Evaluation of natural background levels of high mountain karst aquifers in complex hydrogeological settings. A Gaussian mixture model approach in the Port del Comte (SE, Pyrenees) case study.

The hydrogeological processes driving the hydrochemical composition of groundwater in the alpine pristine aquifer system of the Port del Comte Massif (PCM) are characterized through the multivariate statistical techniques Principal Component Analysis (PCA) and Gaussian Mixture Models (GMM) in the framework of Compositional Data (CoDa) analysis. Also, the groundwater Natural Background Levels (NBLs) for NO3 and SO4 and Cl are evaluated, which are specially important for indicating the occurrence of groundwater contamination derived from the anthropic activities conducted in the PCM. The different hydrogeochemical facies found in the aquifer system of the PCM comprises low mineralized Ca-HCO3 water for the main Eocene karst aquifer, and Ca-SO4 and highly mineralized NaCl water types in the minor aquifers discharging from the PCM. The NBL values of SO4, Cl and NO3 obtained for the main karst aquifer are 14.33, 4.06 and 6.55 mg/L, respectively. These values are 35, 3 and 1.2 times lower than the respective official NBLs values that were determined by the water administration to be compared with in the case of conducting a pollution assessment characterization in the main karst aquifer. Official overestimation of NBLs can put important groundwater resources in the PCM at risk.

Some thoughts on counts in sequencing studies.

Measurements in sequencing studies are mostly based on counts. There is a lack of theoretical developments for the analysis and modelling of this type of data. Some thoughts in this direction are presented, which might serve as a seed. The main issues addressed are the compositional character of multinomial probabilities and the corresponding representation in orthogonal (isometric) coordinates, and modelling distributions for sequencing data taking into account possible effects of amplification techniques.

Compositional data for global monitoring: The case of drinking water and sanitation.

INTRODUCTION: At a global level, access to safe drinking water and sanitation has been monitored by the Joint Monitoring Programme (JMP) of WHO and UNICEF. The methods employed are based on analysis of data from household surveys and linear regression modelling of these results over time. However, there is evidence of non-linearity in the JMP data. In addition, the compositional nature of these data is not taken into consideration. This article seeks to address these two previous shortcomings in order to produce more accurate estimates. METHODS: We employed an isometric log-ratio transformation designed for compositional data. We applied linear and non-linear time regressions to both the original and the transformed data. Specifically, different modelling alternatives for non-linear trajectories were analysed, all of which are based on a generalized additive model (GAM). RESULTS AND DISCUSSION: Non-linear methods, such as GAM, may be used for modelling non-linear trajectories in the JMP data. This projection method is particularly suited for data-rich countries. Moreover, the ilr transformation of compositional data is conceptually sound and fairly simple to implement. It helps improve the performance of both linear and non-linear regression models, specifically in the occurrence of extreme data points, i.e. when coverage rates are near either 0% or 100%.

Hearts of some Antarctic fishes lack mitochondrial creatine kinase.

Creatine kinase (CK; EC 2.7.3.2) functions as a spatial and temporal energy buffer, dampening fluctuations in ATP levels as ATP supply and demand change. There are four CK isoforms in mammals, two cytosolic isoforms (muscle [M-CK] and brain [B-CK]), and two mitochondrial isoforms (ubiquitous [uMtCK] and sarcomeric [sMtCK]). Mammalian oxidative muscle couples expression of sMtCK with M-CK, creating an energy shuttle between mitochondria and myofibrils. We hypothesized that the expression pattern and activity of CK would differ between hearts of red- and white-blooded Antarctic notothenioid fishes due to their striking differences in cardiac ultrastructure. Hearts of white-blooded icefishes (family Channichthyidae) have significantly higher mitochondrial densities compared to red-blooded species, decreasing the diffusion distance for ATP between mitochondria and myofibrils and potentially minimizing the need for CK. The distribution of CK isoforms was evaluated using western blotting and maximal activity of CK was measured in mitochondrial and cytosolic fractions and tissue homogenates of heart ventricles of red- and white-blooded notothenioids. Transcript abundance of sMtCK and M-CK was also quantified. Overall, CK activity is similar between hearts of red- and white-blooded notothenioids but hearts of icefishes lack MtCK and have higher activities of M-CK in the cytosol compared to red-blooded fishes. The absence of MtCK may compromise cardiac function under stressful conditions when ATP supply becomes limiting.

