Antimicrobial activity and mode of action of bacteriocin AS-48 against Mycobacterium tuberculosis

La creciente incidencia de cepas multirresistentes de Mycobacteriumtuberculosis y los pocos medicamentos disponibles para su tratamiento estánpromoviendo el desarrollo de nuevos medicamentos que tratan de resolver estosproblemas. Siguiendo esta idea, este trabajo ha explorado el péptido antibacterianoAS-48, producido por Enterococcus faecalis, cuya diana es la membrana bacterianay, además, es activo contra varias bacterias grampositivas. Se ha demostrado queAS-48 tiene una acción bactericida contra M. tuberculosis, incluyendo H37Rv yotras cepas clínicas y de referencia, también contra algunas especiesmicobacterianas clínicas no tuberculosas. Cabe destacar el efecto sinérgico de lacombinación de AS-48 con lisozima o etambutol (comúnmente utilizado en eltratamiento de la tuberculosis), dos compuestos que aumentan la acciónantimicrobiana de AS-48. En estas condiciones, AS-48 mata a M. tuberculosis a unadosis más baja y muestra una CIM (Concentración Inhibitoria Mínima) cercana aalgunos de los agentes anti-TB de primera línea.Además, se ha ensayado la citotoxicidad de AS-48 contra las líneas celularesde macrófagos THP-1, MHS y J774, y se ha encontrado que a concentracionescercanas a la CIM de AS-48 no se pudo detectar ningún efecto citotóxico. Laactividad de AS-48 para inhibir el crecimiento de M. tuberculosis también seobservó dentro de los macrófagos infectados; en este modelo, también se observósinergia para las combinaciones de AS-48 y etambutol.Se ha explorado el mecanismo de acción de la bacteriocina AS-48 contra M.tuberculosis que muestra que AS-48 está afectando la membrana, que es una de lasdianas menos estudiadas, y que reduciría la aparición de nuevas cepas resistentes.Además, algunos mecanismos relacionados con la aparición de cepas persistentesparecen estar alterados después de tratar M. tuberculosis con AS-48. Se ha realizadoun análisis transcriptómico para comprender mejor el modo de acción AS-48.Curiosamente, se ha demostrado que AS-48 también tiene como diana lamovilidad del ADN, probablemente afectando a otros procesos moleculares. Porlo tanto, podemos considerar que AS-48 es un fármaco multidiana, y como tal, suuso reduciría las probabilidades de desarrollar cepas mutantes resistentes.Se han realizado estudios de toxicidad in vivo que muestran que la cepaBALB/c es menos sensible a AS-48 que C57B/6. Los ensayos de toxicidadsubcrónica muestran que los ratones se mantienen saludables en tratamientos dediez días con dosis de 2-1 mg/Kg de peso corporal de AS-48.Sin embargo, en el ensayo de eficacia, AS-48 no muestra la actividadantituberculosis observada en los ensayos in vitro; incluso junto con etambutol, nodemostró reducir la carga bacteriana en ratones infectados con M. tuberculosis.En resumen, este trabajo revela algunos aspectos positivos de AS-48(actividad antimicrobiana, baja toxicidad, sinergismo con etambutol) pero tambiénotros aspectos que tienen que mejorarse (ausencia de actividad in vivo o más bienalta toxicidad). Así más trabajos y refinamientos son necesarios para poderpresentar a AS-48 como un candidato terapéutico contra tuberculosis.<br /

Infección respiratoria aguda comunitaria en menores de 15 años. Factores de riesgo asociados.

