Tick feeding modulates the human skin immune landscape to facilitate tick-borne pathogen transmission.

During cutaneous tick attachment, the feeding cavity becomes a site of transmission for tick salivary compounds and tick-borne pathogens. However, the immunological consequences of tick feeding for human skin remain unclear. Here, we assessed human skin and blood samples upon tick bite and developed a human skin explant model mimicking Ixodes ricinus bites and tick-borne pathogen infection. Following tick attachment, we observed rapidly occurring patterns of immunomodulation, including increases in neutrophils and cutaneous B and T cells. T cells upregulated tissue residency markers, while lymphocytic cytokine production was impaired. In early stages of Borrelia burgdorferi model infections, we detected strain-specific immune responses and close spatial relationships between macrophages and spirochetes. Preincubation of spirochetes with tick salivary gland extracts hampered accumulation of immune cells and increased spirochete loads. Collectively, we showed that tick feeding exerts profound changes on the skin immune network that interfere with the primary response against tick-borne pathogens.

Combination effect naringin and pravastatin in lipid profile and glucose in obese rats.

AIMS: The purpose of this study was to compare the effect of naringin 100mg/kg in combination with pravastatin 10mg/kg by gavage for 6weeks compared with monotherapy over lipid profiles, glucose levels and weight in murine model of obesity. MAIN METHODS: The study design was planned with 5 groups of 6 male Wistar Albina rats: Group 1: control with balanced food and vehicle (C-); Group 2: control with Obesity and vehicle (C+); Group 3: Obesity+naringin (N); Group 4: Obesity+pravastatin (P); Group 5: Obesity+pravastatin+naringin (NP). Obesity was developed with a food model. KEY FINDINGS: The naringin groups showed a decrease in weight gain and low glucose values compared to the control group (weight NP:311.4 vs C+:348.6; glucose NP: 173.12 vs C+:235.56) (p<0.05); the group with naringin+pravastatin combination showed the total cholesterol (TC), LDL and triglycerides (TGs) to normal levels (TC NP:51.6 vs C+:83.4; LDL NP:9.32 vs C+:32.32; TGs NP:39.4 vs C+:89.4) (p<0.05); but was not statistically significant compared with monotherapy. SIGNIFICANCE: The combination of naringin and pravastatin did not appear to be better than monotherapy on lipids, but its use could generate euglycemic and antiobesogenic effects, in addition to diminishing the adverse hepatic effects of pravastatin in rats.

Online Measurement of Real-Time Cytotoxic Responses Induced by Multi-Component Matrices, such as Natural Products, through Electric Cell-Substrate Impedance Sensing (ECIS).

Natural products are complex matrices of compounds that are prone to interfere with the label-dependent methods that are typically used for cytotoxicity screenings. Here, we developed a label-free Electric Cell-substrate Impedance Sensing (ECIS)-based cytotoxicity assay that can be applied in the assessment of the cytotoxicity of natural extracts. The conditions to measure the impedance using ECIS were first optimized in mice immortalized hypothalamic neurons GT1-7 cells. The performance of four natural extracts when tested using three conventional cytotoxicity assays in GT1-7 cells, was studied. Betula pendula (silver birch tree) was found to interfere with all of the cytotoxicity assays in which labels were applied. The silver birch extract was also proven to be cytotoxic and, thus, served as a proof-of-concept for the use of ECIS. The extract was fractionated and the ECIS method permitted the distinction of specific kinetic patterns of cytotoxicity on the fractions as well as the extract's pure constituents. This study offers evidence that ECIS is an excellent tool for real-time monitoring of the cytotoxicity of complex extracts that are difficult to work with using conventional (label-based) assays. Altogether, it offers a very suitable cytotoxicity-screening assay making the work with natural products less challenging within the drug discovery workflow.

Validated HPLC-Diode Array Detector Method for Simultaneous Evaluation of Six Quality Markers in Coffee.

Nicotinic acid, N-methylpyridinium ion, and trigonelline are well studied nutritional biomarkers present in coffee, and they are indicators of thermal decomposition during roasting. However, no method is yet available for their simultaneous determination. This paper describes a rapid and validated HPLC-diode array detector method for the simultaneous quantitation of caffeine, trigonelline, nicotinic acid, N-methylpyridinium ion, 5-caffeoylquinic acid, and 5-hydroxymethyl furfural that is applicable to three coffee matrixes: green, roasted, and instant. Baseline separation among all compounds was achieved in 30 min using a phenyl-hexyl RP column (250×4.6 mm, 5 µm particle size), 0.3% aqueous formic buffer (pH 2.4)-methanol mobile phase at a flow rate of 1 mL/min, and a column temperature at 30°C. The method showed good linear correlation (r2>0.9985), precision (less than 3.9%), sensitivity (LOD=0.023-0.237 µg/mL; LOQ=0.069-0.711 µg/mL), and recovery (84-102%) for all compounds. This simplified method is amenable for a more complete routine evaluation of coffee in industry.

