Tocilizumab demonstrates superiority in decreasing C-reactive protein levels in hospitalized COVID-19 patients, compared to standard care treatment alone.

Severe acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crisis. The virus triggers the activation of inflammatory reactants including interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP), causing multiorgan damage, particularly affecting the lungs. Tocilizumab, an IL-6 receptor blocker, has the potential to diminish the progression of the disease and reduce organ damage and long-term complications. The aim of this observational retrospective cohort study was to evaluate the efficacy of tocilizumab in decreasing CRP levels in hospitalized coronavirus disease 2019 (COVID-19) patients compared to standard care without the drug. The study included 141 patients during their Hospital Stay (HS), with 100 in the Tocilizumab group and 41 in the non-Tocilizumab group. Clinical information was collected from the electronic clinical record, analyzed using statistical software, and homogenized the CRP levels from the severe group to the levels of the less complicated group at 48 h of hospitalization. The results showed a statistically significant greater decrease in CRP levels in the Tocilizumab group at 48 h after the use of the treatment, with no differences in mortality or length of stay between the groups. In conclusion, tocilizumab accelerates the diminishing of CRP levels compared to standard treatment alone, and its use may have potential benefits in the management of severe COVID-19 patients when used alongside with follow-up quantification of CRP levels reduction.IMPORTANCESevere acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crises. International guidelines for managing coronavirus disease 2019 (COVID-19) give recommendations according to the severity of the disease and the level of oxygen therapy needed. Tocilizumab is an option for the therapeutic management of hospitalized patients with any level of oxygen therapy; IL-6 serum level is the parameter for the follow-up on the efficacy, but it is not available at many hospitals. In this study, we demonstrate that C-reactive protein determination can predict the response to tocilizumab in severe COVID-19, the target patients for treatment with this drug. The use of this affordable and extensively available biomarker supports clinical decisions for the early escalation of the therapy and for the rational use of this drug on those prone to improve with the use of it.

Bacteremia by non-O1/non-O139 Vibrio cholerae: Case description and literature review. / Bacteriemia por Vibrio cholerae no-O1/no-O139: descripción de un caso y revisión de la literatura

Bacteremia by non-O1/non-O139 Vibrio cholerae is a rare entity associated with high mortality rates. We report a case of non-O1/non-O139 V. cholerae bacteremia confirmed by polymerase chain reaction and agglutination tests. The clinicoepidemiological characteristics and therapeutic options for this infection are also described.

La bacteriemia por V. cholerae no-O1/no-O139 es una entidad poco frecuente que se asocia con altas tasas de mortalidad. Reportamos un caso de bacteriemia por V. cholerae no-O1/no-O139 confirmado por reacción en cadena de la polimerasa (PCR) y test de aglutinación. Se describen además las características clínico-epidemiológicas y opciones terapéuticas para esta infección.

Preclinical evaluation of bozepinib in bladder cancer cell lines: modulation of the NPP1 enzyme.

Bladder cancer (BC) is the most common cancer of the urinary tract. Bozepinib (BZP), a purine-derived molecule, is a potential compound for the treatment of cancer. Purinergic signaling consists of the activity of nucleosides and nucleotides present in the extracellular environment, modulating a variety of biological actions. In cancer, this signaling is mainly controlled by the enzymatic cascade involving the NTPDase/E-NPP family and ecto-5'-nucleotidase/CD73, which hydrolyze extracellular adenosine triphosphate (ATP) to adenosine (ADO). The aim of this work is to evaluate the activity of BZP in the purinergic system in BC cell lines and to compare its in vitro antitumor activity with cisplatin, a chemotherapeutic drug widely used in the treatment of BC. In this study, two different BC cell lines, grade 1 RT4 and the more aggressive grade 3 T24, were used along with a human fibroblast cell line MRC-5, a cell used to predict the selectivity index (SI). BZP shows strong antitumor activity, with notable IC50 values (8.7 ± 0.9 µM for RT4; 6.7 ± 0.7 µM for T24), far from the SI for cisplatin (SI for BZP: 19.7 and 25.7 for RT4 and T24, respectively; SI for cisplatin: 1.7 for T24). BZP arrests T24 cells in the G2/M phase of the cell cycle, inducing early apoptosis. Moreover, BZP increases ATP and ADP hydrolysis and gene/protein expression of the NPP1 enzyme in the T24 cell line. In conclusion, BZP shows superior activity compared to cisplatin against BC cell lines in vitro.

Bacteremia by non-O1/non-O139 Vibrio cholerae: Case description and literature review / Bacteriemia por Vibrio cholerae no-O1/no-O139: descripción de un caso y revisión de la literatura

Bacteremia by non-O1/non-O139 Vibrio cholerae is a rare entity associated with high mortality rates. We report a case of non-O1/non-O139 V. cholerae bacteremia confirmed by polymerase chain reaction and agglutination tests. The clinicoepidemiological characteristics and therapeutic options for this infection are also described.

La bacteriemia por Vibrio cholerae no-O1/no-O139 es una entidad poco frecuente que se asocia con altas tasas de mortalidad. Se reporta un caso de bacteriemia por V. cholerae no-O1/no-O139 confirmado por reacción en cadena de la polimerasa y test de aglutinación. Se describen las características clinicoepidemiológicas y las opciones terapéuticas para esta infección.

