Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions.

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women.

Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.

Tratamento compensatório paciente classe III esquelética vertical com técnica Buccal Shelf / Patient class III vertical skeletal compensatory treatment with buccal shelf technique

Resumo A má oclusão de Classe III é a relação dentária baseada na relação anteroposterior entre os primeiros molares, onde o indivíduo apresenta a cúspide mesio-vestibular do primeiro molar superior ocluindo no sulco mesio-vestibular do primeiro molar inferior. A compensação ortodôntica da má oclusão de Classe III, com mini-implantes, usada como ancoragem esquelética na mecânica ortodôntica vem revolucionando o tratamento Classe III esquelética. Optou-se por camuflagem ortodôntica com tratamento ortodôntico corretivo compensador, sendo utilizado aparelho fixo pela técnica Straight Wire (Capelozza III) e mecânica de distalização e verticalização de pré-molares mandibular com fio superior .019" x .025" de aço e inferior .020" de aço, através do Buccal Shelf, mini-implante de aço inserido na região retro molar entre primeiro e segundo molar inferior. Os apinhamentos foram satisfatoriamente corrigidos com um efetivo alinhamento e nivelamento dos arcos. Verticalmente, observou-se considerável alteração, pois houve correção da mordida aberta anterior por extrusão dos incisivos criando um adequado overbite e overjet. O uso de mini-implantes extra-radiculares adaptados na região de Buccal Shelf radicular como recurso de ancoragem mostrou-se eficaz no tratamento compensador da Classe III esquelética em paciente vertical (AU)

Abstract Class III malocclusion is the dental relationship, based on the anteroposterior relationship between the first molars, in which the individual presents the mesiovestibular cusp of the first maxillary molar occluding in the mesiovestibular groove of the first mandibular molar. Orthodontic compensation of Class III malocclusion with mini-implants used as skeletal anchorage in orthodontic mechanics has been revolutionizing the Class III skeletal treatment. Orthodontic camouflage with compensating corrective orthodontic treatment was chosen, using a fixed appliance in the Straight Wire technique (Capelozza III) and distalization and verticalization mechanics of mandibular premolars with a 19×25 upper steel wire and 20 lower steel wire through the Buccal Shelf, a mini steel implant inserted in the retromolar region between the first and second mandibular molars. Crowding was satisfactorily corrected with effective arches alignment and leveling. Vertically, a considerable change was observed, as there was correction of the anterior open bite by extrusion of the incisors creating an adequate overbite and overjet. The use of extra-radicular mini-implants adapted in the root Buccal Shelf region as an anchorage resource proved to be effective in the patient Class III vertical skeletal compensatory treatment (AU)

Description of Genetic Variants in BRCA Genes in Mexican Patients with Ovarian Cancer: A First Step towards Implementing Personalized Medicine.

Gynecologic cancers are among the leading causes of death worldwide, ovarian cancer being the one with the highest mortality rate. Olaparib is a targeted therapy used in patients presenting mutations in BRCA1 and BRCA2 genes. The aim of this study was to describe BRCA1 and BRCA2 gene variants in Mexican patients with ovarian cancer. Sequencing of BRCA1 and BRCA2 genes from tumors of 50 Mexican patients with ovarian cancer was made in a retrospective, non-randomized, and exploratory study. We found genetic variants in 48 of 50 cases. A total of 76 polymorphic variants were found in BRCA1, of which 50 (66%) had not been previously reported. Furthermore, 104 polymorphic variants were found in BRCA2, of which 63 (60%) had not been reported previously. Of these polymorphisms, 5/76 (6.6%) and 4/104 (3.8%) were classified as pathogenic in BRCA1 and BRCA2, respectively. We have described the genetic variants in BRCA1 and BRCA2 of tumors from Northeast Mexican patients with sporadic ovarian cancers. Our results showed that the use of genetic testing helps recognize patients that carry pathogenic variants which could be beneficial for personalized medicine treatments.

Equações para a determinação da idade óssea e maturação sexual de crianças e adolescentes / Equations for determining bone age and sexual maturation of children and adolescents / Ecuaciones para determinar la edad ósea y la maduración sexual de niños y adolescentes

