Effect of antibiotic to induce Clostridioides difficile-susceptibility and infectious strain in a mouse model of Clostridioides difficile infection and recurrence.

The anaerobic bacterium Clostridioides difficile is the leading cause of antibiotic-associated diarrhea that can culminate in life-threating colitis. During the C. difficile infection (CDI), C. difficile produces toxins that generate the clinical symptoms of the disease, and produce spores, which persist in the host during antibiotic treatment and can cause recurrent CDI (R-CDI). In this work, we aimed to compare three antibiotic regimens in the susceptibility of mice to CDI and R-CDI (i.e., antibiotic cocktail followed by clindamycin, 5 days of cefoperazone and 10 days of cefoperazone) with three different C. difficile isolates (i.e., strains 630; R20291, and VPI 10463). We observed that the severity of the clinical symptoms of CDI and R-CDI was dependent on the antibiotic treatment used to induce C. difficile-susceptibility, and that the three strains generated a different onset to diarrhea and weight loss in mice that were administrated with the same antibiotic treatment and which differed in comparison to the effect previously reported by other research groups. Our results suggest that, in our experimental conditions, in those animals treated with antibiotic cocktail followed by clindamycin, infection with strain R20291 had the highest diarrhea manifestation in comparison to strains 630 and VPI 10463. In animals treated with cefoperazone for 5 days, infection with strains R20291 or 630 had the highest diarrhea manifestation in comparison to VPI 10463, while in animals treated with cefoperazone for 10 days, infection with strain R20291 or VPI 10463, but not 630, had the highest diarrhea manifestation.

Increased active phase atrial contraction is related to marathon runner performance.

PURPOSE: Left atrial (LA) contraction is essential for left ventricular (LV) filling during exertion. We sought to evaluate the relationship of LA contraction and exercise capacity in trained athletes. METHODS: Sixteen male marathon runners were recruited and allocated into two groups according to their previous training status (≥ or < 100 km peer week). All subjects underwent a baseline cardiopulmonary test to evaluate maximal aerobic capacity and a transthoracic echocardiography previous and immediate post-marathon. LA contractile function evaluation was accomplished by measuring the negative deformation of the post P wave strain curve (LASa). LASa change was defined as LASa pre-marathon minus LASa immediate post-marathon. RESULTS: Mean age was 39 ± 6 years. LA volume index (39 ± 13 vs. 31 ± 5 mL/m2, p = 0.04), LV mass index (91 ± 21 vs. 73 ± 12 g/m2, p = 0.04), VO2 max (59 ± 3 vs. 50 ± 8 mL/kg/min, p = 0.036) were higher in more intensive trained group and marathon time was lower (185 ± 14 vs. 219 ± 24 min, p = 0.017). An increase in LASa after immediate post-marathon was observed in both groups, which was significantly greater in the highly trained group (18.9 ± 5.8 vs. 6.3 ± 3.5%, p < 0.003). Maximum VO2 measured previous to the marathon was inversely related to marathon time and directly correlated to LASa change (rho = 0.744, p = 0.001, rho = 0.546, p = 0.028, respectively). CONCLUSIONS: Athletes with more intensive training load have larger LV mass and LA size. An increase in LA contraction was seen post-marathon, which was significantly greater in the highly trained group. This increase in the LA contraction was related to the maximum VO2 measured previous to the marathon and to performance in a highly demanding test.

[Exercise and cardiac rehabilitation in secondary cardiovascular prevention]. / Rehabilitación cardiovascular y ejercicio en prevención secundaria.

Exercise and cardiac rehabilitation are indications with type I A evidence in most secondary cardiovascular prevention guidelines. Rehabilitation programs not only include exercise but also provide integral care and education about cardiovascular risk factors. However there is a paucity of such programs in Chile. Moreover there is a lack of awareness about the benefits of exercise and there is lack of knowledge about the details of exercise prescription in secondary prevention. Therefore, the divulgation of this knowledge is of utmost importance.

The chaperone ClpC participates in sporulation, motility, biofilm, and toxin production of Clostridioides difficile.

