Democratic quality and excess mortality during the COVID-19 pandemic.

The aim of this study is to analyse the relationship between democratic quality and excess mortality produced in the year 2020 before COVID-19 vaccinations were generalised. Using cross-sectional data from 80 countries on five continents, multiple linear regression models between excess mortality, the general democracy index and its disaggregation into five categories: electoral process and pluralism, government functioning, political participation, political culture and civil liberties were estimated. The analysis also considered, public health spending per capita, overweight inhabitants, the average temperature of the country, population over 65 years of age, The KOF Globalisation Index, and the Gross National Income per capita as control variables. It was possible to establish a strong inverse association between excess mortality per million inhabitants and the general democracy index and four of its five categories. There was a particularly strong relationship between excess mortality and the political culture dimension (-326.50, p < 0.001). The results suggest that the higher the democratic quality of the political institutions of a State and particularly of their political culture the more improved the response and management of the pandemic was in preventing deaths and protecting their citizens more effectively. Conversely, countries with lower democracy index values have higher excess mortality. Quality democratic political institutions provide more effective public health policies in the face of the COVID-19 pandemic.

Determination of Five Sit-to-Stand Test Performance at Discharge of Stroke Patients.

The early identification of performance in the five-repetition sit-to-stand test (5-STS) at discharge in stroke patients could be of interest because it can determine independence for community-based activities. This study aimed to determine whether the initial measurement of the 5-STS test can be a determinant of the performance level prediction and amount of change in the 5-STS test at discharge in stroke patients. A prospective cohort study was conducted with a sample of 56 patients aged ≤60 d post-stroke. The 5-STS test results, as well as changes in patient condition, were measured at admission (T0) to an outpatient rehabilitation program, after the first month (T1), and at discharge (T2). The mean age was 62.7 (SD = 13.0), 58.9% of the subjects were male, and 75% had suffered an ischemic stroke. A multivariate linear regression model using the 5-STS test at T0 explained 57.7% of the variance in the performance at discharge. Using the 5-STS at T1 increased the variance to 75.5% (p < 0.001). Only the time from stroke onset at T0 significantly contributed to the two models. The measurement of the 5-STS at T0 and the amount of change in its performance at T2 explained 60.2% (p < 0.001) of the variance, while reassessment at T1 explained only 19.3% (p < 0.001). The level of patient performance on the 5-STS test at discharge, as well as any potential change, can be predicted by the admission measure of 5-STS in stroke patients.

The prognosis of pre-frail chronic obstructive pulmonary disease patients for hospitalizations and mortality depends on their level of functional physical performance.

OBJECTIVE: To determine if pre-frail Chronic obstructive pulmonary disease (COPD) patients with poor and non-poor performance in the five-repetition sit-to-stand test (5-STS) had a worse prognosis for hospitalization and mortality at 2 years and for mortality at 5 years than non-frail patients. METHODS: We prospectively included patients with stable COPD, between 40 and 80 years, from a hospital in Spain. Patients were classified according their performance on the 5-STS test and level of frailty. Timing, number of hospitalizations, length of stay, and timing and rate of mortality were outcome measures. Patients were followed for 2 years for exacerbations and for 5 years for mortality. Kaplan-Meier curves and univariate and multivariate Cox proportional-hazard analyses, ANOVA tests and univariate and multivariate linear and logistic regression models were used. RESULTS: Of the 125 patients included, 25.6% were pre-frail with poor performance, 57% pre-frail with non-poor performance, and 17.4% non-frail with non-poor performance. Pre-frail patients with poor performance had a higher number of hospitalizations (adjusted beta: 0.49; 95% CI: 0.01-0.96), mortality rates (odds ratio: 11.33; 95% CI: 1.15-110.81), and risk at 5 years (adjusted hazard ratio: 8.77; 95% CI: 1.02-75.51) than non-frail patients. Pre-frail patients with poor performance also had worse prognoses than non-frail patients with respect to length of hospital stays (increased by 4.16 days) and timing to first hospitalization (HR: 6.01) in unadjusted models, but not when adjusted. CONCLUSION: The COPD prognosis of pre-frail patients with respect to the number of exacerbations with hospitalization and the timing and rate of mortality is dependent of functional performance.

Improving the Reliability Between the BODE Index and the BODS Index in Which the 6-Min Walk Test Was Replaced with the Five-Repetition Sit-to-Stand Test.

