Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice.

One goal of regenerative medicine is to rejuvenate tissues and extend lifespan by restoring the function of endogenous aged stem cells. However, evidence that somatic stem cells can be targeted in vivo to extend lifespan is still lacking. Here, we demonstrate that after a short systemic treatment with a specific inhibitor of the small RhoGTPase Cdc42 (CASIN), transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. In detail, we show that systemic CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Further, we show that CASIN modifies niche localization and H4K16ac polarity of HSCs in vivo. Single-cell profiling reveals changes in HSC transcriptome, which underlie enhanced lymphoid and regenerative capacity in serial transplantation assays. Overall, we provide proof-of-concept evidence that a short systemic treatment to decrease Cdc42 activity improves the regenerative capacity of different endogenous aged stem cells in vivo, and that rejuvenated HSCs exert a broad systemic effect sufficient to extend murine health- and lifespan.

Achieving Lower LDL-C Levels After a Recent Myocardial Infarction Might Be Associated with Lower Healthcare Resource Use and Costs in Spain.

INTRODUCTION: There is little evidence on the relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and costs in patients on lipid-lowering therapy (LLT). We described healthcare resource use and costs (direct and indirect) by achieved LDL-C in patients receiving LLT after a recent myocardial infarction (MI) in Spain. METHODS: This was a retrospective observational study of anonymized electronic medical records from seven regions in Spain (BIG-PAC® database; n = 1.9 million). Eligible patients were adults (≥ 18 years) hospitalized for an MI between January 2015 and December 2017, treated with a statin and/or ezetimibe, and having recorded LDL-C values at baseline and during follow-up. Healthcare resource use and direct and indirect costs (in 2018, €) were described by achieved LDL-C levels during a follow-up of 18 months. RESULTS: Of 6025 patients (mean age, 69.7 years; 77% male), only 11% achieved LDL-C goals as defined in the 2016 ESC/EAS guidelines (< 70 mg/dL), and just 1% reached the lower target (< 55 mg/dL) in the current 2019 guidelines. Achieving lower LDL-C levels translated to lower healthcare resource use and costs. Mean total (direct and indirect) costs ranged from €5044 for patients with LDL-C < 55 mg/dL to €7567 for patients with LDL-C ≥ 130 mg/dL. CONCLUSION: Very few patients achieved recommended LDL-C goals despite using LLT. Achieving lower LDL-C levels after an MI might be associated with lower healthcare resource use and costs. Use of more intensive LLT, leading to greater reductions in LDL-C, could therefore be beneficial both from a clinical and an economic perspective.

Sorptive removal of disinfection by-product precursors from UK lowland surface waters: Impact of molecular weight and bromide.

The current study compared the impact of three different unit processes, coagulation, granular activated carbon (GAC), and a novel suspended ion exchange (SIX) technology, on disinfection by-product formation potential (DBPFP) from two UK lowland water sources with medium to high bromide content. Specific attention was given to the influence of the organic molecular weight (MW) fraction on DBPFP as well as the impact of bromide concentration. Whilst few studies have investigated the impact of MW fractions from Liquid Chromatography with Organic Carbon Detection (LC-OCD) analysis on dissolved organic carbon (DOC) removal by different processes, none have studied the influence of DOC MW fractions from this analysis on DBP formation. The impact of higher bromide concentration was to decrease the total trihalomethane (THM) and haloacetic acid (HAA) mass concentration, in contrast to previously reported studies. Results indicated that for a moderate bromide concentration source (135 µg/L), the THM formation potential was reduced by 22% or 64% after coagulation or SIX treatment, respectively. For a high bromide content source (210 µg/L), the THM formation potential removal was 47% or 69% following GAC or SIX treatment, respectively. The trend was the same for HAAs, albeit with greater differences between the two processes/feedwaters with reference to overall removal. A statistical analysis indicated that organic matter of MW > 350 g/mol had a significant impact on DBPFP. A multiple linear regression of the MW fractions against DBPFP showed a strong correlation (R2 between 0.90 and 0.93), indicating that LC-OCD analysis alone could be used to predict DBP formation with reasonable accuracy, and offering the potential for rapid risk assessment of water sources.