Co-Encapsulation of Curcumin and α-Tocopherol in Bicosome Systems: Physicochemical Properties and Biological Activity.

A novel co-encapsulation system called bicosomes (bicelles within liposomes) has been developed to overcome the limitations associated with the topical application of curcumin (cur) and α-tocopherol (α-toc). The physicochemical properties and biological activity in vitro of bicosome systems were evaluated. Bicelles were prepared with DPPC, DHPC, cur, and α-toc (cur/α-toc-bicelles). Liposomal vesicles loading cur/α-toc-bicelles were prepared with Lipoid P-100 and cholesterol-forming cur/α-toc-bicosomes. Three cur/α-toc-bicosomes were evaluated using different total lipid percentages (12, 16, and 20% w/v). The results indicated that formulations manage to solubilize cur and α-toc in homogeneous bicelles < 20 nm, while the bicosomes reaches 303-420 nm depending on the total lipid percentage in the systems. Bicosomes demonstrated high-encapsulation efficiency (EE) for cur (56-77%) and α-toc (51-65%). The loading capacity (LC) for both antioxidant compounds was 52-67%. In addition, cur/α-toc-bicosomes decreased the lipid oxidation by 52% and increased the antioxidant activity by 60% compared to unloaded bicosomes. The cell viability of these cur/α-toc-bicosomes was >85% in fibroblasts (3T3L1/CL-173™) and ≥65% in keratinocytes (Ha-CaT) and proved to be hematologically compatible. The cur/α-toc-bicelles and cur/α-toc-bicosomes inhibited the growth of C. albicans in a range between 33 and 76%. Our results propose bicosome systems as a novel carrier able to co-encapsulate, solubilize, protect, and improve the delivery performance of antioxidant molecules. The relevance of these findings is based on the synergistic antioxidant effect of its components, its biocompatibility, and its efficacy for dermal tissue treatment damaged by oxidative stress or by the presence of C. albicans. However, further studies are needed to assess the efficacy and safety of cur/α-toc bicosomes in vitro and in vivo.

Percepción del riesgo de desastres en habitantes del municipio de Pijao, Quindío, Colombia / Perception of Disaster Risk Among Inhabitants of the Municipality of Pijao, Quindío, Colombia

Resumen La gestión del riesgo de desastres es un proceso social, por ello toda la comunidad debe estar incluida en ella. El objetivo del estudio fue analizar las percepciones del riesgo de desastres en habitantes del municipio de Pijao (Quindio). Para esto se siguió un enfoque cualitativo desde el diseño de la teoría fundamentada. Se realizó un muestreo no probabilístico en los barrios aledaños al recorrido del Río Lejos del municipio de Pijao (Quindío, Colombia). La muestra estuvo compuesta por un total de 60 sujetos. La teoría sustantiva producto de la investigación es la naturalización de la gestión del riesgo de desastres. Se considera que la naturalización de acciones para la mitigación del riesgo de desastres se posibilita por el nivel de conocimiento de conceptos y acciones de la gestión del riesgo, además del nivel de arraigo cultural. El estudio permitió conocer de primera mano sobre los elementos que se deben trabajar para fortalecer la gestión del riesgo a nivel comunitario.

Abstract Disaster risk management is a social process; therefore, the whole community must be included in it. The objective of the study was to analyze the perceptions of disaster risk in the inhabitants of the municipality of Pijao (Quindio). A qualitative approach was followed from the design of the grounded theory. A non‑probabilistic sampling was carried out in the neighborhoods adjacent to the course of the Lejos River in the municipality of Pijao (Quindio, Colombia). The sample was composed of a total of 60 subjects. The substantive theory resulting from the research is the naturalization of disaster risk management. It is considered that the naturalization of actions for disaster risk mitigation is made possible by the level of knowledge of risk management concepts and actions, in addition to the level of cultural rootedness. The study provided first-hand knowledge of which elements level should be worked on in the community to strengthen risk management.

Tratamiento a la comunicación científica desde la Disciplina Bases Biológicas de la Medicina / Treatment of scientific communication from the Discipline Biological Bases of Medicine / Tratamento da comunicação científica a partir das Bases Biológicas disciplinares da Medicina

RESUMEN La enseñanza médica en Cuba constituye el escenario ideal para la formación de las competencias que garantizan la generación y socialización de resultados investigativos contextualizados a los desafíos actuales. Durante el año 2021, se realizó un estudio descriptivo con enfoque socioformativo en la Universidad de Ciencias Médicas de Camagüey, con el propósito de develar las potencialidades de la disciplina Bases Biológicas de la Medicina (BBM) para la formación de la competencia comunicación científica. A partir del mismo se determinan las causas, carencias teóricas y prácticas que repercuten en la formación de dicha competencia desde la formación inicial en el estudiante de Medicina y su incidencia en la práctica educativa. Fueron identificadas las potencialidades de esta disciplina y su implicación en la formación de una cultura para obtener, elaborar y comunicar los resultados de la actividad investigativa como elementos básicos para la socialización científica. El trabajo metodológico del colectivo de año, enfocado en las potencialidades identificadas desde un enfoque socioformativo posibilita formar y desarrollar la competencia objeto de estudio, orientada hacia la socialización de los resultados de la actividad investigativa que realiza el estudiante durante la educación en el trabajo y actividades extensionistas.