Purpose: The BODS index has been confirmed to have predictive properties similar to the original BODE index for mortality in COPD. We evaluated the agreement between the BODS index and the BODE and explored with an updated BODS how this agreement could be improved and its ability to correctly discriminate individual participants' mortality in a prospective cohort study. Patients and Methods: We included prospectively a consecutive sample of 137 patients with COPD, between 40 and 80 years, during 2014 and followed for 5 years (2014-2019) in the Pneumology section of a public university hospital in Spain. They participated in the baseline data collection, which included BODE- and BODS-related measurements and prognostic factors, and were followed up for 5-year mortality. We used Bland-Altman plots and the kappa coefficient to analyze the agreement between both the original and updated BODS and the BODE index, and we used the areas under ROC curves (AUC) to compare their discriminative abilities for 5-year all-cause mortality. Results: The original BODS index scores and quartiles had weak agreement with the BODE index, and our updated BODS strengthened these agreements (a small, statistically nonsignificant mean bias [<0.03] with LoAs<2 points, and a substantial Kappa coefficient [k =0.63; IC 95%: 0.53-0.73]). In addition, the updated BODS index scores had better summarized ability than the BODS index in discriminating participants' mortality during the following 5 years (AUC: 0.768 versus 0.736; p=0.04). Conclusion: The updated BODS index scores and quartiles may provide prognostic information similar to that provided by the BODE index in COPD. Future research should focus on index improvement through external validation, as well as the assessment of safety and effectiveness in clinical practice by means of impact studies.

Breve historia de las lágrimas y el llanto

Las lágrimas y el llanto son fenómenos biológicos enmarcados en diferentes contextos sociales, culturales y de conocimiento a lo largo de los años. Este artículo es una revisión sobre la construcción de las concepciones alrededor de las lágrimas y el llanto. Se exploran las formulaciones en el tema desde las civilizaciones más antiguas, pasando por la discusión alrededor del origen de las lágrimas (corazón vs. cerebro), así como los hallazgos con la introducción de la disección anatómica y la experimentación fisiológica. Finalmente, se exponen las posturas evolucionistas y psicológicas del llanto para estudiar su funcionalidad en la supervivencia y su papel en las relaciones sociales. El objetivo de este es presentar, en forma sucinta, los aspectos históricos de las lágrimas y el llanto.

SUMMARY Tears and crying are biological phenomena framed in different social and cultural contexts throughout the years. This article is a review of the construction of different conceptions around tears and crying. We explore proposals on the subject from the oldest civilizations, going through the discussion around the origin of tears (heart vs. brain), and the findings with the introduction of anatomical dissection and physiological experimentation. Finally, the evolutionary and psychological positions of crying are exposed, to study its functionality in survival and its role in social relations. The aim of this article is to present, succinctly, what have been the tears and crying through the history.

Notas para una investigación futura sobre la historia del internado médico en Colombia. Segunda parte: el internado en los siglos XX y XXI / Notes for a future research on the history of the internship in medicine, in Colombia. Second part: The Internship in Colombia (20th and 21st centuries)

RESUMEN Este artículo es la segunda parte de una serie que explora la trayectoria histórica de la configuración del internado en la educación y en la práctica médica. En el artículo anterior se estudió el surgimiento del internado en la Francia napoleónica y su posterior consolidación bajo la reforma flexneriana estadounidense en la educación médica. Esta segunda parte explora, en cinco apartados, el proceso de constitución del internado en el contexto colombiano. El primero empieza analizando la influencia francesa a inicios del siglo xx; el segundo revisa el cambio hacia el modelo flexneriano que se dio con la llegada de varias misiones médicas estadounidenses y por sus sugerencias sobre la educación médica; el tercero estudia el proceso de ensamblaje de estos modelos en el país, su regulación y la crisis de esta; el cuarto recoge las propuestas actuales; en el epílogo se reflexiona sobre el futuro del internado en la coyuntura de la pandemia de la COVID-19.

SUMMARY This article is the second part of a series that explores the historical process of the configuration of the intern-ship in medical education and practice. In a previous article, we studied the emergence of the internship in Napoleonic France and its latter configuration trough the North American Flexnerian reforms to medical education. This second part deals with the process by which the internship was constituted in Colombia through five sections. The first one analyses the French influence at the beginning of the 20th century; the second part, the change towards the North American flexnerian model, which was motivated by the arrival of multiple medical missions and their suggestions regarding medical education; the third part studies the process by which these models assembled in the country, their regulation and its crisis; the fourth discusses the actual proposals; and the epilogue talks about the future of the internship in the COVID-19 pandemics.

