The Dynamics of Histone Modifications during Mammalian Zygotic Genome Activation.

Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA), marking the initiation of transcriptional control and gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis have enabled detailed explorations of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.

Polimorfismos genéticos asociados a la respuesta del carcinoma de cabeza y cuello al cetuximab / Genetic polymorphisms associated with the response of head and neck carcinoma to cetuximab

Objetivo: Exponer los principales polimorfismos genéticos que han sido asociados a la respuesta del carcinoma de cabeza y cuello al cetuximab. Método: Se realizó una revisión no exhaustiva de artículos publicados en el período de enero de 2000 a diciembre de 2022, para ello se emplearon las bases de datos Medline (vía Pubmed) y Science Direct. En la evaluación de la calidad metodológica de los artículos incluidos se utilizó la guía para los estudios de asociación genética (Q-Genie). Resultados: Se identificaron un total de 206 artículos, de los cuales 12 cumplieron con los criterios para el análisis final. Se reportaron varios polimorfismos, tales como: EGFR-R521K (AA/GA), FcγRIIIa (158VV) y FcγRIIa (131HH), KRASLCS6 (TG/GG), AKT2:rs8100018, PTEN: rs12569998 en sus variantes mutadas, HIF-1α (CT/TT) y XRCC5 (GG/AA) que se asociaron con las variables de supervivencia, riesgo de progresión, tiempos hasta la progresión de la enfermedad, así como toxicidad cutánea. Conclusiones: Varios polimorfismos pueden asociarse con la respuesta del carcinoma de cabeza y cuello al tratamiento con cetuximab, siendo EGFR-R521K y FcγR IIIa-V158F los más estudiados. La enorme incertidumbre de los resultados alcanzados no permite alcanzar conclusiones firmes sobre la influencia de los polimorfismos genéticos en la respuesta al cetuximab; sin embargo, pueden convertirse en biomarcadores farmacogenéticos en la práctica clínica como una valiosa herramienta en la medicina personalizada, para predecir la respuesta medicamentosa. Para ello se requiere la realización de ensayos controlados con estratos por genotipo, con asignación aleatoria del tratamiento y el análisis de otras variables con valor pronóstico conocido.(AU)

Objective: To present the main genetic polymorphisms that have been associated with the response of head and neck carcinoma to cetuximab. Method: A non-exhaustive review of articles published in the period from January 2000 to December 2022 was carried out, for this purpose the Medline (via Pubmed) and Science Direct databases were used. The guide for genetic association studies (Q-Genie) was used to evaluate the methodological quality of the included articles. Results: A total of 206 articles were identified, of which 12 met the criteria for the final analysis. Several polymorphisms were reported, such as: EGFR-R521K (AA/GA), FcγRIIIa (158VV) and FcγRIIa (131HH), KRAS-LCS6 (TG/GG), AKT2:rs8100018, PTEN: rs12569998 in its mutated variants, HIF- 1α (CT/TT) and XRCC5 (GG/AA) that were associated with survival variables, risk of progression, times to disease progression, as well as skin toxicity. Conclusions: Several polymorphisms can be associated with the response of head and neck carcinoma to treatment with cetuximab, being EGFR-R521K and FcγR IIIa-V158F the most studied. The enormous uncertainty of the results obtained does not allow firm conclusions to be reached about the influence of genetic polymorphisms on the response to cetuximab; however, they can become pharmacogenetic biomarkers in clinical practice as a valuable tool in personalized medicine, to predict drug response. This requires carrying out controlled trials with strata by genotype, with random assignment of treatment and the analysis of other variables with known prognostic value.(AU)

Hematological Alterations in Patients Recovered from SARS-CoV-2 Infection in Havana, Cuba.