Encuesta sobre el conocimiento y manejo de los pacientes con ataque isquémico transitorio entre médicos y enfermería de Atención Primaria / Survey of the knowledge and management of transient ischemic attacks among primary care physicians and nurses

Introducción: La principal fuente de consulta de los pacientes con ataque isquémico transitorio (AIT) agudo en nuestra área sanitaria son los centros de salud de Atención Primaria. Existen muy pocos estudios sobre el conocimiento del AIT y su manejo entre profesionales de la medicina comunitaria y de familia.Objetivo: Estimar el conocimiento del AIT, su manejo y las pruebas complementarias necesarias entre médicos y personal de enfermería de Atención Primaria de nuestra área de influencia. Para ello se envió una encuesta electrónica cerrada a 640 profesionales con 7 preguntas sobre el AIT.Resultados: Se obtuvo una alta tasa de respuestas: 285 (46,7% médicos). 239 (83,9%) participantes mostraron un conocimiento adecuado de la duración del AIT. Sólo 40 (14%) de la sintomatología. Mientras que el 67% contestó adecuadamente que es necesaria una prueba de neuroimagen urgente. Sólo el 42,5% reconoció la necesidad una exploración con dúplex de troncos supraórticos precoz. Únicamente, el 35,4% conocía qué es un doppler transcraneal, mientras que el 78,2% supo que era más adecuado enviar a estos pacientes a urgencias hospitalarias. El predictor independiente de mejor conocimiento fue ser un médico de Atención Primaria (MAP) (odds ratio [OR]: 2,138; IC 95%: 1,124-4,067; p = 0,021) pero no hubo diferencias entre MAP y enfermería en el conocimiento del manejo de estos pacientes. En enfermería fue peor el conocimiento en el ámbito rural (OR: 0,410; IC 95%: 0,189-0,891; p = 0,024). Conclusión: El conocimiento de la actitud ante un AIT es correcto en la mayoría de casos, sin embargo es necesario mejorar el conocimiento de la sintomatología de los AIT (AU)

Introduction: Transient ischaemic attack (TIA) patients often report that Primary Care physicians(PCPs) and nurses are their main medical contacts after onset of symptoms in our healtharea. There are few studies on the knowledge and management of TIA among Community andFamily Medicine professionals.Material and methods: Our aim was to study the current knowledge and practice in the managementof TIA patients among Primary Care physicians and nurses. A cross-sectional survey withseven questions about TIA was conducted among 640 PCPs and nurses from Primary Care centresin our health area.Results: In total, 285 (46.7% PCPs) took participate in the study. Of these, 239 (83.9%) participantsknew the duration of a TIA. However only 40 (14%) recognised all clinical symptoms.An urgent neuroimaging was preferred by 67%. Only 42.5% agreed that an urgent cervicalduplex would be useful in these patients. Transcranial Doppler was recognised by only 35.4%.A majority (78.2%) of participants agreed that TIA patients must be admitted to hospital. PCPshad the best knowledge of TIA (odds ratio [OR] 2.138; 95% CI 1.124-4.067; P = 0.021) but therewere no differences between physicians and nurses on the management of these patients.Nurses from rural Primary Care centers had the worst level of knowledge (OR 0.410; 95% CI0.189-0.891; P = 0.024).Conclusion: TIA was well recognized as a medical emergency. However, knowledge of clinicalsymptoms of TIA must be improved (AU)

Survey of the knowledge and management of transient ischemic attacks among primary care physicians and nurses.

INTRODUCTION: Transient ischaemic attack (TIA) patients often report that Primary Care physicians (PCPs) and nurses are their main medical contacts after onset of symptoms in our health area. There are few studies on the knowledge and management of TIA among Community and Family Medicine professionals. MATERIAL AND METHODS: Our aim was to study the current knowledge and practice in the management of TIA patients among Primary Care physicians and nurses. A cross-sectional survey with seven questions about TIA was conducted among 640 PCPs and nurses from Primary Care centres in our health area. RESULTS: In total, 285 (46.7% PCPs) took participate in the study. Of these, 239 (83.9%) participants knew the duration of a TIA. However only 40 (14%) recognised all clinical symptoms. An urgent neuroimaging was preferred by 67%. Only 42.5% agreed that an urgent cervical duplex would be useful in these patients. Transcranial Doppler was recognised by only 35.4%. A majority (78.2%) of participants agreed that TIA patients must be admitted to hospital. PCPs had the best knowledge of TIA (odds ratio [OR] 2.138; 95% CI 1.124-4.067; P = 0.021) but there were no differences between physicians and nurses on the management of these patients. Nurses from rural Primary Care centers had the worst level of knowledge (OR 0.410; 95% CI 0.189-0.891; P = 0.024). CONCLUSION: TIA was well recognized as a medical emergency. However, knowledge of clinical symptoms of TIA must be improved.