ABSTRACT Medical education in Cuba is the ideal setting for the formation of competencies that guarantee the generation and socialization of research results contextualized to current challenges. During the year 2021, a descriptive study with a socio-formative approach was carried out at the University of Medical Sciences of Camagüey, with the purpose of revealing the potentialities of the discipline Biological Bases of Medicine (BBM) for the formation of scientific communication competence. From it, the causes, theoretical and practical deficiencies that have an impact on the formation of this competence from the initial training in the medical student and its impact on educational practice are determined. The potentialities of this discipline and its involvement in the formation of a culture to obtain, elaborate and communicate the results of the research activity as basic elements for scientific socialization were identified. The methodological work of the year group, focused on the potentialities identified from a socio-formative approach, makes it possible to train and develop the competence under study, oriented towards the socialization of the results of the research activity carried out by the student during education at work and extension activities.

RESUMO A educação médica em Cuba é o cenário ideal para a formação de competências que garantam a geração e a socialização dos resultados da pesquisa contextualizados aos desafios atuais. Durante o ano de 2021, foi realizado um estudo descritivo com abordagem socioamotiva na Universidade de Ciências Médicas de Camagüey, como objetivo de revelar as potencialidades da disciplina Bases Biológicas da Medicina (BBM) para a formação de competência de comunicação científica. A partir de la, são determinadas as causas, deficiências teóricas e práticas que impactam na formação dessa competência a partir da formação inicial do estudante de medicina e seu impacto naprática educacional. Foram identificadas as potencialidades dessa disciplina e seu envolvimento na formação de uma cultura para a obtenção, elaboração e comunicação dos resultados da atividade de pesquisa como elementos básicos para a socialização científica. O grupo metodológico do ano, focado nas potencialidades identificadas a partir de uma abordagem socioamsenária, possibilita a formação e desenvolvimento da competência em estudo, orientada para a socialização dos resultados da atividade de pesquisa realizada pelo aluno durante as atividades de ensino no trabalho e extensão.

Prototipo para el control sanitario internacional en el policlínico universitario "Pedro Borrás Astorga" / Prototype for international health control at Pedro Borras Astorga university polyclinic

RESUMEN Introducción: el programa de Control Sanitario Internacional implementado en Cuba permite el control y seguimiento, en todo el país, de las enfermedades endémicas y transmisibles por vectores, procedentes de otros países. Esto se realiza de forma manual, por teléfono y con el intercambio de documentos. Por ello, se decidió elaborar una herramienta informática que satisfaga las necesidades, en el Departamento de Higiene y Epidemiología del Policlínico. Objetivo: desarrollar el prototipo de una aplicación informática para el control sanitario internacional en el Departamento de Higiene y Epidemiología del Policlínico Universitario "Pedro Borrás Astorga". Métodos: la investigación obedece a un proyecto de innovación tecnológica para definir la arquitectura de la información que se gestiona durante el control sanitario internacional. Se ejecutaron las etapas de análisis y diseño de la aplicación, con el empleo de la metodología ágil para el desarrollo de software. Además, se han aplicado métodos teóricos y empíricos como el histórico-lógico, el analítico-sintético, el inductivo-deductivo, las entrevistas y el análisis documental. Resultados: se describen los primeros resultados de la investigación, a partir del estudio de las necesidades y las carencias actuales del personal del Departamento de Higiene y Epidemiología. Se desarrolló la arquitectura de la información que se gestiona para lograr el control sanitario internacional. Conclusiones: el prototipo obtenido, permitirá a los futuros programadores implementar el software necesario para apoyar al personal del departamento en la toma de decisiones, de forma significativa a la reducción de riesgos por graves epidemias, beneficiará a los profesionales con una herramienta informática que puede simplificar su trabajo, tributar a la optimización del tiempo, la gestión y la seguridad de la información.

ABSTRACT Introduction: the International Sanitary Control Program implemented in Cuba allows the control and follow-up, throughout the country, of endemic and vector-borne diseases from other countries. This is manually done, by telephone and with the exchange of documents. Therefore, it was decided to develop a computerized tool to meet the needs of the Department of Hygiene and Epidemiology of the Polyclinic. Objective: to develop the prototype of a computer application for international sanitary control in the Department of Hygiene and Epidemiology at Pedro Borras Astorga University Polyclinic. Methods: the research complies with a technological innovation project to define the architecture of the information managed during the international sanitary control. The stages of analysis and design of the application were carried out using the agile methodology for software development. In addition, theoretical and empirical methods such as historical-logical, analytical-synthetic, inductive-deductive, interviews and documentary analysis were applied. Results: the first results of the research are described, based on the study of the current needs and deficiencies found for the personnel of the Department of Hygiene and Epidemiology. The architecture of the information managed to achieve international sanitary control was developed. Conclusions: the prototype obtained, will allow future programmers to implement the necessary software to support the staff of the department in decision making, significantly reducing risks due to serious epidemics, it will benefit professionals with a computer tool that can simplify their work, contribute to the optimization of time, management and information security.