Factores de riesgo asociados a la cirugía del adulto con cardiopatía congénita: 22 años de experiencia. ¿Quién debe intervenirlos? / Risk factors for surgery of congenital heart disease in adults: Twenty-two years of experience. Who should operate them?

Objetivo: Analizar la asociación entre mortalidad en cirugía de cardiopatías congénitas del adulto y los factores relacionados con el paciente y la intervención. Método: Estudio descriptivo de intervenciones por cirujanos con actividad habitual en cardiopatías congénitas (238), cardiopatías adquiridas (117) y residentes (108). Se evaluó la asociación de la mortalidad con el riesgo y complejidad quirúrgica, actividad habitual del cirujano, y tiempo de circulación extracorpórea y de pinzamiento aórtico, mediante modelos de regresión logística. Resultados: Se incluyeron 463 cirugías (442 con circulación extracorpórea) entre 1991 y 2012. Edad mediana de intervención: 34 años (52.8% mujeres); primera cirugía 295, reintervención 168. La puntuación mediana del Aristóteles fue 6.8, con complejidad significativamente mayor tras reestructurarse la Unidad en 2001. La mortalidad hospitalaria total fue del 3.9%. La mortalidad se asoció significativamente al número de intervenciones previas (OR: 5.02; IC 95%: 1.44-17.52), intervenciones por cirujanos de cardiopatía adquirida (OR: 3.53; IC 95%: 1.14-10.98), Aristóteles alto (OR: 1,64; IC 95%: 1.18-2.29), y tiempos prolongados de extracorpórea (OR: 1.13; IC 95%: 1.07-1.19). Conclusiones: La mortalidad en cirugía de cardiopatía congénita en adultos es baja. Las intervenciones de alta complejidad, tiempos elevados de extracorpórea y múltiples reintervenciones se asocian con mayor mortalidad. La participación de cirujanos especialistas en cardiopatías congénitas se asocia con mejores resultados.

Objective: To assess the association between mortality in surgery of congenital heart disease in adults, and factors related to patients and operations. Method: Descriptive study of operations performed by specialized surgeons in congenital heart surgery (238), adult acquired surgery (117), and specialty residents (108). The association of mortality with surgical risk and complexity, specialization of surgeon, cardiopulmonary by-pass and aortic cross clamping was assessed fitting logistic regression models. Results: A total of 463 operations were included (442 with cardiopulmonary by-pass) in the study performed between 1991 and 2012. Median age at surgery: 34; 52.8% were women. First surgery: 295, reoperation: 168. Median score of Aristotle was 6.8, with significantly higher complexity since 2001, after restructuring the Unit. Overall hospital mortality was 3.9%. Mortality was significantly associated to number of previous surgeries (OR: 5.02; 95%CI: 1.44-17.52), operations by acquired heart disease surgeons (OR: 3.53; 95%CI: 1.14-10.98), higher Aristotle (OR: 1,64; 95%CI: 1.18-2.29), and high cardiopulmonary by-pass time (OR: 1.13; 95%CI: 1.07-1.19). Conclusions: Surgery of congenital heart disease in adults has been performed with low mortality. High complexity interventions, prolonged cardiopulmonary by-pass times and multiple reoperations were associated to higher mortality. Participation of cardiac surgeons specialized in congenital heart disease is associated with better outcomes.

[Risk factors for surgery of congenital heart disease in adults: twenty-two years of experience. Who should operate them?]. / Factores de riesgo asociados a la cirugía del adulto con cardiopatía congénita: 22 años de experiencia. ¿Quién debe intervenirlos?