OBJECTIVES: Clostridioides difficile is a nosocomial pathogen that is associated with the use of antibiotics. One of the most worrying aspects of C. difficile infection is its ability to resist antimicrobial therapies, owing to spore formation. In several bacterial pathogens, proteases of the Clp family participate in phenotypes associated with persistence and virulence. This suggests that these proteins could be involved in virulence-related traits. In this study, we analysed the role of ClpC chaperone-protease of C. difficile in virulence-related traits by comparing the phenotypes of wild-type and mutant strains lacking the clpC gene (ΔclpC). METHODS: We performed biofilm, motility, spore formation, and cytotoxicity assays. RESULTS: Our results show significant differences between the wild-type and ΔclpC strains in all analysed parameters. CONCLUSIONS: Based on these findings, we conclude that clpC plays a role in the virulence properties of C. difficile.

Assessment of left atrial function in hypertrophic cardiomyopathy and athlete's heart: a left atrial myocardial deformation study.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cause of sudden death in athletes and differentiating this condition from the nonpathological "athlete's heart" remains a challenge. The development of pathological left ventricular hypertrophy (LVH) is associated with left atrial (LA) dilatation and dysfunction. LA strain and strain rate by two-dimensional (2D) speckle tracking are novel indices of LA function and might contribute to differentiate physiological from pathological LVH among athletes with underdiagnosed HCM. METHODS: We evaluated 20 patients with nonobstructive HCM, 20 highly trained athletes and 20 healthy controls matched for age, gender, and body surface area. All patients underwent a transthoracic echocardiogram with evaluation of LA strain: s-wave (LASs); and strain rate: s-wave (LASRs) and a-wave (LASRa). RESULTS: LV mass index, LA volume index, and ejection fraction were comparable between patients with HCM and athletes. Patients with HCM had a significantly lower LASs (19 + 8% vs. 43 + 8%, P < 0.01), LASRs (0.7 + 0.2 s-1 vs. 1.6 + 0.2 s-1, P < 0.01), and LASRa (-0.8 + 0.1 s-1 vs. -1.4 + 0.3 s-1, P < 0.01) compared to athletes. Among hypertrophic subjects, independent predictors of hypertrophy related to HCM were LASs and E/é ratio. CONCLUSIONS: LA myocardial deformation is significantly impaired in patients with HCM compared to athletes and healthy controls. LA strain and strain rate assessed by 2D speckle tracking should be incorporated in the evaluation of trained athletes with LVH and LA dilatation.

CdsH Contributes to the Replication of Salmonella Typhimurium inside Epithelial Cells in a Cysteine-Supplemented Medium.

Salmonella Typhimurium is a facultative, intracellular pathogen whose products range from self-limited gastroenteritis to systemic diseases. Food ingestion increases biomolecules' concentration in the intestinal lumen, including amino acids such as cysteine, which is toxic in a concentration-dependent manner. When cysteine's intracellular concentration reaches toxic levels, S. Typhimurium expresses a cysteine-inducible enzyme (CdsH), which converts cysteine into pyruvate, sulfide, and ammonia. Despite this evidence, the biological context of cdsH's role is not completely clear, especially in the infective cycle. Since inside epithelial cells both cdsH and its positive regulator, ybaO, are overexpressed, we hypothesized a possible role of cdsH in the intestinal phase of the infection. To test this hypothesis, we used an in vitro model of HT-29 cell infection, adding extra cysteine to the culture medium during the infective process. We observed that, at 6 h post-invasion, the wild type S. Typhimurium proliferated 30% more than the ΔcdsH strain in the presence of extra cysteine. This result shows that cdsH contributes to the bacterial replication in the intracellular environment in increased concentrations of extracellular cysteine, strongly suggesting that cdsH participates by increasing the bacterial fitness in the intestinal phase of the S. Typhimurium infection.

Macromolecule release and smoothness of semi-interpenetrating PVP-pHEMA networks for comfortable soft contact lenses.

Knowledge about the microstructure and the release rate of hydrophilic macromolecules is required for a rational development of comfortable and safe contact lenses. Semi-interpenetrating networks of poly(hydroxyethyl methacrylate) (pHEMA) with poly(vinyl pyrrolidone) (PVP) were prepared by free radical polymerization of HEMA in the presence of PVP K30 or K90F, under anhydrous conditions or after addition of water, and evaluated in terms of swelling, porosity, PVP release rate, air-water surface tension, and friction coefficient. The greater water content was during polymerization, the higher was the swelling degree and porosity. Microphase separation above a certain volume of water resulted in hydrogels with bumpy surface and interconnected pores. All hydrogels showed a high optical clarity and slowly released PVP (20% after 9 days). In general, the greater the content of PVP or the higher its molecular weight was, the lower the friction coefficients were. In the case of hydrogels prepared with water, the friction was influenced by the balance between the ability to hold water in the network (which contributes to the sliding and PVP release) and the deleterious effect of an irregular surface. Controlled delivery of PVP revealed as a critical factor for improving the frictional behavior of pHEMA contact lenses.

