Interregional migration and thresholds: evidence in Spain

The aim of this paper is to analyze the effects of labor market conditions in the origin and the destination on interregional migration in Spain, over the period 1988-2010. A basic theoretical framework is developed and the implications of the model suggest that the effect of labor market conditions on migration can vary, depending on a certain threshold. In a second step, the implications of the model are tested with Spanish data, using a new approach based on the presence of thresholds. We show that interregional migration can be explained by labor market fundamentals if the expected wage gap between the origin and the destination is below an endogenously determinate value

Interregional migration and thresholds: evidence in Spain

The aim of this paper is to analyze the effects of labor market conditions in the origin and the destination on interregional migration in Spain, over the period 1988-2010. A basic theoretical framework is developed and the implications of the model suggest that the effect of labor market conditions on migration can vary, depending on a certain threshold. In a second step, the implications of the model are tested with Spanish data, using a new approach based on the presence of thresholds. We show that interregional migration can be explained by labor market fundamentals if the expected wage gap between the origin and the destination is below an endogenously determinate value

Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: studies on TGF-ß1 regulation

This work was supported by grants from Ministerio de Ciencia y Tecnología (MCYT-SAF2007-62471, MCYT-SAF2010-16198; PI070695) and Redes Temáticas de Investigación Cooperativa en Salud from Instituto de Salud Carlos III (ISCIII-RETIC RD06/00160002

Impaired erythropoietin synthesis in chronic kidney disease is caused by alterations in extracellular matrix composition

[EN] Renal fibrosis and anaemia are two of the most relevant events in chronic kidney disease. Fibrosis is characterized by the accumulation of extracellular matrix proteins in the glomeruli and tubular interstitium. Anaemia is the consequence of a decrease in erythropoietin production in fibrotic kidneys. This work analyses the possibility that the accumulation of abnormal collagens in kidney interstitium could be one of the mechanisms responsible for erythropoietin decreased synthesis. In renal interstitial fibroblast grown on collagen I, erythropoietin mRNA expression and HIF-2a protein decreased, whereas focal adhesion kinase protein (FAK) phosphorylation and proteasome activity increased, compared to cells grown on collagen IV. Proteasome inhibition or FAK inactivation in cells plated on collagen I restored erythropoietin and HIF- 2a expression. FAK inhibition also decreased the collagen I-dependent proteasome activation. In a model of tubulointerstitial fibrosis induced by unilateral ureteral obstruction in mice, increased collagen I protein content and an almost complete disappearance of erythropoietin mRNA expression were observed in the ureteral ligated kidney with respect to the contralateral control. Interestingly, erythropoietin synthesis was recovered in obstructed mice treated with proteasome inhibitor. These data suggest that reduced kidney erythropoietin synthesis could be caused by the accumulation of abnormal extracellular matrix proteins

Aging-related hyperphosphatemia impairs myogenic differentiation and enhances fibrosis in skeletal muscle