The five-repetition sit-to-stand test is a predictive factor of severe exacerbations in COPD.

BACKGROUND: Although the six-minute-walk test (6MWT) has been used to predict chronic obstructive pulmonary disease (COPD) exacerbations, additional research is necessary to identify more rapid, simpler tests that are directly associated with exacerbations, such as the five-repetition sit-to-stand (5STS) test and 4-m gait speed (4MGS) test. AIMS: To determine the ability of the 5STS and 4MGS tests in predicting severe exacerbations in stable COPD over the following year, and to assess the ability of the best prognostic test to identify patients at high risk of hospital admission correctly. METHODS: This prospective study included 137 patients with stable COPD. Multiple logistic regression models were constructed to assess whether the 6MWT, 5STS, and 4MGS tests were associated with severe exacerbations in the year following the test. Receiver-operating characteristic curves and the area under the curve (AUC) were evaluated to determine the accuracy of each test for identifying patients with severe exacerbations. RESULTS: Scores of <350 m for the 6WMT and ⩽2 for the 5STS test were associated with severe exacerbations in the model adjusted for age and the number of exacerbations in the previous year. The 5STS test and the 6MWT had very similar predictive and discriminative abilities. Odds ratios were 3.20 (95% confidence interval [CI] 1.14-8.96) and 3.84 (95% CI 1.14-12.94) and AUCs were 0.793 (95% CI 0.704-0.882) and 0.783 (95% CI 0.686-0.879), respectively. CONCLUSIONS: The 5STS test predicted the risk of severe exacerbation within the following year among patients with COPD. The 5STS test could replace the 6MWT for identifying patients at high risk of hospital admission.

Vulvar Pilomatrix Carcinoma: Morphologic and Molecular Features.

Pilomatrix carcinoma (PC) is a rare malignant variant of pilomatrixoma, a skin adnexal tumor originating from hair matrix cells. It is most often located in the head, neck region, upper back and upper extremities. PC has a locally aggressive behavior but metastasis only occur in 10% of cases. Mutations in CTNNB1, the encoding gene of beta-catenin, have been found in both pilomatrixoma and PC, but other molecular alterations are unknown. The authors present a case of PC in the clitoris, the third known reported case located on the external genitalia. The tumor followed an unusual clinical course with the development of multiple metastases. Next-generation sequencing analysis of the tumor identified, in addition to a characteristic CTNNB1 mutation, pathogenic mutations in PTEN, PIK3CA, and ARID1A, which could explain the aggressive course of the disease. The diagnostic criteria of PC and the differential diagnoses of this unusual tumor in the genital area are discussed.

Viruela en Santiago, Concepción y Santafé: comparación de las estrategias higienistas ilustradas (1782-1807) / Smallpox in Santiago, Concepcion and Santafe: A Comparisson of the Enlightened Sanitary Strategies (1782-1807) / Varíola em Santiago, Concepcion e Santafe: Um comparisson das estratégias sanitárias esclarecidas (1782-1807)

Introducción: este artículo pretende estudiar las medidas tomadas en las epidemias de viruela de Santiago (1787), Concepción (1789) y Santafé (1782/1802), para compararlas y entender cómo el estudio de estas epidemias nos puede dar luces para el abordaje del reto de salud pública actual: la pandemia de covid-19. Desarrollo: el artículo está dividido en tres partes: en la primera se exponen las medidas de higiene que se tomaron para subsanar y prevenir estas epidemias, previas a la llegada de la vacunación, comparando el rol desempeñado por los actores locales en cada región; en la segunda se relata y se compara el proceso de llegada y búsqueda de la vacuna contra la viruela en cada territorio, y en la tercera se reflexiona brevemente sobre la pandemia actual. Conclusiones: en el análisis comparativo, se destaca la manera en la que la agenda transcolonial incluye una serie de similitudes para su aplicación en cada territorio, pero también las diferencias que los procesos locales y transcoloniales plantean para su domesticación en cada uno de ellos. Además, se resaltan las particularidades que ha tenido la pandemia de covid-19 y las lecciones que este estudio de caso deja para pensar en la necesidad de enfrentarla desde una perspectiva global.