It was performed a research and some controls to patients with the objective to identify some risk factors of the Acute Respiratory Infection in children under 15 years old belonging to the consults 145B and 18 Floor- Building of Jimmy Hirtzel polyclinic in Bayamo, Granma. The sample was made by 111 patients and 222 controls from a universe of 341 children. For the controls there were selected children under 15 years without respiratory symptoms, they belonged to the same consult. It was studied the association between the acute respiratory disease with the risk factors like: environmental, nutritional and some others related to the mother. The results showed that the low scholarity of the mother was a risk factor statistically outstanding. (OR: 6.67 IC: 5.67-7.84) in relation to the risk of children who acquire acute respiratory infections. It was evidenced that the children whose parents are smokers presented more risks to acquire this disease (OR 4.50, IC 3.34-6.0). Conclusions: all of the studied risk factors contributed to the risk to acquire High Acute Respiratory Infections in the community. The most significant factors were the mother scholarity level, undernutrition and passive exposure to the smoke.Se realizó un estudio, de pacientes y controles, con el objetivo de identificar, algunos factores de riesgo, para adquirir Infección Respiratoria Aguda Alta en la  comunidad, en niños menores de 15 años, perteneciente a los consultorios 145 B  y del 18 Plantas del Policlínico Jimmy Hitrzel, Bayamo, Granma. La muestra estuvo constituida por 111 pacientes y 222 controles de un universo de 341 niños. Se seleccionaron como controles, niños menores de 15 años, sin síntomas respiratorios, perteneciente al mismo consultorio. Se investigó la asociación entre la enfermedad respiratoria aguda con factores de riesgos, como son, ambientales, nutricionales y otros relacionados con la madre. Entre los resultados se obtuvo que la baja escolaridad de la madre fue un factor de riesgo estadísticamente significativo (OR:6.67, IC: 5.67-7.84),  con relación al riesgos de que los niños adquirieran infección aguda respiratoria , se evidencio que los niños cuyos padres son fumadores tuvieron mas riesgos de adquirir la enfermedad  ( OR: 4.50, IC: 3.34-6.0) Se concluye con que todos los factores investigados contribuyeron al riesgo para adquirir Infección Respiratoria Aguda Alta en la comunidad, siendo los de mayor significación, la escolaridad de la madre, desnutrición y exposición pasiva al humo de cigarro

Reconstrucción Infográfica del Castellum de Tamuda (Tetuán, Marruecos)

[ES] Las últimas investigaciones desarrolladas en el solar del castellum romano de Tamuda (Tetuán, Marruecos), especialmente centradas en las puertas de la instalación militar, han puesto de relieve diferentes fases o episodios constructivos en la vida del mismo. Así en este trabajo se presentan diversas restituciones infográficas correspondientes a las fases documentadas en el recinto, centradas de manera específica en las puertas de acceso, ofreciendo una imagen de la evolución de dicha instalación militar a lo largo de casi cuatro siglos, desde los momentos fundacionales en época de Claudio hasta los inicios del s. V d.C.[EN] The last researches developed in the lot of Tamuda's Roman castellum (Tetuan, Morocco), specially centred on the doors of the military installation, have emphasized different phases or constructive episodes in the life of the same one. This way in this work they present diverse restitutions infographics corresponding to the phases documented in the enclosure, centred of a specific way in the doors of access, offering an image of the evolution of the above mentioned military installation throughout almost four centuries, from the moments of the foundation in epoch of Claudio up to the beginnings of Vst. c. A.D.Bermejo Meléndez, J.; Campos Carrasco, JM.; Delgado Aguilar, S.; Fernández Sutilo, L.; Toscano Pérez, C.; Verdugo Santos, J. (2012). Reconstrucción Infográfica del Castellum de Tamuda (Tetuán, Marruecos). Virtual Archaeology Review. 3(6):83-87. https://doi.org/10.4995/var.2012.4449OJS838736BERMEJO, J., CAMPOS, J.M., FERNÁNDEZ, L., GÓMEZ, A., BERNAL, D., GHOTTES, M. (e.p): "Anastylosis virtual de la puerta occidental del Castellum de Tamuda (Tetuan, Marruecos)". Actas del II Congreso de Arqueología Virtual. San José de la Rinconada (Sevilla), Junio de 2010.CAMPOS, J.M., BERMEJO, J., DELGADO, S., FERNÁNDEZ, J.A., FERNÁNDEZ, L., FUERTES, Mª., TOSCANO, C. Y VERDUGO, J. (2011): Proyecto Tamuda (Tetuán Marruecos). Memoria Científica. Inédito. Dirección General de Bienes Culturales. Junta de Andalucía. Sevilla.CAMPOS, J.M., BERMEJO, J., FERNÁNDEZ, L., GÓMEZ, A., RUIZ, J., GHOTTES, M. (2010): "La porta principalis sinistra del castellum de Tamuda". Proyecto Tamuda (Tetuán Marruecos). Memoria Científica. Inédito. Dirección General de Bienes Culturales. Junta de Andalucía. Sevilla.CAMPOS, J.M., BERMEJO, J., FERNÁNDEZ, L., GÓMEZ, A., RUIZ, J., GHOTTES, M. (e.p): "El balneum del castellum de Tamuda. Análisis Arqueoarquitectónico y Arqueológico". Actas del XIX Convegno Internazionale dell'Africa romana