OBJECTIVE: To assess the association between mortality in surgery of congenital heart disease in adults, and factors related to patients and operations. METHOD: Descriptive study of operations performed by specialized surgeons in congenital heart surgery (238), adult acquired surgery (117), and specialty residents (108). The association of mortality with surgical risk and complexity, specialization of surgeon, cardiopulmonary by-pass and aortic cross clamping was assessed fitting logistic regression models. RESULTS: A total of 463 operations were included (442 with cardiopulmonary by-pass) in the study performed between 1991 and 2012. Median age at surgery: 34; 52.8% were women. First surgery: 295, reoperation: 168. Median score of Aristotle was 6.8, with significantly higher complexity since 2001, after restructuring the Unit. Overall hospital mortality was 3.9%. Mortality was significantly associated to number of previous surgeries (OR: 5.02; 95%CI: 1.44-17.52), operations by acquired heart disease surgeons (OR: 3.53; 95%CI: 1.14-10.98), higher Aristotle (OR: 1,64; 95%CI: 1.18-2.29), and high cardiopulmonary by-pass time (OR: 1.13; 95%CI: 1.07-1.19). CONCLUSIONS: Surgery of congenital heart disease in adults has been performed with low mortality. High complexity interventions, prolonged cardiopulmonary by-pass times and multiple reoperations were associated to higher mortality. Participation of cardiac surgeons specialized in congenital heart disease is associated with better outcomes.

Pulmonary hypertension in young adults with repaired coarctation of the aorta: an unrecognised factor associated with premature mortality and heart failure.

BACKGROUND: Adults with repaired coarctation of the aorta (CoA) are at risk for premature cardiovascular death or heart failure (HF). We sought to evaluate risk factors for death or HF in young adults with repaired CoA in childhood. METHODS: The medical records of a cohort of 159 adults diagnosed with CoA repaired at a mean age of 4.1 ± 5.7 years were retrospectively reviewed to identify predictors of a combined endpoint of all cause death or hospitalisation for HF by using Cox proportional hazard models. RESULTS: Over a follow-up of 26 ± 8 years (median 27 years) after repair, 5 patients died and 7 developed HF requiring hospitalisation. Pulmonary artery systolic pressure >40 mm Hg (PH) was the main predictor of death or admission for HF (HR 32; 95% CI 4.0-250; p=0.001). Neither systemic hypertension, recoarctation, aortic aneurysm, intracardiac lesions nor treatment with beta-blockers or ACEi/ARBs were statistically related to death or HF. Restrictive left ventricular physiology (RLVP) was the main predictor of PH by logistic regression analysis (OR 31; 95% CI 10-92; p<0.001). Patients with severe PH (pulmonary artery systolic pressure >60 mm Hg) showed RLVP (9/10), severe elevation of end-diastolic LV pressure at cardiac catheterization (8/8) and subendocardial late gadolinium enhancement on MRI (5/5). Pathological examination of an explanted heart demonstrated extensive left ventricular subendocardial fibrosis. CONCLUSIONS: Pulmonary hypertension related to restrictive left ventricular physiology was the strongest predictor of death or HF in young adults with CoA repaired in childhood. Persistent subendocardial fibrosis might be the structural substrate in some patients.

Exploration of Vanilla pompona from the Peruvian Amazon as a potential source of vanilla essence: quantification of phenolics by HPLC-DAD.

This study provides the first chemical investigation of wild-harvested fruits of Vanilla pompona ssp. grandiflora (Lindl.) Soto-Arenas developed in their natural habitat in the Peruvian Amazon. Flowers were hand-pollinated and the resulting fruits were analysed at different developmental stages using an HPLC-DAD method validated for the quantification of glucovanillin and seven other compounds. The method showed satisfactory linearity (r(2)>0.9969), precision (coefficient of variation <2%), recoveries (70-100%), limit of detection (0.008-0.212 µg/ml), and limit of quantification (0.027-0.707 µg/ml). The evaluation of crude and enzyme-hydrolyzed Soxhlet-extracted samples confirmed the leading role of glucosides in fruit development. LC-ESI-MS studies corroborated the identities of four glucosides and seven aglycones, among them vanillin (5.7/100 g), 4-hydroxybenzyl alcohol (3.6/100 g), and anisyl alcohol (7.1/100 g) were found in high concentrations. The attractive flavor/aroma profile exhibited by wild V. pompona fruits supports studies focused on the development of this species as a specialty crop.

Lineamientos para la conservación de documentos en la Biblioteca Médica Nacional de Cuba / Some guidelines for document conservation in the Cuban´s National Library of Medicine

Con el objetivo de desarrollar una guía para la preservación y conservación de los fondos de la Biblioteca Médica Nacional de Cuba, se establecen una serie de lineamientos para el tratamiento de las diferentes clases de colecciones y documentos. Se tratan los factores externos -temperatura, humedad, luz, polvo, agentes biológicos y otros, cuya acción ejerce una mayor influencia negativa sobre la conservación de los fondos en una institución, así como la seguridad de las colecciones ante el agua, el fuego, las guerras y los fenómenos naturales. Finalmente, se abordan las diferentes técnicas para el rescate de colecciones dañadas(AU)

