Nucleolin Aptamer N6L Reprograms the Translational Machinery and Acts Synergistically with mTORi to Inhibit Pancreatic Cancer Proliferation.

We previously showed that N6L, a pseudopeptide that targets nucleolin, impairs pancreatic ductal adenocarcinoma (PDAC) growth and normalizes tumor vessels in animal models. In this study, we analyzed the translatome of PDAC cells treated with N6L to identify the pathways that were either repressed or activated. We observed a strong decrease in global protein synthesis. However, about 6% of the mRNAs were enriched in the polysomes. We identified a 5'TOP motif in many of these mRNAs and demonstrated that a chimeric RNA bearing a 5'TOP motif was up-regulated by N6L. We demonstrated that N6L activates the mTOR pathway, which is required for the translation of these mRNAs. An inhibitory synergistic effect in PDAC cell lines, including patient-derived xenografts and tumor-derived organoids, was observed when N6L was combined with mTOR inhibitors. In conclusion, N6L reduces pancreatic cells proliferation, which then undergoes translational reprogramming through activation of the mTOR pathway. N6L and mTOR inhibitors act synergistically to inhibit the proliferation of PDAC and human PDX cell lines. This combotherapy of N6L and mTOR inhibitors could constitute a promising alternative to treat pancreatic cancer.

Factors related to the association of social anxiety disorder and alcohol use among adolescents: a systematic review / Fatores relacionados à associação de transtorno de ansiedade social e uso de álcool entre adolescentes: uma revisão sistemática

Abstract Objective: To identify the risk factors related to the association between social anxiety disorder and alcohol use in adolescents. Source of data: The PICO research strategy was used to perform a systematic review in Medline, LILACS, Pubmed, IBECS and Cochrane Library databases. DeCS/MeSH: Phobic Disorders, Adolescent, Behavior, Ethanol, Risk Factors, and the Boolean operator "AND" were used. Inclusion criteria were: cross-sectional, prospective/retrospective cohort, and case-control studies, carried out in adolescents (10-19 years), original articles on social anxiety disorder and alcohol use published between 2010 and 2015. Studies that did not report the terms "anxiety disorder" and "alcohol use" in the title and abstract were excluded. Synthesis of data: 409 articles were retrieved; after the exclusion of 277 repeated articles, the following were eligible: 94 in MEDLINE, 68 in Pubmed, 12 in IBCS, and three in LILACS. Titles and abstracts were independently read by two examiners, which resulted in the selection of eight articles for the analysis. Risk factors associated to the two disorders were female gender, age, peer approval and affective problems for alcohol use, confrontation situations and/or compliance reasons, frequency of alcohol use, and secondary comorbidities, such as depression and generalized anxiety. Conclusions: It is necessary to assess the period of social anxiety disorders first symptom onset, as well as the risks for alcohol use in order to establish corrective intervention guidelines, especially for socially anxious students.

Abstract Objective: To identify the risk factors related to the association between social anxiety disorder and alcohol use in adolescents. Source of data: The PICO research strategy was used to perform a systematic review in Medline, LILACS, Pubmed, IBECS and Cochrane Library databases. DeCS/MeSH: Phobic Disorders, Adolescent, Behavior, Ethanol, Risk Factors, and the Boolean operator "AND" were used. Inclusion criteria were: cross-sectional, prospective/retrospective cohort, and case-control studies, carried out in adolescents (10 to 19 years), original articles on social anxiety disorder and alcohol use published between 2010 and 2015. Studies that did not report the terms "anxiety disorder" and "alcohol use" in the title and abstract were excluded. Synthesis of data: 409 articles were retrieved; after the exclusion of 277 repeated articles, the following were eligible: 94 in MEDLINE, 68 in Pubmed, 12 in IBCS, and three in LILACS. Titles and abstracts were independently read by two examiners, which resulted in the selection of eight articles for the analysis. Risk factors associated to the two disorders were female gender, age, peer approval and affective problems for alcohol use, confrontation situations and/or compliance reasons, frequency of alcohol use, and secondary comorbidities, such as depression and generalized anxiety. Conclusions: It is necessary to assess the period of social anxiety disorders first symptom onset, as well as the risks for alcohol use in order to establish corrective intervention guidelines, especially for socially anxious students.