APRESENTAÇÃO: TRABALHO, HISTÓRIA E MEMÓRIA DOS POVOS DE "NUESTRA AMÉRICA" - TOMO 2

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O feminicídio: realidade ou mentira dentro da política pública colombiana

This academic exercise is based on the state of the art on feminicide in six Latin American countries, including Colombia, over the past two decades to show the need to propose a defiition of feminicide, not as an aggravating aspect of homicide but as a separate offnse under Colombian law. It was written based on the theory of feminicide of Diana Marcela Russell and Lagard, in line with public policy to protect women victims and was the result of two completed research papers. Th conclusion is that a large part of public policy supports a decrease in violence against women and also serves to modify collective concepts.Este ejercicio académico parte del estado del arte del feminicidio en seis países de América Latina —entre ellos Colombia— durante los dos últimos lustros, para evidenciar la necesidad de proponer la tipificación del feminicidio, no como agravante del homicidio, sino como delito autónomo en la legislación colombiana. Se escribió en la línea de política pública, desde las teorías del feminicidio de Diana Russell y de Marcela Lagarde para proteger a las&nbsp;mujeres víctimas, y fue el resultado de dos trabajos de investigación terminados; se concluye&nbsp;con que buena parte de la política pública se apoya la disminución de la violencia contra&nbsp;mujeres y se modifican los imaginarios.Este exercício acadêmico parte do estado da arte do feminicídio em seis países da América Latina —entre eles a Colômbia— durante os dois últimos anos, para evidenciar a necessidade de propor a tipifiação do feminicídio, não como agravante do homicídio, mas sim como delito autônomo na legislação colombiana. Escreveu-se na linha de política pública, desde as teorias do feminicídio de Diana Russell e de Marcela Lagarde para proteger as mulheres vítimas, e foi o resultado de dois trabalhos de pesquisa terminados, conclui-se com que boaparte da política pública se apoia na diminuição da violência contra mulheres e modifiamse os imaginário

Twitter as a Tool for Teaching and Communicating Microbiology: The #microMOOCSEM Initiative

Online social networks are increasingly used by the population on a daily basis. They are considered a powerful tool for science communication and their potential as educational tools is emerging. However, their usefulness in academic practice is still a matter of debate. Here, we present the results of our pioneering experience teaching a full Basic Microbiology course via Twitter (#microMOOCSEM), consisting of 28 lessons of 40-45 minutes duration each, at a tweet per minute rate during 10 weeks. Lessons were prepared by 30 different lecturers, covering most basic areas in Microbiology and some monographic topics of general interest (malaria, HIV, tuberculosis, etc.). Data analysis on the impact and acceptance of the course were largely affirmative, promoting a 330% enhancement in the followers and a >350-fold increase of the number of visits per month to the Twitter account of the host institution, the Spanish Society for Microbiology. Almost one third of the course followers were located overseas. Our study indicates that Massive Online Open Courses (MOOC) via Twitter are highly dynamic, interactive, and accessible to great audiences, providing a valuable tool for social learning and communicating science. This strategy attracts the interest of students towards particular topics in the field, efficiently complementing customary academic activities, especially in multidisciplinary areas like Microbiology.Versión del edito