Objetivo Este estudo teve como objetivo desenvolver e validar equações de predição da Idade óssea e de um índice de maturação sexual para crianças de 9 a 14 anos do gênero masculino da cidade do Rio de Janeiro. Métodos Participaram do estudo 400 crianças e adolescentes, sendo que 300 sujeitos (75 %) tiveram seus resultados utilizados para o desenvolvimento das equações e 100 sujeitos (25 %) para a validação das mesmas. Aplicou-se o método paramétrico de regressão Stepwise Correlation, sendo as variáveis independentes constituídas por medidas antropométricas e tomando-se como base decisória o EPE (Erro Padrão de Estimativa) combinado ao índice de regressão (R) e de determinação (R2). Resultados O modelo preditor mais significativo, correspondeu a:Idade Óssea = 0,062*Estatura(cm) + 0,426*Id.Cronol. + 0,041*MassaCorp.(Kg) - 0,390* Diâmetro Fêmur. No segundo momento, tomou-se como variável dependente a Maturação Sexual segundo os critérios de Tanner (IMT), e nesse contexto adicionou-se como variável independente a Idade Óssea (IO), calculando-se o segundo Modelo preditor nas mesmas condições de aceitabilidade anteriormente mencionadas: Índice Maturação Tuner (IMT) = 0,5423*Idade Óssea estimada - 0,0374*Estatura (cm) + 0,0388*MassaCorp (Kg). Conclusões A obtenção de resultados por métodos não invasivos é um avanço no diagnóstico médico para prevenções de doenças, como também equações com esses objetivos, um facilitador na orientação e seleção esportiva.(AU)

Objective This study had objective develop and validate prediction equations bone age and an index of sexual maturity for children 9 to 14 years old male from the city of Rio de Janeiro. Methods The study included 400 children and adolescents and 300 subjects (75 %) had their results used to develop the equations and 100 subjects (25 %) for the validation of the same. Applied the method parametric regression Stepwise Correlation, being the independent variables consist of anthropometric measurements and taking decisions based on the SEE (Standard Error of Estimate) combined with regression rate (R) and determination (R2). Results The most significant predictor model, accounted for: Age Bone= 0,062 * Height(cm) + 0,426 * Id.Cronol. + 0,041 * MassaCorp.(Kg) - 0,390 * Diameter Femur. Secondly, it was taken as the dependent variable sexual maturation according to the criteria of Tanner (IMT), and in this context was added as an independent variable the bone age (IO), calculating the second predictor model under the same conditions of acceptability previously mentioned: Maturation Index Tuner (IMT) = 0,5423 * age estimated bone - 0,0374 * Height(cm) + 0,0388 * MassaCorp.(Kg). Conclusions The results obtained by non-invasive methods are a breakthrough in medical diagnostics for disease prevention, as well as equations with these objectives, a facilitator in guiding the selection and sports.(AU)

Objetivo El objetivo del estudio fue desarrollar y validar ecuaciones de predicción de la edad ósea y el índice de maduración sexual de los niños de 9 a 14 años del género sexo masculino de la ciudad de Río de Janeiro. Métodos Participaron 400 niños y adolescentes. Los resultados de 300 sujetos (75 %) se utilizaron para desarrollar las ecuaciones y los de 100 sujetos (25 %) para validarlos. Se utilizó método paramétrico de correlación por medio de regresión por pasos. Las variables independientes fueron las medidas antropométricas y las decisiones se tomaron con base en el error estándar estimado, combinado con el índice de regresión (R) y la determinación (R2). Resultados El modelo predictor más significativo es: Edad ósea = 0,062 * Altura (cm) + 0.426 * Id.Cronol. + 0,041 * MassaCorp (Kg.) - 0.390 * Diámetro fémur. La segunda vez, se convirtió en la maduración sexual como variable dependiente en función de criterios de Tanner (IMT), y en ese contexto se agregó como una variable independiente el Medio Bone (IO). Un segundo modelo predictor, obtenido en las mismas condiciones de aceptabilidad mencionadas anteriormente, fue: Índice maduración Tuner (IMT) = 0.5423 * Edad ósea estimada - 0,0374 * Altura (cm) + 0.0388 * MassaCorp (Kg). Conclusión Los resultados obtenidos mediante métodos no invasivos son un avance en el diagnóstico médico para la prevención de enfermedades; las ecuaciones obtenidas con estos objetivos, son un facilitador en la orientación y selección deportiva.(AU)

[Equations for determining bone age and sexual maturation of children and adolescents]. / Equações para a determinação da idade óssea e maturação sexual de crianças e adolescentes.

Objective This study had objective develop and validate prediction equations bone age and an index of sexual maturity for children 9 to 14 years old male from the city of Rio de Janeiro. Methods The study included 400 children and adolescents and 300 subjects (75 %) had their results used to develop the equations and 100 subjects (25 %) for the validation of the same. Applied the method parametric regression Stepwise Correlation, being the independent variables consist of anthropometric measurements and taking decisions based on the SEE (Standard Error of Estimate) combined with regression rate (R) and determination (R2). Results The most significant predictor model, accounted for: Age Bone= 0,062 * Height(cm) + 0,426 * Id.Cronol. + 0,041 * MassaCorp.(Kg) - 0,390 * Diameter Femur. Secondly, it was taken as the dependent variable sexual maturation according to the criteria of Tanner (IMT), and in this context was added as an independent variable the bone age (IO), calculating the second predictor model under the same conditions of acceptability previously mentioned: Maturation Index Tuner (IMT) = 0,5423 * age estimated bone - 0,0374 * Height(cm) + 0,0388 * MassaCorp.(Kg). Conclusions The results obtained by non-invasive methods are a breakthrough in medical diagnostics for disease prevention, as well as equations with these objectives, a facilitator in guiding the selection and sports.

