Genome-wide DNA methylation profiling in tongue squamous cell carcinoma.

OBJECTIVES: To provide a comprehensive characterization of DNA methylome of oral tongue squamous cell carcinoma (OTSCC) and identify novel tumor-specific DNA methylation markers for early detection using saliva. MATERIAL AND METHODS: Genome-wide DNA methylation analysis including six OTSCC matched adjacent non-tumoral tissue and saliva was performed using Infinium MethylationEPIC array. Differentially methylated levels of selected genes in our OTSCC cohort were further validated using OTSCC methylation data from The Cancer Genome Atlas database (TCGA). The methylation levels of a set of tumor-specific hypermethylated genes associated with a downregulated expression were evaluated in saliva. Receiver operating characteristic (ROC) curves were performed to assess the diagnostic value of DNA methylation markers. RESULTS: A total of 25,890 CpGs (20,505 hypomethylated and 5385 hypermethylated) were differentially methylated (DMCpGs) between OTSCC and adjacent non-tumoral tissue. Hypermethylation of 11 tumor-specific genes was validated in OTSCC TCGA cohort. Of these 11 genes, A2BP1, ANK1, ALDH1A2, GFRA1, TTYH1, and PDE4B were also hypermethylated in saliva. These six salivary methylated genes showed high diagnostic accuracy (≥0.800) for discriminating patients from controls. CONCLUSIONS: This is the first largest genome-wide DNA methylation study on OTSCC that identifies a group of novel tumor-specific DNA methylation markers with diagnostic potential in saliva.

Unusual Nasal Insufficiency in an Infant: What's Behind the Nostril?

OBJECTIVES: Inflammatory myofibroblastic tumor (IMT) is a rare benign lesion, especially in the pediatric age. There are several cases described in pulmonary, digestive and renal localizations, but involvement in head and neck area is infrequent. METHODS: Case report and review of the literature. RESULTS: A 1 year and 11 months old child, during 2 months had clinical signs of nasal respiratory insufficiency and epistaxis subsequently developing a purulent rhinorrhea and a sleep apnea. His pediatrician previously requested a sinus and cavum X-ray with the finding of an image compatible with an intranasal mass. Endoscopic resection was performed of the mass with further immunohistochemical analysis showing the result of a lesion compatible with IMT. CONCLUSIONS: Even though there are very few cases in scientific literature of a tumor with these characteristics in infants, IMT must be present as a differential diagnosis of intranasal masses. The role of the pathologist is essential to reach the definitive diagnosis and the performance of an early surgical treatment decreases aesthetic consequences in this pathology.

Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway.

OBJECTIVES: Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved. MATERIAL AND METHODS: Mutation and copy-number variation in PIK3CA, and whole-genome expression profiles, were analyzed in primary HNSCC tumors from The Cancer Genome Atlas (TCGA) cohort (n = 243). The results were validated in an independent cohort form the University Hospital of A Coruña (UHAC, n = 62). Expression of the PIK3CA gene protein product (PI3K p110α) and nuclear YAP were assessed in tissue microarrays in a cohort from the University Hospital 12 de Octubre (UH12O, n = 91). RESULTS: Only high expression of the PIK3CA gene was associated with poor clinical outcome. The study of gene expression, transcription factor and protein signatures suggested that the activation of the Hippo-YAP pathway, involved in organ size, stem cell maintenance and tumorigenesis, could underlie tumor progression in PI3KCA overexpressing tumors. Tissue arrays showed that PI3K p110α levels correlated with YAP nuclear localization in HNSCC tumors. CONCLUSIONS: High expression of PIK3CA in HNSCC primary tumors identifies patients at high risk for recurrence. In these tumors, progression could rely on the Hippo-YAP pathway instead of the canonical Akt/mTOR pathway. This observation could have important implications in the therapeutic options for patients.

Congenital Malformations of the Central Nervous System in Rural Western Honduras: A 6-Year Report on Trends.

