Polymorphic variants in oxidative stress genes and acute toxicity in breast cancer patients receiving radiotherapy

Purpose. Reactive oxygen species (ROS) are generated as an indirect product of radiation therapy (RT). Genetic variation in genes related to ROS metabolism may influence the level of RT-induced adverse effects. We evaluated the potential association of single nucleotide polymorphism (SNP)-related response to radiotherapy injury in breast cancer patients undergoing RT. Materials and Methods. Eighty patients receiving conventional RT were included. Acute effects were evaluated according to the Radiation Therapy Oncology Group (RTOG) scores. DNA was extracted from blood and buccal swab samples. SNPs were genotyped for GSTP1, GSTA1, SOD2, and NOS3 genes by polymerase chain reaction-based restriction fragment length polymorphism. Univariate analysis (odds ratios [ORs] and 95% confidence interval [CI]) and principal component analysis were used for correlation of SNPs and factors related to risk of developing ≥ grade 2 acute effects. Results. Sixty-five patients (81.2%) showed side effects, 32 (40%) presented moderate to severe acute skin toxicity, and 33 (41.2%) manifested minimal acute skin reactions by the end of treatment. In both univariate and multivariate analyses, nominally significant associations were found among body mass index (OR, 3.14; 95% CI, 8.5338 to 1.1274; p=0.022), breast size (OR, 5.11; 95% CI, 17.04 to 1.54; p=0.004), and grade ≥ 2 acute radiation skin toxicity. A significant association was also observed between NOS3 G894T polymorphism (OR, 9.8; 95% CI, 211.6 to 0.45; p=0.041) and grade ≥ 2 acute radiation skin toxicity in patients with neo-adjuvant chemotherapy treatment. Conclusion. The analysis of the factors involved in individual radiosensitivity contributed to the understanding of the mechanisms underlying this trait.Facultad de Ciencias ExactasFacultad de Ciencias MédicasInstituto de Genética Veterinari

Single nucleotide polymorphisms in ATM, TNF-α and IL6 genes and risk of radiotoxicity in breast cancer patients

Although oncological therapies have improved in the last decades, breast cancer (BC) remains a serious health problem worldwide. Radiotherapy (RT) is one of the most frequently used treatments for cancer aimed at eliminating tumor cells. However, it can also alter the surrounding normal tissue, especially the skin, and patient reactions may vary as a result of extrinsic and intrinsic factors. We evaluated the association of gene polymorphisms ATM Asp1853Asn, IL-6 G-174C and TNF-α G-308A involved in central phenotype pathways and development of individual radiosensitivity in BC patients with an exacerbated response to RT. Although univariate analysis results did not show a significant association with this trait, the interaction analysis between polymorphisms showed an increased risk of patients presenting wild-type TNF-α G-308A genotype and mutant IL-6 G-174C genotype, and heterozygous TNF-α G-308A genotype and heterozygous IL-6G-174C genotype. On the other hand, our results showed that breast size and patient age influenced the determination of RT-associated effects. Considering that the trait is multifactorial, other significant elements for the determination of individual radiosensitivity should be considered, together with the establishment of specific polymorphic variants.Fil: Cordoba, Elisa Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de la Plata, Facultad de Ciencias Exactas; ArgentinaFil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas, CINIBA- Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas, CINIBA- Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Fernández, Eduardo. 21st Century Oncology, Inc.; Estados UnidosFil: Güerci, Alba Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina. Universidad Nacional de la Plata, Facultad de Ciencias Exactas; Argentin

Single nucleotide polymorphisms in ATM, TNF-α and IL6 genes and risk of radiotoxicity in breast cancer patients

Although oncological therapies have improved in the last decades, breast cancer (BC) remains a serious health problem worldwide. Radiotherapy (RT) is one of the most frequently used treatments for cancer aimed at eliminating tumor cells. However, it can also alter the surrounding normal tissue, especially the skin, and patient reactions may vary as a result of extrinsic and intrinsic factors. We evaluated the association of gene polymorphisms ATM Asp1853Asn, IL-6 G-174C and TNF-α G-308A involved in central phenotype pathways and development of individual radiosensitivity in BC patients with an exacerbated response to RT. Although univariate analysis results did not show a significant association with this trait, the interaction analysis between polymorphisms showed an increased risk of patients presenting wild-type TNF-α G-308A genotype and mutant IL-6 G-174C genotype, and heterozygous TNF-α G-308A genotype and heterozygous IL-6G-174C genotype. On the other hand, our results showed that breast size and patient age influenced the determination of RT-associated effects. Considering that the trait is multifactorial, other significant elements for the determination of individual radiosensitivity should be considered, together with the establishment of specific polymorphic variants.Centro de Investigaciones Inmunológicas Básicas y AplicadasInstituto de Genética Veterinari

