Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Predictive biomarkers are crucial in clarifying the best strategy to use poly(ADP-ribose) polymerase inhibitors (PARPi) for the greatest benefit to ovarian cancer patients. PARPi are specifically lethal to cancer cells that cannot repair DNA damage by homologous recombination (HR), and HR deficiency is frequently associated with BRCA1/2 mutations. Genetic tests for BRCA1/2 mutations are currently used in the clinic, but results can be inconclusive due to the high prevalence of rare DNA sequence variants of unknown significance. Most tests also fail to detect epigenetic modifications and mutations located deep within introns that may alter the mRNA. The aim of this study was to investigate whether quantitation of BRCA1/2 mRNAs in ovarian cancer can provide information beyond the DNA tests. Using the nCounter assay from NanoString Technologies, we analyzed RNA isolated from 38 ovarian cancer specimens and 11 normal fallopian tube samples. We found that BRCA1/2 expression was highly variable among tumors. We further observed that tumors with lower levels of BRCA1/2 mRNA showed downregulated expression of 12 additional HR genes. Analysis of 299 ovarian cancer samples from The Cancer Genome Atlas (TCGA) confirmed the coordinated expression of BRCA1/2 and HR genes. To facilitate the routine analysis of BRCA1/2 mRNA in the clinical setting, we developed a targeted droplet digital PCR approach that can be used with FFPE samples. In conclusion, this study underscores the potential clinical benefit of measuring mRNA levels in tumors when BRCA1/2 DNA tests are negative or inconclusive.This research was funded by the Fundação para a Ciência e a Tecnologia, Portugal (PTDC/MED-ONC/29469/2017) and an unrestricted grant from AstraZeneca to M.C.-F. R.S. was a recipient of an EMBO Long-Term Fellowship (EMBO ALTF 101-2019). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 842695.info:eu-repo/semantics/publishedVersio

Diversidade molecular entre populações de Spodoptera frugiperda no Brasil avaliada por marcadores AFLP

The objective of this work was to evaluate the molecular diversity, by AFLP markers, of six Spodoptera frugiperda populations collected in maize crops in different geographical regions of Brazil. DNA was extracted from fourth‑instar larvae, and AFLP reactions were performed with seven oligonucleotide primer combinations. From the six studied S. frugiperda populations, a major group was identified, formed by three more genetically‑related populations. The evaluated S. frugiperda populations show high genetic variability, with a maximum of 58% similarity.O objetivo deste trabalho foi avaliar a diversidade molecular, por meio de marcadores AFLP, de seis populações de Spodoptera frugiperda coletadas na cultura do milho, em diferentes regiões geográficas do Brasil. O DNA foi extraído de lagartas de quarto instar, e as reações de AFLP foram realizadas com sete combinações de oligonucleotídeos iniciadores. A partir das seis populações de S. frugiperda estudadas, foi identificado um grupo principal formado por três populações geneticamente mais relacionadas. As populações de S. frugiperda analisadas mostram alta variabilidade genética, com máximo de 58% de similaridade

Molecular diversity among populations of Spodoptera frugiperda in Brazil evaluated by AFLP markers

O objetivo deste trabalho foi avaliar a diversidade molecular, por meio de marcadores AFLP, de seis populações de Spodoptera frugiperda coletadas na cultura do milho, em diferentes regiões geográficas do Brasil. O DNA foi extraído de lagartas de quarto instar, e as reações de AFLP foram realizadas com sete combinações de oligonucleotídeos iniciadores. A partir das seis populações de S. frugiperda estudadas, foi identificado um grupo principal formado por três populações geneticamente mais relacionadas. As populações de S. frugiperda analisadas mostram alta variabilidade genética, com máximo de 58% de similaridade.The objective of this work was to evaluate the molecular diversity, by AFLP markers, of six Spodoptera frugiperda populations collected in maize crops in different geographical regions of Brazil. DNA was extracted from fourth‑instar larvae, and AFLP reactions were performed with seven oligonucleotide primer combinations. From the six studied S. frugiperda populations, a major group was identified, formed by three more genetically‑related populations. The evaluated S. frugiperda populations show high genetic variability, with a maximum of 58% similarity

