DKK1 inhibits canonical Wnt signaling in human papillomavirus-positive penile cancer cells

Penile squamous cell cancer (PSCC) is the most frequent penile malignant disease. Infections with human papillomaviruses (HPV) are a major etiologic driver of PSCC. However, the molecular details of the underlying carcinogenesis are understudied because of rare clinical specimens and missing cell lines. Here, we investigated if the expression of high-risk HPV16 oncogenes causes an augmentation of the Wnt pathway using unique HPV-positive penile cancer (PeCa) cell lines in monolayer and organotypic 3D raft cultures as well as tissue micro arrays containing clinical tissue specimens. The HPV oncoproteins enhanced the expression of Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and the HPV-positive PeCa cells expressed a signature of Wnt target and stemness-associated genes. However, the notable lack of nuclear β-catenin in vitro and in situ raised the question if the enhanced expression of Wnt pathway factors is tantamount to an active Wnt signaling. Subsequent TOP-flash reporter assays revealed Wnt signaling as absent and not inducible by respective Wnt ligands in PeCa cell lines. The HPV-positive PeCa cells and especially HPV-positive PeCa specimens of the tumor core expressed the Wnt antagonist and negative feedback-regulator Dickkopf1 (DKK1). Subsequent neutralization experiments using PeCa cell line-conditioned media demonstrated that DKK1 is capable to impair ligand-induced Wnt signaling. While gene expression analyses suggested an augmented and active canonical Wnt pathway, the respective signaling was inhibited due to the endogenous expression of the antagonist DKK1. Subsequent TMA stainings indicated Dkk1 as linked with HPV-positivity and metastatic disease progression in PeCa suggesting potential as a prognostic marker

Caso 1/19: “E eu nunca fumei, doutor!”

Caso relatado na Reunião de Discussão de Casos Clínicos do Hospital Universitário Prof. Polydoro Ernani de São Thiago, iniciada pelos Profs. Jorge Dias de Matos, Marisa Helena César Coral e Rosemeri Maurici da Silva, em julho de 2017. No dia 11 de abril de 2019, no bloco do curso de medicina, realizou-se a apresentação e discussão do caso cujo registro é apresentado a seguir: uma paciente de 54 anos vem à emergência com tosse, rinorréia e disfonia. Não é tabagista. Apesar da melhora dos sintomas com o tratamento, há imagem persistente no raio-x de tórax. Qual é o diagnóstico

A experiência de amamentar durante a pandemia do Covid-19: um estudo qualitativo com servidoras da Universidade Federal de Santa Catarina.

TCC (graduação) - Universidade Federal de Santa Catarina. Centro de Ciências da Saúde. Medicina.A pandemia do COVID-19 necessitou de inúmeras medidas para sua contenção, e, entre elas, isolamento social. Como estratégia para atenuação desse agravo, muitas instituições optaram pelo funcionamento remoto durante o período. Em Santa Catarina, a Universidade Federal de Santa Catarina (UFSC), em seus diferentes campi de atuação, operou no formato à distância entre 31 de agosto de 2020 e 17 de abril de 2022. O objetivo deste estudo foi avaliar como as consequências da pandemia do COVID-19 puderam impactar no processo de amamentação de servidoras da UFSC que solicitaram licença-maternidade entre janeiro de 2018 e março de 2021. A metodologia escolhida foi a qualitativa, por valorizar a riqueza dos diferentes relatos de 102 participantes. Dentre os resultados obtidos, observou-se que 1) a pandemia propiciou maior proximidade do binômio mãe e filho, aumentando a frequência de mamadas, protelando o desmame e alterando a organização do tempo da nutriz; 2) o isolamento social em si promoveu fortalecimento da figura paterna no apoio à mãe, redução de palpites relacionados à amamentação, enfraquecimento da rede de apoio e ansiedade frente à situação da pandemia; 3) a própria doença COVID-19 teve duplo papel facilitador ou impeditivo à amamentação.The COVID-19 pandemic required numerous measures to contain it, including social distancing. As a strategy to mitigate this problem, many institutions opted for remote operation during the period. In Santa Catarina, the Federal University of Santa Catarina (UFSC), on its different campuses, operated in remote format between August 31, 2020 and April 17, 2022. The objective of this study was to assess how the consequences of COVID-19 pandemic could impact the breastfeeding process of UFSC employees who requested maternity leave between January 2018 and March 2021. The methodology chosen was qualitative, as it values the richness of the different reports of 102 participants. Among the results obtained, it was observed that 1) the pandemic provided greater proximity between the mother and child, increasing the frequency of breastfeeding, delaying weaning and changing the organization of the mother's time; 2) social isolation itself promoted strengthening of the father figure, reduction of nosy guesses related to breastfeeding, weakening of the support network and anxiety in the face of the pandemic situation; 3) the COVID-19 disease itself played a dual role in facilitating or impeding breastfeeding

Bibliothèque Filigrane: traitement et mise en adéquation d'un nouveau fond de vidéocassettes avec la politique documentaire de l'institution

