BRCA2 promotes DNA-RNA hybrid resolution by DDX5 helicase at DNA breaks to facilitate their repair‡.

The BRCA2 tumor suppressor is a DNA double-strand break (DSB) repair factor essential for maintaining genome integrity. BRCA2-deficient cells spontaneously accumulate DNA-RNA hybrids, a known source of genome instability. However, the specific role of BRCA2 on these structures remains poorly understood. Here we identified the DEAD-box RNA helicase DDX5 as a BRCA2-interacting protein. DDX5 associates with DNA-RNA hybrids that form in the vicinity of DSBs, and this association is enhanced by BRCA2. Notably, BRCA2 stimulates the DNA-RNA hybrid-unwinding activity of DDX5 helicase. An impaired BRCA2-DDX5 interaction, as observed in cells expressing the breast cancer variant BRCA2-T207A, reduces the association of DDX5 with DNA-RNA hybrids, decreases the number of RPA foci, and alters the kinetics of appearance of RAD51 foci upon irradiation. Our findings are consistent with DNA-RNA hybrids constituting an impediment for the repair of DSBs by homologous recombination and reveal BRCA2 and DDX5 as active players in their removal.

Effect of Preoperative Home-Based Exercise Training on Quality of Life After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial.

BACKGROUND: Preoperative exercise training is recommended for improvement of clinical outcomes after lung cancer (LC) surgery. However, its effectiveness in preventing postoperative decline in quality of life (QoL) remains unknown. This study investigated the effect of preoperative home-based exercise training (PHET) on QoL after LC surgery. METHODS: Patients awaiting LC resection were randomized to PHET or a control group (CG). The PHET program combined aerobic and resistance exercise, with weekly telephone supervision. Primary outcome was QoL-assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) at baseline, before surgery, and 1 month after surgery. The secondary outcomes were hospital length of stay and physical performance. The main analysis included a factorial repeated-measures analysis of variance. Additionally, the proportion of patients experiencing clinical deterioration from baseline to post-surgery was assessed. RESULTS: The study included 41 patients (68.1 ± 9.3 years; 68.3% male) in the intention-to-treat analysis (20 PHET patients, 21 CG patients). A significant group × time interaction was observed for global QoL (p = 0.004). Between-group differences in global QoL were statistically and clinically significant before surgery (mean difference [MD], 13.5 points; 95% confidence interval [CI], 2.4-24.6; p = 0.019) and after surgery (MD, 12.4 points; 95% CI, 1.3-23.4; p = 0.029), favoring PHET. Clinical deterioration of global QoL was reported by 71.4% of the CG patients compared with 30 % of the PHET patients (p = 0.003). Between-group differences in favor of PHET were found in pain and appetite loss as well as in physical, emotional and role functions after surgery (p < 0.05). Compared with CG, PHET was superior in improving preoperative five-times sit-to-stand and postoperative exercise capacity (p < 0.05). No between-group differences in other secondary outcomes were observed. CONCLUSION: The study showed that PHET can effectively prevent the decline in QoL after LC surgery.

Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance.

Mph1 is a member of the conserved FANCM family of DNA motor proteins that play key roles in genome maintenance processes underlying Fanconi anemia, a cancer predisposition syndrome in humans. Here, we identify Mte1 as a novel interactor of the Mph1 helicase in Saccharomyces cerevisiae. In vitro, Mte1 (Mph1-associated telomere maintenance protein 1) binds directly to DNA with a preference for branched molecules such as D loops and fork structures. In addition, Mte1 stimulates the helicase and fork regression activities of Mph1 while inhibiting the ability of Mph1 to dissociate recombination intermediates. Deletion of MTE1 reduces crossover recombination and suppresses the sensitivity of mph1Δ mutant cells to replication stress. Mph1 and Mte1 interdependently colocalize at DNA damage-induced foci and dysfunctional telomeres, and MTE1 deletion results in elongated telomeres. Taken together, our data indicate that Mte1 plays a role in regulation of crossover recombination, response to replication stress, and telomere maintenance.

Unlocking the Potential of Citrus medica L.: Antioxidant Capacity and Phenolic Profile across Peel, Pulp, and Seeds.

Citrus medica L. is a traditional citrus fruit that is rich in bioactive compounds and has the potential to be used as a natural source of food additives. This study aims to evaluate the antioxidant capacity and characterize the phenolic compounds present in the peels (including flavedo and albedo), pulp, and seeds of citron. The results showed that, compared to the other parts, the pulp had a substantially higher Antioxidant Activity Coefficient (AAC) of 168.2. The albedo and the seeds had significantly lower AAC values, while the green and yellow flavedo showed noteworthy results. O-coumaric acid was the predominant phenolic acid in all of the citron fractions; it was found in the highest concentration in albedo (37.54 µg/g FW). Flavanones and flavanols were the primary flavonoids in the pulp, peel, and seeds, with total flavonoid concentration ranging from ~9 µg/g FW in seeds to 508 µg/g FW in the pulp. This research offers significant insights into the antioxidant properties of this ancient fruit, emphasizing its potential applications as a natural source of antioxidants to be used in different applications.

Effect of phage vB_EcoM_FJ1 on the reduction of ETEC O9:H9 infection in a neonatal pig cell line.