Imagen corporal y trastornos alimentarios en estudiantes del País Vasco: un estudio piloto / Body shape and eating disorders in a sample of students in the Basque Country: a pilot study

Objetivo. Estudiar el grado de insatisfacción con la imagen corporal (IC) y los síntomas de trastornos alimentarios (TA) en estudiantes del país vasco.Método. Una muestra intencional formada por 969 estudiantes de 11-18 años, 508 chicas y 461 chicos, cumplimentaron el Body Shape Questionnaire (Cooper, Taylor, Cooper y Fairburn, 1987), el Eating Attitudes Test (Garner y Garfinkel, 1979) y la escala de insatisfacción corporal del Eating Disorders Inventor (Garner, Olmstead y Polivy 1983). Resultados. La prevalencia de síntomas de trastornos alimentarios hallada es del 7,1 por ciento de las chicas y el 2,4 por ciento de los chicos. La preocupación por la imagen corporal aparece en el 32,5 por ciento de las chicas, aumentando con la edad, y el 8,9 por ciento de los chicos. En ambos sexos la relación entre la preocupación por la IC y el índice de masa corporal (IMC) es positiva. Discusión. Estos resultados confirman estudios anteriores y reafirman la necesidad de evaluar sistemáticamente estos aspectos en la población preadolescente y adolescente, cara a realizar campañas de prevención (AU)

Red wine intake prevents nuclear factor-kappaB activation in peripheral blood mononuclear cells of healthy volunteers during postprandial lipemia.

BACKGROUND: Several epidemiological studies have demonstrated the beneficial effect of red wine intake in reducing total and cardiovascular mortality. This effect has been attributed in part to its antioxidant properties. Because the monocytes/macrophages and the nuclear transcription factor kappaB (NF-kappaB) are implicated in the pathogenesis of atherosclerotic lesions, we examined the effect of red wine intake on the activation of NF-kappaB in peripheral blood mononuclear cells. METHODS AND RESULTS: Sixteen healthy volunteers were studied 3 times each: after a moderate dose, a low dose, and no wine with a fat-enriched breakfast. Lipid profile and NF-kappaB activation (electrophoretic mobility shift assay) were examined in blood samples taken before and 3, 6, and 9 hours after wine intake. In addition, mononuclear cells were incubated with VLDL in the presence of some antioxidants (quercetin and alpha-tocopherol succinate) contained in red wine to study their effects on NF-kappaB activation. Subjects receiving a fat-enriched breakfast had increased NF-kappaB activation in peripheral blood mononuclear cells coinciding with the augmentation in total triglycerides and chylomicrons. Red wine intake prevented NF-kappaB activity even though it induced a certain increase in serum lipids, particularly VLDL, that did not increase after the fat ingestion alone. However, another form of alcohol intake (vodka) did not modify the NF-kappaB activation provided by postprandial lipemia. In cultured mononuclear cells, isolated human VLDL caused NF-kappaB activation in a time-dependent manner that did not occur in the presence of the red wine antioxidants quercetin and alpha-tocopherol. CONCLUSIONS: Our results provide a new potential mechanism to explain the beneficial effects of red wine intake in the reduction of cardiovascular mortality.

Atorvastatin reduces NF-kappaB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells.

