Presumed TP53 mosaicism: variants detected using a NGS hereditary cancer multigene panel

Aims/Context: NGS multigene panels are routinely used to identify germline pathogenic variants in cancer susceptibility genes. In addition, NGS allows the identification of low-level mosaicism events that may not be detectable by conventional Sanger sequencing. We describe two cases of presumed TP53 mosaic variants detected by NGS on blood-derived DNA, and confirmed by ARMS-PCR and Sanger sequencing. Case 1: female, 87 years old, colon cancer at 83 and metachronous breast cancer at 86, no history of familial cancer. Case 2: female, 75 years old, ovarian cancer at 71, local relapse at 74. Methods: NGS using TruSight® Cancer Sequencing Panel and TruSight® Rapid Capture kit (Illumina) and paired-end sequencing on MiSeq® platform (Illumina). Bioinformatic analysis with MiSeq Reporter, Enrichment, VariantStudio, VEP, Alamut Visual, VarAFT, VarSome and IGV. ARMS-PCR and Sanger sequencing were used to confirm the TP53 variants. Results and Conclusions: Two cases of presumed TP53 mosaic variants were studied. Case 1: the missense alteration TP53: c.764T>G, p.(Ile255Ser) was detected with a variant allele frequency (VAF) of 26% (39/150 reads). This variant is described in ClinVar as a somatic alteration, classified as likely pathogenic. It is not reported in gnomAD and VarSome software classified it as a variant of uncertain significance. Case 2: missense variant TP53: c.524G>A, p.(Arg175His) detected with a VAF of 15% (10/58 reads). This variant is described as pathogenic in HGMD Professional, LOVD and ClinVar, in association with Li-Fraumeni syndrome. These two cases seem to represent TP53 mosaicism, supported by: i) VAF lower than 30%, ii) detection at the sensitivity limit of Sanger sequencing and iii) confirmation by ARMS-PCR. Confirming this hypothesis by studying tumor and other tissue samples and offspring analysis (underway in both cases), is essential for disease diagnosis, assessing recurrence risk and genetic counseling. The hypothesis of acquired aberrant clonal expansion limited to the hematologic compartment, versus a germline variant should be considered in similar cases, and confirmatory methodologies are mandatory.info:eu-repo/semantics/publishedVersio

A brief overview of current drug repurposing approaches for COVID-19 management

This brief overview is intended to shed light on the current drug repositioning (also called drug repurposing) in the therapeutics of the novel coronavirus disease which emerged in 2019 (COVID-19). In this sense, the repositioning drugs for new indications can offer a better risk-versus-reward trade-off when compared to other drug development strategies, given that it makes use of drugs whose safety profile are already understood. Nonetheless, this approach allows healthcare professionals to promptly tackle the disease by investigating readily available drugs against it

Анализ на поведението при решения на топ треньори от висша лига преди и след спортното състезание

Submitted article is thorough study of top coaches behavioral responses during the competition. A detailed analysis of the literature /from the last 15 years / is made, focusing on various determinants of sporting success which determine the role of the coach to shine and not be underestimated. It stressed the need to examine current trends, that elucidate the process complexity / behavioral and cognitive / in coaching job.Представената статия е задълбочено проучване на поведенчески реакции на топ треньори по време на състезание. Подробен анализ на литературата / от последните 15 години / е направен, фокусиран върху различните детерминанти на спортния успех, който да подчертае ролята на треньора. Обръща се внимание на необходимостта, да се разгледат съвременните тенденции, които осветляват сложността на процеса /поведенческа и когнитивна/ в треньорската работа.info:eu-repo/semantics/publishedVersio

Efeito da Eletropuntura vs TENS acupuntural na dor, temperatura e atividade mioelétrica do Trigger Point do trapézio superior

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciado em FisioterapiaObjetivo: Analisar o efeito de um protocolo de tratamento de eletropuntura vs TENS acupuntural comparativamente a um grupo controlo, na redução de dor, na temperatura cutânea local e atividade muscular, no trigger point latente do trapézio superior e a relação entre as diferentes técnicas utilizadas. Metodologia: Participaram no estudo 30 indivíduos, distribuídos de forma aleatória em 3 grupos: controlo, TENS acupuntural e Eletropuntura. Foram avaliados: o limiar álgico através do Algómetro de pressão, a dor através da Escala Numérica da dor, atividade muscular através da Eletromiografia de superfície e temperatura cutânea através da termografia. Foram realizadas 2 sessões por semana durante 4 semanas. Aplicou-se uma corrente de 2 Hz por 300 μs durante 20 minutos. Resultados: Verificou-se que, apenas o grupo de eletropuntura apresentou diferenças significativas comparativamente aos outros grupos com uma diminuição da dor, um aumento do limiar da dor, uma diminuição da temperatura e uma diminuição da atividade muscular. Neste mesmo grupo verificou-se ainda uma correlação positiva entre a dor e atividade muscular e negativa entre ativação muscular e limiar álgico. Conclusão: Concluímos que a técnica de Eletropuntura isolada aparenta atuar de forma mais eficaz, na dor, atuando na temperatura e atividade muscular comparativamente aos outros grupos em estudo.Aim: Analyze the effect of a treatment protocol of electropuncture vs TENS in pain reduction, local skin temperature and muscular activity and comparing it with a control group, on the trigger point of superior trapezius, and its relation to the different techniques used. Methodology: 30 different subjects participated in the study, and they were randomly assigned into 3 groups: control, TENS and electropuncture. The pain threshold through the pressure algometer, pain through the numerical pain scale, muscular activity through surface electromyography and skin temperature through thermography were evaluated. In this study, 2 sessions per week during 4 weeks were done, where a current of 2Hz with 300 μs was applied for 20 minutes. Results: Only the electropuncture group has shown significant differences comparing to other groups, with a decrease in pain, temperature and muscular activity, and an increase of the pain threshold. In the same group, there was also a positive correlation between pain and muscular activity, while there was a negative one between muscular activation and the pain threshold. Conclusion: Comparing to all other study groups, the isolated electropuncture technique seems to be more effective in pain, influencing temperature and muscular activity.N/