Snowmelt as a determinant factor in the hydrogeological behaviour of high mountain karst aquifers: The Garcés karst system, Central Pyrenees (Spain).

Time series of environmental tracers (groundwater stable isotope composition, electrical conductivity and temperature) and concentration breakthrough curves of artificial tracers (uranine, eosine, amino-G and naphtionate) have been analyzed to characterize fast preferential and slow matrix in-transit recharge flows in the Paleocene-Eocene limestone aquifer of the Ordesa and Monte Perdido National Park, an alpine karst system drained by a water table cave, a rare hydrological feature in high mountain karst systems with similar characteristics. Snowmelt favors the areal recharge of the system. This process is reflected in the large proportion of groundwater flowing through the connected porosity structure of the karst aquifer, which amounts the 75% of the total system water discharge. From the perspective of water resources recovery, the water capacity of the fissured-porous zone (matrix) represents 99% of the total karst system storage. The volume associated to the karst conduits is very small. The estimated mean travel times are 9 days for conduits and 475 days for connected porosity. These short travel times reveal high vulnerability of the karst system to pollutants in broad sense and a great impact of climate change on the associated water resources.

Immunophenotypic Pattern of De Novo Malignancy After Liver Transplantation.

Long-term survival after liver transplantation is affected by de novo neoplasia. The incidence of this type of malignancy is increased in the setting of immunosuppressive therapy. The aim of this study was to characterize the immunologic pattern of liver transplant recipients with de novo malignancies. Fifty-one liver recipients were studied, 19 of whom had a history of de novo neoplasia. Immunophenotypic patterns among patients with/without tumors were compared. The subpopulations of CD4+ T lymphocytes and CD8+ T lymphocytes differed between the 2 types of patients studied. In patients with tumor, activation membrane markers in CD4+ T lymphocytes and CD8+ T-lymphocytes, such as CD56 or CD25, were expressed in a greater proportion, whereas activation markers CD314 and CD16 were reduced in CD56bright natural killer (NK) cells. We concluded that cytotoxic response seems to be more activated in de novo neoplasia patients, which highlights the still unknown malignancy risk effect on these immune cells.

Magnetic resonance imaging abnormalities in children with epilepsy.

BACKGROUND AND PURPOSE: The aim of this study is to analyze the proportional distribution of epilepsy and epileptic syndromes in children and to describe the magnetic resonance imaging (MRI) abnormalities found in these patients. METHODS: Data from 457 children aged 1 month to 15 years at the time of diagnosis of epilepsy were recorded. A routine MRI has been requested in all patients with epilepsy at diagnosis according to a standardized pediatric seizure protocol. Abnormalities on MRI were classified as either significant or non-significant (standardized scoring system). International League Against Epilepsy criteria were used for diagnoses. RESULTS: The prevalence of significant MRI abnormalities was 21.9% (in infants 42.3%, in childhood 18.2%, and in adolescents 15.9%). The most common abnormalities included white-matter lesions (27.6%), volume loss (19.6%), gray-matter lesions (19.6%), and ventricular enlargement (12%). CONCLUSIONS: The use of MRI and a reliable standardized scoring system at diagnosis of epilepsy in children identified a high rate of significant abnormalities findings. This may have important implications for practice guidelines in this population.

Monocyte-derived dendritic cells from HCV-infected patients transduced with an adenovirus expressing NS3 are functional when stimulated with the TLR3 ligand poly(I:C).

Dendritic cells (DC) transfected with an adenovirus encoding hepatitis C virus (HCV) NS3 protein (AdNS3) induce potent antiviral immune responses when used to immunize mice. However, in HCV infected patients, controversial results have been reported regarding the functional properties of monocyte-derived DC (MoDC), a cell population commonly used in DC vaccination protocols. Thus, with the aim of future vaccination studies we decided to characterize MoDC from HCV patients transfected with AdNS3 and stimulated with the TLR3 ligand poly(I:C). Phenotypic and functional properties of these cells were compared with those from MoDC obtained from uninfected individuals. PCR analysis showed that HCV RNA was negative in MoDC from patients after the culture period. Also, phenotypic analysis of these cells showed lower expression of CD80, CD86, and CD40, but similar expression of HLA-DR molecules as compared to MoDC from uninfected individuals. Functional assays of MoDC obtained from patients and controls showed a similar ability to activate allogeneic lymphocytes or to produce IL-12 and IL-10, although lower IFN-alpha levels were produced by cells from HCV patients after poly(I:C) stimulation. Moreover, both groups of MoDC induced similar profiles of IFN-gamma and IL-5 after stimulation of allogeneic T-cells. Finally, migration assays did not reveal any difference in their ability to respond to CCL21 chemokine. In conclusion, MoDC from HCV patients are functional after transduction with AdNS3 and stimulation with poly(I:C). These findings suggest that these cells may be useful for therapeutic vaccination in chronic HCV infection.

