This study aimed to identify and classify genetic variants in consensus moderate-to-high-risk predisposition genes associated with Hereditary Breast and Ovarian Cancer Syndrome (HBOC), in BRCA1/2-negative patients from Brazil.
The study comprised 126 index patients who met NCCN clinical criteria and tested negative for all coding exons and intronic flanking regions of BRCA1/2 genes. Multiplex PCR-based assays were designed to cover the complete coding regions and flanking splicing sites of six genes implicated in HBOC. Sequencing was performed on HiSeq2500 Genome Analyzer.
Overall, we identified 488 unique variants. We identified five patients (3.97%) that harbored pathogenic or likely pathogenic variants in four genes ATM (1), CHEK2 (2), PALB2 (1), and TP53 (1). One hundred and thirty variants were classified as variants of uncertain significance (VUS), 10 of which were predicted to disrupt mRNA splicing (seven non-coding variants and three coding variants), while other six missense VUS were classified as probably damaging by prediction algorithms.
A detailed mutational profile of non-BRCA genes is still being described in Brazil. In this study, we contributed to filling this gap, by providing important data on the diversity of genetic variants in a Brazilian high-risk patient cohort. ATM, CHEK2, PALB2 and TP53 are well established as HBOC predisposition genes, and the identification of deleterious variants in such actionable genes contributes to clinical management of probands and relatives.
A detailed mutational profile of non-BRCA genes is still being described in Brazil. In this study, we contributed to filling this gap, by providing important data on the diversity of genetic variants in a Brazilian high-risk patient cohort. ATM, CHEK2, PALB2 and TP53 are well established as HBOC predisposition genes, and the identification of deleterious variants in such actionable genes contributes to clinical management of probands and relatives.Microbial population of soils irrigated with industrial wastewater may contain certain exopolysaccharides (EPS) and indole-3-acetic acid (IAA) producing bacterial strains having the ability to tolerate heavy metals along with plant growth-promoting (PGP) traits. As cadmium is one of the most toxic heavy metals for soils, plants, animals, and human beings, the present study was planned to isolate and characterize EPS- and IAA-producing, Cd-tolerant bacterial strains having tolerance against heavy metals along with plant growth-promoting traits. A total of 30 rhizobacterial strains (FN1-FN30) were isolated from rhizosphere soil collected from fields around industrial areas and roadsides irrigated with industrial wastewater. Out of these, eight isolates with the combined ability of IAA production and EPS production were characterized for PGP traits. On the basis of multifarious PGP traits and the results of root colonization assay, three most efficient EPS- and IAA-producing, Cd-tolerant plant growth-promoting strains, i.e., FN13, FN14, and FN16, were selected for multiple metal (Cd, Pb, Ni, and Cu) tolerance test along with quantification of growth, and IAA and EPS production abilities under Cd stress. Increasing levels of Cd stress negatively affected the tested characteristics of these strains, but FN13 showed more stability in growth, IAA production (18.24 μg mL-1), and EPS production (148.99 μg mL-1) compared to other strains under Cd stress. check details The morphological and biochemical analysis confirmed FN13 as Gram-positive, rod-shaped bacteria with smooth colonies of yellow appearance. The strain FN13 has strong root colonization (3.36 × 106 CFU g-1) ability for mustard seedlings and can solubilize Zn and phosphate along with the production of HCN, ammonia, and siderophores. The 16S rRNA sequencing confirmed it as the Bacillus safensis strain FN13. It can be explored as potential phytostabilizing biofertilizer for heavy metal-contaminated soils.
HIV prevention interventions which support engagement in care and increased awareness of biomedical options, including pre-exposure prophylaxis (PrEP), are highly desired for disproportionately affected Black/African American, Hispanic/Latinx and gay, bisexual, and other men who have sex with men (GBMSM) populations in the United States (US). However, in almost 40years of HIV research, few interventions have been developed directly by and for these priority populations in domestic counties most at risk. We submit that interventions developed by early-career scientists who identify with and work directly with affected subgroups, and which include social and structural determinants of health, are vital as culturally tailored HIV prevention and care tools.
We reviewed and summarized interventions developed from 2007 to 2020 by historically underrepresented early-career HIV prevention scientists in a federally funded research mentoring program. We mapped these interventions to determine which were in jurisdicing streams should remain a priority as one of the tools for national HIV prevention.
To determine the test-retest reproducibility and observer variability of CMR-derived LA function, using (i) LA strain (LAS) and strain rate (LASR), and (ii) LA volumes (LAV) and emptying fraction (LAEF).
Sixty participants with and without cardiovascular disease (aortic stenosis (AS) (n = 16), type 2 diabetes (T2D) (n = 28), end-stage renal disease on haemodialysis (n = 10) and healthy volunteers (n = 6)) underwent two separate CMR scans 7-14 days apart. LAS and LASR, corresponding to LA reservoir, conduit and contractile booster-pump function, were assessed using Feature Tracking software (QStrain v2.0). LAEF was calculated using the biplane area length method (QMass v8.1). Both were assessed using 4- and 2-chamber long-axis standard steady-state free precession cine images, and average values were calculated. Intra- and inter-observer variabilities were assessed in 10 randomly selected participants.
The test-retest reproducibility was moderate to poor for all strain and strain rate parameters. Overallssment, with lower coefficient of variances and narrower limits of agreement on Bland-Altman plots. • Biplane LA volumetric measurement also has better intra- and inter-observer variability compared to strain assessment.
• LA strain and strain rate assessment using Feature Tracking on CMR has moderate to poor test-retest reproducibility across disease states. • The test-retest reproducibility for the biplane method of assessing LA function is better than strain assessment, with lower coefficient of variances and narrower limits of agreement on Bland-Altman plots. • Biplane LA volumetric measurement also has better intra- and inter-observer variability compared to strain assessment.check details
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