Pluronic and tetronic copolymers with polyglycolyzed oils as self-emulsifying drug delivery systems.

The potential of poly(ethylene oxide)-poly(propylene oxide) block copolymers Pluronic F127 (PF127) and Tetronic 304 (T304), 904 (T904) and 1307 (T1307) as components of solid self-(micro)emulsifying dosage forms, S(M)EDDS, was evaluated. The dependence of the self-associative properties of Tetronics on pH explained the low ability of the micelles to solubilize griseofulvin at acid pH (sevenfold increase) compared to at alkaline pH (12-fold). Blends of polyglycolyzed glycerides (Labrasol, Labrafac CC, and Labrafil M 1944CS) with each copolymer at two different weight ratios (80:20 and 60:40) were prepared, diluted in water, and characterized in terms of globule size, appearance and griseofulvin solubility. The blends with Labrasol led to microemulsions that are able to increase drug solubility up to 30-fold. SMEDD hard gelatine capsules filled with griseofulvin and Labrasol or Labrasol/copolymer 80:20 showed a remarkable increase in drug solubility and dissolution rate, particularly when T904, T1307 or PF127 was present in the blend. This effect was more remarkable when the volume of the dissolution medium was 200 ml (compared to 900 ml), which can be related to a higher stability of the microemulsion when there is a greater concentration of the copolymer and glyceride in the medium.

Household survey data of adoption of improved varieties and management practices in rice production, Ecuador.

This article provides a description of an agricultural household survey data of rice growers collected in Ecuador between October 2014 and March 2015. The household survey was implemented using a structured questionnaire administered among 1028 households in the main rice production areas of Ecuador (i.e. Guayas, Los Rios, Manabi, and El Oro provinces). Information collected was provided by household heads (male or female) and included household and plot level data. The survey information includes household socio-demographic characteristics (e.g. age, education, gender, main economic activity, etc.), farm characteristics (e.g. farm land size, assets ownership, other crops planted, etc.), rice management practices (e.g. variety and input use, production costs, etc.), and rice production and utilization (e.g. yields, prices, sales, etc.). Additional socio-economic context variables were also recorded such as government subsidies to rice production, participation in rural organizations, and food security related questions. The dataset contains a total of 6288 variables among numeric, categorical and string variables. The dataset is shared publicly on the Harvard dataverse site and provide access to questionnaires, the complete data and a brief report.

Potential adverse cardiac remodelling in highly trained athletes: still unknown clinical significance.

Moderate endurance exercise has long been considered an essential element to maintain cardiovascular health, and sedentary behaviour in the general population has been related to a significant increase in all-causes of mortality, cardiovascular disease mortality and cardiovascular disease incidence. However, a growing group of people performs an intense exercise that leads to multiple heart adaptive changes that are collectively called "athlete's heart". In this review, we discussed the evidence of cardiac remodelling process secondary to repetitive and strenuous exercise in some predisposed athletes that produces intense and probably deleterious changes in cardiac morphology and function with no clear clinical significance in long-term follow-up. Moreover, we also discussed the individual biological response to exercise assessed by myocardial damage, inflammation, oxidative stress, fibrosis and ventricular hypertrophy biomarkers showing different intensities with equivalent exertion.

[Gallstone ileus, surgical management review]. / Íleo biliar, revisión del manejo quirúrgico.