Filigrane, une bibliothèque axant sa politique documentaire autour de la condition féminine et de l'égalité des droits entre hommes et femmes, a reçu un fonds de vidéos spécialisées sur le thème des relations parents-enfants et de l’éducation. Ces cassettes ayant été cédées à la bibliothèque par l’Ecole des Parents dans le cadre d’une collaboration entre ces deux institutions, il était primordial que ces vidéos entrent en concordance avec le fonds actuel de la bibliothèque, tant sur un plan intellectuel, que matériel. Le but principal de ce travail de diplôme consistait donc à poser une réflexion quant à la mise en adéquation de ce fonds avec la collection de Filigrane et à analyser et traiter ce dernier. Pour ce faire nous avons dû non seulement désherber les cassettes de mauvaise qualité, mais également celles qui ne correspondaient pas aux critères élaborés, et ce au moyen d’outils et autres méthodes idoines conçus pour ce travail. De plus, il a fallu examiner le contenu et contenant des vidéos retenues en vue du traitement effectué ultérieurement et réfléchir au devenir du fonds, en orientant nos réflexions sur les thématiques présentes, la valorisation, le support et le droit, le but étant d’intégrer ces cassettes dans les collections de l’institution

Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed or refractory neuroblastoma: A European Innovative Therapies for Children with Cancer-SIOP-European Neuroblastoma study.

PURPOSE: To assess objective response rate (ORR) after two cycles of temozolomide in combination with topotecan (TOTEM) in children with refractory or relapsed neuroblastoma. PATIENTS AND METHODS: This multicenter, non-randomised, phase II study included children with neuroblastoma according to a two-stage Simon design. Eligibility criteria included relapsed or refractory, measurable or metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior treatment. Temozolomide was administered orally at 150mg/m(2) followed by topotecan at 0.75mg/m(2) intravenously for five consecutive days every 28days. Tumour response was assessed every two cycles according to International Neuroblastoma Response Criteria (INRC), and reviewed independently. RESULTS: Thirty-eight patients were enroled and treated in 15 European centres with a median age of 5.4years. Partial tumour response after two cycles was observed in 7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median response duration of 8.5months. Tumour control rate (complete response (CR)+partial response (PR)+mixed response (MR)+stable disease (SD)) was 68% (95% CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58% respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47% of courses in 71% of patients; three patients (8%) had febrile neutropenia. CONCLUSION: Temozolomide-Topotecan combination results in very encouraging ORR and tumour control in children with heavily pretreated recurrent and refractory neuroblastoma with favourable toxicity profile

Amelogenesis imperfecta: Next-generation sequencing sheds light on Witkop’s classification

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic rare diseases disrupting enamel development (Smith et al., Front Physiol, 2017a, 8, 333). The clinical enamel phenotypes can be described as hypoplastic, hypomineralized or hypomature and serve as a basis, together with the mode of inheritance, to Witkop’s classification (Witkop, J Oral Pathol, 1988, 17, 547–553). AI can be described in isolation or associated with others symptoms in syndromes. Its occurrence was estimated to range from 1/700 to 1/14,000. More than 70 genes have currently been identified as causative.Objectives: We analyzed using next-generation sequencing (NGS) a heterogeneous cohort of AI patients in order to determine the molecular etiology of AI and to improve diagnosis and disease management.Methods: Individuals presenting with so called “isolated” or syndromic AI were enrolled and examined at the Reference Centre for Rare Oral and Dental Diseases (O-Rares) using D4/phenodent protocol (www.phenodent.org). Families gave written informed consents for both phenotyping and molecular analysis and diagnosis using a dedicated NGS panel named GenoDENT. This panel explores currently simultaneously 567 genes. The study is registered under NCT01746121 and NCT02397824 (https://clinicaltrials.gov/).Results: GenoDENT obtained a 60% diagnostic rate. We reported genetics results for 221 persons divided between 115 AI index cases and their 106 associated relatives from a total of 111 families. From this index cohort, 73% were diagnosed with non-syndromic amelogenesis imperfecta and 27% with syndromic amelogenesis imperfecta. Each individual was classified according to the AI phenotype. Type I hypoplastic AI represented 61 individuals (53%), Type II hypomature AI affected 31 individuals (27%), Type III hypomineralized AI was diagnosed in 18 individuals (16%) and Type IV hypoplastic-hypomature AI with taurodontism concerned 5 individuals (4%). We validated the genetic diagnosis, with class 4 (likely pathogenic) or class 5 (pathogenic) variants, for 81% of the cohort, and identified candidate variants (variant of uncertain significance or VUS) for 19% of index cases. Among the 151 sequenced variants, 47 are newly reported and classified as class 4 or 5. The most frequently discovered genotypes were associated with MMP20 and FAM83H for isolated AI. FAM20A and LTBP3 genes were the most frequent genes identified for syndromic AI. Patients negative to the panel were resolved with exome sequencing elucidating for example the gene involved ie ACP4 or digenic inheritance.Conclusion: NGS GenoDENT panel is a validated and cost-efficient technique offering new perspectives to understand underlying molecular mechanisms of AI. Discovering variants in genes involved in syndromic AI (CNNM4, WDR72, FAM20A … ) transformed patient overall care. Unravelling the genetic basis of AI sheds light on Witkop’s AI classification