Papillary cystadenoma of the epididymis.

Background: Papillary cystadenoma is a rare benign neoplasm of the epididymis. It may occur sporadically or in association with von Hippel-Lindau disease (VHLD). Papillary cystadenoma of the epididymis (PCE) is a benign mimic of metastatic clear cell renal cell carcinoma (CCRCC) given their histologic similarities. Case presentation: Herein, we present the case of a 40-year-old man with a four-year history of microhematuria and a recently detected right paratesticular mass. A testicular sonogram revealed a hypoechoic, hypervascular solid mass in the right epididymal head treated by surgical excision. Histopathological examination demonstrated a 1.1 cm papillary cystadenoma of the epididymis. Genetic testing performed later showed no signs of VHLD. However, heterozygous mutations in three genes - CASR, POT1, and RAD51D - were found which have never been reported in PCE before. Conclusions: Papillary cystadenoma of the epididymis should always be considered in the differential diagnosis of epididymal lesions, especially those that are cystic. The mainstay of treatment remains surgical excision, which provides an excellent prognosis.

Tratamiento a la comunicación científica desde la Disciplina Bases Biológicas de la Medicina / Treatment of scientific communication from the Discipline Biological Bases of Medicine

La enseñanza médica en Cuba constituye el escenario ideal para la formación de las competencias que garantizan la generación y socialización de resultados investigativos contextualizados a los desafíos actuales. Durante el año 2021, se realizó un estudio descriptivo con enfoque socio formativo en la Universidad de Ciencias Médicas de Camagüey, con el propósito de develar las potencialidades de la disciplina Bases Biológicas de la Medicina (BBM) para la formación de la competencia comunicación científica. A partir del mismo se determinan las causas, carencias teóricas y prácticas que repercuten en la formación de dicha competencia desde la formación inicial en el estudiante de Medicina y su incidencia en la práctica educativa. Fueron identificadas las potencialidades de esta disciplina y su implicación en la formación de una cultura para obtener, elaborar y comunicar los resultados de la actividad investigativa como elementos básicos para la socialización científica. El trabajo metodológico del colectivo de año, enfocado en las potencialidades identificadas desde un enfoque socio formativo posibilita formar y desarrollar la competencia objeto de estudio, orientada hacia la socialización de los resultados de la actividad investigativa que realiza el estudiante durante la educación en el trabajo y actividades extensionistas(AU)

Medical education in Cuba is the ideal setting for the formation of competencies that guarantee the generation and socialization of research results contextualized to current challenges. During the year 2021, a descriptive study with a socio-formative approach was carried out at the University of Medical Sciences of Camagüey, with the purpose of revealing the potentialities of the discipline Biological Bases of Medicine (BBM) for the formation of scientific communication competence. From it, the causes, theoretical and practical deficiencies that have an impact on the formation of this competence from the initial training in the medical student and its impact on educational practice are determined. The potentialities of this discipline and its involvement in the formation of a culture to obtain, elaborate and communicate the results of the research activity as basic elements for scientific socialization were identified. The methodological work of the year group, focused on the potentialities identified from a socio-formative approach, makes it possible to train and develop the competence under study, oriented towards the socialization of the results of the research activity carried out by the student during education at work and extension activities(EU)

Diseño y validación del cuestionario de autocuidado preventivo del pie diabético NAPD / Design and validation of diabetic foot preventive self-care questionnaire NAPD / Desenvolvimento e validação do questionário de autocuidado preventivo do pé diabético NAPD

Objetivo: Realizar el diseño y la validación del cuestionario "Nivel de autocuidado en la prevención del pie diabético" en términos de su contenido, constructo, confiabilidad y sen-sibilidad. Material y método: Estudio psicométrico desarrollado en tres fases: diseño del instrumento, a partir de las categorías teóricas que surgen de 8 entrevistas a personas con diabetes mellitus; validación aparente y de contenido, contando con la participación de 20 jueces expertos; y, validez del constructo, confiabilidad y sensibilidad, contando con 158 mediciones del instrumento. Resultados: El proceso de teorización dio origen a la versión inicial del cuestionario con 23 ítems; sin embargo, en la validación facial y de contenido requirió mejorías en la redacción y retirar un ítem, cambios que se efectuaron siguiendo las observaciones de los expertos tales como: Índice de Validez de Contenido de 0.88 y Kappa de Fleiss de 0.7606 (p=0.000). Finalmente se obtuvo la versión 2 del cuestionario NAPD.V2 con 22 ítems agrupados en 5 dimensiones: automanejo de la diabetes, percepción sobre el pie diabético, impacto emocional de la enfermedad, el cuidado rutinario de los pies y la percep-ción sobre el soporte social. Además, el análisis factorial exploratorio mostró una adecuada validez del constructo y su confiabilidad evidenció buen rendimiento -Alfa de Cronbach de 0,942- y una sensibilidad significativa sobre la -prueba Wilcoxon p=0.000-. Conclusiones: Tras el diseño y la validación se obtiene el cuestionario NAPD.V2 con propiedades psi-cométricas adecuadas para ser usado en la población con diabetes mellitus colombiana