Cardiovascular mortality, mainly due to the rupture of unstable atherosclerotic plaques, is reduced by 3-hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Inflammatory cells, attracted to the vascular lesion by chemokines, have been implicated in the process of the plaque rupture. In cultured vascular smooth muscle cells (VSMC) and U937 mononuclear cells we have studied the effect of Atorvastatin (Atv) on nuclear factor kappaB (NF-kappaB) activity, an inducer of the mRNA expression of chemokines such as interferon-inducible protein 10 (IP-10) and monocyte chemoattractant protein 1 (MCP-1). Angiotensin II (Ang II) and tumor necrosis factor alpha (TNF-alpha) increased NF-kappaB activity in VSMC (2 and 5-fold, respectively). Preincubation of cells with 10(-7) mol/l Atv diminished this activation (44 and 53%). The inhibition was reversed by mevalonate, farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP), but not by other isoprenoids. Coinciding with the NF-kappaB activation in VSMC, there was a diminution of cytoplasmic IkappaB levels that was recovered by pretreatment with Atv. Ang II and TNF-alpha induced the expression of IP-10 (1.5 and 3.4-fold) and MCP-1 (2.4 and 4-fold) in VSMC. Atv reduced this overexpression around 38 and 35% (IP-10), and 54 and 39% (MCP-1), respectively. Our results strongly suggest that Atv, through the inhibition of NF-kappaB activity and chemokine gene expression, could reduce the inflammation within the atherosclerotic lesion and play a role in the stabilization of the lesion.

HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis.

OBJECTIVES: To study the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitor atorvastatin on the potential mechanisms involved in the recruitment of monocytic cells into the vessel wall. BACKGROUND: Inhibitors of HMG-CoA-reductase reduce cardiovascular mortality though the mechanisms yet elucidated. Most ischemic events are secondary to disruption of atherosclerotic plaques highly infiltrated by macrophages. METHODS: Atherosclerosis was induced in the femoral arteries of rabbits by endothelial damage and atherogenic diet for 4 weeks. Then, animals were switched to standard chow and randomized to receive either no treatment or atorvastatin (5 mg/kg/d) and killed after 4 weeks. RESULTS: Atorvastatin induced a significant reduction in serum lipids and in lesion size. Arterial macrophage infiltration was abolished by the treatment, and monocyte chemoattractant protein-1 (MCP-1) was significantly diminished in the neointima and in the media. Nuclear factor kappa-B (NF-kappaB) was activated in the 60% of the lesions, both in macrophages and vascular smooth muscle cells (VSMC), of the untreated group while only in 30% of the atorvastatin group. NF-kappaB activity was also lower in the uninjured aorta and liver of treated compared with untreated rabbits. In cultured VSMC, MCP-1 expression and NF-kappaB activity induced by tumor necrosis factor alpha were downregulated by atorvastatin. CONCLUSIONS: In a rabbit atherosclerosis model, atorvastatin diminishes the neointimal inflammation, and this could contribute to the stabilization of the atherosclerotic plaque. This may be an additional explanation for the reduction of acute ischemic events in patients treated with statins.

ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent proinflammatory factors but not of collagen I in a rabbit model of atherosclerosis.

Increasing evidence supports an association between inflammation and plaque rupture. Macrophages and vascular smooth muscle cells are a source of cytokines and growth factors, which contribute to ongoing inflammation during atherogenesis. In a rabbit model of atherosclerosis, we evaluated the effect of the ACE inhibitor quinapril on different parameters implicated in the pathogenesis of the plaque, such as the presence of chemokines (interleukin-8, monocyte chemoattractant protein-1), collagen I, and vascular smooth muscle cell proliferation (PDGF-B). Since nuclear factor kappaB (NF-kappaB) has been implicated in the control of chemokine transcription and cell proliferation, we also investigated its activation and localization in the lesion. Quinapril administration for 28 days caused a down-regulation in arterial expression of interleukin-8 and monocyte chemoattractant protein-1 (mRNA and protein). However, collagen I expression (mRNA and protein) was not modified. PDGF-B expression was reduced in both the intima and the media. Active NF-kappaB, found in both macrophages and vascular smooth muscle cells, was also reduced by quinapril. Nevertheless, no significant changes were noted in the mild neointima formation, although a certain trend toward normalization was found in the quinapril-treated group. In conclusion, our results show that quinapril treatment attenuates several parameters associated with inflammation within the atherosclerotic lesions that are controlled by NF-kappaB, although it has no effect on collagen I expression. Both effects could contribute to the stabilization of the atherosclerotic plaque.

3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture.