Single nucleotide polymorphisms in ATM, TNF-α and IL6 genes and risk of radiotoxicity in breast cancer patients

Although oncological therapies have improved in the last decades, breast cancer (BC) remains a serious health problem worldwide. Radiotherapy (RT) is one of the most frequently used treatments for cancer aimed at eliminating tumor cells. However, it can also alter the surrounding normal tissue, especially the skin, and patient reactions may vary as a result of extrinsic and intrinsic factors. We evaluated the association of gene polymorphisms ATM Asp1853Asn, IL-6 G-174C and TNF-α G-308A involved in central phenotype pathways and development of individual radiosensitivity in BC patients with an exacerbated response to RT. Although univariate analysis results did not show a significant association with this trait, the interaction analysis between polymorphisms showed an increased risk of patients presenting wild-type TNF-α G-308A genotype and mutant IL-6 G-174C genotype, and heterozygous TNF-α G-308A genotype and heterozygous IL-6G-174C genotype. On the other hand, our results showed that breast size and patient age influenced the determination of RT-associated effects. Considering that the trait is multifactorial, other significant elements for the determination of individual radiosensitivity should be considered, together with the establishment of specific polymorphic variants.Centro de Investigaciones Inmunológicas Básicas y AplicadasInstituto de Genética Veterinari

Polymorphic variants in oxidative stress genes and acute toxicity in breast cancer patients receiving radiotherapy

Purpose. Reactive oxygen species (ROS) are generated as an indirect product of radiation therapy (RT). Genetic variation in genes related to ROS metabolism may influence the level of RT-induced adverse effects. We evaluated the potential association of single nucleotide polymorphism (SNP)-related response to radiotherapy injury in breast cancer patients undergoing RT. Materials and Methods. Eighty patients receiving conventional RT were included. Acute effects were evaluated according to the Radiation Therapy Oncology Group (RTOG) scores. DNA was extracted from blood and buccal swab samples. SNPs were genotyped for GSTP1, GSTA1, SOD2, and NOS3 genes by polymerase chain reaction-based restriction fragment length polymorphism. Univariate analysis (odds ratios [ORs] and 95% confidence interval [CI]) and principal component analysis were used for correlation of SNPs and factors related to risk of developing ≥ grade 2 acute effects. Results. Sixty-five patients (81.2%) showed side effects, 32 (40%) presented moderate to severe acute skin toxicity, and 33 (41.2%) manifested minimal acute skin reactions by the end of treatment. In both univariate and multivariate analyses, nominally significant associations were found among body mass index (OR, 3.14; 95% CI, 8.5338 to 1.1274; p=0.022), breast size (OR, 5.11; 95% CI, 17.04 to 1.54; p=0.004), and grade ≥ 2 acute radiation skin toxicity. A significant association was also observed between NOS3 G894T polymorphism (OR, 9.8; 95% CI, 211.6 to 0.45; p=0.041) and grade ≥ 2 acute radiation skin toxicity in patients with neo-adjuvant chemotherapy treatment. Conclusion. The analysis of the factors involved in individual radiosensitivity contributed to the understanding of the mechanisms underlying this trait.Facultad de Ciencias ExactasFacultad de Ciencias MédicasInstituto de Genética Veterinari