Objective: Carry out the design and validation of the questionnaire "Level of self-care in the prevention of diabetic foot" in terms of its content, construct, reliability and sensitivity. Ma-terial and method: Psychometric study developed in three phases: design of the instrument, based on the conceptualized theoretical categories of 8 interviews with people with diabetes mellitus; face and content validity, with the participation of 20 expert judges; and construct validity, reliability, and sensitivity, through 158 instrument measurements. Results: The the-orization process gave rise to the initial version of the questionnaire with 23 items; however, the face and content validity required improvements in writing and removing an item, these changes were made following the experts' observations such as: Content Validity Index of 0.88 and Fleiss' Kappa of 0.7606 (p = 0.000). Finally, the second version of the questionnaire was made with 22 items grouped in 5 dimensions: self-management of diabetes, perception of the diabetic foot, emotional impact of the disease, routinary foot care and perception of so-cial support. Furthermore, the exploratory factor analysis showed adequate construct validity, and its reliability evidenced good performance -Cronbach's Alpha of 0.942- and significant sensitivity -Wilcoxon test p = 0.000-. Conclusions: After design and validation, a question-naire with adequate psychometric properties was obtained to be used in the Colombian pop-ulation with diabetes mellitus

Objetivo: Desenvolver e validar o questionário "Nível de autocuidado na prevenção do pé di-abético" em termos de conteúdo, construto, confiabilidade e sensibilidade. Material e méto-do: Estudo psicométrico desenvolvido em três fases: desenvolvimento do instrumento, a par-tir das categorias teóricas que surgiram de oito entrevistas à pessoas com Diabetes Mellitus; validação aparente e de conteúdo, contando com a participação de vinte juízes expertos; e, validez de construto, confiabilidade e sensibilidade com a realização de 158 medições do in-strumento. Resultados: O processo de teorização deu origem à versão inicial do questionário com 23 itens; entretanto, a validação facial e de conteúdo sugeriu melhorar a redação e tirar um item, mudanças efetivadas seguindo o parecer dos expertos: índice de validez de con-teúdo de 0,88 e Kappa de Fleiss de 0,7606 (p=0,000). Finalmente, obteve-se a versão 2 do questionário NAPD.V2 com 22 itens agrupados em cinco dimensões: autogestão do diabetes, percepções do pé diabético, impacto emocional da doença, cuidados rotineiros com os pés e percepção do apoio social. Além disso, o analise fatorial exploratório mostrou adequada validação de construto e a confiabilidade do questionário evidencio bom rendimento (Alpha de Cronbach=0,92) e uma sensibilidade significativa na prova de Wilcoxon p=0,000. Con-clusões: Obteve-se o questionário NAPD.V2 posterior a procedimentos de desenvolvimento e validação obtendo propriedades psicométricas adequadas para o seu uso na população com diabetes mellitus colombiana

Papillary cystadenoma of the epididymis

ABSTRACT Background Papillary cystadenoma is a rare benign neoplasm of the epididymis. It may occur sporadically or in association with von Hippel-Lindau disease (VHLD). Papillary cystadenoma of the epididymis (PCE) is a benign mimic of metastatic clear cell renal cell carcinoma (CCRCC) given their histologic similarities. Case presentation Herein, we present the case of a 40-year-old man with a four-year history of microhematuria and a recently detected right paratesticular mass. A testicular sonogram revealed a hypoechoic, hypervascular solid mass in the right epididymal head treated by surgical excision. Histopathological examination demonstrated a 1.1 cm papillary cystadenoma of the epididymis. Genetic testing performed later showed no signs of VHLD. However, heterozygous mutations in three genes - CASR, POT1, and RAD51D - were found which have never been reported in PCE before. Conclusions Papillary cystadenoma of the epididymis should always be considered in the differential diagnosis of epididymal lesions, especially those that are cystic. The mainstay of treatment remains surgical excision, which provides an excellent prognosis.

Identificación de brechas en gestión de la innovación en empresas de Alimentos y Bebidas en Caldas / Identification of gaps in innovation management in Food and Beverage companies in Caldas / Identifcação de gaps na gestão da inovação em empresas de Alimentos e Bebidas em Caldas

RESUMEN El programa de Alianzas para la Innovación desarrollado en el Eje Cafetero Colombiano, con el apoyo del Ministerio de Ciencias y la Cámara de Comercio de Manizales por Caldas fomenta la mentalidad y la cultura innovadora y el cierre de brechas en innovación. Los impactos de este programa, para el sector de Alimentos y Bebidas de Caldas, fueron evaluados en este estudio, producto de una investigación aplicada, de tipo descriptivo, en 16 micro, medianas y pequeñas empresas (Mipymes) donde se realizó la caracterización de las capacidades e indicadores de innovación, la identificación de beneficios, impulsores, barreras e impactos del programa y las brechas en gestión de la innovación. Los hallazgos evidencian avances en mentalidad y cultura innovadora, pero se requiere una mayor alineación con la estrategia organizacional, así como la definición de portafolios y proyectos de innovación. La participación de las Mipymes en programas como Pactos por la Innovación y Sistemas de Innovación es clave, para una mayor apropiación de la Ruta de la Innovación y consolidar la gestión de la innovación, eje fundamental de la competitividad regional. CLASIFICACIÓN JEL 031, O32