Introduction: This study aimed to investigate and compare measures implemented during the smallpox epidemics in Santiago (1787), Concepción (1789), and Santafé (1782/1802). In addition, we also tried to understand how the study of these epidemics could help identify an approach for managing the current public health challenge, i.e., the covid-19 pandemic. Development: The article is divided into three parts: the first part studies the hygienic measures that were taken to face and prevent the epidemics as well as compares the role played by local actors in each region; the second part studies the processes of searching and acquiring smallpox vaccine in Santafé and Santiago; and the third part reflects on the current pandemic scenario. Conclusions: Through comparative analysis, we evaluated the similarities in the application of transcolonial agenda in each territory and the differences brought about by local and transcolonial processes implemented for its domestication. Furthermore, we highlighted particular processes conducted for managing and treating covid-19 as well as lessons learnt from this case study about the need of dealing with covid-19 from a global perspective.

Introdução: este artigo tem como objetivo estudar as medidas tomadas nas epidemias de varíola de Santiago (1787), Concepción (1789) e Santafé (1782/1802), compará-las e compreender como o estudo des-sas epidemias pode lançar luz sobre a abordagem do desafio atual da saúde pública: a pandemia covid-19. Desenvolvimento: o artigo está dividido em três partes: na primeira, são expostas as medidas de higiene que foram tomadas para corrigir e prevenir estas epidemias, antes da chegada da vacinação, comparando o papel desempenhado pelos atores locais em cada região; na segunda, relaciona-se e compara-se o processo de chegada e busca da vacina contra a varíola em cada território; e, na terceira, faz uma breve refle-xão sobre a atual pandemia. Conclusões: na análise comparativa, destacamos a forma como a agenda transcolonial suscita uma série de semelhanças para a sua aplicação em cada território, mas também as diferenças que os processos locais e transcoloniais colocam para a sua domesticação em cada um deles. Além disso, destacamos as particularidades que a pandemia covid-19 teve e as lições que este estudo de caso deixa para pensar a necessidade de enfrentá-la a partir de uma perspectiva global.

Patterns and predictors of low physical activity in patients with stable COPD: a longitudinal study.

BACKGROUND: Despite the frequency and negative impact of low physical activity among patients with chronic obstructive pulmonary disease (COPD), little is known about how it persists and remits over time or the factors predicting new states of low physical activity. The aim of the study was to determine the probability of a transition between states of low and nonlow physical activity in a cohort of patients with stable COPD followed for 2 years. We also investigated different potentially modifiable factors to determine whether they can predict new states of low physical activity. METHODS: We prospectively included 137 patients with stable COPD (mean age 66.9 ± 8.3 years). Physical activity was measured at baseline and at 1 and 2 years of follow up. Low physical activity was defined according to energy expenditure by cut-off points from the Fried frailty model. The likelihood of annual transition towards new states and recovery was calculated. We evaluated demographic, frailty, nonrespiratory, and respiratory variables as potential predictors, using generalized estimating equations. RESULTS: At baseline, 37 patients (27%) presented with low physical activity. During the study period, a total of 179 annual transitions were identified with nonlow physical activity at the beginning of the year; 17.5% transitioned to low physical activity. In contrast, 34.3% of the 67 transitions that started with low physical activity recovered. Predictors of transition to new states of low physical activity were dyspnea ⩾2 (odds ratio = 3.21; 95% confidence interval: 1.20-8.61) and poor performance on the five sit-to-stand test (odds ratio = 4.75; 95% confidence interval: 1.30-17.47). CONCLUSIONS: The change between levels of low and nonlow physical activity is dynamic, especially for recovery. Annual transitions toward new states of low physical activity are likely among patients with dyspnea or poor performance on the five sit-to-stand test. The reviews of this paper are available via the supplemental material section.

Patterns and Predictors of Recovery from Poor Health Status Measured with the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test in Patients with Stable COPD: A Longitudinal Study.