INTRODUCTION: COVID-19 sequelae, or the short-, medium-, and long-term manifestations of the disease are under continuous study. There are currently few reports on the evolution of hematological variables following a demonstrated absence of SARS-CoV-2 after infection. OBJECTIVE: Identify hematological alterations in Cuban adults recovered from SARS-CoV-2 infection, and their relation with disease severity. METHODS: We selected 348 persons recovered from COVID-19 residing in Havana, Cuba with an RT-PCR study negative for SARS-CoV-2 performed two weeks after hospital discharge; a structured survey was administered to obtain clinical-epidemiological data. Three groups were established according to COVID-19 clinical criteria: asymptomatic, mild/moderately symptomatic, and severely symptomatic, which, in turn, were divided according to hospital discharge date and blood sample collection date. We performed hemograms with differential leukocyte counts and compared results among groups. We then measured the associations between hematological variables, personal medical history, and relevant lifestyle habits (smoking). RESULTS: All hematological variables were within normal reference limits, although men from the group of severely ill patients had increased total leukocytes, neutrophils and lymphocytes, and decreased hemoglobin and eosinophils, which was also evident in those with a recovery time of 31-90 days. CONCLUSIONS: The relation between hematological variables and degree of clinical severity offers evidence as to persistence of systemic alterations (possibly inflammatory) associated with viral infection. Their identification and characterization can facilitate personalized patient followup and rehabilitation.

Assessment of changes in immune status linked to COVID-19 convalescent and its clinical severity in patients and uninfected exposed relatives.

INTRODUCTION: The immune response during and after SARS-CoV-2 infection can be complex and heterogeneous, and it can be affected by the severity of the disease. It can also contribute to an unfavorable evolution and bring about short and long term effects. The aim of this study was to characterize the lymphocyte composition according to the severity of COVID-19, as well as its degree of relationship to the specific humoral response to SARS-CoV-2 in convalescents up to 106 days after the infection and in their exposed relatives. METHODS: An applied research was carried out with a cross-section analytical design, from March 11 to June 11, 2020 in Cuba. The sample consisted of 251 convalescents from COVID-19 over 18 years of age and 88 exposed controls who did not become ill. The B and T cell subpopulations, including memory T cells, as well as the relationship with the humoral immune response against SARS-CoV-2, were identified by flow cytometry and enzyme immunoassay. RESULTS: Convalescent patients, who evolved with severe forms, showed a decrease in frequency and a greater proportion of individuals with values ​​lower than the minimum normal range of B cells, CD3 + CD4 + cells and the CD4 + / CD8 + ratio, as well as a higher frequency and a greater proportion of individuals with values ​​above the normal maximum range of CD3 + CD8 + and NK cells. Convalescent patients with severe forms of COVID-19 that exhibited IgG / RBD titers ≥ 1/200 had a lower frequency of TEMRA CD8 + cells (p = 0.0128) and TEMRA CD4 + (p = 0.0068). IgG / RBD titers were positively correlated with the relative frequency of CD4 + CM T memory cells (r = 0.4352, p = 0.0018). CONCLUSIONS: The identified alterations of B and T lymphocytes suggest that convalescent patients with the severe disease could be vulnerable to infectious, autoimmune or autotinflammatory processes; therefore, these individuals need medical follow-up after recovering from the acute disease. Furthermore, the role of T cells CD4 + CM in the production of antibodies against SARS-CoV-2 is confirmed, and it is noted that the defect of memory T cells CD8 + TEMRA could contribute to the development of severe forms of COVID-19.

The role of tumor necrosis factor alpha - 308A > G polymorphism on the clinical states of SARS-CoV-2 infection.

Background: Tumor necrosis factor-alpha (TNFɑ) is a cytokine that manages the host defense mechanism, which may play a role in the pathogenesis of COVID-19 patients. Several single-nucleotide polymorphisms, described in the promoter region of the TNFα gene, have a significant role on its transcriptional activity. These include the - 308A > G polymorphism which increases the TNFα levels with the expression of the A allele. The aim of this study was to explore whether the TNFα.- 308A > G polymorphism affects the clinical state of COVID-19 patients. The study included a total of 1028 individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which were distributed in 3 groups: asymptomatic, mild symptomatic and severe symptomatic patients. The amplification-refractory mutation system was used to determine the genotype of the TNFα.- 308A > G polymorphism. Results: Results show a higher tendency of being asymptomatic in individuals carrying the GG genotype (336 of 411; OR 1.24, 95% CI 0.91-1.70). The development of a severe form of SARS-CoV-2 infection was not found in subjects with the A allele compared to those with the G allele (OR 0.96, 95% CI 0.51-1.79), except in the eastern region of the country where the risk increased (OR 4.41, 95% CI 1.14-17.05). However, the subjects carrying the A allele had a higher chance of developing symptoms (OR 1.24, 95% CI 0.91-1.70) compared to those with the G allele. Conclusion: The TNFα.- 308A allele has an influence on developing symptoms of COVID-19 in Cuban patients, and that it particularly increases the risk of presenting severe forms of the disease in the eastern region of the country.