Disinfection by-product formation during UV/Chlorine treatment of pesticides in a novel UV-LED reactor at 285 nm and the mitigation impact of GAC treatment.

The UV/Chlorine process has gained attention in recent years due to the high quantum yield and absorbance of the chlorine species. However, there are still many unknowns around its application as a treatment for drinking water. The potential for the formation of disinfection by-products (DBPs) is one of them. There are no studies reporting on the formation of trihalomethanes (THMs) or haloacetic acids (HAAs) in complex matrices, such as real source waters, at UV wavelengths tailored to the UV/Chlorine process, which has been possible thanks to the development of light emitting diodes (LEDs). In addition, consideration of mitigation measures that might be needed after UV/Chlorine treatment for full scale application have not been previously reported. Specifically, the novelty of this work resides in the use of an innovative reactor using UV-LEDs emitting at 285 nm for the removal of three pesticides (metaldehyde, carbetamide and mecoprop), the evaluation of THM, HAA and bromate formation in real water sources by UV/Chlorine treatment and the mitigation effect of subsequent GAC treatment. A new parameter, the applied optical dose (AOD), has been defined for UV reactors, such as the one in the present study, where the irradiated volume is non-uniform. The results showed the feasibility of using the UV/Chlorine process with LEDs, although a compromise is needed between pH and chlorine concentration to remove pesticides while minimising DBP formation. Overall, the UV/Chlorine process did not significantly increase THM or HAA formation at pH 7.9-8.2 at the studied wavelength. At acidic pH, however, THM formation potential increased up to 30% after UV/Chlorine treatment with concentrations up to 60 µg/L. HAA formation potential increased between 100 and 180%, although concentrations never exceeded 35 µg/L. In all cases, GAC treatment mitigated DBP formation, reducing THM formation potential to concentrations between 3 and 16 µg/L, and HAA formation potential between 4 and 30 µg/L.

Elasticidades de demanda de un medicamento antidepresivo en Colombia como estrategia para evaluar poder de mercado / Elasticity of Demand of an Antidepressant Drug in Colombia as an Strategy to Assess Market Power / Elasticidades de demanda de um medicamento antidepressivo na Colômbia como estratégia para avaliar o poder de mercado

Resumen En este artículo se desarrolló un ejercicio de estimación de la elasticidad precio de la demanda de un medicamento "tipo" utilizado para el tratamiento de la depresión. Este trastorno afecta física y mentalmente a un gran número de personas en el mundo y constituye un problema de salud pública con prevalencia creciente. Se estimaron dos modelos econométricos vectoriales para el periodo anterior a la expedición de la circular 03 del 2013 que regula los precios de los medicamentos en Colombia. Como resultado se obtuvo una elasticidad precio no significativa de 0.35%, es decir, que los cambios en el precio no generan la respuesta esperada en la demanda, comportamiento que sugiere la existencia de un alto poder de mercado de la empresa que elabora dicho producto "tipo", lo cual es evidencia de la necesidad de implementar dicha circular.

Abstract This article develops an estimation of the price elasticity of demand of a medication "type" for treating depression. This disorder affects physically and mentally a big part of the population around the world. This disorder is considered an important public health problem whose prevalence has been increasing. For the purpose of this research two econometric models of vectors were estimated for the previous period of the issuance of Circular 03 of 2013, which regulates the price of medications in Colombia. The outcomes of the estimation show a non-significant price elasticity of 0.35%, that is to say, changes in price do not generate the expected response in demand. This result suggests that the company, which produces this type of medication, exerts significant power in the market. Therefore, this result proves the need to implement the Circular.

Resumo Neste artigo é desenvolvido um exercício de estimação da elasticidade-preço da demanda de um medicamento "tipo" utilizado para tratamento da depressão. Tal transtorno afeta física e mentalmente um grande número de pessoas no mundo e constitui um problema de saúde pública com prevalência crescente. Estimaram-se dois modelos econométricos vetoriais para o período anterior à emissão do edital 03 de 2013 que regula os preços dos medicamentos na Colômbia. Como resultado, foi obtida uma elasticidade-preço não significativa de 0.35%, ou seja, que as mudanças no preço não geram a resposta esperada na demanda, comportamento que sugere a existência de alto poder de mercado da empresa que elabora tal produto "tipo", evidenciando a necessidade de implementar o edital.