[Health related quality of life in patients with diabetes mellitus type 2]. / Calidad de vida relacionada con la salud en pacientes con diabetes mellitus tipo 2.

BACKGROUND: To evaluate the impact of diabetes mellitus type 2 on health related quality of life. METHODS: Cross-sectional study. Site: a basic health zone of the Foral Community of Navarre (12,200 inhabitants). Selection through simple random sampling (n=95) of the universe of patients diagnosed with diabetes mellitus type 2 of our basic health zone (n=655). Methods: Health Related Quality of Life evaluated with generic questionnaires SF-36 and EQ-5D; comparison of the general population samples carried out in Spain (SF-36), general population y>65 years of Navarre and Spanish diabetic population (EQ-5D). RESULTS: The diabetic patients have a tendency to show results lower than the general population in the following health concepts of the SF-36: "Physical Function" (76.6 +/- 27.2 SD), "Bodily Pain" (73.7 +/- 26.2 SD) , "General Health" (54.7 +/- 22.4 SD), "Social Function" (84.2 +/- 21.7 SD), "Role Emotional" (84.7 +/- 28.9 SD). Comparing the data with the general population >60 years, only two health concepts -"General Health" and "Role Emotional"- are equal to the reference values. With respect to the rates of respondents to some problem in the dimensions of the EQ-5D, the "Anxiety/Depression" dimension is outstanding with 43%. The value of the analogical visual scale in the diabetic patients is 64.6. CONCLUSIONS: This study increases the evidence that diabetes mellitus type 2 is related to a worse perception of quality of life related to health. The impact of certain diseases on the patients should not be measured only through the quantification of objective clinical parameters (such as morbidity or mortality).

Calidad de vida relacionada con la salud en pacientes con diabetes mellitus tipo 2 / Health Related Quality of life in patients with diabetes mellitus type 2

Fundamento. Evaluar el impacto de la diabetes mellitus tipo 2 en calidad de vida relacionada con la salud. Material y métodos. Estudio observacional transversal. Emplazamiento: una zona básica de salud de la Comunidad Foral Navarra (12.200 habitantes). Selección mediante muestreo aleatorio simple (n=95) del universo de pacientes diagnosticados de diabetes mellitus tipo 2 de nuestra zona básica de salud (n=655). Métodos: Calidad de vida relacionada con la salud valorada con los cuestionarios genéricos SF-36 y EQ-5D; comparación con las muestras de población general realizadas en España (SF-36), población general y >65 años de Navarra y población diabética española (EQ-5D). Resultados. Los pacientes diabéticos tienen una tendencia a presentar resultados inferiores a la población general en los siguientes conceptos de salud del SF-36: “Función Física” (76,6 ± 27,2 DE), “Dolor Corporal” (73,7 ± 26,2 DE), “Salud General” (54,7 ± 22,4 DE), “Función Social” (84,2 ± 21,7 DE), “Rol Emocional" (84,7 ± 28,9 DE). Comparando los datos con la población general >60 años, sólo dos conceptos de salud –“Salud General” y “Rol Emocional”– están igualados a los valores de referencia. Respecto a las tasas de respondedores a algún problema en las dimensiones del EQ-5D, destaca la dimensión “Ansiedad/Depresión” con un 43%. El valor de la escala visual analógica en los pacientes diabéticos es de 64,6. Conclusiones. Este trabajo aumenta la evidencia de que la diabetes mellitus tipo 2 se relaciona con una peor percepción de la calidad de vida relacionada con la salud. El impacto de determinadas enfermedades en los pacientes no debería ser medido únicamente mediante la cuantificación de parámetros clínicos objetivos (como la morbi-mortalidad)

