PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.

High-risk human papillomaviruses (HR-HPVs) are the causal agents of cervical, anogenital and a subset of head and neck carcinomas (HNCs). Indeed, oropharyngeal cancers are a type of HNC highly associated with HR-HPV infections and constitute a specific clinical entity. The oncogenic mechanism of HR-HPV involves E6/E7 oncoprotein overexpression for promoting cell immortalization and transformation, through the downregulation of p53 and pRB tumor suppressor proteins, among other cellular targets. Additionally, E6/E7 proteins are involved in promoting PI3K/AKT/mTOR signaling pathway alterations. In this review, we address the relationship between HR-HPV and PI3K/AKT/mTOR signaling pathway activation in HNC with an emphasis on its therapeutic importance.

Interaction between Cigarette Smoke and Human Papillomavirus 16 E6/E7 Oncoproteins to Induce SOD2 Expression and DNA Damage in Head and Neck Cancer.

Even though epidemiological studies suggest that tobacco smoking and high-risk human papillomavirus (HR-HPV) infection are mutually exclusive risk factors for developing head and neck cancer (HNC), a portion of subjects who develop this heterogeneous group of cancers are both HPV-positive and smokers. Both carcinogenic factors are associated with increased oxidative stress (OS) and DNA damage. It has been suggested that superoxide dismutase 2 (SOD2) can be independently regulated by cigarette smoke and HPV, increasing adaptation to OS and tumor progression. In this study, we analyzed SOD2 levels and DNA damage in oral cells ectopically expressing HPV16 E6/E7 oncoproteins and exposed to cigarette smoke condensate (CSC). Additionally, we analyzed SOD2 transcripts in The Cancer Genome Atlas (TCGA) Head and Neck Cancer Database. We found that oral cells expressing HPV16 E6/E7 oncoproteins exposed to CSC synergistically increased SOD2 levels and DNA damage. Additionally, the SOD2 regulation by E6, occurs in an Akt1 and ATM-independent manner. This study suggests that HPV and cigarette smoke interaction in HNC promotes SOD2 alterations, leading to increased DNA damage and, in turn, contributing to development of a different clinical entity.

High-Risk Human Papillomavirus Infection in Lung Cancer: Mechanisms and Perspectives.

Lung cancer is a very prevalent and heterogeneous group of malignancies, and most of them are etiologically associated with tobacco smoking. However, viral infections have been detected in lung carcinomas, with high-risk human papillomaviruses (HR-HPVs) being among them. The role of HR-HPVs in lung cancer has been considered to be controversial. This issue is due to the highly variable presence of this virus in lung carcinomas worldwide, and the low viral load frequently that is detected. In this review, we address the epidemiological and mechanistic findings regarding the role of HR-HPVs in lung cancer. Some mechanisms of HR-HPV-mediated lung carcinogenesis have been proposed, including (i) HPV works as an independent carcinogen in non-smoker subjects; (ii) HPV cooperates with carcinogenic compounds present in tobacco smoke; (iii) HPV promotes initial alterations being after cleared by the immune system through a "hit and run" mechanism. Additional research is warranted to clarify the role of HPV in lung cancer.

Characterization of High-Risk HPV/EBV Co-Presence in Pre-Malignant Cervical Lesions and Squamous Cell Carcinomas.

High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. However, a low proportion of HR-HPV-infected women finally develop this cancer, which suggests the involvement of additional cofactors. Epstein−Barr virus (EBV) has been detected in cervical squamous cell carcinomas (SCCs) as well as in low- (LSIL) and high-grade (HSIL) squamous intraepithelial lesions, although its role is unknown. In this study, we characterized HR-HPV/EBV co-presence and viral gene expression in LSIL (n = 22), HSIL (n = 52), and SCC (n = 19) from Chilean women. Additionally, phenotypic changes were evaluated in cervical cancer cells ectopically expressing BamHI-A Rightward Frame 1 (BARF1). BARF1 is a lytic gene also expressed in EBV-positive epithelial tumors during the EBV latency program. HPV was detected in 6/22 (27.3%) LSIL, 38/52 (73.1%) HSIL, and 15/19 (78.9%) SCC cases (p < 0.001). On the other hand, EBV was detected in 16/22 (72.7%) LSIL, 27/52 (51.9%) HSIL, and 13/19 (68.4%) SCC cases (p = 0.177). HR-HPV/EBV co-presence was detected in 3/22 (13.6%) LSIL, 17/52 (32.7%) HSIL, and 11/19 (57.9%) SCC cases (p = 0.020). Additionally, BARF1 transcripts were detected in 37/55 (67.3%) of EBV positive cases and in 19/30 (63.3%) of HR-HPV/EBV positive cases. Increased proliferation, migration, and epithelial-mesenchymal transition (EMT) was observed in cervical cancer cells expressing BARF1. Thus, both EBV and BARF1 transcripts are detected in low- and high-grade cervical lesions as well as in cervical carcinomas. In addition, BARF1 can modulate the tumor behavior in cervical cancer cells, suggesting a role in increasing tumor aggressiveness.