The challenges of municipal solid waste management systems provided by public-private partnerships in mature tourist destinations: The case of Mallorca.

This article analyzes the influence of tourism on the municipal solid waste management (MSWM) system taking as reference the case study of Mallorca, an internationally renowned destination. The characteristics of tourism such as seasonality and land scarcity, set interesting challenges to public-private partnerships related to MSWM system. The analysis of Mallorca's experience shows that land endowment strongly influences the choice of treatment technologies in tourism destinations. Furthermore, tourism seasonality significantly affects management costs which should be considered on PPP contracts. Finally, the tariff system in this kind of environmental PPPs in tourist destinations still need to improve to promote waste minimization and recycling.

The Greening Role of Tour Operators.

This paper shows that the tour operators (TOs) can play a coordinating role in the adoption of environmental management upstream the tourism supply chain. This is done using a dynamic model to analyze the environmental management adoption by hotels in a tourism destination induced by a TO. The TO can create incentives to greening hotels' management through the sharing of an environmental price premium. We show that the extent of green management adoption depends on interest rate, the willingness to pay for environmental quality, and hotels' organizational inertia. We also show how the financial yields from green management are shared between TOs and hotels. Finally, we consider a destination manager that subsidizes hotels' green management. If the destination manager does not take the greening role of TOs into account, she could mistake the true trade-off that she faces between the destination's economic and environmental outcomes for the win-win setting that characterizes the general problem.

Tourism and solid waste generation in Europe: A panel data assessment of the Environmental Kuznets Curve.

The relationship between tourism growth and municipal solid waste (MSW) generation has been, until now, the subject of little research. This is puzzling since the tourism sector is an important MSW generator and, at the same time, is willing to avoid negative impacts from MSW mismanagement. This paper aims to provide tools for tourism and MSW management by assessing the effects of tourism volume, tourism quality and tourism specialization on MSW generation in the UE. This is done using the Environmental Kuznets Curve (EKC) framework. The study considers a panel data for 32 European economies in the 1997-2010 periods. Empirical results support the EKC hypothesis for MSW and shows that northern countries tend to have lower income elasticity than less developed countries; furthermore, results confirm a non-linear and significant effect of tourism arrivals, expenditure per tourist and tourism specialization on MSW generation.

Risk factors associated with cardiovascular morbidity and mortality in Spanish incident hemodialysis patients: two-year results from the ANSWER study.

AIMS: To identify factors associated with cardiovascular (CV) disease in hemodialysis. METHODS: Multicenter, prospective, 2-year, observational study in 2,310 incident patients (3,496 patient-years). Multivariate Cox models determined baseline characteristics associated with CV disease. RESULTS: Main factors associated with CV deaths (6.3/100 patient-years) were: high Charlson score (hazard ratio (HR) 3.6; 95% confidence interval (CI) 1.7-7.5 for ≥9 vs. ≤4); low Karnofsky score (KS; HR 2.2; 95% CI 1.5-3.3 for KS ≤50 vs. >70); female gender (HR 1.4; 95% CI 1.1-1.9); catheter access (HR 1.4; 95% CI 1.0-1.9); low (<3.5 g/dl) albumin (HR 2.5; 95% CI 1.8-3.3); ferritin deficiency (HR 1.6; 95% CI 1.2-2.2 for <100 vs. ≥100-500 ng/ml) and low body mass index (BMI; HR 1.9; 95% CI 1.2-3.0 for <20 vs. 20-25). A BMI of ≥30 was a protective factor (HR 0.6; 95% CI 0.4-0.9). CONCLUSIONS: There is a high CV risk, especially in older patients with high comorbidity, low BMI, low albumin or iron deficiency. Catheter access increases the CV death risk.

Hall-effect based semi-fast AC on-board charging equipment for electric vehicles.