Background. To evaluate the impact of diabetes mellitus type 2 on health related quality of life Methods. Cross-sectional study. Site: a basic health zone of the Foral Community of Navarre (12,200 inhabitants). Selection through simple random sampling (n=95) of the universe of patients diagnosed with diabetes mellitus type 2 of our basic health zone (n=655). Methods: Health Related Quality of Life evaluated with generic questionnaires SF-36 and EQ-5D; comparison of the general population samples carried out in Spain (SF-36), general population y>65 years of Navarre and Spanish diabetic population (EQ-5D). Results. The diabetic patients have a tendency to show results lower than the general population in the following health concepts of the SF-36: “Physical Function” (76.6 ± 27.2 SD), “Bodily Pain” (73.7 ± 26.2 SD) , “General Health” (54.7 ± 22.4 SD), “Social Function” (84.2 ± 21.7 SD), “Role Emotional” (84.7 ± 28.9 SD). Comparing the data with the general population >60 years, only two health concepts –“General Health” and “Role Emotional”– are equal to the reference values. With respect to the rates of respondents to some problem in the dimensions of the EQ-5D, the “Anxiety/Depression” dimension is outstanding with 43%. The value of the analogical visual scale in the diabetic patients is 64.6. Conclusions. This study increases the evidence that diabetes mellitus type 2 is related to a worse perception of quality of life related to health. The impact of certain diseases on the patients should not be measured only through the quantification of objective clinical parameters (such as morbidity or mortality)

[Impact of common reasons for consultation on the feeling of vitality and the physical performance of the over-65s]. / Impacto de los motivos comunes de consulta en el sentimiento de vitalidad y en el rendimiento físico de personas mayores de 65 años.

OBJECTIVES: To measure two functional dimensions (vitality and physical function) involved in the quality of life of the over-65s and to find what relationship they maintain with the commonest reasons for consultation. DESIGN: Cross-sectional, descriptive study. SETTING: Primary care. PARTICIPANTS: Randomised sample of 179 patients over 65 from 14 primary care clinics in Navarra. METHODS: SF-36 quality-of-life questionnaire and most common reasons for consultation. Personal and family details and ongoing drug prescription were also recorded. RESULTS: The most common reasons for consultation were insomnia (31.8%), arthrosis (48%), and urinary symptoms (16.2%). The greatest differences in the SF-36 scales occurred in patients with insomnia. In the multiple regression models, inverse associations were found for each of the reasons for consultation with the vitality and physical function dimensions. Vitality was associated with urinary symptoms, with an adjusted beta coefficient of -11.2 points (95% CI, -18.6 to -3.7). Insomnia was associated with significant decline in vitality and physical function, with beta of -7.7 points (95% CI, -13.9 to -1.5) and -10.3 points (95% CI, -19.1 to -1.6), respectively. Arthrosis symptoms behaved in a similar way. CONCLUSIONS: The most common pathologies or symptoms causing primary care consultations in the over-65s affect significantly the quality-of-life dimensions relating to the pursuit of normal daily life.

Impacto de los motivos comunes de consulta en el sentimiento de vitalidad y en el rendimiento físico de personas mayores de 65 años / Impact of common reason for consultation on the feeling of vitality and the physical performance of the over-65s

Objetivo. Medir 2 dimensiones funcionales (vitalidad y rol físico) implicadas en la calidad de vida de las personas > 65 años y conocer qué relación mantienen con los motivos de consulta más habituales. Diseño. Estudio descriptivo, transversal. Emplazamiento. Atención primaria. Participantes. Muestra aleatoria de 179 pacientes > 65 años procedentes de 14 consultas de atención primaria de Navarra. Métodos. Cuestionario de calidad de vida SF-36 y motivos de consulta más frecuentes. Se recogieron también datos demográficos, familiares y de prescripción continuada de fármacos. Resultados. Los motivos de consulta más frecuentes fueron: insomnio (31,8%), artrosis (48%) y síntomas miccionales (16,2%). Las mayores diferencias en las escalas del SF-36 se produjeron en los pacientes con insomnio. Se observaron asociaciones inversas de cada uno de los motivos de consulta indicados con las dimensiones vitalidad y rol físico en los modelos de regresión múltiple. La vitalidad se asoció con presencia de síntomas miccionales, con un coeficiente β ajustado de –11,2 puntos (intervalo de confianza [IC] del 95%, –18,6 a –3,7). El insomnio se asoció con descensos significativos de la vitalidad y el rol físico, con β de –7,7 puntos (IC del 95%, –13,9 a –1,5) y –10,3 puntos (IC del 95%, –19,1 a –1,6), respectivamente. Un comportamiento similar se obtuvo para los síntomas artrósicos. Conclusiones. Las enfermedades o los síntomas más frecuentes que motivan consultas de atención primaria en > 65 años afectan significativamente a las dimensiones de la calidad de vida relacionadas con el desarrollo de una actividad diaria normal