BACKGROUND: Gallstone ileus (GI) represents a rare cause of mechanical intestinal occlusion, which is caused by the impaction of a gallstones at the gastrointestinal tract, being most frequently the terminal ileum; its etiology is due to the passage of a calculum through a biliary-enteric fistula. Due to its low incidence, diagnostic suspicion and adequate initial surgical treatment are essential for an adequate clinical evolution. OBJECTIVE: A bibliographic review on the current surgical management of GI was carried out and exemplified by the presentation a clinical case. CLINICAL CASE: 78-year-old male with bowel obstruction, upon undergoing a CT scan, a gallstone at the level of distal ileum is displayed, therefore, an exploratory laparotomy (ex lap) is performed with enterotomy and extraction of the calculus. The patient bestowed adequate postoperative clinical evolution, and the presence of a cholecystoduodenal fistula is documented by an upper endoscopy. DISCUSSION: GI represents an uncommon pathology, however, there is discrepancy in the literature regarding the initial surgical management, especially in whether or not a biliary procedure should be associated with emergency enterolithotomy. CONCLUSION: GI is associated with complications secondary to diagnostic delay and its late surgical resolution, although the initial treatment is aimed at resolving the intestinal obstruction through enterotomy and gallstone extraction, there is controversy regarding the preferred time for cholecystectomy and repair of biliary-enteric fistula, being the two-stage surgery the surgical procedure of choice, especially in patients with a high risk of complications.

ANTECEDENTES: El íleo biliar (IB) es una causa poco frecuente de oclusión intestinal mecánica, causado por la impactación de un cálculo biliar en el tubo digestivo, siendo la localización más frecuente el íleon terminal; se debe al paso de un cálculo a través de una fístula bilioentérica. Debido a su baja incidencia, la sospecha diagnóstica y el tratamiento quirúrgico inicial adecuado son de gran importancia para la evolución clínica. OBJETIVO: Realizar una revisión bibliográfica sobre el manejo quirúrgico actual del IB y ejemplificarlo mediante la presentación de un caso clínico. CASO CLÍNICO: Varón de 78 años con cuadro de oclusión intestinal, con presencia de cálculo biliar en el íleon distal por tomografía. Se realiza laparotomía exploradora con enterotomía y extracción del cálculo. Cursa con adecuada evolución posquirúrgica, documentándose fístula colecistoduodenal por panendoscopia. DISCUSIÓN: El IB es una patología poco común, por lo cual existe discrepancia en cuanto al tipo de manejo quirúrgico ideal, sobre todo en si se debe o no asociar un procedimiento biliar a la enterolitotomía de urgencia. CONCLUSIÓN: El IB se asocia a complicaciones secundarias al retraso diagnóstico y a una mala elección de la técnica quirúrgica inicial. Si bien el tratamiento está encaminado a resolver la obstrucción intestinal mediante enterotomía y extracción del cálculo biliar, existe controversia en cuanto al tiempo preferido para realizar la colecistectomía y la reparación de la fístula bilioentérica, siendo la cirugía en dos tiempos el procedimiento quirúrgico de elección, sobre todo en pacientes con alto riesgo de complicaciones.

Remarkable Diagnostic Magnetic Resonance Imaging Findings in Sellar Xanthogranuloma: Report of Three First Cases in Latin America.

The sellar xanthogranuloma is a rare lesion of the sellar-parasellar region difficult to differentiate from other tumors such as craniopharyngiomas or Rathke's cleft cyst in the preoperative evaluation. As they are recently recognized as a separate entity and the few number of reports in the literature, its etiology is unknown and its impact remains uncertain. This article will describe the first three cases reported in Latin America, identified in one of them an imaging feature that may be helpful to elucidate an imaging growth pattern. Current evidence will be described regarding to the clinicopathological features, imaging diagnosis, and etiology origin theories.

Imprinted soft contact lenses as norfloxacin delivery systems.

Soft contact lenses are receiving an increasing attention not only for correcting mild ametropia but also as drug delivery devices. To provide poly(hydroxyethyl methacrylate), PHEMA, lenses with the ability to load norfloxacin (NRF) and to control its release, functional monomers were carefully chosen and then spatially ordered applying the molecular imprinting technology. Isothermal titration calorimetry (ITC) studies revealed that maximum binding interaction between NRF and acrylic acid (AA) occurs at a 1:1, and that the process saturates at 1:4 molar ratio. Hydrogels were synthesized using different NRF:AA molar ratios (1:2 to 1:16), at two fix AA total concentrations (100 and 200 mM), and using moulds of different thicknesses (0.4 and 0.9 mm). The cross-linker molar concentration was 1.6 times that of AA. Control (non-imprinted) hydrogels were prepared similarly but with the omission of NRF. All hydrogels showed a similar degree of swelling (55%) and, once hydrated, presented adequate optical and viscoelastic properties. After immersion in 0.025, 0.050 and 0.10 mM drug solutions, imprinted hydrogels loaded greater amounts of NRF than the non-imprinted ones. Imprinted hydrogels synthesized using NRF:AA 1:3 and 1:4 molar ratios showed the greatest ability to control the release process, sustaining it for more than 24 h. These results prove that ITC is a useful tool for the optimization of the structure of the imprinted cavities in order to obtain efficient therapeutic soft contact lenses.

