Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours

Vulnerabilidades ao HIV/aids no Contexto Brasileiro: iniquidades de gênero, raça e geração

OBJETIVO: Analisar o conhecimento da população sobre DST/aids, bem como os discursos sobre o uso do preservativo e das práticas sexuais. MÉTODOS: Pesquisa qualitativa com 64 indivíduos jovens e adultos, brancos e negros, sexualmente ativos, de ambos os sexos. A vulnerabilidade ao HIV/aids foi discutida a partir da perspectiva racial (negros ou brancos), geracional (entre 16 e 24 anos ou 45 e mais) e de gênero (masculino ou feminino). Foram realizadas entrevistas em profundidade com roteiro semiestruturado nas cidades de São Paulo (SP) e Recife (PE), sobre os temas: conhecimento e percepção sobre DST/aids, percepção de risco individual, negociação e uso de preservativos, iniciação sexual e práticas sexuais. RESULTADOS: Os indivíduos menos escolarizados, os homens, os mais velhos e os moradores de Recife foram os menos informados sobre DST/aids. Pessoas acima de 45 anos e os menos escolarizados possuíam conhecimento incipiente sobre as formas de transmissão e prevenção das DST/aids. O uso do preservativo entre os entrevistados de ambas as cidades foi relativamente baixo; a não utilização do preservativo entre as mulheres em relação estável foi atribuída à negativa do parceiro. Entre os entrevistados que declararam usar o preservativo, o tipo de relação estabelecida e a fase do relacionamento resultaram em padrões de uso diversificados; o uso consistente do preservativo foi mais frequente nas parcerias eventuais. CONCLUSÕES: O conhecimento incipiente aliado à prática sexual insegura coloca mulheres unidas, de baixa escolaridade, menor renda, sobretudo acima dos 45 anos, e os residentes de Recife em situação de maior vulnerabilidade às DST/aids.OBJECTIVE: The objective of this paper is to assess the level of knowledge and information held by the population about HIV/AIDS, and to analyze discourses about condom use and sexual practices. METHODS: Qualitative research with 64 young people and adults, black and white, sexually active men and women. Vulnerability to HIV/AIDS was discussed from the perspective of racial (black or white), generational (between 16 and 45 or 24 years or older) and gender (male or female). In-depth interviews were conducted with a semi-structured script in the cities of São Paulo (SP) and Recife (PE) on the following themes: knowledge and perception about STD/AIDS, perception of individual risk, negotiation and condom use, sexual initiation and practices. RESULTS: The least-educated, men, elders and residents of Recife were the least informed persons as regards to HIV/AIDS. People over 45 years and the less educated had incipient knowledge about transmission and prevention of STD/AIDS. Condom use among respondents in both cities was relatively low, non-use of condoms among women in stable relationship was attributed to partner's refusal to using it. Among respondents who reported using condoms, the type of relationship established and the phase of the relationship resulted in varied patterns of use; the consistent use of condoms was more common in occasional partnerships. CONCLUSIONS: The incipient knowledge in association with unsafe sexual practice puts women in stable relationship, poorly educated, lower income, particularly above 45 years, and residents of Recife in a situation of greater vulnerability to STD/AIDS

Control de la fustraci?n laboral

49 p

Moderated milk replacer restriction of ewe lambs alters gut immunity parameters during the pre-weaning period and impairs liver function and animal performance during the replacement phase

Undernutrition during the first stages of life may impair maturation of the immune system, harming the health status permanently. Thus, the aim of the present study was to define the impact of moderated milk replacer (MR) restriction during the artificial rearing period on the gut-associated lymphoid tissues of pre-weaned ewe lambs and long-term effects on biochemical profile and animal performance during the replacement period. Forty female Assaf lambs [average live body weight (LBW) 4.73 \ub1 0.116 kg] were penned individually. The first group of lambs (n = 20) was fed MR ad libitum (ADL) whereas the second one (restricted, RES; n = 20) only received approximately 62.5% of the MR intake measured in the ADL group. All the lambs were weighed twice a week until they were 35-days-old. Then, 8 lambs from each group (pre-weaned) were harvested and ileal samples collected. The rest of the lambs (12 ADL vs. 12 RES) were weaned progressively, and then offered a total mixed ration (TMR) ad libitum until the end of the experiment (7.5-months-old). The lower nutrient intake of RES pre-weaned lambs caused greater percentages for T lymphocytes (CD4+, CD8+, WC1+) and an increased secretory immunoglobulin A (sIgA) production in the ileum compared to the ADL group (P < 0.05). These results, together with the significant differences in the expression of toll-like receptors and cytokines at this level (e.g., interferon gamma was increased in the RES group; P<0.05) suggest the existence of pro-inflammatory conditions in the ileum of pre-weaned lambs promoted by early feed restriction. Moreover, the biochemical profile revealed that liver function (e.g., albumin, gamma glutamyl transpeptidase) was impaired during several months once the feed restriction period was finished, whereas the average daily gain during the replacement phase was reduced for the early feed restricted lambs (182 vs. 202 g/day for RES and ADL groups, respectively; P < 0.05). Therefore it can be concluded that moderated MR restriction promoted both, pro-inflammatory conditions at ileal level in the pre-weaned lambs and an altered liver function which lasted several months after the end of feed restriction. Both circumstances might have impaired animal performance during the replacement phase of the ewe lambs

Role of Peer Influence and Thin-ideal Internalization on Body Dissatisfaction and Disordered Eating in Mexican Girls

Con el objetivo de examinar el rol de la influencia de pares y de la interiorizaci�n del ideal de delgadez sobre la insatisfacci�n corporal y la alimentaci�n no saludable en una muestra comunitaria, se aplic� el Test de Actitudes Alimentarias, el Cuestionario de Imagen Corporal y el Cuestionario de Influencias del Modelo Est�tico Corporal a 130 mujeres estudiantes, cuya media de edad fue de 19.44 a�os. El an�lisis de datos revel� que la interiorizaci�n del ideal de delgadez medi� la relaci�n entre la influencia de pares y la insatisfacci�n corporal (?=0.14, p>.05), as� como la relaci�n entre la influencia de pares y la alimentaci�n no saludable (?=0.09, p>.05). Este estudio apoya la hip�tesis de que la interiorizaci�n del ideal de delgadez es un importante mediador sobre la insatisfacci�n corporal y la alimentaci�n no saludable en j�venes mexicanas