterns but they have different capacities to eliminate them. The education of the NK cells depending on the HLA, the balance of KIR3DL1/KIR3DL2 licensed NK cells and the different capacities of these receptors to eliminate pathogens could be involved in the etiopathogenesis of BD
Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus
Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci
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