The expected increase in the penetration of electric vehicles (EV) and plug-in hybrid electric vehicles (PHEV) will produce unbalanced conditions, reactive power consumption and current harmonics drawn by the battery charging equipment, causing a great impact on the power quality of the future smart grid. A single-phase semi-fast electric vehicle battery charger is proposed in this paper. This ac on-board charging equipment can operate in grid-to-vehicle (G2V) mode, and also in vehicle-to-grid (V2G) mode, transferring the battery energy to the grid when the vehicle is parked. The charger is controlled with a Perfect Harmonic Cancellation (PHC) strategy, contributing to improve the grid power quality, since the current demanded or injected has no harmonic content and a high power factor. Hall-effect current and voltage transducers have been used in the sensor stage to carry out this control strategy. Experimental results with a laboratory prototype are presented.

Mortality in incident haemodialysis patients: time-dependent haemoglobin levels and erythropoiesis-stimulating agent dose are independent predictive factors in the ANSWER study.

BACKGROUND: Although the association between low haemoglobin levels and mortality is well established in haemodialysis patients, data are conflicting regarding levels >12 g/dl. In addition, divergent results have been reported on the relation between erythropoiesis-stimulating agents (ESAs) and mortality. METHODS: This was a multicentre, observational, prospective, 24-month study, which recruited Spanish incident haemodialysis patients (N = 2310). Univariate and multivariate time-dependent Cox regression models examined the longitudinal association of mortality with haemoglobin and ESA dose; adjustment was made for iron deficiency and other confounders. RESULTS: After adjusting for age, functional status, body mass index, albumin levels, catheter as vascular access, previous history of cardiovascular disease, neoplasia, and ESA dose, mortality decreased with increasing haemoglobin. Adjusted hazard ratios relative to the reference category (11-12 g/dl) and 95% confidence intervals were: 1.36 (1.01-1.86) for 13 g/dl. Independent of haemoglobin, patients on sustained ESA doses of 1-4000 IU/week and 8001-16 000 IU/week had better survival than non-treated (reference) patients, with adjusted hazard ratios of 0.61 (0.41-0.90) and 0.68 (0.49-0.94), respectively. No significant difference was found for doses of 4001-8000 IU/week or >16,000 IU/week, adjusted hazard ratios of 0.87 (0.63-1.20) and 0.89 (0.63-1.28), respectively. CONCLUSIONS: Higher haemoglobin levels are associated with lower mortality in Spanish incident haemodialysis patients, regardless of ESA dose, comorbidity, vascular access or malnutrition. No increase in mortality occurs for high ESA doses, independent of haemoglobin levels.

Visual and refractive outcomes in hyperopic pseudophakic patients implanted with the Acri.LISA 366D multifocal intraocular lens.

PURPOSE: To assess the visual quality after bilateral implantation of the Acri.LISA 366D intraocular lens (IOL; Carl Zeiss Meditec, Jena, Germany) in patients with hyperopia. DESIGN: Prospective, nonrandomized study. METHODS: One hundred and seventy eyes of 85 patients had bilateral implantation of the Acri.LISA 366D IOL. The patients were divided into 2 groups: low to moderate hyperopia (IOL power, 21 to 24.5 diopters [D]) and high hyperopia (IOL power, 25 to 36 D). Monocular and binocular best spectacle-corrected visual acuity (BSCVA), best distance-corrected near visual acuity (BCNVA), binocular best distance-corrected intermediate visual acuity (VA), and distance contrast sensitivity (CSF) under photopic (85 cd/m(2)) and mesopic (5 cd/m2) conditions were determined. RESULTS: At the 6-month postoperative visit, there were no statistically significant differences in monocular and binocular BSCVA (P = .06 and P = .09, respectively). Monocular and binocular BCNVA were comparable between both groups (P = .24 and P = .42, respectively). The mean binocular best distance-corrected intermediate VA changed significantly as a function of the distance of the test (P < .01) in both groups, and there were no statistically significant differences between groups at any distance. Differences were not found between groups in binocular CSF under mesopic and photopic conditions. CONCLUSIONS: Bilateral implantation of the Acri.LISA 366D in patients with high hyperopia provided a satisfactory full-range of vision comparable with that obtained in patients with low to moderate hyperopia.

[Improved effectiveness in the management of cardiovascular risk among type 2 diabetic patients in primary health care]. / Mejora de la efectividad en el manejo del riesgo cardiovascular de pacientes diabéticos tipo 2 en atención primaria.