Epstein-Barr Virus Infection in Lung Cancer: Insights and Perspectives.

Lung cancer (LC) is the leading cause of cancer death worldwide. Tobacco smoke is the most frequent risk factor etiologically associated with LC, although exposures to other environmental factors such as arsenic, radon or asbestos are also involved. Additionally, the involvement of some viral infections such as high-risk human papillomaviruses (HR-HPVs), Merkel cell polyomavirus (MCPyV), Jaagsiekte Sheep Retrovirus (JSRV), John Cunningham Virus (JCV), and Epstein-Barr virus (EBV) has been suggested in LC, though an etiological relationship has not yet been established. EBV is a ubiquitous gamma herpesvirus causing persistent infections and some lymphoid and epithelial tumors. Since EBV is heterogeneously detected in LCs from different parts of the world, in this review we address the epidemiological and experimental evidence of a potential role of EBV. Considering this evidence, we propose mechanisms potentially involved in EBV-associated lung carcinogenesis. Additional studies are warranted to dissect the role of EBV in this very frequent malignancy.

The Oral Health of Patients with DiGeorge Syndrome (22q11) Microdeletion: A Case Report.

BACKGROUND: DiGeorge syndrome (DG) is a genetic disorder associated with 22q11 deletion. It involves various phenotypes, including craniofacial abnormalities, congenital heart disorders, endocrine dysfunction, cognitive deficits, and psychiatric disorders. Cases commonly involve multiple anomalies. However, little is known about the condition of the oral cavity in this disorder, although palate fissure, abnormal mandible, malocclusion, and tooth hypoplasia have been identified. We aimed to determine the odontological features of patients with 22q11.2 microdeletion, in relation to gingival health and oral hygiene. We report the systemic manifestations of nine patients and results of oral evaluation of two patients. In the oral examination, oral hygiene and gingivitis were evaluated. CASE PRESENTATION: In terms of the systemic manifestations, we found high frequencies of low weight and height at birth. In terms of the oral manifestations, both examined patients presented malocclusion, enamel hypoplasia, dental crowding, anodontia, and healthy periodontium. CONCLUSION: Although DG has been documented to involve periodontium disease, the patients in this study exhibited more dental manifestations such as enamel defects, misalignment between the teeth and the two dental arches, anodontia, and dental crowding. As such, a multidisciplinary approach combining dentistry and healthcare is recommended in this case.

Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Cervical Cancer: Epidemiology, Mechanisms and Perspectives.

High-risk human papillomavirus (HR-HPV) is etiologically associated with the development and progression of cervical cancer, although other factors are involved. Epstein-Barr virus (EBV) detection in premalignant and malignant tissues from uterine cervix has been widely reported; however, its contribution to cervical cancer development is still unclear. Here, a comprehensive analysis regarding EBV presence and its potential role in cervical cancer, the frequency of EBV/HR-HPV coinfection in uterine cervix and EBV infection in tissue-infiltrating lymphocytes were revised. Overall, reports suggest a potential link of EBV to the development of cervical carcinomas in two possible pathways: (1) Infecting epithelial cells, thus synergizing with HR-HPV (direct pathway), and/or (2) infecting tissue-infiltrating lymphocytes that could generate local immunosuppression (indirect pathway). In situ hybridization (ISH) and/or immunohistochemical methods are mandatory for discriminating the cell type infected by EBV. However, further studies are needed for a better understanding of the EBV/HR-HPV coinfection role in cervical carcinogenesis.