14 p.Background Hyperphosphatemia has been related to the development of sarcopenia in aging mice. We describe the intracellular mechanisms involved in the impairment of the myogenic differentiation promoted by hyperphosphatemia and analyse these mechanisms in the muscle from older mice. Methods C2C12 cells were grown in 2% horse serum in order to promote myogenic differentiation, in the presence or absence of 10 mM beta-glycerophosphate (BGP) for 7 days. Troponin T, paired box 7 (Pax-7), myogenic factor 5 (Myf5), myogenic differentiation 1 (MyoD), myogenin (MyoG), myocyte enhancer factor 2 (MEF2C), P300/CBP-associated factor (PCAF), histone deacetylase 1 (HDAC1), fibronectin, vimentin, and collagen I were analysed at 48, 72, and 168 h, by western blotting or by immunofluorescence staining visualized by confocal microscopy. Studies in mice were performed in 5- and 24-month-old C57BL6 mice. Three months before sacrifice, 21-month-old mice were fed with a standard diet or a low phosphate diet, containing 0.6% or 0.2% phosphate, respectively. Serum phosphate concentration was assessed by a colorimetric method and forelimb strength by a grip test. Fibrosis was observed in the tibialis anterior muscle by Sirius Red staining. In gastrocnemius muscle, MyoG, MEF2C, and fibronectin expressions were analysed by western blotting. Results Cells differentiated in the presence of BGP showed near five times less expression of troponin T and kept higher levels of Pax-7 than control cells indicating a reduced myogenic differentiation. BGP reduced Myf5 about 50% and diminished MyoD transcriptional activity by increasing the expression of HDAC1 and reducing the expression of PCAF. Consequently, BGP reduced to 50% the expression of MyoG and MEF2C. A significant increase in the expression of fibrosis markers as collagen I, vimentin, and fibronectin was found in cells treated with BGP. In mice, serum phosphate (17.24 ± 0.77 mg/dL young; 23.23 ± 0.81 mg/dL old; 19.09 ± 0.75 mg/dL old with low phosphate diet) correlates negatively (r = 0.515, P = 0.001) with the muscular strength (3.13 ± 0.07 gf/g young; 1.70 ± 0.12 gf/ g old; 2.10 ± 0.09 gf/g old with low phosphate diet) and with the expression of MyoG (r = 0.535, P = 0.007) and positively with the expression of fibronectin (r = 0.503, P = 0.001) in gastrocnemius muscle. The tibialis anterior muscle from old mice showed muscular fibrosis. Older mice fed with a low phosphate diet showed improved muscular parameters relative to control mice of similar age. Conclusions Hyperphosphatemia impairs myogenic differentiation, by inhibiting the transcriptional activity of MyoD, and enhances the expression of fibrotic genes in cultured myoblasts. Experiments carried out in older mice demonstrate a close relationship between age-related hyperphosphatemia and the decrease in the expression of myogenic factors and the increase in factors related to muscle fibrosis.Instituto de Salud Carlos IIIPrincipado de AsturiasComunidad de Madri

Degradation of malachite green by a pulsed light/H2O2 process

Pulsed light (PL) is a type of photonic technology characterized by intense short light pulses that enhance the speed of photochemical reactions and might be useful as light source in advanced oxidation processes (AOPs). This work aimed to test PL as light source for the degradation of the dye malachite green by combining PL with H2O2. To this, the effect of dye and H2O2 concentrations and pH on the degradation rate of malachite green was studied and a degradation pathway was proposed. Dye degradation followed a pseudo-first order kinetics; it increased with low initial dye concentration, high H2O2 concentration and low pH. Complete decolourization was achieved after 35 light pulses (75 J/cm2), with a degradation rate of 0.0710 cm2/J. The degradation mechanism was initiated by the attack of hydroxyl radicals to the central carbon of malachite green generating 4-(dimethylamino)benzophenone (DLBP) followed by the addition of hydroxyl radicals to the non-amino aromatic ring of DLBP and the demethylation of the amino group. Results indicate that PL technology has potential to be implemented to decrease the environmental impact of dyeing industries.Ciencias Ambientale

Hyperphosphatemia-Induced Oxidant/Antioxidant Imbalance Impairs Vascular Relaxation and Induces Inflammation and Fibrosis in Old Mice