ABSTRACT The Alliances for Innovation program developed in the Colombian Coffee-growing Axis with the support of the Ministry of Sciences and the Chamber of Commerce of Manizales for Caldas, fosters an innovative mindset and culture and the closing of innovation gaps. The impacts of this program for the Food and Beverage sector in Caldas were evaluated in this study, as a result of an applied, descriptive research in 16 micro, medium and small enterprises (MSMEs) where the characterization of innovation capabilities and indicators, the identification of benefits, drivers, barriers and impacts of the program and the gaps in innovation management were carried out. The findings show progress in innovative mindset and culture, but a greater alignment with organizational strategy is required, as well as the definition of innovation portfolios and projects. The participation of MSMEs in programs such as Innovation Pacts and Innovation Systems is key for a greater appropriation of the Innovation Route and to consolidate innovation management, a fundamental axis of regional competitiveness. JEL CLASSIFICATION 031, O32

RESUMO O programa Aliança para a Inovação, desenvolvido na região cafeeira colombiana, com o apoio do Ministério das Ciências e da Câmara de Comércio de Manizales por Caldas, fomenta uma mentalidade e cultura inovadoras e elimina lacunas de inovação. Os impactos deste programa, para o setor de Caldas Alimentos e Bebidas, foram avaliados neste estudo, como resultado de uma pesquisa aplicada e descritiva, em l6 micro, médias e pequenas empresas (MPMEs) onde foi realizada a caracterização das capacidades e indicadores de inovação, identificação dos benefícios, motivadores, barreiras e impactos do programa e lacunas na gestão da inovação. Os resultados mostram avanços na mentalidade e cultura inovadoras, mas é necessário um maior alinhamento com a estratégia organizacional, bem como a definição de portfólios e projetos de inovação. A participação das MPMEs em programas como os Pactos de Inovação e Sistemas de Inovação é fundamental, para uma maior apropriação da Rota da Inovação e consolidação da gestão da inovação, eixo fundamental da competitividade regional. CLASSIFICÃO JEL 031, O32

Development of bozepinib-loaded nanocapsules for nose-to-brain delivery: preclinical evaluation in glioblastoma.

Aim: To develop and characterize bozepinib-loaded lipid-core nanocapsules (BZP-LNC+) as a potential treatment for glioblastoma (GBM). Methods: Characterization of nanocapsules was performed by diameter, polydispersity index, Zeta potential, pH and encapsulation efficiency. GBM cell viability, cell cycle and Annexin/PI were evaluated after BZP-LNC+ treatment. Synergism between BZP-LNC+ and temozolomide (TMZ) was performed by CompuSyn software and confirmed in vitro and in vivo. Results: BZP-LNC+ showed adequate particle sizes, positive Zeta potential, narrow size distribution and high encapsulation efficiency. BZP-LNC+ reduces GBM growth by inducing apoptosis. BZP-LNC+ and TMZ showed synergistic effect in vitro and reduced the in vivo glioma growth by approximately 81%. Conclusion: The present study provides proof-of-principle insights for the combination of these drugs for GBM treatment.

New insights into cytotoxic mechanisms of bozepinib against glioblastoma.

Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults and the current treatments only have a modest effect on patient survival. Recent studies show that bozepinib (BZP), a purine derivative, has potential applications in cancer treatment. The aim of this study was to evaluate the effect of BZP against GBM cells, specially concerning the purinergic system. Thus, GBM cells (C6 and U138 cell lines) were treated with BZP and cell viability, cell cycle, and annexin/PI assays, and active caspase-3 measurements were carried out. Besides, the effect of BZP over the purinergic system was also evaluated in silico and in vitro. Finally, we evaluate the action of BZP against important markers related to cancer progression, such as Akt, NF-κB, and CD133. We demonstrate here that BZP reduces GBM cell viability (IC50 = 5.7 ± 0.3 µM and 12.7 ± 1.5 µM, in C6 and U138 cells, respectively), inducing cell death through caspase-dependent apoptosis, autophagosome formation, activation of NF-κB, without any change in cell cycle progression or on the Akt pathway. Also, BZP modulates the purinergic system, inducing an increase in CD39 enzyme expression and activity, while inhibiting CD73 activity and adenosine formation, without altering CD73 enzyme expression. Curiously, one cycle of treatment resulted in enrichment of GBM cells expressing NF-κB and CD133+, suggesting resistant cells selection. However, after another treatment round, the resistant cells were eliminated. Altogether, BZP presented in vitro anti-glioma activity, encouraging further in vivo studies in order to better understand its mechanism of action.