In silico analysis of genomic variables associated to HPV16 integration sites / Análisis in silico de variables genómicas asociadas a sitios de integración de HPV16

Background: Despite current prophylactic interventions, a significant proportion of patients suffers a cancer-specific mortality, leading to a global awareness of the importance of identifying factors associated to the etiology of HPV-associated cancer. According to this, HPV-DNA integration into human genome is an important event in the pathogenesis. Purpose: To identify in silico, molecular regions of the genome where the HPV integration events occur Methods: We performed a bioinformatic study based on a systematic search in Medline through PubMed, Embase and Lilacs from inception to April 2019. We used the UCSC Genome Browser Home (https://genome.ucsc.edu) to evaluate the genetic environment. Results: HPV integration sites by anatomical location related to cervical cancer were 374 (61%). In addition, 325 (87%) of these integration sites had HPV-16, 21 (5%) had HPV-18 and 28 (7%) had another type of genotype. Oro-pharyngeal cavity was the second anatomic site with 162 (26%) integration sites. It is noteworthy that the HPV-16 was found integrated into 160 (99%) analyzed sites. Conclusion: Our results suggest that many of the integration sites reported in the scientific literature are HPV 16 from squamous cell carcinomas and 50% of HPV16 were integrated into transcriptional units that might affect the expression of gene target.

Antecedentes: A pesar de las intervenciones profilácticas actuales, una proporción significativa de pacientes muere debido al cáncer, lo que aumenta la conciencia global de la importancia de identificar los factores asociados a la etiología del cáncer asociado al VPH. Según esto, la integración del ADN-VPH en el genoma humano es un evento importante en la patogénesis. Propósito: Identificar in silico, las regiones moleculares del genoma donde ocurren los eventos de integración del VPH Métodos: Realizamos un estudio bioinformático basado en una búsqueda sistemática en Medline a través de PubMed, Embase y Lilacs desde el inicio hasta abril de 2019. Utilizamos el UCSC Genome Browser Home (https://genome.ucsc.edu) para evaluar el entorno genético. Resultados: Los sitios de integración del VPH relacionados con el cáncer de cuello uterino fueron 374 (61%). Además, 325 (87%) de estos sitios de integración tenían VPH-16, 21 (5%) tenían VPH-18 y 28 (7%) tenían otro tipo de genotipo. La cavidad orofaríngea fue el segundo sitio anatómico con 162 (26%) sitios de integración. Es de destacar que el VPH-16 se encontró integrado en 160 (99%) sitios analizados. Conclusión: Nuestros resultados sugieren que muchos de los sitios de integración reportados en la literatura científica que presentan al VPH-16 son carcinomas de células escamosas y que el 50% de estos VPH-16 se integraron en unidades transcripcionales que podrían afectar la expresión de algún gen objetivo.

Merkel cell polyomavirus detected in head and neck carcinomas from Chile.

BACKGROUND: The role of human polyomaviruses (HPyVs) in epithelial tumors such as head and neck carcinomas (HNSCCs) including oral and oropharyngeal carcinomas has not been established. In this study, we evaluated for the first time the presence of Merkel cell polyomavirus (MCPyV), BK human polyomavirus (BKPyV), and JC human polyomavirus (JCPyV) in HNSCCs from Chilean subjects. METHODS: One hundred and twenty HNSCCs were analyzed for the presence of MCPyV, BKPyV and JCPyV using real-time polymerase chain reaction procedures. In addition, 54 oral brushes from age- and sex-paired subjects were analyzed. RESULTS: Of the total of 120 HNSCCs, 15 were positive for MCPyV (12.5%). Only one case was positive for BKPyV (0.8%) and none for JCPyV (0%). In subjects without cancer, only one case (1.8%) resulted positive for MCPyV and none for JCPyV and BKPyV. MCPyV was associated with HNSCCs (p = 0.0239; OR = 7.571; 95% CI: 1.192-81.46). No association was found between age (p = 0.1996), gender (p = 0.7111) or differentiation status (p > 0.9999) and MCPyV presence in HNSCCs. CONCLUSIONS: MCPyVs were detected in HNSCCs from Chilean patients and were not detected in oral brushes from patients without cancer. More studies are warranted for defining an etiological role and clinical/molecular consequences of these viruses in HNSCCs.