Isolamento e identificação presuntiva de Staphylococcus coagulase positiva e coagulase negativa em queijos minas frescal artesanal comercializados em feiras livres de Ipatinga – MG / Isolation and presucific identification of positive coagulase and negative coagulase Staphylococcus in artisanal minas fresh cheesese marketed at fairs in Ipatinga - MG

Introdução: dentre os diferentes tipos de queijos existentes no Brasil, o Minas Frescal Artesanal destaca-se por ser um produto alimentício bastante consumido e frequentemente fabricado com higiene precária. Por apresentar alto teor de umidade e baixo teor de sal, o queijo Minas Frescal Artesanal é susceptível a contaminações microbianas resultantes, tanto do leite utilizado como matéria-prima, como de contaminações cruzadas na manipulação e no pós-processamento. Os microrganismos contaminantes podem causar deterioração do produto ou até doenças em quem o ingerir, como a intoxicação alimentar. Objetivos: o estudo objetiva verificar de forma presuntiva a existência de Staphylococcus coagulase positiva e negativa por meio do isolamento em uma amostragem de queijos Minas Frescal Artesanal comercializados em feiras livres do Município de Ipatinga, Minas Gerais. Método: foram coletadas amostras de 6 queijos Minas Frescal Artesanal de feiras livres de Ipatinga-MG, sendo cada um deles pertencentes aos seguintes locais: Canaã, Veneza 2, Bom Jardim, Bom Retiro, Ipatingão e Cariru. A partir destas amostras foi isolado o microrganismo Staphylococcus coagulase positiva e negativa por meio de cultura e identificação da bactéria pelo método de Gram e das provas de catalase e coagulase. Resultados: foi constatado que 100% das amostras de queijo Minas Frescal Artesanal apresentaram contaminação em relação à contagem e análise presuntiva de Staphylococcus sp. Conclusão: os produtos analisados obtiveram valores de contaminação por Staphylococcus sp. acima do permitido pela legislação vigente, demonstrando uma precariedade nas boas práticas de fabricação. Dessa forma, entende-se que a fiscalização pelos órgãos competentes precisa ser mais eficaz e rigorosa nas feiras livres do município de Ipatinga.

In-hospital mortality and severe outcomes after hospital discharge due to COVID-19: A prospective multicenter study from Brazil.

BackgroundWe evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort.MethodsThis prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed.Findings1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs<40 years; age=60-69 years-aHR=1.89 (95%CI,1.08-3.32); age=70-79 years-aHR=2.52 (95%CI,1.42-4.45); age≥80-aHR=2.90 (95%CI 1.54-5.47)]; noninvasive or mechanical ventilation at admission [vs facial-mask or none; aHR=1.69 (95%CI 1.30-2.19)]; SAPS-III score≥57 [vs<57; aHR=1.47 (95%CI 1.13-1.92)] and SOFA score≥10 [vs <10; aHR=1.51 (95%CI 1.08-2.10)] were independently associated with in-hospital mortality. A total of 65 individuals [6.7% (95%CI 5.3-8.4)] had a rehospitalization or death [rate=323 (95%CI 250-417) per 1000 person-years] in a median time of 52 (range 1-280) days post-hospital discharge. Age ≥ 60 years [vs <60, aHR=2.13 (95%CI 1.15-3.94)] and SAPS-III ≥57 at admission [vs <57, aHR=2.37 (95%CI 1.22-4.59)] were independently associated with rehospitalization or death after hospital discharge.InterpretationHigh in-hospital mortality rates due to COVID-19 were observed and elderly people remained at high risk of rehospitalization and death after hospital discharge.FundingFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa INOVA-FIOCRUZ