Recent evidence suggests that apoptosis may be involved in the control of vascular smooth muscle cell (VSMC) number in atherosclerotic lesions. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to induce apoptosis in a variety of tumor cell lines. To evaluate whether these agents also induce apoptosis of VSMCs, cultured rat VSMCs were treated with increasing doses of atorvastatin in the presence of FBS as a survival factor. The presence of apoptosis was evaluated by morphological criteria, annexin V binding, and DNA fragmentation and quantified as the proportion of hypodiploid cells by flow cytometry. Atorvastatin induced apoptosis in a dose-dependent manner, an effect also seen with simvastatin and lovastatin, but not with the hydrophilic drug pravastatin. The proapoptotic effect of statins was seen only when the inhibition of acetate incorporation into sterols was >95% and was fully reversed by mevalonate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate but not by isopentenyl adenosine, ubiquinone, or squalene, suggesting a role for prenylated proteins in the regulation of VSMC apoptosis. To further assess the role of protein prenylation, VSMCs were exposed to the prenyl transferase inhibitors perillic acid and manumycin A. Both agents induced VSMC apoptosis as evaluated by the above-mentioned criteria. Finally, VSMC treatment with lipophilic statins was associated with decreased prenylation of p21-Rho B, further supporting the role of protein prenylation inhibition in statin-induced VSMC apoptosis. The present data suggest that interference with protein prenylation by HMG-CoA reductase inhibitors or other agents may provide new strategies for the prevention of neointimal thickening.

Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-kappa B activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis.

BACKGROUND: The migration of monocytes into the vessel wall is a critical event leading to the development of atherosclerosis. Monocyte chemoattractant protein-1 (MCP-1) is the main chemotactic factor involved in this phenomenon, and nuclear factor-kappa B (NF-kappa B) is one of the nuclear factors controlling its expression. ACE inhibitors have been useful in some experimental models of atherosclerosis. In this work, we addressed the hypothesis that angiotensin II (Ang II) may be implicated in the recruitment of monocytes into the vessel wall through the activation of NF-kappa B and the induction of MCP-1 expression. METHODS AND RESULTS: Accelerated atherosclerosis was induced in the femoral arteries of rabbits by endothelial desiccation and atherogenic diet for 7 days. Atherosclerotic vessels exhibited an increase in NF-kappa B-like activity, and p50 and p65 NF-kappa B subunits were identified as components of this activity. MCP-1 (mRNA and protein) was also expressed in the injured vessels coincidently with the neointimal macrophage infiltration. ACE inhibition with quinapril reduced these three parameters. In cultured monocytic and vascular smooth muscle cells. Ang II elicited an increase in NF-kappa B activation and MCP-1 expression that was prevented by preincubation of cells with pyrrolidinedithiocarbamate, an inhibitor of NF-kappa B activation. CONCLUSIONS: The present data support a role for Ang II in neointimal monocyte infiltration through NF-kappa B activation and MCP-1 expression in a model of accelerated atherosclerosis in rabbits. Our results suggest that ACE inhibitors may have a beneficial effect in early atherosclerosis.

Effects and interactions of endothelin-1 and angiotensin II on matrix protein expression and synthesis and mesangial cell growth.

Mesangial cell growth and accumulation of extracellular matrix proteins constitute key features of progressive glomerular injury. Endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictor agents, evoke a number of similar responses in mesangial cells. In rat mesangial cells, we compared ET-1 and Ang II effects on matrix protein production and cell proliferation as well as the potential interaction between the two hormones. When cells in 0.5% fetal calf serum were incubated for 24 hours with various concentrations of ET-1 or Ang II, both peptides stimulated, in a dose-dependent manner, fibronectin and type IV collagen mRNA expression, fibronectin synthesis, and mitogenesis. Incubation with specific receptor antagonists of both hormones demonstrated that endothelin subtype A (ETA) and angiotensin type 1 (AT1) receptors were involved. Preincubation of cells with two different protein kinase C inhibitors or with a neutralizing anti-transforming growth factor-beta antibody, but not an unrelated IgG, diminished the peptide-induced fibronectin synthesis. A dual interrelation seems to exist between ET-1 and Ang II. Thus, the AT1 receptor antagonist losartan and the angiotensin-converting enzyme inhibitors quinaprilat and captopril diminished the ET-1-mediated effects, whereas, the ETA receptor antagonist BQ-123 diminished the Ang II-induced fibronectin synthesis and mesangial cell proliferation. Our results suggest that ET-1 and Ang II stimulate matrix protein synthesis and mesangial cell mitogenesis through ETA and AT1 receptors, respectively, by complicated mechanisms, implicating protein kinase C activation, synthesis of transforming growth factor-beta, and release of one peptide by the other. These data could be important for a better understanding of the participation of vasoactive substances in the pathogenesis of glomerulosclerosis.