Recent recommendations for chronic obstructive pulmonary disease (COPD) suggest that evaluation and management should focus on patient health status. Despite the frequency of poor health status and its negative impact on patients with COPD, little is known about how poor or non-poor health status persists and/or remits over time or what factors might predict recovery from a poor health status. The aim was to determine the likelihood of transitioning between poor and non-poor health status in patients with stable COPD followed for 2 years and to investigate factors that might predict recovery from poor health status. We prospectively included 137 patients with stable COPD (mean age, 66.9 years ± 8.3). Health status was measured at baseline and after 1 and 2 years with the COPD assessment test (CAT). Higher scores indicated worse health status, and 10 was the cut-off score for discriminating between non-poor and poor health status. The likelihoods of annual transitions to new episodes and recovery were calculated. We evaluated demographic, non-respiratory, and respiratory variables as potential predictors with generalized estimating equations. At baseline, 37 patients (27%) reported non-poor health status. Within the group of patients displaying poor health status at the beginning of the year, 176 annual transitions were identified during the study period: 15.9% were transitions to recovery from poor health status. In contrast, of the 70 transitions from a starting non-poor health status, 32.4% worsened. Predictors of transitions to recovery were: current non-smoker status (odds ratio (OR) = 3.88; 95% confidence interval (CI): 0.64-5.54) and handgrip strength (OR = 1.08; 95% CI: 1.00-1.16). This study suggests that self-reported health status, measured with the CAT, has a dynamic nature in patients with COPD. Annual transitions towards recovery from poor health status are most likely among current non-smoking patients and those with high handgrip strength.

Relación entre el sexo, edad e índice de masa corporal y el Foot Function Index en pacientes con fascitis plantar / Relationship between sex, age and body mass index and the Foot Function Index in patients with plantar fasciitis

La fascitis plantar es una de las patologías de miembro inferior que más impacto causan en la persona produciendo dolor, discapacidad y limitación funcional. Una serie de factores incrementan el riesgo de sufrir fascitis plantar tales como predominio del sexo femenino, edad avanzada y un índice de masa corporal (IMC) elevado. El impacto que produce la fascitis plantar en la persona ser cuantificado por escalas para darnos información en la clínica acerca del estado de nuestros pacientes. Métodos y objetivos: Se realizó un estudio observacional transversal con 28 participantes que sufrían fascitis plantar y se les administra la encuesta FFI-sp con el propósito de determinar la relación entre las subescalas incluidas en el FFI-sp con el sexo, edad e IMC en pacientes con fascitis plantar. Resultados: No se han obtenido resultados significativos que indiquen relación del sexo, edad e IMC con las subescalas incluidas en el FFI-sp. Conclusión: No se ha encontrado relación entre FFI-sp y las variables sexo, edad e IMC

Background: Plantar fasciitis is one of the lower limb pathologies that causes more impact on the person and it produces pain, disability and functional limitation. Some factors which increase the risk of plantar fasciitis such as female predominance, advanced age, and high body mass index (BMI). The impact of plantar fasciitis on people is quantified by scales to give us information in the clinic about the state of our patients. Methods and Objetives: A cross-sectional observational study was performed with 28 participants who are suffering plantar fasciitis and administered the FFI-sp in order to determine the relationship between the subcategories included in the FFI-sp with gender, age and BMI in patients with plantar fasciitis. Results: There have not been significant results indicating a relationship between gender, age and BMI with the subscales included in the FFI-sp. Conclusion: There's no relationship between gender, age and body mass index with the Foot Function Index in patients with plantar fasciitis

Valor del Test de Silfverskiöld para el diagnóstico de la fascitis plantar / Value of the Silfverskiöld Test for the diagnosis of plantar fasciitis

La fascitis plantar (FP) está descrita como la causa más común de dolor en el talón. Aunque se considera una patología multifactorial, la limitación de la dorsiflexión del tobillo es uno de los factores más determinantes, predisponiendo al desarrollo de patologías en el miembro inferior. Objetivo: Determinar la exactitud del test de Silfverskiöld como herramienta diagnóstica de la FP a partir del análisis de varios indicadores (sensibilidad, especifidad, valor predictivo positivo y negativo, y razones de verosimilitud positiva y negativa). Método: Se realizó un estudio de validez transversal en 16 sujetos (9 mujeres y 7 hombres) diagnosticados de fascitis plantar unilateral de al menos 3 meses de evolución. Un fisioterapeuta se encargó de evaluar el déficit de dorsiflexión en ambos tobillos mediante el Test de Silfverskiöld. Resultados: Fueron descartados aquellos pies sin problemas de movilidad en dorsiflexión de tobillo, por lo que finalmente fueron analizados 14 pies afectos y 8 sanos. los indicadores de eficacia diagnóstica del test de Silfverskiöld en la FP. Al determinar la eficacia del test de Silfverskiöld como predictor de FP encontramos una sensibilidad de 93,7%, especificidad del 75%, valor predictivo positivo (VPP) de 86,6% y valor predictivo negativo (VPN) de 85,7%. La razón de verosimilitud positiva (RV+) fue de 3,74, mientras que la negativa (RV-) resultó 12,5. Conclusión: El test de Silfverskiöld puede ser considerado una prueba eficaz para el diagnóstico de la FP. Existe una importante asociación entre la limitación en la dorsiflexión de tobillo por restricción de gemelos y la probabilidad de padecer FP

