PlA2 Polymorphism of Platelet Glycoprotein IIb/IIIa and C677T Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR), but Not Factor V Leiden and Prothrombin G20210A Polymorphisms, Are Associated with More Severe Forms of Legg-Calvé-Perthes Disease

The possible association of common polymorphic variants related to thrombophilia (the rs6025(A) allele encoding the Leiden mutation, rs1799963(A), i.e., the G20210A mutation of the prothrombin F2 gene, the rs1801133(T) variant of the methylenetetrahydrofolate reductase (MTHFR) gene that encodes an enzyme involved in folate metabolism, and rs5918(C), i.e., the "A2" allele of the platelet-specific alloantigen system that increases platelet aggregation induced by agonists), with the risk of Legg-Calvé-Perthes disease (LCPD) and the degree of hip involvement (Catterall stages I to IV) was analyzed in a cohort study, including 41 children of ages 2 to 10.9 (mean 5.4, SD 2.2), on the basis of clinical and radiological criteria of LCPD. In 10 of the cases, hip involvement was bilateral; thus, a total of 51 hips were followed-up for a mean of 75.5 months. The distribution of genotypes among patients and 118 controls showed no significant differences, with a slightly increased risk for LCPD in rs6025(A) carriers (OR: 2.9, CI: 0.2-47.8). Regarding the severity of LCPD based on Catterall classification, the rs1801133(T) variant of the MTHFR gene and the rs5918(C) variant of the platelet glycoprotein IIb/IIIa were associated with more severe forms of Perthes disease (Catterall III-IV) (p < 0.05). The four children homozygous for mutated MTHFR had a severe form of the disease (Stage IV of Catterall) and a higher risk of non-favorable outcome (Stulberg IV-V).This research was funded by a grant from the Spanish government, 2002–2005, grant number FIS (00/0015) and University of Cantabria code 06.3842.64001 and The APC was funded by University of Cantabria-IDIVAL

Efecto de paricalcitol sobre el metabolismo mineralóseo en pacientes trasplantados renales con hiperparatiroidismo secundario

ResumenIntroducciónEl hiperparatiroidismo secundario es muy prevalente en pacientes trasplantados renales. Cursa con frecuencia con hipercalcemia y se ha asociado al desarrollo de osteopenia y fracturas óseas. El paricalcitol ha mostrado su eficacia en el control del hiperparatiroidismo secundario en la enfermedad renal crónica con y sin diálisis, con una baja incidencia de hipercalcemia. La experiencia con paricalcitol en trasplantados renales es muy escasa. El objetivo de este trabajo fue mostrar el efecto sobre el metabolismo mineralóseo del paricalcitol en trasplantados renales con hiperparatiroidismo secundario.Material y métodosEstudio retrospectivo multicéntrico con trasplantados renales de más de 18 años de edad y más de 12 meses de evolución postrasplante, con función renal estable, que hayan sido tratados con paricalcitol durante más de 12 meses, con seguimiento clínico hasta los 24 meses de tratamiento.ResultadosSe incluyó a 69 pacientes, con 120±92 meses postrasplante, con creatinina inicial de 2,2±0,9mg/dl y FG-MDRD 36±20ml/min/1,73 m2. La dosis de paricalcitol se incrementó progresivamente durante el estudio: basal 3,8±1,9μg/semana, 12 meses 5,2±2,4μg/semana; 24 meses 6,0±2,9μg/semana (p<0,001). Los niveles séricos de PTH descendieron de forma rápida y significativa: basal 288±152 pg/ml; 6 meses 226±184 pg/ml; 12 meses 207±120; 24 meses 193±119 pg/ml (p<0,001). Observamos una reducción sobre PTH basal ≥30% en el 42,4% de los pacientes a los 12 meses y en el 65,2% de los pacientes a los 24 meses. La fosfatasa alcalina descendió también significativamente en los 6 primeros meses para luego estabilizarse: basal 92±50 UI/l; 6 meses 85±36 UI/l, 12 meses 81±39 UI/l (p<0,001). Globalmente no hubo modificaciones en el calcio o fósforo séricos ni en la excreción urinaria de calcio. La reducción de PTH fue más importante en trasplantados con niveles séricos más elevados de partida. Observamos que los pacientes con calcio basal más bajo mostraron un incremento significativo de sus cifras de 0,5-0,6mg/dl en promedio aunque manteniéndose en rango de normalidad, mientras que pacientes con calcio basal>10mg/dl mostraron una reducción progresiva de sus cifras. Quince (21,7%) pacientes seguían tratamiento previo con calcitriol y al cambiarlos a paricalcitol precisaron dosis significativamente mayores que los pacientes que no habían recibido calcitriol. El paricalcitol fue asociado a cinacalcet en 11 pacientes, con reducciones significativas de PTH, con evolución similar al resto de la población y con dosis de paricalcitol también similares.ConclusionesParicalcitol es eficaz en el tratamiento del hiperparatiroidismo secundario de trasplantados renales. Globalmente no observamos modificaciones significativas de los niveles de calcio ni de fósforo, ni en su excreción urinaria. Los pacientes en tratamiento previo con calcitriol precisaron dosis mayores de paricalcitol. Cuando el paricalcitol se administra a pacientes tratados con cinacalcet, se observa un descenso significativo de la PTH con dosis de paricalcitol similar a pacientes sin cinacalcet.AbstractIntroductionSecondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism.Material and methodsA retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period.ResultsA total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2±0.9mg/dl y GFR-MDRD was 36±20ml/min/1.73m2. Paricalcitol doses were gradually increased during the study: baseline 3.8±1.9μg/week, 12 months 5.2±2.4μg/week; 24 months 6.0±2.9μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288±152 pg/ml; 6 months 226±184 pg/ml; 12 months 207±120; 24 months 193±119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92±50 IU/l; 6 months 85±36 IU/l, 12 months 81±39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar.ConclusionsParicalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet

Bacterial antigen translocation and age as BMI-independent contributing factors on systemic inflammation in NAFLD patients

Background & Aims Low‐grade systemic inflammation is a crucial landmark in NAFLD favouring disease progression and comorbidities. We evaluated the input of circulating bacterial antigens on systemic markers of inflammation in NAFLD patients. Patients & Methods Multicenter cross‐sectional study including consecutive patients with biopsy‐proven NAFLD. Demographic, metabolic and fibrosis‐related variables were collected. Circulating bacterial antigens were quantified in blood. Toll‐like receptor SNPs were genotyped. Serum cytokine levels were evaluated. Peripheral blood mononuclear cell response to bacterial antigens was evaluated in vitro. Results Three hundred and fifteen patients from five Spanish hospitals were distributed by BMI. At least, one bacterial antigenic type was found in 66 patients with BMI 30 (77.3%) (P = .014). HOMA‐IR was significantly higher in the presence of circulating antigens among patients with BMI < 30. NASH and significant fibrosis in non‐obese patients were more frequent in the presence of at least two circulating antigenic types. Allelic frequencies of TLR variants were similar to controls and did not affect clinical or laboratory parameters. Pro‐inflammatory cytokines were significantly increased in patients with bacterial antigens, regardless of BMI. TLR gene and protein expression levels were significantly increased in PBMCs from patients with bacterial antigens. Antigen concentrations independently influenced TNF‐α and IL‐6, in both BMI subgroups of patients. Age independently influenced TNF‐α and IL‐6 in non‐obese patients, and TNF‐α in obese patients. Conclusion Serum circulating bacterial antigens as well as age were BMI‐independent factors related to increased systemic inflammation in NAFLD and provides insight on the multifaceted sources of inflammation in these patients.This work has been funded by grants PI16/0967 and PI17/0535 from Instituto de Salud Carlos III, Madrid, Spain, and PROMETEO 2016/001 from Generalitat Valenciana, Valencia, Spain. IGH was recipient of a Young Investigator Grant by CIBERehd, Instituto de Salud Carlos III, Madrid, Spain

Climatology, bioclimatology and vegetation cover: tools to mitigate climate change in olive groves

This work establishes the relationship between bioclimatology and agronomy. Bioclimatic indices are obtained for several areas under olive cultivation and correlated with olive yields. Due to the effect of climate change on cultivation and the high economic losses it produces, we propose a sustainable development model for the territorial classification of crops based on bioclimatic knowledge. Bioclimatic diagrams are prepared to provide information on water stress in crops so that irrigation can be carried out at the most effective time, a measure that has been shown to lead to water and energy savings for growers. In addition to this development model, we propose the application of non-aggressive cultivation techniques such as the use of living plant cover to ensure the protection of the soil and avoid losses due to climate irregularities. Studies conducted up to the present on applied bioclimatology have yielded promising results in the fields of farming and forestry. The maps and bioclimatic indices of Professor Rivas-Martínez, Ic, Io and It/Itc, are essential for bioclimatic classification. The agricultural development model with a bioclimatic basis ensures economic savings for growers and minimizes the environmental impact of cultivation. In the case of olive cultivation we detected that in 2005 all the cultivated areas that were not in their thermoclimatic optimum were damaged by frost. The widespread cultivation of olive groves in the Mediterranean basin, and mainly in the south of Spain, is reason enough to establish a relationship between its production and its bioclimatic environment. The ombroclimatic study in certain localities under olive cultivation shows that areas with Io Stellarietea mediae constitutes the basis for establishing either natural or sown vegetation cover.info:eu-repo/semantics/publishedVersio