Curcumin decreases epithelial­mesenchymal transition by a Pirin­dependent mechanism in cervical cancer cells.

Curcumin is a natural antioxidant polyphenol, which decreases epithelial­mesenchymal transition (EMT) and cell migration in cervical cancer cells. However, the mechanism by which such a decrease occurs is unclear. It is well established that cervical cancer can be caused by high­risk human papillomavirus (HPV), which overexpresses E6 and E7 oncoproteins. Recent findings have suggested that viral oncoproteins regulate the expression of Pirin, which is an oxidative stress sensor involved in EMT and cell migration. Molecular markers associated with EMT, pirin and HPV were evaluated using reverse transcription­reverse quantitative PCR and western blotting. In addition, the migratory ability of cells was evaluated using a Transwell assay. In order to evaluate the role of Pirin in curcumin­mediated inhibition of EMT, SiHa cervical carcinoma cells, which contain two integrated copies of HPV16, were exposed to curcumin. Cell migration, and the expression levels of EMT biomarkers and the pirin protein, which is a product of the PIR gene, were subsequently evaluated. The results demonstrated a significant decrease in EMT following exposure to 20 µM curcumin for 72 h. This finding was supported by a decrease in the protein expression levels of N­cadherin, Vimentin and Slug. Furthermore, it was observed that PIR expression and Pirin protein levels were significantly decreased when SiHa cells were exposed to curcumin. Subsequently, to analyze the effects of Pirin on EMT, SiHa cells were transfected with a small interfering RNA (siRNA) to knockdown PIR. A significant increase in E­cadherin mRNA expression and a decrease in N­cadherin protein expression were observed. In addition, a similar decrease was observed when SiHa cells were exposed to both PIR siRNA and curcumin. Finally, a significant decrease in SiHa cell migration was observed in the presence of 20 µM curcumin compared with in the control group. These findings suggested that curcumin may decrease EMT, at least in part by a Pirin­dependent mechanism. Therefore, Pirin protein may be an important pharmacological target for cervical cancer treatment.

Detección del virus Epstein Barr en escolares adolescentes en la ciudad de Cali, Colombia / Detection of epstein barr virus in adolescent students in the city of cali, colombia

Objetivo: Detectar el virus Epstein-Barr en estudiantes de secundaria entre los 14 y 17 años de la ciudad de Cali, Colombia y su posible asociación con la edad, sexo y grado escolar. Métodos: Estudio retrospectivo de corte transversal en donde se analizaron 374 muestras de saliva, tomadas entre el año 2015 y 2016, mediante PCR convencional y PCR en Tiempo real. Se evalúo la asociación entre la detección del ADN viral y las características demográficas, además de un análisis de razón de oportunidades para evaluar la medida de la asociación. Resultados: El ADN viral fue detectado en el 45% (167/374) de las muestras orales, encontrándose una presencia viral mayor en los escolares de los grados octavo y noveno (p=0,004); en donde los estudiantes de 14 años presentaron un riesgo de 2,4 veces mayor para la detección del virus (IC 95%:1,12-4,9) en comparación con los estudias de más edad. Conclusión: En el presente estudio se evidencio la exposición del VEB en la cavidad oral de estudiantes de secundaria, lo cual hace necesario que se tomen acciones de vigilancia que permitan monitorear las implicaciones de estos hallazgos en la salud de los escolares.

Objective: To detect the Epstein Barr virus in adolescent students between 14 and 17 years old in the city of Cali, Colombia and its possible association with age, gender and school grade. Methods: Retrospective cross-sectional study where 374 mouthwash samples collected between the years 2015 and 2016 was analyzed through conventional and real-time PCR. Association between viral DNA detection and sociodemographic characteristics were evaluated. The odds ratio analysis was used to assess the extent of this association. Results: The viral DNA was present in 45% (167/374) of the samples, with a higher DNA detection in the students of eighth and ninth grades (p=0.004); where the 14 years old students present a 2.4 times higher risk of detecting the virus (IC 95%: 1,12-4.9) in comparison with older students. Conclusion: In the present study, the Epstein Barr virus exposition in the oral cavity was evidenced, which make necessary to take actions on surveillance that allow monitoring the implications of these fndings in the teenage student's health.

The effectiveness of vaccination to prevent the papillomavirus infection: a systematic review and meta-analysis.