Background: Plantar fasciitis (PF) is described as the most common cause of heel pain. Although it is considered a multifactorial pathology, the limitation of dorsiflexion of the ankle is one of the most determining factors, predisposing to the development of pathologies in the lower limb. Objective: To determine the accuracy of the Silfverskiöld test as a diagnostic tool for PF, based on the analysis of several indicators (sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios). Method: A cross-sectional validity study was conducted in 16 subjects (9 women and 7 men) diagnosed with unilateral plantar fasciitis of at least 3 months evolution. A physiotherapist was responsible for assessing the deficit of dorsiflexion in both ankles by the Silfverskiöld test. Outcome: Those feet without mobility problems in ankle dorsiflexion were discarded, so finally 14 affected feet and 8 healthy ones were analyzed. the indicators of diagnostic efficacy of the Silfverskiöld test in PF. When determining the efficacy of the Silfverskiöld test as a predictor of PF, we found a sensitivity of 93.7%, specificity of 75%, positive predictive value (PPV) of 86.6% and negative predictive value (NPV) of 85.7%. The positive likelihood ratio (LR+) was 3.74, while the negative (LR-) ratio was 12.5. Conclusion: The Silfverskiöld test can be considered an effective test for the diagnosis of PF. There is an important association between limitation in dorsiflexion of the ankle due to restriction of twins and the probability of suffering PF

IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein.

BACKGROUND: Cytokines and macrophages play a central role in the development of atherosclerosis. Interleukin (IL)-17 is a pro-inflammatory cytokine with differential effects on innate immune cells. We investigated the effects of IL-17 on macrophage differentiation and foam cell formation and activation in response to oxidized low-density lipoprotein (oxLDL). METHODS: Human monocytes were treated with IL-17 to induce macrophage differentiation. As controls, human monocytes were differentiated into M1 macrophages (M1) or M2 macrophages (M2). Subsequently, we analyzed the expression levels of markers such as CD80, CD36 and Toll-like receptors (TLRs) as well as foam cell formation and cytokines in M1, M2 and macrophages differentiated with IL-17 with or without oxLDL. RESULTS: The expression of M1 or M2 markers or cytokines was not induced in macrophages differentiated with IL-17. Macrophages differentiated with IL-17 formed few foam cells, with an average proportion of 20%, and expressed 3 times as much TLR2 and 3.8 times as much TLR4 as M0 macrophages. Additionally, macrophages differentiated with IL-17 acquired inflammatory capacity in response to oxLDL through the expression of specific markers, such as CD80, which increased 18-times compared with macrophages differentiated with IL-17 alone, and secreted 1.3 times less tumor necrosis factor (TNF)-α than M1. Additionally, oxLDL increased the levels of CD80, CD86 and IL-6 by 5.7, 2.8 and 1.4 times in M1 compared with M1 in the absence of oxLDL. In M2, oxLDL induced increases in the secretion of IL-6 and TNF-α that were 1.9 times and 1.2 times smaller, respectively, than those observed in M1. CONCLUSION: Our study demonstrates that differentiation of macrophages with IL-17 does not induce the expression of markers or cytokines characteristic of M1 or M2 and these macrophages form few foam cells; however, the expression of TLR is increased. Moreover, these macrophages acquire the inflammatory capacity as evidenced by the expression of costimulatory molecules and secretion of pro-inflammatory cytokines in response to oxLDL. These findings suggest that the activation of macrophages differentiated with IL-17 by oxLDL contributes to the inflammatory process of atherosclerosis.

In vivo eye surface residence determination by high-resolution scintigraphy of a novel ion-sensitive hydrogel based on gellan gum and kappa-carrageenan.

In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology. The aim of the present work was to use a well-established approach based on scintigraphy to quantitatively estimate the residence time of the previously proposed hydrogel. The rat corneal residence time of a topic ophthalmic formulation containing gellan gum and kappa carragenan (0.82% w/v) labeled with 99mTc-DTPA radiotracer was evaluated and compared with the residence of an aqueous solution. Ophthalmic safety studies such as eye irritation or passage through the cornea were also carried out. After 1.5h of contact, 77% of the hydrogel remained in the ocular surface, presenting kinetics of disappearance one-phase decay and a half time of 262min. We conclude that the novel ophthalmic hydrogel developed with kappa carrageenan and gellan gum remains for long periods of time on the corneal surface, presenting a drop that fits an exponential decay.