Lineamientos para la conservación de documentos en la Biblioteca Médica Nacional de Cuba / Some guidelines for document conservation in the Cuban´s National Library of Medicine

Con el objetivo de desarrollar una guía para la preservación y conservación de los fondos de la Biblioteca Médica Nacional de Cuba, se establecen una serie de lineamientos para el tratamiento de las diferentes clases de colecciones y documentos. Se tratan los factores externos -temperatura, humedad, luz, polvo, agentes biológicos y otros, cuya acción ejerce una mayor influencia negativa sobre la conservación de los fondos en una institución, así como la seguridad de las colecciones ante el agua, el fuego, las guerras y los fenómenos naturales. Finalmente, se abordan las diferentes técnicas para el rescate de colecciones dañadas

[Surgical closure of atrial septal defect before or after the age of 25 years. Comparison with the natural history of unoperated patients]. / Cierro quirúrgico de la comunicación interauricular antes o después de los 25 años de edad. Comparación con la evolución natural en pacientes no operados.

INTRODUCTION: Surgical closure of an atrial septal defect (ASD) before the age of 25 years has been demonstrated to reduce complications during adulthood. However, the outcome for patients operated after the age of 25 is still debated. METHODS: In a retrospective study we examined the outcome of early and late surgical repair of ASD in adults, as compared with the natural evolution of unoperated patients. The study population was 280 patients (mean age 40 18 years) with non-restrictive ASD: 102 patients (group 1) underwent surgery before the age of 25 years, 90 patients (group 2) underwent surgery after the age of 25 years, and 88 unoperated patients were older than 25 years at the time of study (group 3). The variables analyzed were left ventricular systolic function, left atrial dimensions, systolic pulmonary pressure, right ventricular dimensions, the degree of mitral and tricuspid regurgitation, and the prevalence of late atrial fibrillation. RESULTS: Left ventricular systolic function and the degree of mitral regurgitation were not statistically different between groups. Compared with the patients in group 2, the patients in group 1 had a significantly lower systolic pulmonary arterial pressure (p < 0.001) and less dilated right ventricle (p < 0.001) and left atrium (p < 0.001). The degree of tricuspid regurgitation (p < 0.001) and prevalence of atrial fibrillation (p < 0.001) were significantly higher in the patients of group 2. Compared with group 3, the patients in group 2 had a significantly lower systolic pulmonary arterial pressure (p < 0.001) and less dilated right ventricle (p < 0.001). However, the left atrial dimensions, degree of tricuspid regurgitation, and prevalence of atrial fibrillation did not differ in a statistically significant way between the two groups. CONCLUSIONS: Surgical repair of an atrial septal defect in patients over 25 years of age does not fully prevent hemodynamic deterioration and the development of atrial arrhythmias. Therefore it seems that the surgical closure of ASD before adulthood should be strongly recommended.

[Multiplane transesophageal echocardiography in the preoperative evaluation of the sinus of Valsalva fistula to right chambers]. / Ecocardiografía transesofágica multiplana en la valoración preoperatoria de fístulas de senos de Valsalva en cavidades derechas.

INTRODUCTION AND OBJECTIVES: Ruptured sinus of Valsalva aneurysm to right cardiac chambers is an uncommon lesion in Western countries. The prognosis is usually serious unless the condition is promptly treated surgically. For this reason an accurate anatomical and functional evaluation is necessary. The main purpose of this report is to compare the usefulness of multiplane transesophageal echocardiography with transthoracic echocardiography and angiocardiography in the preoperative evaluation of ruptured sinus of Valsalva aneurysm to right chambers. PATIENTS AND METHOD: Since January 1990, 9 patients (mean age 36,3 18 yr, 6 males) with ruptured sinus of Valsalva aneurysm to right chambers were studied. The pathogenesis was congenital aneurysm in 6 patients, aortic prosthesis endocarditis in one and two cases of iatrogenia: during a percutaneous mitral valvuloplasty and after cardiac surgery. Transthoracic echocardiography was performed in all cases, transesophageal echocardiography in 7 and angiocardiography in 8. Two patients died before surgery, and 7 were successfully operated on. RESULTS: Transesophageal echocardiography was more useful when compared to transthoracic echocardiography and angiocardiography in detecting: a) the fistula; b) the sinus involved; c) the right chamber affected; d) congenital aneurysms morphology and size; e) aneurysm prolapse through a ventricular septal defect, y f) the identification of other cardiac congenital or acquired anomalies. CONCLUSIONS: Multiplane TEE is the most accurate tool in the preoperative evaluation of ruptured sinus of Valsalva aneurysm to right chambers.