Detection of serum biomarkers of HPV-16 driven oropharynx and oral cavity cancer in Brazil.

BACKGROUND: HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16INK4a status was also accessed. METHODS: HPV was genotyped by PCR-hybridization. All HPV DNA positive and ∼10 % HPV DNA negative cases underwent p16INK4a immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively. RESULTS: The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16INK4 (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors. CONCLUSIONS: Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.

Working memory and arithmetic impairments in children with FMR1 premutation and gray zone alleles.

Expansive mutations in familial mental retardation 1 (FMR1) gene have been associated with different phenotypes. Full mutations are associated with intellectual disability and autism spectrum disorder; premutations are associated with math learning difficulties and working memory impairments. In gray zone, neuropsychological development has not yet been described. Objectives: This study aimed to describe the frequency of FMR1 premutation and gray zone alleles in a school population sample representing a broad spectrum of variation in math achievement and detail school achievement and cognitive performance in the children identified with FMR1 premutation or gray zone alleles. Methods: We described a two-phase study. In the first phase, 2,195 school-age children were screened for math achievement. In the second phase, 378 children with normal intelligence were neuropsychologically assessed and genotyped for FMR1. Of these, 121 children (61 girls) performed below percentile 25 in mathematics (MD group) and 257 children (146 girls) performed above percentile 25 (control group). Results: Four pupils presented expanded alleles, one premutation and three gray zone alleles. The girl with the premutation and one boy with a gray zone allele presented impairments in working memory and arithmetic performance below percentile 6, compatible with the diagnosis of developmental dyscalculia. These children's difficulties were not associated with inaccuracy of nonsymbolic number representations or literacy impairments. Dyscalculia in these children seems to be associated mainly with working memory impairments. Conclusions: FMR1 expansions in the gray zone may contribute to dyscalculia in otherwise healthy and normally intelligent children.

Mutações expansivas no gene FMR1 têm sido associadas a diferentes fenótipos. Mutações completas estão associadas a deficiência intelectual e transtorno do espectro do autismo; pré-mutações, com dificuldades de aprendizagem de matemática e comprometimentos de memória de trabalho. Na zona cinzenta o desenvolvimento neuropsicológico ainda não foi descrito. Objetivos: Descrever a frequência de alelos pré-mutados e zona cinzenta em uma amostra escolar que representa amplo espectro de variação do desempenho em Matemática e detalhar o desempenho escolar e cognitivo em crianças identificadas com alelos pré-mutados ou zona cinzenta. Métodos: Aqui, descrevemos um estudo de duas fases. Na primeira fase, 2.195 crianças em idade escolar foram selecionadas para desempenho em Matemática. Na segunda fase, 378 crianças com inteligência normal foram avaliadas neuropsicologicamente e, em seguida, por genotipagem FMR1. Resultados: Tiveram desempenho abaixo do percentil 25 em Matemática (grupo DM) 121 crianças (61 meninas), e tiveram desempenho acima do percentil 25 (grupo controle) 257 crianças (146 meninas). Quatro alunos apresentaram alelos expandidos, sendo uma pré-mutação e três alelos da zona cinza. A menina com a pré-mutação e um menino com o alelo da zona cinza apresentaram prejuízos na memória de trabalho e desempenho aritmético abaixo do percentil 6, compatíveis com o diagnóstico de discalculia do desenvolvimento. As dificuldades dessas crianças não foram associadas à imprecisão de representações não simbólicas de números ou deficiências de alfabetização. A discalculia nessas crianças parece estar associada principalmente a deficiências da memória de trabalho. Conclusões: Em conclusão, expansões na zona cinzenta do FMR1 podem contribuir para a discalculia em crianças saudáveis com inteligência normal.

Survey of genome organization and gene content of Corynebacterium pseudotuberculosis.

Corynebacterium pseudotuberculosis is an intracellular pathogen that causes Caseous lymphadenitis (CLA) disease in sheep and goats. The widespread occurrence and the economic importance of this pathogen have prompted investigation of its pathogenesis. We used a genomic library of C. pseudotuberculosis to generate 1440 genomic survey sequences (GSSs); these were analyzed in silico with bioinformatics tools, using public databases for comparative analyses. We employed non-redundant unique sequences as a query for BLAST searches against the genome, the translated genome and the proteome of four other Corynebacterium species that have been completely sequenced. We were able to characterize approximately 8% of the genome of C. pseudotuberculosis, including previously undescribed functional group genes, based on the COG database; the GSSs classification into categories gave 13% information storage and processing, 14% cellular processes and 23% metabolism. We found a close relation between C. pseudotuberculosis and C. diphtheriae conserved-gene synteny in Corynebacteria species.