OBJECTIVES: To determine the impact of the implementation of a guidelines in the assessment of cardiovascular risk in high-risk patients (type 2 diabetes) in health centres, and to analyse the appropriateness of antihypertensive and antiplatelet treatment in diabetic patients. DESIGN: Quasi-experimental, non-randomised, prospective study with concurrent control group. PLACEMENT: Two health centres in Málaga. PARTICIPANTS: General practitioners of the two centres. INTERVENTIONS: The guideline was implemented through a multifaceted intervention in family physicians in the experimental centre. MAIN OUTCOMES: Rate of cardiovascular risk assessment in high risk population. Secondary: appropriateness of antihypertensive and antiplatelet treatment. RESULTS: Large differences were detected in the cardiovascular risk assessment, improving in the experimental group (74.36% vs. 7.63%; RR = 9.74; 95% CI, 5.15-18.43; P = .0001). Similarly, the antiplatelet use was more in line with the guidelines recommendations in the intervention group (51.28% vs. 36.44%; RR = 1.407; 95% CI, 1.04-1.89; P = .026), and in antihypertensive drugs, although with no statistical significance (80% vs. 66.27%; RR = 1.207; 95% CI, 0.99-1.46). CONCLUSIONS: A multifaceted intervention for the implementation of a guideline for the management of high risk cardiovascular patients, improves the adherence to effective interventions by family physicians.

Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER--a multicentre, prospective, observational cohort study.

BACKGROUND: The ANSWER study aims to identify risk factors leading to increased cardiovascular morbidity and mortality in a Spanish incident haemodialysis population. This paper summarizes the baseline characteristics of this population. METHODS: A prospective, observational, one-cohort study, including all consecutive incident haemodialysis patients from 147 Spanish nephrology services, was conducted. Patients were enrolled between October 2003 and September 2004. Sociodemographic, clinical, laboratory and health care characteristics were collected. RESULTS: Baseline characteristics are described for 2341 incident haemodialysis patients [mean (SD) age 65.2 (14.5) years, 63% males]. The main cause of renal failure was diabetic nephropathy (26%). The majority of patients (57%) had a Karnofsky score of 80-100 and 27% were followed up by a nephrologist for 500 ng/ml, 41% and saturated transferrin <20 or >40%, 50%) despite previous treatment with erythropoiesis-stimulating agents in 41% of cases. CONCLUSIONS: There is excessive use of temporary catheters and a high prevalence of uraemia-related cardiovascular risk factors among incident haemodialysis patients in Spain. The poor control of hypertension, anaemia, malnutrition and mineral metabolism and late referral to a nephrologist indicate the need for improving the therapeutic management of patients before the onset of haemodialysis.

[Previous restenosis as a prognostic indicator in new conventional stent implantation at a different location]. / El comportamiento reestenótico previo como predictor pronóstico ante nueva implantación de stent convencional en distinta localización.

INTRODUCTION AND OBJECTIVES: The aim was to determine whether data on restenosis of a previous stent are useful for predicting outcome in patients who need to undergo a second conventional stent implantation at a different location because of coronary disease progression. METHODS: The study included 80 patients who, during 2000-2004, underwent a second conventional (i.e., not drug-eluting) stent implantation for de novo lesions at a different location to that of the previous stent. Major adverse cardiac events (MACE) were defined as death, non-fatal myocardial infarction, or the need for target lesion revascularization (TLR). RESULTS: One year after the second procedure, the cumulative incidence of MACE was significantly higher in patients who experienced significant restenosis of the previous stent than in those who did not (40.6% vs 12.5%, P=.004). Univariate predictors of MACE were: evidence of previous stent restenosis, previous myocardial infarction, and a small vessel (< or =2.75 mm). However, the only independent predictor (Cox regression) of a MACE was previous stent restenosis (hazard ratio 3.85, 95% confidence interval, 1.46-10.18; P=.007). At one year, the TLR rate was also higher in patients with previous stent restenosis (31.3% vs 8.3%; P=.008), in those with small vessels, and in diabetics. Previous stent restenosis and a small vessel were independent predictors of TLR. CONCLUSIONS: Restenosis of a previous stent is a strong predictor of major adverse events in patients undergoing a second conventional stent implantation at a different location because of coronary disease progression.