Exercise Increases Serum Fibroblast Growth Factor 21 (FGF21) Levels

Fibroblast growth factor 21 (FGF21) increases glucose uptake. It is unknown if FGF21 serum levels are affected by exercise.This was a comparative longitudinal study. Anthropometric and biochemical evaluation were carried out before and after a bout of exercise and repeated after two weeks of daily supervised exercise. The study sample was composed of 60 sedentary young healthy women. The mean age was 24±3.7 years old, and the mean BMI was 21.4±7.0 kg/m². The anthropometric characteristics did not change after two weeks of exercise. FGF21 levels significantly increased after two weeks of exercise (276.8 ng/l (142.8-568.6) vs. (460.8 (298.2-742.1), p<0.0001)). The delta (final-basal) log of serum FGF21, adjusted for BMI, showed a significant positive correlation with basal glucose (r = 0.23, p = 0.04), mean maximal heart rate (MHR) (r = 0.54, p<0.0001), mean METs (r = 0.40, p = 0.002), delta plasma epinephrine (r = 0.53, p<0.0001) and delta plasma FFAs (r = 0.35, p = 0.006). A stepwise linear regression model showed that glucose, MHR, METs, FFAs, and epinephrine, were factors independently associated with the increment in FGF21 after the exercise program (F = 4.32; r² = 0.64, p<0.0001).Serum FGF21 levels significantly increased after two weeks of physical activity. This increment correlated positively with clinical parameters related to the adrenergic and lipolytic response to exercise.ClinicalTrials.gov NCT01512368

The relapsed acute lymphoblastic leukemia network (ReALLNet): a multidisciplinary project from the spanish society of pediatric hematology and oncology (SEHOP)

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with survival rates exceeding 85%. However, 15% of patients will relapse; consequently, their survival rates decrease to below 50%. Therefore, several research and innovation studies are focusing on pediatric relapsed or refractory ALL (R/R ALL). Driven by this context and following the European strategic plan to implement precision medicine equitably, the Relapsed ALL Network (ReALLNet) was launched under the umbrella of SEHOP in 2021, aiming to connect bedside patient care with expert groups in R/R ALL in an interdisciplinary and multicentric network. To achieve this objective, a board consisting of experts in diagnosis, management, preclinical research, and clinical trials has been established. The requirements of treatment centers have been evaluated, and the available oncogenomic and functional study resources have been assessed and organized. A shipping platform has been developed to process samples requiring study derivation, and an integrated diagnostic committee has been established to report results. These biological data, as well as patient outcomes, are collected in a national registry. Additionally, samples from all patients are stored in a biobank. This comprehensive repository of data and samples is expected to foster an environment where preclinical researchers and data scientists can seek to meet the complex needs of this challenging population. This proof of concept aims to demonstrate that a network-based organization, such as that embodied by ReALLNet, provides the ideal niche for the equitable and efficient implementation of “what's next” in the management of children with R/R ALL

SARS-CoV-2 omicron (B.1.1.529)-related COVID-19 sequelae in vaccinated and unvaccinated patients with cancer: results from the OnCovid registry

Background COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. Methods OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. Findings At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [ 50 center dot 7%] of 1902 patients with sex data were female and 938 [49 center dot 3%] were male). Overall, 317 (16 center dot 6%; 95% CI 14 center dot 8-18 center dot 5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the prevaccination phase (191 [19 center dot 1%; 95% CI 16 center dot 4-22 center dot 0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16 center dot 8%; 13 center dot 8- 20 center dot 3] of 653 patients, p=0 center dot 24), but significantly lower in the omicron phase (16 [6 center dot 2%; 3 center dot 5-10 center dot 2] of 256 patients, p<0 center dot 0001). In the alpha- delta phase, 84 (18 center dot 3%; 95% CI 14 center dot 6-22 center dot 7) of 458 unvaccinated patients and three (9 center dot 4%; 1 center dot 9- 27 center dot 3) of 32 unvaccinated patients in the omicron phase had sequelae. Patients who received a booster and those who received two vaccine doses had a significantly lower prevalence of overall COVID-19 sequelae than unvaccinated or partially vaccinated patients (ten [7 center dot 4%; 95% CI 3 center dot 5-13 center dot 5] of 136 boosted patients, 18 [9 center dot 8%; 5 center dot 8-15 center dot 5] of 183 patients who had two vaccine doses vs 277 [ 18 center dot 5%; 16 center dot 5-20 center dot 9] of 1489 unvaccinated patients, p=0 center dot 0001), respiratory sequelae (six [4 center dot 4%; 1 center dot 6-9 center dot 6], 11 [6 center dot 0%; 3 center dot 0-10 center dot 7] vs 148 [9 center dot 9%; 8 center dot 4- 11 center dot 6], p= 0 center dot 030), and prolonged fatigue (three [2 center dot 2%; 0 center dot 1-6 center dot 4], ten [5 center dot 4%; 2 center dot 6-10 center dot 0] vs 115 [7 center dot 7%; 6 center dot 3-9 center dot 3], p=0 center dot 037)