Objectives. To measure two functional dimensions (vitality and physical function) involved in the quality of life of the over-65s and to find what relationship they maintain with the commonest reasons for consultation. Design. Cross-sectional, descriptive study. Setting. Primary care. Participants. Randomised sample of 179 patients over 65 from 14 primary care clinics in Navarra. Methods. SF-36 quality-of-life questionnaire and most common reasons for consultation. Personal and family details and ongoing drug prescription were also recorded. Results. The most common reasons for consultation were insomnia (31.8%), arthrosis (48%), and urinary symptoms (16.2%). The greatest differences in the SF-36 scales occurred in patients with insomnia. In the multiple regression models, inverse associations were found for each of the reasons for consultation with the vitality and physical function dimensions. Vitality was associated with urinary symptoms, with an adjusted beta coefficient of –11.2 points (95% CI, –18.6 to –3.7). Insomnia was associated with significant decline in vitality and physical function, with beta of –7.7 points (95% CI, –13.9 to –1.5) and –10.3 points (95% CI, –19.1 to –1.6), respectively. Arthrosis symptoms behaved in a similar way. Conclusions. The most common pathologies or symptoms causing primary care consultations in the over-65s affect significantly the quality-of-life dimensions relating to the pursuit of normal daily life

Environmental transformation of the Bilbao estuary, N. Spain: microfaunal and geochemical proxies in the recent sedimentary record.

The distribution and abundance of benthic foraminifera and a range of elements have been analysed in six long cores (up to 10 m long) from the Bilbao estuary, N. Spain, to document environmental transformation of this estuarine ecosystem and to determine sediment contamination levels. Three different environmental zones could be distinguished in the recent sedimentary record based on its microfaunal and geochemical contents. Initially, a pre-industrial zone containing very abundant and diverse foraminiferal assemblages together with baseline metal levels. Secondly, an older industrial zone exhibiting co-existence of abundant and diverse foraminiferal assemblages with high concentrations of metals. Finally, a younger industrial zone with extreme concentrations of metals and barren of indigenous foraminifera. This environmental transformation has been caused by the discharge of untreated domestic and industrial effluents during the last 150 years. The occurrence of foraminifera in the two industrial zones and along the estuary is not related to defined levels of metals, and this seems to confirm oxygen limitation as the key factor to explain complete estuarine defaunation during deposition of the younger industrial zone (period 1950-2000). Effectiveness of current regeneration schemes could be assessed using microfaunal and geochemical proxies as environmental quality indicators.

Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure.

BACKGROUND: Glaucoma is a blinding disease usually associated with high intraocular pressure (IOP). In some families, abnormal anterior segment development contributes to glaucoma. The genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. Bone morphogenetic proteins (BMPs) participate in various developmental processes. We tested the importance of Bmp4 gene dosage for ocular development and developmental glaucoma. RESULTS: Bmp4+/- mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and Schlemm's canal drainage structures. Mice with severe drainage structure abnormalities, over 80% or more of their angle's extent, have elevated IOP. The penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the C57BL/6J background and absent on some other backgrounds. On the C57BL/6J background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve. CONCLUSIONS: We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. The abnormalities are similar to those in human patients with developmental glaucoma. Thus, BMP4 is a strong candidate to contribute to Axenfeld-Rieger anomaly and other developmental conditions associated with human glaucoma. BMP4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the C57BL/6J background. Bmp4+/- mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.

The mouse anterior chamber angle and trabecular meshwork develop without cell death.

BACKGROUND: The iridocorneal angle forms in the mammalian eye from undifferentiated mesenchyme between the root of the iris and cornea. A major component is the trabecular meshwork, consisting of extracellular matrix organized into a network of beams, covered in trabecular endothelial cells. Between the beams, channels lead to Schlemm's canal for the drainage of aqueous humor from the eye into the blood stream. Abnormal development of the iridocorneal angle that interferes with ocular fluid drainage can lead to glaucoma in humans. Little is known about the precise mechanisms underlying angle development. There are two main hypotheses. The first proposes that morphogenesis involves mainly cell differentiation, matrix deposition and assembly of the originally continuous mesenchymal mass into beams, channels and Schlemm's canal. The second, based primarily on rat studies, proposes that cell death and macrophages play an important role in forming channels and beams. Mice provide a potentially useful model to understand the origin and development of angle structures and how defective development leads to glaucoma. Few studies have assessed the normal structure and development of the mouse angle. We used light and electron microscopy and a cell death assay to define the sequence of events underlying formation of the angle structures in mice. RESULTS: The mouse angle structures and developmental sequence are similar to those in humans. Cell death was not detectable during the period of trabecular channel and beam formation. CONCLUSIONS: These results support morphogenic mechanisms involving organization of cellular and extracellular matrix components without cell death or atrophy.

Genetic modification of glaucoma associated phenotypes between AKXD-28/Ty and DBA/2J mice.