Características clínico-epidemiológicas de pacientes cubanos residentes en La Habana afectados por la COVID-19 / Clinical-epidemiological characteristics of patients affected by COVID-19 residing in Havana

Introducción: La Habana fue el territorio más complejo a nivel nacional en el enfrentamiento al primer brote de la COVID-19. Su condición de capital, la densidad poblacional, la escasa delimitación geográfica entre sus municipios, el elevado flujo intermunicipal e interprovincial de personas, sumado a que es la provincia que mayor número de viajeros recibe procedentes del extranjero, confirieron a este territorio particularidades en el enfrentamiento a la pandemia. Objetivo: Determinar las principales características clínico-epidemiológicas de pacientes cubanos residentes en La Habana afectados por la COVID-19. Métodos: Se realizó un estudio observacional, analítico, de corte transversal. La muestra quedó formada por 431 pacientes, mayores de un año, de alta epidemiológica de la infección por SARS-CoV-2. Para la recolección de información se aplicó un cuestionario a través de una entrevista. Resultados: La edad promedio de la muestra fue de 45 años. Más de la mitad de los casos evolucionaron de modo sintomático (no grave o grave). La fiebre fue la manifestación clínica más frecuente. Los individuos incluidos en la muestra, con grupo sanguíneo O, o con antecedentes de asma, mostraron menos riesgo de presentar formas sintomáticas de la enfermedad. Conclusiones: Los resultados sugieren que la edad constituye el principal factor de riesgo para desarrollar formas sintomáticas (no graves o graves) de la COVID-19. De modo contrario, el grupo sanguíneo O y el antecedente de asma son factores de protección para estas formas de evolución clínica(AU)

Introduction: Havana city was the most complex territory at the national level facingthe first outbreak of COVID-19. Its condition of capital, the population density, the limited geographical delimitation between its municipalities, the high inter-municipal and inter-provincial flow of people, added to the fact that it is the province that receives the largest number of travelers from abroad, conferred particularities on this territory. Objective: To determine the main clinical-epidemiological characteristics of patients affected by COVID-19 living in Havana. Methods: An observational, analytical, cross-sectional study was carried out. The sample contained 431 patients, older than one year, with epidemiological discharge from the SARS-CoV-2 infection. To collect information, a questionnaire was applied through an interview. Results: The average age of the sample was 45 years. More than half of the cases evolved in a symptomatic way (not serious or serious). Fever was the most frequent clinical manifestation. The individuals included in the sample, with blood group O or with a background of asthma, showed less risk of presenting symptomatic forms of the disease. Conclusions: The results suggest that age is the main risk factor for developing symptomatic forms (not severe or severe) of COVID-19. On the contrary, blood group O and a history of asthma are protective factors for these forms of clinical evolution(AU)

Aspectos generales sobre la estructura del coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2) / General aspects about the structure of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Introduction: In late 2019, a new coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes respiratory-related illness was reported in Wuhan, China. This virus can attack human lung cells causing a disease called coronavirus disease 2019 (COVID-19), which can lead to pneumonia and acute respiratory distress syndrome. Objective: Describe the structural characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Methods: A review was written from 47 bibliographic references. Articles and information from national and international journals available in the PubMed, Scopus, Medline, SciELO databases were used. The quality, reliability and validity of the selected articles were analyzed to carry out an adequate review. Analysis-synthesis and logical deduction methods were applied. Development: An introduction to the general aspects of the structure of SARS-CoV-2 is provided by stating the characteristics of the structural and non-structural proteins encoded by the viral genome, which provides the basis for understanding viral entry mechanisms to the host cell, and may be useful to stimulate the search for novel insights and possible therapeutic targets to fight the infection. Conclusions: Knowledge of the structure of the SARS-CoV-2 virus and the characteristics of the structural and non-structural proteins provides the basis for understanding the viral mechanisms of infection and the strategies for developing effective therapeutics(AU)