Relación genética entre toros de inseminación comercializados en Chile por distintas empresas proveedoras de semen: un estudio de caso en las razas Holstein y Angus / Genetic relationship between insemination bulls marketed in Chile by two semen suppliers: a case study in Holstein and Angus breeds / Relação genética entre touros de inseminação comercializados no Chile por diferentes empresas fornecedoras de sêmen: um estudo de caso nas raças Holstein e Angus

Resumen La inseminación artificial (IA) es actualmente el manejo reproductivo preferido para la mayoría de los ganaderos que trabajan con razas deganado internacionales como Holstein Friesian y Aberdeen Angus. En relación con esto, varios autores han descrito que a lo largo de los años ha habido una alteración en parámetros de productivos, lo que se asociaría significativamente con un aumento en el grado de endogamia en los animales. Esta situación tendría su origen a nivel de los núcleos genéticos, en los que se llevan a cabo programas de mejora, debido al pequeño número de líneas familiares a las que pertenecen los animales seleccionados como reproductores. Este estudio evaluó el grado de parentesco entre toros de inseminación Holstein Friesian y Aberdeen Angus comercializados en Chile por dos empresas de distribución de semen. Se estudiaron un total de 86 toros disponibles en catálogos hasta el año 2017. La información genealógica de cada toro se remonta hasta trastatarabuelo y luego se construyó un registro genealógico consolidado para cada raza. Este análisis consideró la estimación del porcentaje de endogamia (F) de cada toro y la construcción de una matriz de parentesco aditivo (A) entre los animales. Los resultados indicaron que el 99% de los toros Holstein y el 79% de los toros Angus están emparentados. Como resultado de lo anterior, se concluye que es esencial que en Chile se inicie un programa de gestión de información genealógica para controlar adecuadamente los niveles de endogamia y poder mitigar los problemas que puedan surgir a causa de este fenómeno.

Abstract Artificial insemination (AI) is currently the preferred reproductive management for most cattle farmers working with international cattle breeds likes Holstein Friesian and Aberdeen Angus. In relation to this, several authors have described that over the years there has been an alteration in the production parameters, which would be significantly associated with an increase in the inbreeding degree of the animals. This fact would have its origin at the genetic nucleus level, in which improvement programs are carried out, due to the small number of family lines which the animals selected as breeding stock belong to. This study evaluated the degree of kinship between Holstein Friesian and Aberdeen Angus insemination bulls marketed in Chile by two semen distribution companies. A total of 86 bulls available in catalogues until 2017 were studied. The genealogical information of each bull was traced back up to great-great-grandfather and then a consolidated genealogical record was built for each breed. This analysis considered the estimation of each bull's inbreeding percentage (F) and the construction of a co-ancestry matrix among animals. Results indicated that 99% of Holstein bulls and 79% of Angus bulls, are related to some extent. As a result of the above, it is concluded that is essential that in Chile a program management of genealogical information be initiated to adequately control inbreeding problems that may arise from the use of related animals.

Resumo A inseminação artificial (IA) atualmente é o manejo reprodutivo preferido da maioria dos criadores de gado que trabalham com raças de gado internacionais, como o Holstein Friesian e o Aberdeen Angus. Nesse âmbito, vários autores assinalam que, ao longo dos anos, tem ocorrido uma alteração dos parâmetros produtivos, que poderia estar associada de forma significativa com um aumento no nível de endogamia nos animais. A origem dessa situação poderia estar nos núcleos genéticos, pois nos programas de melhoria, os animais que são selecionados como reprodutores pertencem a um reduzido número de linhas familiares. Esta pesquisa avalia os graus de parentesco entre touros para inseminação Holstein Friesian e Aberdeen Angus comercializados no Chile por duas empresas de distribuição de sêmen. No total, 86 touros foram analisados, disponíveis em catálogos de até 2017. As informações genealógicas de cada touro remontam aos tetravós. Posteriormente, foi elaborado um registro genealógico consolidado para cada raça. A análise considerou a estimação da porcentagem de endogamia (F) de cada touro e a construção de uma matriz de parentesco aditivo (A) entre os animais. Os resultados indicam que 99% dos touros Holstein e 79% dos touros Angus são aparentados. Como resultado disso, chega-se à conclusão de que é essencial se ter um programa de gestão de informações genealógicas no Chile para controlar adequadamente os níveis de endogamia e assim mitigar os possíveis problemas gerados por esse fenômeno.

Improving Cell Penetration of Gold Nanorods by Using an Amphipathic Arginine Rich Peptide.

INTRODUCTION: Gold nanorods are highly reactive, have a large surface-to-volume ratio, and can be functionalized with biomolecules. Gold nanorods can absorb infrared electromagnetic radiation, which is subsequently dispersed as local heat. Gold nanoparticles can be used as powerful tools for the diagnosis and therapy of different diseases. To improve the biological barrier permeation of nanoparticles with low cytotoxicity, in this study, we conjugated gold nanorods with cell-penetrating peptides (oligoarginines) and with the amphipathic peptide CLPFFD. METHODS: We studied the interaction of the functionalized gold nanorods with biological membrane models (liposomes) by dynamic light scattering, transmission electron microscopy and the Langmuir balance. Furthermore, we evaluated the effects on cell viability and permeability with an MTS assay and TEM. RESULTS AND DISCUSSION: The interaction study by DLS, the Langmuir balance and cryo-TEM support that GNR-Arg7CLPFFD enhances the interactions between GNRs and biological membranes. In addition, cells treated with GNR-Arg7CLPFFD internalized 80% more nanoparticles than cells treated with GNR alone and did not induce cell damage. CONCLUSION: Our results indicate that incorporation of an amphipathic sequence into oligoarginines for the functionalization of gold nanorods enhances biological membrane nanoparticle interactions and nanoparticle cell permeability with respect to nanorods functionalized with oligoarginine. Overall, functionalized gold nanorods with amphipathic arginine rich peptides might be candidates for improving drug delivery by facilitating biological barrier permeation.