RepA-WH1 prionoid: Clues from bacteria on factors governing phase transitions in amyloidogenesis.

In bacterial plasmids, Rep proteins initiate DNA replication by undergoing a structural transformation coupled to dimer dissociation. Amyloidogenesis of the 'winged-helix' N-terminal domain of RepA (WH1) is triggered in vitro upon binding to plasmid-specific DNA sequences, and occurs at the bacterial nucleoid in vivo. Amyloid fibers are made of distorted RepA-WH1 monomers that assemble as single or double intertwined tubular protofilaments. RepA-WH1 causes in E. coli an amyloid proteinopathy, which is transmissible from mother to daughter cells, but not infectious, and enables conformational imprinting in vitro and in vivo; i.e. RepA-WH1 is a 'prionoid'. Microfluidics allow the assessment of the intracellular dynamics of RepA-WH1: bacterial lineages maintain two types (strains-like) of RepA-WH1 amyloids, either multiple compact cytotoxic particles or a single aggregate with the appearance of a fluidized hydrogel that it is mildly detrimental to growth. The Hsp70 chaperone DnaK governs the phase transition between both types of RepA-WH1 aggregates in vivo, thus modulating the vertical propagation of the prionoid. Engineering chimeras between the Sup35p/[PSI(+)] prion and RepA-WH1 generates [REP-PSI(+)], a synthetic prion exhibiting strong and weak phenotypic variants in yeast. These recent findings on a synthetic, self-contained bacterial prionoid illuminate central issues of protein amyloidogenesis.

Characterization of selenium-enriched wheat by agronomic biofortification.

Agronomic biofortification of staple crops is an effective way to enhance their contents in essential nutrients up the food chain, with a view to correcting for their deficiencies in animal or human status. Selenium (Se) is one such case, for its uneven distribution in the continental crust and, therefore, in agricultural lands easily translates into substantial variation in nutritional intakes. Cereals are far from being the main sources of Se on a content basis, but they are likely the major contributors to intake on a dietary basis. To assess their potential to assimilate and biotransform Se, bread and durum wheat were enriched with Se through foliar and soil addition at an equivalent field rate of 100 g of Se per hectare (ha), using sodium selenate and sodium selenite as Se-supplementation matrices, in actual field conditions throughout. Biotransformation of inorganic Se was evaluated by using HPLC-ICP-MS after enzymatic hydrolysis for Se-species extraction in the resulting mature wheat grains. Selenomethionine and Se(VI) were identified and quantified: the former was the predominant species, representing 70-100 % of the total Se in samples; the maximum amount of inorganic Se was below 5 %. These results were similar for both supplementation methods and for both wheat varieties. Judging from the present results, one can conclude that agronomic biofortification of wheat may improve the nutritional quality of wheat grains with significant amounts of selenomethionine, which is an attractive option for increasing the Se status in human diets through Se-enriched, wheat-based foodstuff.

Preparation and characterization of a laboratory scale selenomethionine-enriched bread. Selenium bioaccessibility.

This study focuses on the preparation at lab scale of selenomethionine-enriched white and wholemeal bread. Selenium was supplemented either by adding selenite directly to the dough or by using lab-made selenium-enriched yeast. The best results were obtained when using fresh selenium-enriched yeast. The optimum incubation time for selenomethionine-enriched yeast preparation, while keeping formation of selenium byproducts to a minimum, was 96 h. Selenium content measured by isotope dilution analysis (IDA)-ICP-MS in Se-white and Se-wholemeal bread was 1.28 ± 0.02 µg g­1 and 1.16 ± 0.02 µg g­1 (expressed as mean ± SE, 3 replicates), respectively. HPLC postcolumn IDA-ICP-MS measurements revealed that selenomethionine was the main Se species found in Se-enriched bread, which accounted for ca. 80% of total selenium. In vitro gastrointestinal digestion assay provided selenium bioaccessibility values of 100 ± 3% and 40 ± 1% for white and wholemeal Se-enriched bread, respectively, being selenomethionine the main bioaccessible Se species in white bread, while in wholemeal bread this compound was undetectable.