Our purpose was to determine the effectiveness and harms of vaccination in patients with any sexual history to prevent the prevalence of papillomavirus infection. A search strategy was conducted in the MEDLINE, CENTRAL, EMBASE and LILACS databases. Searches were also conducted in other databases and unpublished literature. The risk of bias was evaluated with the Cochrane Collaboration's tool. Analysis of fixed effects was conducted. The primary outcome was the infection by any and each human papillomavirus (HPV) genotype, serious adverse effects and short-term adverse effects. The measure of the effect was the risk difference (RD) with a 95% confidence interval (CI). The planned interventions were bivalent vaccine/tetravalent/nonavalent vs. placebo/no intervention/other vaccines. We included 29 studies described in 35 publications. Bivalent HPV vaccine offers protection against HPV16 (RD -0.05, 95% CI -0.098 to -0.0032), HPV18 (RD -0.03, 95% CI -0.062 to -0.0004) and HPV16/18 genotypes (RD of -0.1, 95% CI -0.16 to -0.04). On the other side, tetravalent HPV vaccine offered protection against HPV6 (RD of -0.0500, 95% CI -0.0963 to -0.0230), HPV11 (RD -0.0198, 95% CI -0.0310 to -0.0085). Also, against HPV16 (RD of -0.0608, 95% CI -0.1126 to -0.0091) and HPV18 (RD of -0.0200, 95% CI -0.0408 to -0.0123). There was a reduction in the prevalence of HPV16, 18 and 16/18 genotypes when applying the bivalent vaccine, with no increase in adverse effects. Regarding the tetravalent vaccine, we found a reduction in the prevalence of HPV6, 11, 16 and 18 genotypes, with no increase in adverse effects.

Effect of vaccination against oral HPV-16 infection in high school students in the city of Cali, Colombia.

INTRODUCTION: In recent years, an association between HPV-16 and oropharyngeal cancers has been reported. Therefore, it is necessary to evaluate whether vaccination decreases the exposure of HPV-16 in the oral cavity. OBJECTIVE: To evaluate the effect of vaccination on oral HPV-16 infection in high school students in the city of Cali, Colombia. METHODS: In this cross-sectional study, HPV-16 DNA was detected in samples from the oral cavity and throat of 1,784 high school students of both genders, aged 14-17 years old, in 21 schools in the city of Cali, Colombia. The number in vaccinated girls were 944 vs., 95 unvaccinated girls and 745 unvaccinated boys. RESULTS: The HPV exposure percentages were: 0.7% in vaccinated girls, 3.2% in unvaccinated girls and 2.3% in unvaccinated boys. The odds ratio (OR) of detection of HPV-16 in vaccinated versus unvaccinated students was 0.28 (95% CI: 0.07-0.88), representing a 72% reduction in HPV-16 detection in students immunized with two doses. The odds of detection of HPV-16 in unvaccinated male students were 3.6 times those of vaccinated girls (OR = 3.6, 95% CI: 1.21-12.81) and increased to almost eight-fold in boys who had initiated sexual activity (OR = 7.74, 95% CI: 1.53-75.09). CONCLUSIONS: HPV vaccination was associated with the reduction of HPV-16 exposure percentages in the oral and oropharyngeal cavity.