BACKGROUND: Central nervous system (CNS) malformations, including neural tube defects (NTDs), are the second most common type of birth defects worldwide and are major causes of childhood disability and mortality. We report the first analysis of birth prevalence in Western Honduras of CNS malformations including NTDs over 6 consecutive years. METHODS: Data from all patients with congenital CNS malformations and total live births for the period 2010-2015 were obtained through institution and regional registries from all 3 public referral hospitals in Western Honduras, representing 67 municipalities. Cases were identified using the International Classification of Diseases, Tenth Revision CNS malformation codes. Birth prevalence was calculated as cases per 10,000 live births. RESULTS: From 123,903 live births, 275 cases of CNS malformations were identified (54% females, 58% NTDs). Six-year birth prevalence of CNS malformations was 13.9-31.1. Spina bifida variants and anencephaly represented 80% and 19% of reported NTDs, respectively. Total 6-year prevalence of NTDs in Western Honduras was 7.0-17.4 over years studied. In 6 municipalities, average prevalence was >30 (maximum 49.0). CONCLUSION: This is the first study reporting disease burden of CNS malformations in Western Honduras. The nationwide birth prevalence of NTDs in rural Honduras may have decreased since the implementation of prenatal health policies in 2005. However, we identified regions with unexpectedly elevated prevalence, indicating high regional prevalence that could be targeted for improved preventive efforts, ultimately decreasing the burden of these conditions.

Florence Nightingale, la primera enfermera investigadora / Florence Nightingale, the first research nurse

RESUMEN Fundamento: Florence Nightingale fue una enfermera, escritora y estadística británica, considerada pionera de la enfermería moderna y creadora del primer modelo conceptual de enfermería. Objetivo: analizar a Florence Nightingale como la primera enfermera investigadora. Métodos: se realizó una revisión bibliográfica con el método de análisis bibliográfico a través de una búsqueda realizada entre los años 1994 al 2017, donde se consultaron bases de datos especializadas y se seleccionaron 28 publicaciones científicas sobre el tema. Resultados: se insistió en algunos tópicos dentro del tema, como los conocimientos de Florence Nigthingale en cuanto a la filosofía, historia, artes, matemáticas, estadísticas, religión que le permitieron desarrollar innovaciones de técnicas en los análisis estadísticos con lo cual mostró, como un fenómeno social que podía ser medido de manera objetiva y analizado matemáticamente. Conclusiones: Florence Nightingale fue la primera enfermera investigadora, su experiencia ha ejercido una gran influencia en el mundo de las matemáticas, las estadísticas y la Enfermería.

ABSTRACT Background: Florence Nightingale was a British nurse, writer and statistician, considered to be a pioneer of the modern infirmary and creator of the first conceptual model of infirmary. Objective: to analyze Florence Nightingale as the first research nurse. Methods: a bibliographical review was carried out with the method of bibliographical analysis through a search donefrom 1994 to 2017, where specialized databases were consulted and 28 scientific publications on the topic were selected. Results: it was insisted on some topics, as the knowledge of Florence Nigthingale as for the philosophy, history, arts, mathematics, statistics, religion that allowed her to develop technique innovations in the statistical analyses with which she showed, as a social phenomenon that could be measured in an objective way and analyzed mathematically. Conclusions: Florence Nightingale was the first reearch nurse, her experience has exercised a great influence in the world of the mathematics, the statistics and the Infirmary.

A case of generalized eruptive histiocytosis.

Histiocytoses are a heterogeneous group of diseases, characterized by the accumulation of reactive or neoplastic histiocytes in various tissues. Generalized eruptive histiocytosis belongs to cutaneous non-Langerhans' cell histiocytoses and is a rare, generalized, self-healing disorder that usually follows a benign clinical course. Herein, we report a case of generalized eruptive histiocytosis in a 41-year-old woman with peculiar clinical and histological features. Clinically, the papules showed a marked distribution into the seborrhoeic areas of the trunk, with a great tendency to coalesce. Furthermore, immunohistochemical labelling demonstrated that the histiocytes were positive for CD68, but negative for CD34, S100, CD1a and XIIIa factor. This is the second report of generalized eruptive histiocytosis with a negative XIIIa factor. We discuss the differential diagnoses of the clinical picture and emphasize that this benign cutaneous disorder should be subjected to close follow-up, owing to the possibility of evolution to a more severe type of histiocytosis or the association with underlying diseases. Spontaneous regression was observed in this actual case.