Introducción: A finales de 2019 se informó el brote de un nuevo coronavirus en Wuhan, China, llamado Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) que causa alteraciones en el aparato respiratorio. Este virus puede atacar las células humanas del pulmón causando una enfermedad denominada enfermedad por coronavirus 2019 (COVID-19), que puede producir neumonía y un síndrome de dificultad respiratoria aguda. Objetivo: Describir las características estructurales del virus SARS-CoV-2. Métodos: Se realizó una revisión bibliográfica a partir de 47 referencias. Se utilizaron artículos e información de revistas nacionales e internacionales disponibles en las bases de datos PubMed, Scopus, Medline, SciELO. Para llevar a cabo una revisión adecuada, se analizaron la calidad, fiabilidad y validez de los artículos seleccionados. Se aplicaron métodos de análisis-síntesis y deducción lógica. Desarrollo: Se proporciona una introducción de los aspectos generales de la estructura del SARS-CoV-2. Se enuncian las características de las proteínas estructurales y no estructurales codificadas por el genoma viral, lo que provee la base para comprender los mecanismos virales de entrada a la célula huésped. El artículo resulta de utilidad para estimular la búsqueda de nuevos conocimientos y posibles objetivos terapéuticos para combatir la infección. Conclusiones: El conocimiento sobre la estructura del virus SARS-CoV-2 y las características de las proteínas estructurales y no estructurales que lo forman ampara significativamente las bases para entender los mecanismos virales de la infección y las estrategias para el desarrollo terapéutico efectivo(AU)

Polimorfismo +405G> C del gen del factor de crecimiento de endotelio vascular en población cubana / Vascular Endothelial Growth Factor gene +405G> C polymorphism in the Cuban population

Introducción: El factor de crecimiento endotelial vascular (VEGF) es una proteína involucrada en la proliferación y migración celular del endotelio vascular, en cuyo gen se ha reportado el polimorfismo +405G>C. Se reconoce que no existen reportes genéticos poblacionales de esta variante en Cuba, que permitan caracterizar los perfiles inmunogenéticos a nivel molecular, para su aplicación en estudios de asociación alélica. Objetivo: Describir las frecuencias génicas y genotípicas del polimorfismo VEGF (+405 G>C) en la población cubana. Material y Métodos: Se realizó un estudio observacional, descriptivo, transversal, entre octubre de 2017 y marzo de 2018 en 162 neonatos cubanos, de ambos sexos y sanos, para el pesquisaje neonatal de enfermedades metabólicas, cuyas muestras biológicas se conservaban en el banco de ADN del Centro Nacional de Genética Médica. La caracterización molecular de los genotipos fue realizada mediante un PCR-ARMS. Se utilizó el software GENEPOP 4.4 y el paquete estadístico STATISTICA 8.0 para los cálculos de las frecuencias génicas y genotípicas. Resultados: La población no se ajustó al modelo de equilibrio de Hardy Weinberg para el gen evaluado. Las frecuencias génicas estimadas para el polimorfismo VEGF (+405 G>C) fueron de 0,33 para el alelo G y de 0,67 para el alelo C. El cálculo de las frecuencias genotípicas resultó en 0,14, 0,37 y 0,49, para las variantes GG, GC y CC, respectivamente. Conclusiones: Las frecuencias alélicas VEGF.C fueron superiores a la del alelo VEGF.G, siendo el genotipo VEGF.GG el de menor representación en el conjunto estudiado(AU)