Tabelas de referências das qualidades físicas básicas de meninos de 9 a 14 anos / Basic physical attribute reference (anthropometric) tables for 9 to 14 year-old children / Tablas de referencia de capacidades físicas básicas en niños de 9 a 14 años

Objetivo Desenvolver tabelas de referência da antropometria e qualidades físicas coordenação, força explosiva de membros inferiores e velocidade de deslocamento de meninos entre 9 e 14 anos. Método Foram avaliados 536 indivíduos em antropometria (peso e estatura), protocolos de velocidade (30 metros), coordenação (Burpee) e Força Explosiva (sargent jump test). A metodologia foi descritiva por survey normativo, as tabelas sendo classificadas a partir das médias obtidas e seus desvios padrão. Para valores acima da média em um desvio-padrão (Acima da média) em dois desvios-padrão (Excelente) e valores abaixo da média em um desvio padrão (Abaixo da média) em dois desvios padrão (Muito abaixo da média), tendo como parâmetro a idade cronológica. Resultados Nas idades 09 e 11 anos, existe uma progressão dos valores no estudo, pois alcançando 12 e 13 anos, observa-se que a estatura e velocidade deixam de evoluir como anteriormente, com o grupo de 12 anos apresentando melhores resultados nessas variáveis do que 13 anos. A força explosiva de membros inferiores progrediu com a estatura exceto na idade 13 anos, onde os resultados foram menores do que aos 12 anos. A Coordenação Motora, diferenciou-se nas idades 9 e 10 anos onde apresentaram o mesmo comportamento. Aos 14 anos, a diferença em relação às idades 11,12 e 13 anos, recaem na faixa excelente da tabela, pois alcançam o escore de 08 repetições no teste. Conclusão As tabelas de referência demonstram aplicabilidade facilitando a comparação dos parâmetros do estudo para jovens brasileiros.(AU)

Objective Developing anthropometric reference tables and physical qualities regarding coordination, lower limb explosive power and speed of movement for 9 to 14 year-old children. Method Anthropometric factors (weight and height), speed protocols (30 meters), coordination (Burpee) and strength (Sargent jump test) were assessed in 536 individuals. Descriptive methodology was used for survey standards, tables being sorted by their averages and standard deviations, values above average standard deviation (above the mean) by two standard deviations (excellent) and those below average standard deviation (below the mean) by two standard deviations (very much below average) regarding chronological age. Results Study values progressed up to age 9 to 11, whilst height and speed no longer evolved as before at age 12 and 13, the 12 year-old group presenting better results regarding these variables than the 13 year-old group. The lower limbs' explosive force progressed with height up to age 13, even though results were not so good in this group compared to the 12-year old group. Motor coordination was the same in the 9 and 10 year-old groups and differed from that for those aged 14, and 11,12 and 13 years where they entered the range of values considered excellent in the table, because the score reached 08 repeats for the test. Conclusion The reference tables appeared to be applicable, facilitating the comparison of parameters for studying young Brazilians.(AU)

Objetivo Desarrollar tablas de referencia de antropometría y capacidades físicas de coordinación, fuerza explosiva de las extremidades inferiores y velocidad de movimiento de los niños entre 9 y 14 años. Método Se evaluaron 536 individuos en antropometría (peso y talla), protocolos de velocidad (30 metros), coordinación (Burpee) y concentración (prueba de salto Sargent). La metodología fue descrita por las normas de la encuesta, las tablas que se ordenan a partir de los promedios y sus desviaciones estándar. Para valores superiores al promedio de desviación estándar (encima de la media) en dos desviaciones estándar (Excelente) y los valores por debajo de la desviación estándar promedio (debajo de la media) en dos desviaciones estándar (muy por debajo del promedio), con el parámetro de la edad cronológica. Resultados En la edad de 9 a 11 años hay una progresión en los valores en el estudio mientras que en las edades de 12 y 13 años se observa que la altura y la velocidad no progresan como antes, pero el grupo de 12 años presenta mejores resultados en estas variables que el de 13 años. La fuerza explosiva de las extremidades inferiores progresó con la altura hasta la edad de 13 años, excepto en los menores de 12 años de edad. La coordinación motora presentó el mismo comportamiento en las edades de 9 y 10 años y difirió de las de 14 años y las de 11, 12 y 13 años que entran en la clasificación considerada excelente de la tabla, ya que la puntuación llega a 08 repeticiones de la prueba. Conclusión Las tablas de referencia se aplican para facilitar la comparación de los parámetros del estudio para los jóvenes brasileños.(AU)