Amelogénesis imperfecta en una familia / Amelogenesis imperfecta in a family

Introducción: la amelogénesis imperfecta consiste en un grupo de desórdenes hereditarios que afectan el desarrollo del esmalte dental, de tal forma que se ve comprometida la apariencia clínica de todos o casi todos los dientes, tanto temporales como permanentes. Objetivo: informar las características y condiciones clínicas de la dentición de tres individuos de una misma familia con diagnóstico presuntivo de amelogénesis imperfecta. Presentación de casos: se realizó examen intrabucal a tres individuos con rango de consanguinidad de primer grado (madre y dos hijos) quienes presentaban alterado estructuralmente el esmalte de los dientes. De acuerdo con las características clínicas dentales y el método de Witkop, los individuos fueron diagnosticados de forma presuntiva con amelogénesis imperfecta hipomadura tipo II (madre), caracterizada por hipomaduración del esmalte y fragmentación por desgaste en los bordes incisales; amelogénesis imperfecta hipoplásica tipo I (hijo mayor), con amplias zonas de dentina expuesta opaca y con manchas pardas generalizadas; y amelogénesis imperfecta hipomadura tipo II (hijo menor), con predominio de lesiones en forma de copo de nieve o motas de algodón. Conclusiones: el diagnóstico clínico de la amelogénesis imperfecta basado en métodos fenotípicos resulta impreciso debido a la imposibilidad de establecer el origen de las alteraciones macroestructurales del esmalte. Sin embargo, de acuerdo con la descripción de los tres casos, son las afecciones en la cantidad y calidad del esmalte las que permiten realizar un diagnóstico clínico presuntivo, que guía la implementación de un tratamiento odontológico direccionado a la solución del compromiso estético y a la prevención del compromiso del órgano dentino-pulpar. En esta presentación de casos, la manifestación fenotípica de la enfermedad pasó de la madre a ambos hijos, siendo la amelogénesis imperfecta hipomadura dominante en el hijo menor(AU)

Introduction: amelogenesis imperfecta consists of a group of hereditary disorders that affect the development of the dental enamel in such a way that the clinical appearance of all or almost all primary and permanent teeth is compromised. Objective: report the clinical characteristics and conditions of the dentition of three individuals from the same family with a presumptive diagnosis of amelogenesis imperfecta. Case presentation: intraoral examination was performed of three first-degree relatives (mother and two children) with structurally altered tooth enamel. Based on their clinical dental characteristics and the results of the Witkop method, the individuals were presumptively diagnosed with hypomaturation amelogenesis imperfecta type II (mother), characterized by enamel hypomaturation and fragmentation by wear on the incisal edges; hypoplastic amelogenesis imperfecta type I (elder son), with large areas of opaque exposed dentin and generalized brown spots; and hypomaturation amelogenesis imperfecta type II (younger son), with a predominance of lesions in the shape of snowflakes or cotton wads. Conclusions: clinical diagnosis of amelogenesis imperfecta based on phenotypic methods is imprecise, since it is not possible to establish the origin of the macrostructural alterations of the enamel. However, according to the description of the three cases, quantitative and qualitative damage to the enamel makes it possible to establish a presumptive clinical diagnosis which will guide the implementation of a dental treatment aimed at resolving the aesthetic commitment and preventing involvement of the dentine-pulp complex. In this case presentation, the phenotypic manifestation of the disease passed from the mother to both children, and hypomaturation amelogenesis imperfecta was dominant in the younger son(AU)

Amelogénesis imperfecta en una familia / Amelogenesis imperfecta in a family

Introducción: la amelogénesis imperfecta consiste en un grupo de desórdenes hereditarios que afectan el desarrollo del esmalte dental, de tal forma que se ve comprometida la apariencia clínica de todos o casi todos los dientes, tanto temporales como permanentes. Objetivo: informar las características y condiciones clínicas de la dentición de tres individuos de una misma familia con diagnóstico presuntivo de amelogénesis imperfecta. Presentación de casos: se realizó examen intrabucal a tres individuos con rango de consanguinidad de primer grado (madre y dos hijos) quienes presentaban alterado estructuralmente el esmalte de los dientes. De acuerdo con las características clínicas dentales y el método de Witkop, los individuos fueron diagnosticados de forma presuntiva con amelogénesis imperfecta hipomadura tipo II (madre), caracterizada por hipomaduración del esmalte y fragmentación por desgaste en los bordes incisales; amelogénesis imperfecta hipoplásica tipo I (hijo mayor), con amplias zonas de dentina expuesta opaca y con manchas pardas generalizadas; y amelogénesis imperfecta hipomadura tipo II (hijo menor), con predominio de lesiones en forma de copo de nieve o motas de algodón. Conclusiones: el diagnóstico clínico de la amelogénesis imperfecta basado en métodos fenotípicos resulta impreciso debido a la imposibilidad de establecer el origen de las alteraciones macroestructurales del esmalte. Sin embargo, de acuerdo con la descripción de los tres casos, son las afecciones en la cantidad y calidad del esmalte las que permiten realizar un diagnóstico clínico presuntivo, que guía la implementación de un tratamiento odontológico direccionado a la solución del compromiso estético y a la prevención del compromiso del órgano dentino-pulpar. En esta presentación de casos, la manifestación fenotípica de la enfermedad pasó de la madre a ambos hijos, siendo la amelogénesis imperfecta hipomadura dominante en el hijo menor(AU)