Enterotoxigenic Escherichia coli (ETEC) colonizes the intestine of young pigs causing severe diarrhoea and consequently bringing high production costs. The rise of antibiotic selective pressure together with ongoing limitations on their use, demands new strategies to tackle this pathology. The pertinence of using bacteriophages as an alternative is being explored, and in this work, the efficacy of phage vB_EcoM_FJ1 (FJ1) in reducing the load of ETEC EC43-Ph (serotype O9:H9 expressing the enterotoxin STa and two adhesins F5 and F41) was assessed. Foreseeing the oral application on piglets, FJ1 was encapsulated on calcium carbonate and alginate microparticles, thus preventing phage release under adverse conditions of the simulated gastric fluid (pH 3.0) and allowing phage availability in simulated intestinal fluid (pH 6.5). A single dose of encapsulated FJ1, provided to IPEC-1 cultured cells (from intestinal epithelium of piglets) previously infected by EC43, provided bacterial reductions of about 99.9% after 6 h. Although bacteriophage-insensitive mutants (BIMs) have emerged from treatment, the consequent fitness costs associated with this new phenotype were demonstrated, comparatively to the originating strain. The higher competence of the pig complement system to decrease BIMs' viability, the lower level of colonization of IPEC-1 cells observed with these mutants, and the increased survival rates and health index recorded in infected Galleria mellonella larvae supported this observation. Most of all, FJ1 established a proof-of-concept of the efficiency of phages to fight against ETEC in piglet intestinal cells.

How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP).

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.

Applications of Antioxidant Secondary Metabolites of Sargassum spp.

Sargassum is one of the largest and most diverse genus of brown seaweeds, comprising of around 400 taxonomically accepted species. Many species of this genus have long been a part of human culture with applications as food, feed, and remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of natural antioxidant compounds of great interest, including polyphenols, carotenoids, meroterpenoids, phytosterols, and several others. Such compounds provide a valuable contribution to innovation that can translate, for instance, into the development of new ingredients for preventing product deterioration, particularly in food products, cosmetics or biostimulants to boost crops production and tolerance to abiotic stress. This manuscript revises the chemical composition of Sargassum seaweeds, highlighting their antioxidant secondary metabolites, their mechanism of action, and multiple applications in fields, including agriculture, food, and health.

Off-label use of a vena caval filter in the SVC in an adolescent with upper deep vein thrombosis.

Vena caval filters remain as a useful tool in patients with deep vein thrombosis and contraindications to anticoagulation. Although they are rarely used in paediatric patients, they have been shown to be safe and effective when used in the inferior vena cava.In this case report, we describe the off-label use of a retrievable vena caval filter in the superior vena cava in an adolescent with acute lymphoblastic leukaemia with extensive thrombosis of the right upper neck veins as a means to reduce the risk of pulmonary embolism.

Genome-Scale Characterization of Mycobacterium abscessus Complex Isolates from Portugal.

The Mycobacterium abscessus complex (MABC) is an emerging, difficult to treat, multidrug-resistant nontuberculous mycobacteria responsible for a wide spectrum of infections and associated with an increasing number of cases worldwide. Dominant circulating clones (DCCs) of MABC have been genetically identified as groups of strains associated with higher prevalence, higher levels of antimicrobial resistance, and worse clinical outcomes. To date, little is known about the genomic characteristics of MABC species circulating in Portugal. Here, we examined the genetic diversity and antimicrobial resistance profiles of 30 MABC strains isolated between 2014 and 2022 in Portugal. The genetic diversity of circulating MABC strains was assessed through a gene-by-gene approach (wgMLST), allowing their subspecies differentiation and the classification of isolates into DCCs. Antimicrobial resistance profiles were defined using phenotypic, molecular, and genomic approaches. The majority of isolates were resistant to at least two antimicrobials, although a poor correlation between phenotype and genotype data was observed. Portuguese genomes were highly diverse, and data suggest the existence of MABC lineages with potential international circulation or cross-border transmission. This study highlights the genetic diversity and antimicrobial resistance profile of circulating MABC isolates in Portugal while representing the first step towards the implementation of a genomic-based surveillance system for MABC at the Portuguese NIH.

Decline in human T-cell lymphotropic virus seroprevalence in blood donors from Minas Gerais, Brazil over a 12-year period (2006-2017).

To investigate a 12-year historical series (2006-2017) of human T-cell lymphotropic virus (HTLV)-positive blood donations from Fundação Hemominas, Minas Gerais, Brazil, an observational retrospective study was performed to evaluate data of blood donor candidates who were screened for HTLV-1/2 by enzyme-linked immunosorbent assay or chemiluminescence assays and confirmed by Western blot. We analyzed 3 309 716 blood donations covering 2006-2017 that were extracted from the institutional database. In a total of 3 308 738 donations that have complete algorithm tests, the global frequency of HTLV-positive donations was 0.012%. The seroprevalence in first-time blood donors was 28.82/100 000 donors; 0.95/100 000 donations were HTLV-positive in repeat blood donors. The frequency of HTLV-seropositive females was significantly higher than males (odds ratio = 1.85, p < 0.001) in first-time donors. The median age of HTLV-positive first-time and repeat donors was similar (36 and 32 years, respectively). First-time donors ≥41 years had higher odds to be infected. There was a clear tendency of decline in the HTLV-positive donations in the period analyzed, going from 19.26/100 000 donations to 8.50/100 000 donations. The increase in the proportion of repeat donors over the period analyzed (from 23% in 2006 to 67% in 2017) must be the principal factor that contributed to this drop. Our results showed a continuous decline in the frequency of HTLV-positive donations from Minas Gerais, Brazil throughout 12 years and emphasize the importance of having a high rate of repeat donors in blood centers to reduce the residual risk of transfusion-transmitted infections.