Aging impairs vascular function, but the mechanisms involved are unknown. The aim of this study was to analyze whether aging-related hyperphosphatemia is implied in this effect by elucidating the role of oxidative stress. C57BL6 mice that were aged 5 months (young) and 24 months (old), receiving a standard (0.6%) or low-phosphate (0.2%) diet, were used. Isolated mesenteric arteries from old mice showed diminished endothelium-dependent vascular relaxation by the down-regulation of NOS3 expression, increased inflammation and increased fibrosis in isolated aortas, compared to those isolated from young mice. In parallel, increased Nox4 expression and reduced Nrf2, Sod2-Mn and Gpx1 were found in the aortas from old mice, resulting in oxidant/antioxidant imbalance. The low-phosphate diet improved vascular function and oxidant/antioxidant balance in old mice. Mechanisms were analyzed in endothelial (EC) and vascular smooth muscle cells (SMCs) treated with the phosphate donor ss-glycerophosphate (BGP). In EC, BGP increased Nox4 expression and ROS production, which reduced NOS3 expression via NF kappa B. BGP also increased inflammation in EC. In SMC, BGP increased Collagen I and fibronectin expression by priming ROS production and NF kappa B activity. In conclusion, hyperphosphatemia reduced endothelium-dependent vascular relaxation and increased inflammation and vascular fibrosis through an impairment of oxidant/antioxidant balance in old mice. A low-phosphate diet achieved improvements in the vascular function in old mice

A Multiple Stakeholder Multicriteria Decision Analysis in Diabetic Macular Edema Management: The MULTIDEX‑EMD Study

Background The clinical and economic management of retinal diseases has become more complex following the introduction of new intravitreal treatments. Multicriteria decision analysis (MCDA) offers the potential to overcome the challenges associated with traditional decision-making tools. Objectives A MCDA to determine the most relevant criteria to decision-making in the management of diabetic macular edema (DME) based on the perspectives of multiple stakeholders in Spain was developed. This MCDA was termed the MULTIDEX-EMD study. Methods Nineteen stakeholders (7 physicians, 4 pharmacists, 5 health authorities and health management experts, 1 psychologist, and 2 patient representatives) participated in this three-phase project. In phase A, an advisory board defined all of the criteria that could influence DME treatment decision-making. These criteria were then screened using a discrete choice experiment (DCE) (phase B). Next, a multinomial logit model was fitted by applying the backward elimination algorithm (relevant criteria: p value = 15 letters (p value < 0.001), effect duration per administration (p value = 0.008), retinal detachment (p value < 0.001), endophthalmitis (p value = 0.012), myocardial infarction (p value < 0.001), intravitreal hemorrhage (p value = 0.021), annual treatment cost per patient (p value = 0.001), health-related quality of life (HRQoL) (p value = 0.004), and disability level (p value = 0.021). Conclusions From a multi-stakeholder perspective, the selection of an appropriate treatment for DME patients should guarantee patient safety and maximize the visual acuity improvement and treatment effect duration. It should also contribute to system sustainability by being affordable, it should have a positive impact on HRQoL, and it should prevent disability

Relevance of nutritional assessment and treatment to counteract cardiac cachexia and sarcopenia in chronic heart failure

Chronic heart failure (CHF) is frequently associated with the involuntary loss of body weight and muscle wasting, which can determine the course of the disease and its prognosis. While there is no gold standard malnutrition screening tool for their detection in the CHF population, several bioelectrical and imaging methods have been used to assess body composition in these patients (such as Dual Energy X-Ray Absorptiometry and muscle ultrasound, among other techniques). In addition, numerous nutritional biomarkers have been found to be useful in the determination of the nutritional status. Nutritional considerations include the slow and progressive supply of nutrients, avoiding high volumes, which could ultimately lead to refeeding syndrome and worsen the clinical picture. If oral feeding is insufficient, hypercaloric and hyperproteic supplementation should be considered. β-Hydroxy-β-methylbutyrate and omega-3 polyunsaturated fatty acid administration prove to be beneficial in certain patients with CHF, and several interventional studies with micronutrient supplementation have also described their possible role in these subjects. Taking into account that CHF is sometimes associated with gastrointestinal dysfunction, parenteral nutritional support may be required in selected cases. In addition, potential therapeutic options regarding nutritional state and muscle wasting have also been tested in clinical studies. This review summarises the scientific evidence that demonstrates the necessity to carry out a careful nutritional evaluation and nutritional treatment to prevent or improve cardiac cachexia and sarcopenia in CHF, as well as improve its courseS