Introduction: amelogenesis imperfecta consists of a group of hereditary disorders that affect the development of the dental enamel in such a way that the clinical appearance of all or almost all primary and permanent teeth is compromised. Objective: report the clinical characteristics and conditions of the dentition of three individuals from the same family with a presumptive diagnosis of amelogenesis imperfecta. Case presentation: intraoral examination was performed of three first-degree relatives (mother and two children) with structurally altered tooth enamel. Based on their clinical dental characteristics and the results of the Witkop method, the individuals were presumptively diagnosed with hypomaturation amelogenesis imperfecta type II (mother), characterized by enamel hypomaturation and fragmentation by wear on the incisal edges; hypoplastic amelogenesis imperfecta type I (elder son), with large areas of opaque exposed dentin and generalized brown spots; and hypomaturation amelogenesis imperfecta type II (younger son), with a predominance of lesions in the shape of snowflakes or cotton wads. Conclusions: clinical diagnosis of amelogenesis imperfecta based on phenotypic methods is imprecise, since it is not possible to establish the origin of the macrostructural alterations of the enamel. However, according to the description of the three cases, quantitative and qualitative damage to the enamel makes it possible to establish a presumptive clinical diagnosis which will guide the implementation of a dental treatment aimed at resolving the aesthetic commitment and preventing involvement of the dentine-pulp complex. In this case presentation, the phenotypic manifestation of the disease passed from the mother to both children, and hypomaturation amelogenesis imperfecta was dominant in the younger son(AU)

Association between TMPRSS2:ERG fusion gene and the prostate cancer: systematic review and meta-analysis.

INTRODUCTION: To identify the association between the TMPRSS2:ERG fusion gene, their variants and the onset of localized prostate cancer. MATERIAL AND METHODS: A systematic search strategy was carried out through MEDLINE, EMBASE, LILACS, CENTRAL and unpublished literature. We included randomized control trials, cohort, case-control and cross-sectional studies that involved patients >18 years-old assessing the association between TMPRSS2 fusion gene, its single nucleotide polymorphisms and prostate cancer. The primary outcome was prostate cancer defined by histology of the tumor coming from transrectal ultrasound guided biopsy, transurethral resection of the prostate or radical prostatectomy. We assessed the risk of bias with QUADAS2 and performed a meta-analysis with Stata 14. RESULTS: We found 241 records with the search strategies. After duplicates were removed, 18 studies were included in qualitative analysis and 15 studies in meta-analysis. All included studies that had no applicability concerns and low risk of bias for flow and timing. Nine studies had an unclear risk of bias for index and reference tests, since they did not describe the blinding assessment appropriately. Regarding the association between TMPRSS2:ERG and prostate cancer, we found an odds ratio (OR) 2.24 and a 95% confidence interval (CI) (1.29 to 3.91). Regarding the kind of sample, urine showed an OR 2.79 and a 95% CI (1.12 to 6.98) and when using a DNA molecular template, the OR was 3.55 with a 95% CI (1.08 to 11.65). CONCLUSIONS: There was an association between TMPRSS2:ERG fusion gene with the diagnosis of prostate cancer, mainly in urine samples and DNA-based molecular templates. TMPRSS2:ERG might be used as the gold standard biomarker for diagnosis and stratification of PCa.

Clinical, pathological, and immunohistochemical analysis of schwannoma in oral cavity: a case report / Análisis clínico, patológico e inmunohistoquímico de schwannoma en cavidad oral: reporte de caso

ABSTRACT. A schwannoma is a slow-growing benign neoplasm of the peripheral nerves composed of Schwann cells. Pathologically, is characterized by solid, subcutaneous, asymptomatic lesions. Histologically, it is made of prototypes of cellular organization called Antoni A and Antoni B. The most common site for its occurrence is the tongue, followed by the palate, the floor of the mouth, the buccal mucosa, the lips, and the mandible. This article describes the case of a 55-year-old woman presenting with a firm, nodular, encapsulated mass in the sub mucous area of the vestibular zone behind the right cheek. The clinical, pathological, and immunohistochemical analysis showed that this was a case of intraoral schwannoma.