BACKGROUND: Glaucoma is a common disease but its molecular etiology is poorly understood. It involves retinal ganglion cell death and optic nerve damage that is often associated with elevated intraocular pressure. Identifying genes that modify glaucoma associated phenotypes is likely to provide insights to mechanisms of glaucoma. We previously reported glaucoma in DBA/2J mice caused by recessive alleles at two loci, isa and ipd, that cause iris stromal atrophy and iris pigment dispersion, respectively. A approach for identifying modifier genes is to study the effects of specific mutations in different mouse strains. When the phenotypic effect of a mutation is modified upon its introduction into a new strain, crosses between the parental strains can be used to identify modifier genes. The purpose of this study was to determine if the effects of the DBA/2J derived isa and ipd loci are modified in strain AKXD-28/Ty. RESULTS: AKXD-28/Ty mice develop glaucoma characterized by intraocular pressure elevation, retinal ganglion loss, and optic nerve excavation. In AKXD-28/Ty, isa causes an iris stromal atrophy phenotype as in DBA/2J. However, the iris pigment dispersion phenotype associated with ipd in DBA/2J does not occur in AKXD-28/Ty. Additionally, a greater severity and speed of retinal and optic nerve damage following intraocular pressure elevation in AKXD-28/Ty compared to DBA/2J mice suggests that AKXD-28/Ty is more susceptible to pressure-induced cell death. CONCLUSIONS: The consequences of the ipd and isa mutations are modified in the AKXD-28/Ty background. These strains provide a resource for the identification of modifier genes that modulate pigment dispersion and susceptibility to pressure-induced cell death.

Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development.

Anterior segment developmental disorders, including Axenfeld-Rieger anomaly (ARA), variably associate with harmfully elevated intraocular pressure (IOP), which causes glaucoma. Clinically observed dysgenesis does not correlate with IOP, however, and the etiology of glaucoma development is not understood. The forkhead transcription factor genes Foxc1 (formerly Mf1 ) and Foxc2 (formerly Mfh1 ) are expressed in the mesenchyme from which the ocular drainage structures derive. Mutations in the human homolog of Foxc1, FKHL7, cause dominant anterior segment defects and glaucoma in various families. We show that Foxc1 (+/-)mice have anterior segment abnormalities similar to those reported in human patients. These abnormalities include small or absent Schlemm's canal, aberrantly developed trabecular meshwork, iris hypoplasia, severely eccentric pupils and displaced Schwalbe's line. The penetrance of clinically obvious abnormalities varies with genetic background. In some affected eyes, collagen bundles were half normal diameter, or collagen and elastic tissue were very sparse. Thus, abnormalities in extracellular matrix synthesis or organization may contribute to development of the ocular phenotypes. Despite the abnormalities in ocular drainage structures in Foxc1 (+/-)mice, IOP was normal in almost all mice analyzed, on all genetic backgrounds and at all ages. Similar abnormalities were found in Foxc2 (+/-)mice, but no disease-associated mutations were identified in the human homolog FKHL14 in 32 ARA patients. Foxc1 (+/-)and Foxc2 (+/-)mice are useful models for studying anterior segment development and its anomalies, and may allow identification of genes that interact with Foxc1 and Foxc2 (or FKHL7 and FKHL14 ) to produce a phenotype with elevated IOP and glaucoma.

Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice.

Glaucomas are a major cause of blindness. Visual loss typically involves retinal ganglion cell death and optic nerve atrophy subsequent to a pathologic elevation of intraocular pressure (IOP). Some human glaucomas are associated with anterior segment abnormalities such as pigment dispersion syndrome (PDS) and iris atrophy with associated synechiae. The primary causes of these abnormalities are unknown, and their aetiology is poorly understood. We recently characterized a mouse strain (DBA/2J) that develops glaucoma subsequent to anterior segment changes including pigment dispersion and iris atrophy. Using crosses between mouse strains DBA/2J (D2) and C57BL/6J (B6), we now show there are two chromosomal regions that contribute to the anterior segment changes and glaucoma. Progeny homozygous for the D2 allele of one locus on chromosome 6 (called ipd) develop an iris pigment dispersion phenotype similar to human PDS. ipd resides on a region of mouse chromosome 6 with conserved synteny to a region of human chromosome 7q that is associated with human PDS. Progeny homozygous for the D2 allele of a different locus on chromosome 4 (called isa) develop an iris stromal atrophy phenotype (ISA). The Tyrpl gene is a candidate for isa and likely causes ISA via a mechanism involving pigment production. Progeny homozygous for the D2 alleles of both ipd and isa develop an earlier onset and more severe disease involving pigment dispersion and iris stromal atrophy.