Proyecto para la mejora de la empleabilidad mediante el alineamiento de las competencias de los títulos de la Facultad de Economía y Empresa

Memoria ID-0143. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017

Sinusoidal obstruction syndrome after liver transplantation: A multicenter observational study

Diagnosis of sinusoidal obstruction syndrome (SOS) after hematopoietic cell transplantation (HCT) is based on clinical criteria including weight gain, ascites, hepatomegaly, and jaundice.[1] However, clinical and histological features and prognosis of SOS after liver transplantation (LT) seem to differ from SOS after HCT.[2, 3] We aimed to determine the characteristics and outcomes of SOS after LT

Ingeniería Geológica en Terrenos Volcánicos. Métodos, Técnicas y Experiencias en las Islas Canarias

La presente obra es un compendio de conceptos, metodologías y técnicas útiles para acometer proyectos y obras en terrenos volcánicos desde el punto de vista de la ingeniería geológica y la geotecnia. El libro se presenta en tres partes diferenciadas. La primera es conceptual y metodológica, con capítulos que tratan sobre la clasificación de las rocas volcánicas con fines geotécnicos, la caracterización geomecánica, los problemas geotécnicos y constructivos asociados a los distintos materiales, y una guía metodológica para la redacción de informes geotécnicos para la edificación. La segunda parte aborda las aplicaciones a obras de ingeniería, incluyendo deslizamientos, obras subterráneas,infraestructuras marítimas y obras públicas. La tercera parte recoge capítulos dedicados a describir distintos casos prácticos de obras y proyectos en los que la problemática geotécnica en terrenos volcánicos ha tenido un papel relevante. Los capítulos han sido elaborados por técnicos y científicos de reconocido prestigio en el campo de la ingeniería geológica en terrenos volcánicos, que han plasmado en ellos sus conocimientos y experiencias en la materia.Los editores y autores de parte de los capítulos del libro, los Doctores Luis E. Hernández Gutiérrez (Geólogo) y Juan Carlos Santamarta Cerezal (Ingeniero de Montes, Civil y Minas), son los responsables del grupo de investigación INGENIA (Ingeniería Geológica, Innovación y Aguas). Su actividad investigadora comprende más de 200 publicaciones en el área de la ingeniería geológica, la geotecnia, medio ambiente y el aprovechamiento del agua en islas y terrenos volcánicos. En relación a la docencia han impartido y dirigido más de 90 seminarios y cursos de especialización a nivel nacional e internacional, incluyendo la organización de 4 congresos internacionales. Fueron premiados por la Universidad de La Laguna en los años 2012, 2013 y 2014 por su calidad docente e innovación universitaria, y son pioneros en los laboratorios virtuales para la enseñanza de la ingeniería. Participan activamente como profesores colaboradores e investigadores en varias universidades e instituciones españolas e internacionales. Todas sus publicaciones están disponibles en internet, con libre acceso. Ingeniería geológica en terrenos volcánicos, es una obra de gran interés para, consultores, técnicos de administraciones públicas, proyectistas y demás profesionales implicados en obras y proyectos de infraestructuras en terrenos volcánicos; también es útil para académicos y estudiantes de ingeniería o ciencias geológicas que quieran investigar o iniciarse en las singularidades que presentan los materiales volcánicos en la edificación o en la ingeniería civil y minera

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations

Studies of the mass composition of cosmic rays and proton-proton interaction cross-sections at ultra-high energies with the Pierre Auger Observatory

In this work, we present an estimate of the cosmic-ray mass composition from the distributions of the depth of the shower maximum (Xmax) measured by the fluorescence detector of the Pierre Auger Observatory. We discuss the sensitivity of the mass composition measurements to the uncertainties in the properties of the hadronic interactions, particularly in the predictions of the particle interaction cross-sections. For this purpose, we adjust the fractions of cosmic-ray mass groups to fit the data with Xmax distributions from air shower simulations. We modify the proton-proton cross-sections at ultra-high energies, and the corresponding air shower simulations with rescaled nucleus-air cross-sections are obtained via Glauber theory. We compare the energy-dependent composition of ultra-high-energy cosmic rays obtained for the different extrapolations of the proton-proton cross-sections from low-energy accelerator data