Introduction: The vascular endothelial growth factor (VEGF) is a protein involved in the proliferation and cell migration of the vascular endothelium. In its gene, +405G>C Polymorphism has been reported. There are no population genetic reports of this variant in Cuba that allow the characterization of immunogenetic profiles at a molecular level for its application to allelic association studies. Objectives: To describe the genic and genotypic frequencies of the VEGF (+405 G>C) polymorphism in the Cuban population. Material and Methods: A descriptive cross-sectional observational study was carried out from October 2017 to March 2018 in 162 Cuban healthy newborns of both sexes for the neonatal screening for metabolic diseases, whose biological samples were conserved in the DNA bank of the National Center for Medical Genetics. The molecular characterization of the genotypes was carried out using a PCR-ARMS. The GENEPOP 4.4 software and the statistical software package STATISTICA 8.0 were used for the analysis of genic and genotypic frequencies. Results: The population did not adjust to the Hardy-Weinberg equilibrium model for the gene evaluated. The estimated gene frequencies of VEGF +405 G> C polymorphism were 0.33 for the G allele and 0.67 for the C allele. The calculation of the genotypic frequencies resulted in 0.14, 0.37 and 0.49, for the variants GG, GC and CC, respectively. Conclusions: The allelic frequencies of VEGF.C were higher than the frequencies of the VEGF.G allele, being the VEGF GG the least represented genotype in the group studied(AU)

Polimorfismo -308A>G en la región promotora del gen del factor de necrosis tumoral alfa en población cubana / -308A>G polymorphism in the promoter region of the tumor necrosis factor alpha gene in the Cuban population

El factor de necrosis tumoral alfa (TNFα) es una citoquina proinflamatoria en cuyo gen se ha notificado el polimorfismo -308A>G. No existen informes genéticos poblacionales de esta variante en Cuba, que permitan caracterizar los perfiles inmunogenéticos a nivel molecular para su aplicación en estudios de asociación alélica. Objetivos: Describir las frecuencias génicas y genotípicas del polimorfismo TNFα (-308A>G) en la población cubana. Métodos: Se realizó un estudio observacional, descriptivo, transversal, entre octubre de 2017 y marzo de 2018, en 162 neonatos cubanos, de ambos sexos y sanos, para el pesquisaje neonatal de enfermedades metabólicas, cuyas muestras biológicas se conservaban en el banco de ADN del Centro Nacional de Genética Médica. La caracterización molecular de los genotipos fue realizada mediante un PCR-ARMS. Se utilizó el software GENEPOP 4.4 y el paquete estadístico STATISTICA 8.0 para el análisis de genética poblacional. Resultados: La población estudiada no se ajustó al modelo de equilibrio de Hardy Weinberg para el gen evaluado. Las frecuencias génicas estimadas para el polimorfismo TNFα (-308A>G) fueron de 0,09 para el alelo A y de 0,91 para…(AU)

La cultura en salud bucal como problema actual de la sociedad / The culture in oral health as current problem of the society i:en

La promoción de salud constituye una de las acciones sanitarias más importante relacionada con la labor del estomatólogo general. Es un concepto más amplio que la prevención, ya que abarca las esferas biológica, ambiental, social y cultural, por citar algunas, donde la voluntad política del Estado desempeña una función fundamental, en aras de elevar cada día la calidad de vida de la población cubana en materia de salud bucal. Los resultados relacionados con la promoción son mediatos, de mayor impacto y generalmente requieren de una inversión en salud a largo plazo, a diferencia de los tratamientos médicos, cuyos resultados son más rápidos, pero menos duraderos y profundos. Tomando en consideración estos argumentos se llevó a cabo la presente investigación, con vistas a describir los nuevos enfoques sobre la promoción de salud y brindar una información más actualizada sobre el tema.

Health promotion constitutes one of the most important health tasks related to the work of the general stomatologist. It is a wider concept than prevention, since it comprises the biological, environmental, social and cultural fields, to mention some, where the political will of the State plays a fundamental role, for rising each day the life quality of the Cuban population regarding oral health. The results related to the promotion are mediate, of higher impact and they generally require an investment in health at long term, contrary to the medical treatments, results of which are faster, but less durable and deep. Taking in consideration these arguments, the present investigation was carried out, aimed at describing the new approaches on the health promotion and to offer a more updated information on the topic.