Effects of o,p'-DDE, a Mitotane Metabolite, in an Adrenocortical Carcinoma Cell Line.

In South Brazil, the incidence of pediatric adrenocortical carcinoma (ACC) is higher than in other regions and countries worldwide. The ACC treatment includes therapy with mitotane, the only adrenolytic drug approved by the FDA. The mitotane metabolism occurs via two main reactions: the ß-hydroxylation, which yields the final product o,p'-DDA, and the α-hydroxylation, which will give the final product o,p'-DDE. It is speculated that o,p'-DDE may be an active metabolite since it has a cytotoxic effect on adrenocortical carcinoma cells (H295R). No further studies have been conducted to confirm this hypothesis; however, it was found that mitotane and its metabolites are present at significantly different concentrations in the plasma of the patients. Our study aimed to assess the in vitro effects of o,p'-DDE and o,p'-DDD in cell death pathways, oxidative parameters, and interaction with adrenal CYP's involved in the steroidogenic process in the H295R cell line. It was found that o,p'-DDE had a different effect than the o,p'-DDD on apoptosis, inhibiting this cell death pathway, but it promotes cell necrosis at higher concentrations. In contrast to o,p'-DDD, the o,p'-DDE did not have effects on the different oxidative parameters evaluated, but exhibited stimulatory interactions with steroidogenic CYP's, at intermediate concentrations. Therefore, we demonstrated important cell effects of o,p'-DDE; its plasma levels during mitotane therapy should be monitored as an important therapeutic parameter.

Psychological Impact of TP53-Variant-Carrier Newborns and Counselling on Mothers: A Pediatric Surveillance Cohort.

Counselling and genetic testing (CGT) after neonatal screening may increase depression and anxiety (DA) levels during cancer surveillance. This study assessed the DA scores in mothers of newborns from Paraná state, Southern Brazil, carrying the TP53 p.R337H variant. To understand and adjust DA conditions during term of pregnancy, we initially detected sociodemographic covariates [marital status (MS), number of children (NC), and/or education level (EL): MS-NC-EL] on an independent group of pregnant women (not subjected to genetic testing). The Hospital Anxiety and Depression Scale (HADS) was used to assess risk factors in pregnant (cross-sectional analysis) and unrelated mothers (at 2-month intervals, longitudinal study) of TP53 p.R337H-tested newborns (three sessions of HADS analysis) using Wilcoxon (Mann-Whitney) and Kruskal-Wallis nonparametric tests. Lower anxiety levels were observed in mothers of noncarriers (without MS-NC-EL = 6.91 ± 1.19; with MS-NC-EL = 6.82 ± 0.93) than in mothers of p.R337H carriers in the first session (without MS-NC-EL = 6.82 = 8.49 ± 0.6025, with MS-NC-EL = 6.82 = 9.21 ± 0.66). The anxiety levels significantly decreased 4 months after CGT (third session) in mothers of p.R337H carriers. We did not find a significant change in depression scores. Mothers with mental health instability requiring medications need periodical psychological support during and after CGT.

Leadership, management and teamwork learning through an extra-curricular project for medical students: descriptive study / Liderança, gestão e aprendizagem de trabalho em equipe através de projeto extracurricular para estudantes de medicina: estudo descritivo

CONTEXT AND OBJECTIVE: Professionalism in medicine requires preparation for the globalized world. Our objective was to describe a project that introduces medical students to the community, hospital and laboratory activities, thereby allowing them to gain experience in people management, leadership and teamwork. DESIGN AND SETTING: Descriptive study of the process applied at a philanthropic medical school in Curitiba, Paraná. METHOD: Inclusion of management and leadership practices as part of the medical degree program. RESULTS: The study groups consisted of fifteen students. After six months, any of the participants could be elected as a subcoordinator, with responsibility for managing tasks and representing the team in hospital departments and the community. The activities required increasing levels of responsibility. In medical schools, students' involvement in practical activities is often limited to observation. They are not required to take responsibilities or to interact with other students and stakeholders. However, they will become accountable, which thus has an adverse effect on all involved. The learning space described here aims to fill this gap by bringing students closer to the daily lives and experiences of healthcare professionals. CONCLUSION: Being a physician requires not only management and leadership, but also transferrable competencies, communication and critical thinking. These attributes can be acquired through experience of teamwork, under qualified supervision from teaching staff. Students are thus expected to develop skills to deal with and resolve conflicts, learn to share leadership, prepare others to help and replace them, adopt an approach based on mutual responsibility and discuss their performance. .

CONTEXTO E OBJETIVO: Profissionalismo na medicina requer formação para o mundo globalizado. Nosso objetivo é descrever um projeto que introduz os estudantes de medicina em atividades laboratoriais, comunitárias e hospitalares, oferecendo experiência em gestão de pessoas, liderança e trabalho em equipe. TIPO DE ESTUDO E LOCAL: Estudo descritivo do processo aplicado a uma escola medica filantrópica de Curitiba, Paraná. MÉTODO: Inclusão de práticas de gestão e liderança como parte do programa de graduação médica. RESULTADOS: Os grupos de trabalho eram constituídos por 15 estudantes. Após seis meses de participação, o estudante podia ser eleito como subcoordenador, responsável por gerenciar tarefas e representar a equipe junto aos setores do hospital e na comunidade. Na faculdade de medicina, frequentemente, o envolvimento dos alunos em atividades práticas restringe-se à observação, não existem demandas sobre a sua responsabilidade ou sua interação com outros alunos e atores. Entretanto, serão cobrados por isso, resultando em efeito adverso sobre todos os envolvidos. O espaço de aprendizagem aqui descrito visa preencher essa lacuna, trazendo os alunos para mais perto do cotidiano e das experiências dos profissionais de saúde. CONCLUSÃO: Ser médico exige, ao lado de gestão e liderança, competências transferíveis, comunicação e pensamento crítico. Atributos adquiridos pela experiência do trabalho em equipe sob supervisão qualificada do corpo docente, quando os estudantes devem desenvolver habilidades para lidar e resolver conflitos, aprender a compartilhar a liderança, preparar outras pessoas para ajudar e substituir, adotar uma abordagem baseada na mútua responsabilidade e na análise de desempenho. .

Leadership, management and teamwork learning through an extra-curricular project for medical students: descriptive study.

CONTEXT AND OBJECTIVE: Professionalism in medicine requires preparation for the globalized world. Our objective was to describe a project that introduces medical students to the community, hospital and laboratory activities, thereby allowing them to gain experience in people management, leadership and teamwork. DESIGN AND SETTING: Descriptive study of the process applied at a philanthropic medical school in Curitiba, Paraná. METHOD: Inclusion of management and leadership practices as part of the medical degree program. RESULTS: The study groups consisted of fifteen students. After six months, any of the participants could be elected as a subcoordinator, with responsibility for managing tasks and representing the team in hospital departments and the community. The activities required increasing levels of responsibility. In medical schools, students' involvement in practical activities is often limited to observation. They are not required to take responsibilities or to interact with other students and stakeholders. However, they will become accountable, which thus has an adverse effect on all involved. The learning space described here aims to fill this gap by bringing students closer to the daily lives and experiences of healthcare professionals. CONCLUSION: Being a physician requires not only management and leadership, but also transferrable competencies, communication and critical thinking. These attributes can be acquired through experience of teamwork, under qualified supervision from teaching staff. Students are thus expected to develop skills to deal with and resolve conflicts, learn to share leadership, prepare others to help and replace them, adopt an approach based on mutual responsibility and discuss their performance.