Genome Sequence of Clostridium paraputrificum 373-A1 Isolated in Chile from a Patient Infected with Clostridium difficile.

Clostridium paraputrificum is a gut microbiota member reported in several cases of bacteremia and coinfections. So far, only one genome sequence of a C. paraputrificum (AGR2156) isolate is available. Here, we present the draft genome of C. paraputrificum strain 373-A1, isolated from stools from a patient with C. difficile infection.

Biomarcadores de fibrosis y función ventricular derecha en maratonistas con distinto grado de entrenamiento: estudio en la maratón de Santiago / Fibrosis and right ventricular function biomarkers in marathon runners: a study at the Santiago, Chile marathon

Resumen: Introducción: Atletas altamente entrenados muestran cambios cardíacos estructurales como adaptación a la sobrecarga, producto del ejercicio repetitivo y extenuante. Se han evidenciado elevación de biomarcadores de remodelado y fibrosis miocárdica posterior al ejercicio intenso en atletas. Sin embargo, el comportamiento de estos biomarcadores según el nivel de entrenamiento previo no se ha evaluado. Objetivo: Investigar biomarcadores de fibrosis y función ventricular derecha en maratonistas con distinto nivel de entrenamiento previo. Métodos: Se incluyeron 36 maratonistas hombres, sanos, que completaron 42 km en la maratón de Santiago. Se dividieron según entrenamiento previo en dos grupos, Grupo 1 (G1): ≥100 km/semana y Grupo 2 (G2): <100 km/semana. Se realizó ecocardiografía transtorácica y se evaluaron niveles plasmáticos de galectina-3 y del propéptido amino terminal del procolágeno tipo III (PIIINP) en la semana previa a la carrera e inmediatamente posterior a ésta. Resultados: Posterior a la maratón, la función sistólica del ventrículo derecho disminuyó en el grupo G2 junto con un aumento significativo de los niveles plasmáticos de PIIIPNP (61±16 a 94±24 ng/mL, p=0,01). Estos cambios no se observaron en el grupo G1 (65 ± 11 a 90±29 ng/mL, p=0,10). Los niveles plasmáticos de galectina-3 aumentaron significativamente en ambos grupos posterior al ejercicio (6,8±2,2 a 19,7±4,9 ng/mL, p 0,012 y 6,0±1,1 a 19,4 ± 5,9 ng/mL, p 0,01) en los grupos G1 y G2, respectivamente). Conclusiones: Atletas con menor grado de entrenamiento, presentan posterior a una maratón un significativo aumento de productos de degradación del colágeno (PIIIPNP) asociado a disminución de la función del ventrículo derecho. Los niveles de galectina-3 plasmática aumentan significativamente en ambos grupos post-esfuerzo independiente del entrenamiento previo.

Abstracts: Introduction: Highly trained athletes show structural cardiac changes as adaptation to overload. Rise in remodeling biomarkers and myocardial fibrosis after intense exercise in athletes has been evidenced; however, the behavior of these biomarkers according to pre-competition training level has not been evaluated. Objective: To evaluate fibrosis biomarkers levels and right ventricle function in marathon runners according to their previous training level, in the period prior to a marathon race and immediately after it. Methods: Thirty-six healthy male marathon runners were included. Subjects were grouped according to their previous training level: Group 1 (G1): ≥100 km/week and Group 2 (G2): <100 km/week. Transthoracic echocardiography along with plasmatic levels of galectin-3 and amino terminal propeptide of type III procollagen (PIIINP) were measured one week previous and immediately after the marathon. Results: Post-effort right ventricle systolic function decreased in G2, together with a significant elevation of PIIIPNP (61±16 to 94±24 ng/mL, p=0.01). These changes were not observed in G1 (from 65±11 to 90±29 ng/mL, p=0.10). Plasma galectin-3 increased significantly in both groups immediately post-exercise (6.8±2.2 to 19.7±4.9 ng/mL, p=0.012, and 6.0±1.1 to 19.4±5.9 ng/mL, p=0.01, in G1 and G2. respectively). Conclusion: Less trained athletes evidenced higher post marathon levels of PIIIPNP which is associated with a decreased global right ventricle function. Plasma galectin-3 levels increased significantly after intense exertion regardless of the intensity of previous training.