Juegos de Salud Pública: la gamificación como método de aprendizaje

[ES] La innovación en el proceso de enseñanza-aprendizaje se ha convertido en un aspecto fundamental que posibilita un cambio en el paradigma educativo y permite alcanzar el “aprendizaje significativo”. En los últimos años, con motivo de la pandemia se ha puesto aún más si cabe la necesidad de prevención de enfermedades infecciosas, mediante el lavado de manos. En las asignaturas de Salud Pública del Grado de Enfermería y Podología impartidas por el Área de Medicina Preventiva y Salud Pública de la Universidad de León, se imparten dichos contenidos de una forma teórico/práctica tradicional, reportando opiniones de los alumnos relacionadas con baja motivación, interés y/o comprensión de estos contenidos. Ante estos problemas, el objetivo de la presente innovación docente fue mejorar las competencias, la motivación y la autorregulación del aprendizaje de los estudiantes, en la importancia de la higiene de manos en la prevención de enfermedades infecciosas, mediante la gamificación de una práctica. Se llevó a cabo una actividad de gamificación a través de un breakout con una narrativa relacionada con la historia biográfica de Ignaz Semmelweis. Se evaluaron los resultados mediante dos encuestas de satisfacción, y se realizó una comparación entre las opiniones de los estudiantes que habían participado en la práctica gamificada y aquellos asignados a la metodología tradicional. El grado de satisfacción con la práctica gamificada ha sido mayor respecto a los alumnos que recibieron la práctica de forma tradicional, obteniendo valores estadísticamente significativos en todos los ítems (p<0,05). Además, cabe destacar el interés de los estudiantes con “la aplicación de la gamificación a otras prácticas” que fue la pregunta que obtuvo una mayor valoración. Por otra parte, los resultados sobre los conocimientos adquiridos durante la misma fueron satisfactorios, por lo que en el futuro sería interesante plantear esta metodología para la adquisición de otros conocimientos de la asignatura

Structure-activity relationship study of cationic carbosilane dendritic systems as antibacterial agents

This work focuses on the antibacterial activity against Gram-positive Staphylococcus aureus and Gramnegative Escherichia coli and the hemolytic properties of two types of ammonium cationic carbosilane systems: dendrimers and dendrons. The effects of: i) the generation, ii) the type of peripheral groups near the cationic charges (a SiMe2 moiety or a S atom depending on the synthetic procedure, hydrosilylation or thiol-ene addition, respectively), iii) the core of dendrimers (polyphenoxo vs. Si atom) and iv) the focal point of dendrons (-N3, -NH2, -OH) have been assessed. The structure-activity relationship analysis indicates the importance of an adequate balance between the hydrophilic and lipophilic fragments of these molecules to reach the best antibacterial activity. Regarding hemolysis, lowest toxicity values were registered for dendritic systems with a sulfur atom close to the surface and, in the particular case of dendrons, for those with a hydroxyl focal point. One dendrimer and one dendron, both bearing a sulfur atom close to the surface, scored best in the activity-toxicity relationship analysis and were chosen for resistance assays. No changes in the inhibitory and bactericidal capacity in the case of the dendron and only a slight increase of these values for the dendrimer were observed after 15 subculture cycles. Furthermore, these two compounds stayed active towards different strains of resistant bacteria and avoid formation of biofilm at concentrations over the minimum inhibitory concentration (MIC).Ministerio de Economía y Empres

Gamificación como herramienta de interacción en clases teóricas de Salud Pública

[ES] En las asignaturas de Salud Pública del Grado de Enfermería impartidas por el Área de Medicina Preventiva y Salud Pública de la Universidad de León, se vienen impartiendo contenidos teóricos de una forma tradicional. Las encuestas de evaluación al profesorado de la Universidad de León llevadas a cabo por el alumnado han reportado una baja motivación y participación, así como un reducido interés y/o comprensión de estos contenidos. Por esta razón, el objetivo de la presente innovación docente es mejorar la retroalimentación con el alumnado, a través de la gamificación, para incrementar el interés de los alumnos, la participación y detectar los conceptos en los que se debe hacer hincapié o repasar antes de finalizar la clase. Para ello, se llevó a cabo una docencia mixta, con gamificación a través de Quizizz© y sin gamificación (docencia tradicional). Para valorar el impacto sobre el interés, la participación y la motivación del alumnado, se realizó un cuestionario de escala Likert al finalizar la asignatura, para analizar el grado de satisfacción, el interés de la materia y la motivación en ambas metodologías de enseñanza en 31 alumnos/as. Los resultados obtenidos en las encuestas indican según el 93,5% de los alumnos que la gamificación promueve la participación en clase, y el 87,1% consideró útil esta herramienta para su aprendizaje y que además aumentó su interés por la materia. Considerando estos resultados, podemos indicar que la metodología de gamificación mejora la participación y el interés de los alumnos por la materia

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19