Mastoplastia reductora con analgesia acupuntural / A mamaplastic reduction using acupunctural analgesia

Se realizó un ensayo clínico prospectivo y descriptivo con 40 pacientes portadoras de hipertrofia mamaria que acudieron a consulta de Cirugía Plástica en el Hospital Universitario "Abel Santamaría Cuadrado" de Pinar del Río entre septiembre de 2002 y agosto de 2003 a las que se les realizó mastoplastia reductora con analgesia acupuntural (puntos C1, IG4, VC17, VG20 y un punto especial) evaluando la calidad de la analgesia acupuntural transoperatoria, el comportamiento hemodinámico transoperatorio y la ocurrencia de complicaciones postoperatorias. Para la validación estadística se utilizó el paquete Systat Con nivel de ajuste µ= 0.05. Se logró con la acupuntura un nivel analgésico transoperatorio satisfactorio en el 50 % de los casos, incluyendo pacientes de todos los grupos de edad, sobre todo en intervenciones que duraran hasta dos horas, independientemente del grado de hipertrofia mamaria. El comportamiento hemodinámico transoperatorio fue satisfactorio en las pacientes operadas con acupuntura; con esta técnica el registro de complicaciones fue inferior al reportado con anestesia general endotraqueal por otros autores, sin que se reportaran reacciones adversas por el uso de la acupuntura.

A prospective descriptive clinical trial was carried out in a sample of 40 patients suffering from breast hypertrophy who attended Cosmetic Surgery Office at Abel Santamaría General Hospital between September 2002 and August 2003. A reductive mastoplasia using acupunctural analgesia was carried out (C1, IG4, VC17, VG20 points and special one) assessing the quality of transoperative acupunctural analgesia, transoperative hemodynamic behaviour and the occurrence of postoperative complications. Systat pack was used for statistical validation with a fitted level of a = 0.05. a transoperative analgesic level was achieved successfully in 50 % of cases including patients from every age group particularly in up to two hours surgeries irrespective of the breast hypertrophy. The transoperative homodynamic behaviour was successful in patients operated under acupuncture, using this technique it was found that endotraqueal general anaesthesia by other authors, reporting no eventful experiences when performing acupuncture.

Deceleration time of early filling in patients with left ventricular systolic dysfunction: functional and prognostic independent value.

BACKGROUND: Although diastolic function parameters have been mentioned as significant predictors of functional capacity and prognosis in patients with left ventricular (LV) systolic dysfunction, it has not been fully elucidated whether they keep an independent predictive value when multiple parameters from a wide variety of examinations are considered. METHODS: We prospectively studied 60 patients with New York Heart Association (NYHA) class II-IV chronic heart failure symptoms and LV ejection fraction <0.4. At the time of entry into the study, demographic data and functional class were obtained, and usual Doppler echocardiographic, radionuclide ventriculographic, cardiopulmonary exercise testing and hemodynamic variables were determined. Deceleration time of early filling (DT) and NYHA functional class were the only independent predictors of functional capacity as assessed by means of peak oxygen uptake (peak VO2). Mean follow-up was 21 +/- 6 months, and event-free survival was defined as the absence of cardiac death, urgent cardiac transplantation, or hospital admission requiring inotropic or mechanical support. RESULTS: Multivariate Cox analysis showed that DT (P =.008), peak VO2 (P =.01), and NYHA class (P =.02) were independent predictors of event-free survival at 1 year. Patients in the lowest tertile of DT (<130 ms) had a significantly lower event-free survival than patients in the intermediate (44% vs 80%, P =.03) and in the highest tertile (44% vs 83%, P =.02). Patients with both a DT <130 milliseconds and a peak VO2 <14 mL/kg/min had the highest rate of events at 1 year (83% vs 22% for the remaining patients, relative risk 3.75, P <.001). CONCLUSIONS: In patients with LV systolic dysfunction, DT is a powerful independent predictor of functional capacity and prognosis among a wide variety of variables. A shortened DT (<130 ms) identifies a subgroup of patients with a worse outcome, especially when combined with a reduced peak VO2 (<14 mL/kg/min).