Factores determinantes de éxito de la rehabilitación cardiovascular en pacientes coronarios sometidos a revascularización miocárdica / Cardiovascular Rehabilitation in patients following myocardial revascularization: factors associated to program success

Resumen: Introducción: La rehabilitación cardiovascular ha demostrado tener efectos beneficiosos en pacientes con antecedentes de patología coronaria. Objetivos: Identificar los factores que determinan el resultado de un programa de rehabilitación cardiovascular (PRC) aplicado a pacientes coronarios revascularizados. Métodos: 67 pacientes sometidos a cirugía de bypass o angioplastia fueron evaluados en su capacidad funcional mediante el test de marcha de 6 minutos (TM) al inicio y al completar el programa de rehabilitación cardiovascular. La distancia recorrida en el test de marcha fue correlacionada con la edad, capacidad funcional previa al PRC, tiempo en completar el pro-grama, tiempo que media entre la intervención y el inicio del programa, duración del programa y tipo de revascularización. Además, se comparó el incremento de la capacidad funcional entre los pacientes que fueron derivados a 36 sesiones con los referidos a solo 12. Resultados: 67 pacientes cumplieron los criterios para evaluación del PRC. Globalmente, se observó una mejoría de 12% (511,4 a 573,4 m) en la distancia del TM (p<0.001)). El mayor beneficio, en términos de distancia en el TM se obtuvo al efectuar un programa con más sesiones (36 vs 12) con valores de 20% y 8%, respectivamente (p<0.002). El poder terminar el PRC de 36 sesiones más rápidamente (entre 10 y 13 semanas vs entre 14 y 24 semanas se asoció a una mayor incremente en el TM con valores de 19% vs 10%, respectivamente (p<0,003). El incremento en el TM no difirió entre 3 grupos de edad (desde 49 a 85 años); en el tiempo que transcurre entre la intervención y el inicio del PRC (antes vs después de la 8a semana post revascularización), al tipo de revascularización a la que fue sometido el paciente (cirugía o angioplastía) y a la capacidad funcional previa que estos presentan al inicio del PRC. Conclusión: El PRC es efectivo en mejorar significativamente la capacidad funcional de pacientes revascularizados, especialmente cuando el número de sesiones del programa es mayor y cuando se realiza con una frecuencia de al menos 3 veces por semana. El PRC es igualmente efectivo en pacientes enviados a rehabilitación en forma más precoz, como también lo es en sujetos más añosos. Estos efectos fueron independientes del tipo de revascularización.

Abstracts: Introduction : Background: Cardiovascular Rehabilitation Programs (CRP) have been shown to produce be-neficial effects in patients with coronary artery disease. Aim: to identify factors associated to CRP success in patients who underwent myocardial revascularization Methods: 67 patients who underwent coronary artery bypass surgery (CABG) or percutaneous coronary artery angioplasty (PTCA) were evaluated for functional capacity by means of a standard 6 min walking test (6mWT), before and after completion of the CRP. Distance covered during the test was correlated with age, prior functional class, time employed to complete CRP, time from coronary intervention and CRP initiation, CRP duration and type of revascularization. In addition, patients referred for a 36 sessions CRP were compared to those referred to only 12 sessions. Results: 67 patients met inclusion criteria. Overall, there was a 12% increase (511,4 to 573,4 m) in 6mWT distance (p<0.001). The greatest benefit was obtained with the 36 session CRP as compared to a 12 session CRP (20 vs 8% (p<0.002). Also, completion of a 36 session CRP between 10 and 13 weeks compared to 14 to 24 weeks revealed a greater benefit in the former group (19% vs 10%, respectively (p<0.003). There was no difference in 6minWT distance in 3 groups of age (extending from 49 to 85 years-old); In addition, time from intervention to initiation of CRP (before vs after 8 weeks), type of revascularization or functional capacity at the beginning of CRP showed any difference in 6mWT distance. Conclusion: CRP is a highly effective intervention to improve functional capacity in patients following myocardial revascularization, more so when more sessions are employed and when at least 3 sessions per week are implemented. The program is equally effective in patients starting CRP early after revascularization, and benefit is independent from patient age.