Prevalencia de marcadores infecciosos en donantes de sangre / Prevalence of viral markers in blood donors

Objetivo: El objetivo de este artículo es realizar una revisión actualizada sobre prevalencia de marcadores virales en donantes del Banco de sangre. Materiales y métodos: La búsqueda bibliografía se ha realizado en Pubmed, Medline y Scielo. Como criterios de selección se tomó en cuenta información publicada en dichas fuentes dada la confiabilidad de las mismas, con una antigüedad no mayor de 5 años, tanto en idioma español como inglés. Resultados: Se encontró un total de seis artículos: en México, se encontró un descenso de 5,375 (prevalencia=0.47) a 2,675 (prevalencia=0.15) casos seropositivos para VHB. El marcador serológico del VHC presentó un aumento de 8,170 (prevalencia=0.69) a 10,217 (prevalencia=0.57). En Colombia el marcador infeccioso más frecuentemente encontrado en los donantes fue Sífilis (1,73%), seguido por Hepatitis B (1,53%), Hepatitis C (0,46%) HTLV I-II (0,21%), la enfermedad de Chagas (0,27%) y VIH (0,17%). En Cuba se encontró una prevalencia de AgsHB 1,0 %, VHC 2,3 %, VIH 3,4 % y sifilis 2,3 %. En Perú el 0,6% (n=156) fue reactivo para HBsAg; 5,2% (n=1465) para anti-HBcAb 0,8% (n=232) para Anti-HVC y 1.21% para HTLV I-II. Conclusiones: Las cifras de prevalencia reportadas en los estudios son coherentes con los reportes de la OPS y coinciden entre ellos.La prevalencia constante de estos marcadores se debe a la poca educación sanitaria al respecto de las enfermedades transmisibles en cuanto a su transmisibilidad, diagnóstico y tratamiento oportuno. (AU)

Objective: The objective of this article is to carry out an updated review on the prevalence of viral markers in Blood Bank donors. Materials and methods: The bibliography search was carried out in Pubmed, Medline and Scielo. As criteria for selection, information published in said sources was taken into account given the reliability of the same, with an age of no more than 5 years, in both Spanish and English. Results: Six articles were found: in Mexico, a decrease of 5.375 (prevalence = 0.47) to 2.675 (prevalence = 0.15) was found for seropositive cases for HBV. The serological marker of HCV showed an increase of 8,170 (prevalence = 0.69) to 10,217 (prevalence = 0.57). In Colombia, the infectious marker most frequently found in the donors was Syphilis (1.73%), followed by Hepatitis B (1.53%), Hepatitis C (0.46%), HTLV I-II (0.21%), Chagas disease (0.27%) and HIV (0.17%). In Cuba, a prevalence of HBsAg 1.0%, HCV 2.3%, HIV 3.4% and syphilis 2.3% was found. In Peru, 0.6% (n = 156) was reactive for HBsAg; 5.2% (n = 1465) for anti-HBcAb 0.8% (n = 232) for Anti-HVC and 1.21% for HTLV I-II. Conclusions: The prevalence figures reported in the studies are consistent with the PAHO reports and coincide among them.The constant prevalence of these markers is due to the lack of health education regarding communicable diseases in terms of their transmissibility, diagnosis and timely treatment. (AU)

Carlos Marx y José Martí: coincidencias en las concepciones sociopolíticas y culturales / Coincidences in the social-political and cultural conceptions of Carlos Marx and José Martí

RESUMEN El presente estudio está dirigido a establecer coincidencias entre el pensamiento de José Martí y de Carlos Marx en el terreno filosófico. Ambos representan los más altos exponentes del saber filosófico y humanista de la cultura europea y latinoamericana del siglo XIX, respectivamente, con un alcance genuinamente universal. No fue objetivo en modo alguno convertir a Martí en marxista, del mismo modo que sería absurdo afiliar a Marx a las ideas y las concepciones martianas. Sin embargo, no es posible dejar de subrayar la profundidad del ideario martiano en el terreno filosófico, político, social y económico y sus aproximaciones a las concepciones marxistas o al socialismo científico.

ABSTRACT The present study is directed to establish coincidences between the thought of José Martí and Carlos Marx in the philosophical area. Both are represented by the highest exponents of the philosophical and humanist knowledge of the European and Latin-American culture of the 19th century, respectively, with an authentically universal scope. It was not objective in any way to turn Martí into Marxist, in the same way that it would be absurd to affiliate Marx to the ideas and the Martí´s conceptions. Nevertheless, it is not possible to stop underlining the depth of the Martí´s ideology in the philosophical, political, social and economic area and his approaches to the Marxist conceptions or to the scientific socialism.