RESUMEN. El schwannoma es una neoplasia benigna de crecimiento lento de los nervios periféricos compuestos por células de Schwann. Su anatomía patológica se caracteriza por lesiones sólidas, subcutáneas y asintomáticas. Histológicamente está compuesto por prototipos de organización celular denominados Antoni A y Antoni B. La lengua es el sitio más común, seguido por paladar, piso de boca, mucosa bucal, labios y mandíbula. En este trabajo se describe un caso de una mujer de 55 años que presenta una masa firme, nodular y encapsulada en la zona submucosa del vestíbulo derecho detrás del carrillo. Después del análisis clínico, patológico e inmunohistoquímico, se determinó que era un caso de schwannoma intraoral.

Differences in Al tolerance between Plantago algarbiensis and P. almogravensis reflect their ability to respond to oxidative stress.

We evaluated the impact of low pH and aluminum (Al) on the leaves and roots of Plantago almogravensis Franco and Plantago algarbiensis Samp., focusing on energy partitioning in photosystem II, H2O2 levels, lipid peroxidation, electrolyte leakage (EL), protein oxidation, total soluble protein content and antioxidant enzyme activities. In both species, Al triggered more changes in oxidative metabolism than low pH alone, particularly in the roots. We found that Al increased the levels of H2O2 in P. algarbiensis roots, but reduced the levels of H2O2 in P. almogravensis leaves and roots. Neither low pH nor Al affected the spatial heterogeneity of chlorophyll fluorescence, the maximum photochemical efficiency of PSII (Fv/Fm), the actual quantum efficiency of PSII (ϕPSII) or the quantum yields of regulated (ϕNPQ) and nonregulated (ϕNO) energy dissipation, and there was no significant change in total soluble protein content and EL. In P. algarbiensis, Al increased the carbonyl content and the activities of superoxide dismutase (SOD) and catalase (CAT) in the roots, and also CAT, ascorbate peroxidase and guaiacol peroxidase activities in the leaves. In P. almogravensis, Al reduced the level of malondialdehyde in the roots as well as SOD activity in the leaves and roots. We found that P. almogravensis plantlets could manage the oxidative stress caused by low pH and Al, whereas the P. algarbiensis antioxidant system was unable to suppress Al toxicity completely, leading to the accumulation of H2O2 and consequential protein oxidation in the roots.

Prevalencia de fluorosis dental de 5 a 9 años de la institución educativa Pedro Apóstol, con acceso único a agua de la quebrada el Chocho / Prevalence of dental fluososis in children 5 to 9 years age from Pedro Apóstol School, with exclusive water access from el Chocho brook

Objective: To determine the prevalence of fluorosis in children from 5-9 years of age, who have lived since birth in the corregimiento de Montebello (Cali), and studying in the Institución Educativa San Pedro Apóstol. Materials and methods: Cross-sectional study with a sample of 60 school children. It was divided into three phases: Phase I: Measurement of minerals from the water fountain at school. Phase II: Data Co - llection on: risk factors and oral hygiene, through a survey of 27 questions. Phase III: Clinical examination to identify the presence of fluorosis using the TFI index. Results: The average concentration of fluoride in water was 1.0202 ppm. The prevalence of fluorosis was 78.4%. Conclusion: The study population has a high prevalence of dental fluorosis. Key words: Fluoride, dental fluorosis, epidemiology, oral health...(Au)

Objetivo: Determinar la prevalencia de fluorosis, en niños de 5 a 9 años de edad, que han vivido desde su nacimiento en el corregimiento de Montebello (Santiago de Cali), y que estudian en la Institución Educativa San Pedro Apóstol. Materiales y métodos: Estudio descrip - tivo transversal, con una muestra de 60 escolares. Se dividió en tres fases: Fase I: Medición de minerales desde la fuente de agua del colegio. Fase II: Recolección de datos sobre: factores de riesgo y hábitos de higiene oral, por medio de una encuesta de 27 preguntas. Fase III: Examen clínico para identificar la presencia de fluorosis utilizando el índices TFI. Resultados: El promedio de concentración de flúor en el agua fue de 1,0202 ppm. La prevalencia de fluorosis fue del 78.4%. Conclusión: La población evaluada presen - ta una alta prevalencia de fluorosis dental...(Au)