Factors related to the association of social anxiety disorder and alcohol use among adolescents: a systematic review.

OBJECTIVE: To identify the risk factors related to the association between social anxiety disorder and alcohol use in adolescents. SOURCE OF DATA: The PICO research strategy was used to perform a systematic review in Medline, LILACS, Pubmed, IBECS and Cochrane Library databases. DeCS/MeSH: Phobic Disorders, Adolescent, Behavior, Ethanol, Risk Factors, and the Boolean operator "AND" were used. Inclusion criteria were: cross-sectional, prospective/retrospective cohort, and case-control studies, carried out in adolescents (10-19 years), original articles on social anxiety disorder and alcohol use published between 2010 and 2015. Studies that did not report the terms "anxiety disorder" and "alcohol use" in the title and abstract were excluded. SYNTHESIS OF DATA: 409 articles were retrieved; after the exclusion of 277 repeated articles, the following were eligible: 94 in MEDLINE, 68 in Pubmed, 12 in IBCS, and three in LILACS. Titles and abstracts were independently read by two examiners, which resulted in the selection of eight articles for the analysis. Risk factors associated to the two disorders were female gender, age, peer approval and affective problems for alcohol use, confrontation situations and/or compliance reasons, frequency of alcohol use, and secondary comorbidities, such as depression and generalized anxiety. CONCLUSIONS: It is necessary to assess the period of social anxiety disorders first symptom onset, as well as the risks for alcohol use in order to establish corrective intervention guidelines, especially for socially anxious students.

Caracterização dos seminários por webconferência sobre saúde do adolescente e jovem da rede de núcleos de telessaúde de Pernambuco / A characterization of web-conference seminars on the health of adolescents and young people at cyber-health centers in the Brazilian State of Pernambuco

Caracterizar o perfil dos seminários por webconferência sobre saúde do adolescente e jovem, a partir dos registros do serviço de tele-educação da Rede de Núcleos de Telessaúde (RedeNUTES) de Pernambuco. MÉTODOS: estudo retrospectivo, descritivo e exploratório, de abordagem quantitativa, com dados de 1348 participações de profissionais de saúde nos seminários ocorridos no ano de 2009. RESULTADOS: a RedeNUTES esteve presente em 45 por cento dos municípios de Pernambuco. Foram realizados 148 seminários (19 por cento - saúde do adolescente e jovem) com participação de todas as Gerências Regionais de Saúde; destacando a participação das equipes de enfermagem (51 por cento) e saúde bucal (16,5 por cento). No momento de troca de experiências foram feitos 151 esclarecimentos de dúvidas (média de 5,4 dúvidas por seminário), destacando as mesmas equipes em 55,5 por cento e 19,7 por cento, respectivamente. CONCLUSÕES: existe uma necessidade de estimular a participação dos profissionais de saúde nas capacitações permanentes para fortalecer as ações de promoção da saúde e o cuidado integral de forma contínua ao grupo dos adolescentes...

To characterize the profile of web-conference seminars on the health of adolescents and young people using registers from the cyber-education service of the Pernambuco Network of Cyber-Health Units (RedeNUTES). METHODS: a quantitative, retrospective, descriptive, exploratory study was carried out with dada from 1348 occasions on which health workers participated in seminars in the year 2009. RESULTS: RedeNUTES were in existence in 45 percent of municipalities in Pernambuco. 148 seminars were held (19 percent in the field of the health of adolescents and young people) with the participation of all the Regional Health Management Teams; with an especially strong participation on the part of nursing (51 percent) and dental health teams (16.5 percent). During the exchange of experiences, 151 questions were answered (an average of 5.4 per seminar), with strong participations of 55.5 percent and 19.7 percent from the aforementioned groups. CONCLUSIONS: is a need to encourage the participation of health workers in on-going training to strengthen continuous health promotion and all-round care for adolescents...