Supercritical fluid-assisted preparation of imprinted contact lenses for drug delivery.

The aim of this work was to develop an innovative supercritical fluid (SCF)-assisted molecular imprinting method to endow commercial soft contact lenses (SCLs) with the ability to load specific drugs and to control their release. This approach seeks to overcome the limitation of the common loading of preformed SCLs by immersion in concentrated drug solutions (only valid for highly water soluble drugs) and of the molecular imprinting methods that require choice of the drug before polymerization and thus to create drug-tailored networks. In particular, we focused on improving the flurbiprofen load/release capacity of daily wear Hilafilcon B commercial SCLs by the use of sequential SCF flurbiprofen impregnation and extraction steps. Supercritical carbon dioxide (scCO2) impregnation assays were performed at 12.0 MPa and 40 °C, while scCO2 extractions were performed at 20.0 MPa and 40 °C. Conventional flurbiprofen sorption and drug removal experiments in aqueous solutions were carried out for comparison purposes. SCF-processed SCLs showed a recognition ability and a higher affinity for flurbiprofen in aqueous solution than for the structurally related ibuprofen and dexamethasone, which suggests the creation of molecularly imprinted cavities driven by both physical (swelling/plasticization) and chemical (carbonyl groups in the network with the C-F group in the drug) interactions. Processing with scCO2 did not alter some of the critical functional properties of SCLs (glass transition temperature, transmittance, oxygen permeability, contact angle), enabled the control of drug loaded/released amounts (by the application of several consecutive processing cycles) and permitted the preparation of hydrophobic drug-based therapeutic SCLs in much shorter process times than those using conventional aqueous-based molecular imprinting methods.

Computational modeling and molecular imprinting for the development of acrylic polymers with high affinity for bile salts.

This work has focused on the rational development of polymers capable of acting as traps of bile salts. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for cholate salts in aqueous medium. The screening of a virtual library of 18 monomers, which are commonly used for imprinted networks, identified N-(3-aminopropyl)-methacrylate hydrochloride (APMA.HCl), N,N-diethylamino ethyl methacrylate (DEAEM) and ethyleneglycol methacrylate phosphate (EGMP) as suitable functional monomers with medium-to-high affinity for cholic acid. The polymers were prepared with a fix cholic acid:functional monomer mole ratio of 1:4, but with various cross-linking densities. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to remove sodium cholate from aqueous medium. High affinity APMA-based particles even resembled the performance of commercially available cholesterol-lowering granules. The imprinting effect was evident in most of the networks prepared, showing that computational modeling and molecular imprinting can act synergistically to improve the performance of certain polymers. Nevertheless, both the imprinted and non-imprinted networks prepared with the best monomer (APMA.HCl) identified by the modeling demonstrated such high affinity for the template that the imprinting effect was less important. The fitting of adsorption isotherms to the Freundlich model indicated that, in general, imprinting increases the population of high affinity binding sites, except when the affinity of the functional monomer for the target molecule is already very high. The cross-linking density was confirmed as a key parameter that determines the accessibility of the binding points to sodium cholate. Materials prepared with 9% mol APMA and 91% mol cross-linker showed enough affinity to achieve binding levels of up to 0.4 mmol g(-1) (i.e., 170 mg g(-1)) under flow (1 mL min(-1)) of 0.2 mM sodium cholate solution.

Rehabilitación cardiovascular y ejercicio en prevención secundaria / Exercise and cardiac rehabilitation in secondary cardiovascular prevention

Exercise and cardiac rehabilitation are indications with type I A evidence in most secondary cardiovascular prevention guidelines. Rehabilitation programs not only include exercise but also provide integral care and education about cardiovascular risk factors. However there is a paucity of such programs in Chile. Moreover there is a lack of awareness about the benefits of exercise and there is lack of knowledge about the details of exercise prescription in secondary prevention. Therefore, the divulgation of this knowledge is of utmost importance.