Comparison of promestriene with vaginal fractional CO2 laser and radiofrequency treatments of genitourinary syndrome of menopause.

OBJECTIVE: To compare the effects of fractional CO2 laser and microablative fractional radiofrequency treatment with promestriene topical estrogen on sexual function and genitourinary syndrome of menopause symptoms. METHODS: This was a prospective randomized open-label clinical trial conducted with 62 postmenopausal women assigned to three intervention groups: a) topical promestriene for 90 days (n = 17); b) fractional CO2 laser treatment (n = 24); and c) microablative fractional radiofrequency treatment (n = 21). Each of the latter two groups underwent three treatment sessions at 4-week intervals. At baseline and at the end of the study, all participants had a gynecological examination that included vaginal pH measurement, and the completion of the Vaginal Symptom Score, the Vaginal Health Index, and the Female Sexual Function Index. For the energy treatment groups, adverse effects were evaluated after each session. Group homogeneity was assessed at baseline, and results were evaluated over time (from baseline to the end of treatment) and between groups over time. RESULTS: All baseline parameters were similar among studied groups. At the end of the study, all 3 treatments had produced similar effects: a reduction of vaginal pH, and an improvement of vulvovaginal symptoms (Vaginal Symptom Score and Vaginal Health Index scores) as well as sexual function (higher total Female Sexual Function Index scores, and in the desire, arousal, lubrication and pain domain scores), with no differences observed between groups. Side-effects were slight for both energy treatment groups, mainly represented by vaginal discharge. CONCLUSION: The present study suggests that the two energy treatments were efficient along with promestriene at improving postmenopausal genitourinary and sexuality symptoms. Clinical trial identification numberNCT04717245.

Functional neuroimaging and behavioral correlates of multisite tDCS as an add-on to language training in a person with post-stroke non-fluent aphasia: a year-long case study.

Mary, who experienced non-fluent aphasia as a result of an ischemic stroke, received 10 years of personalized language training (LT), resulting in transient enhancements in speech and comprehension. To enhance these effects, multisite transcranial Direct Current Stimulation (tDCS) was added to her LT regimen for 15 sessions. Assessment using the Reliable Change Index showed that this combination improved her left inferior frontal connectivity and speech production for two months and significantly improved comprehension after one month. The results indicate that using multisite transcranial direct current stimulation (tDCS) can improve the effectiveness of language therapy (LT) for individuals with non-fluent aphasia.

Development, Survival and Reproduction of Nezara viridula (Hemiptera: Pentatomidae) in Sesame Cultivars and Implications for the Management.

Sesame, an oilseed plant with multiple applications, is susceptible to infestations by the stink bug Nezara viridula (Linnaeus, 1758) (Hemiptera: Pentatomidae). This pest suctions the seeds of this plant and injects toxins into them. Possible sources of resistance on sesame cultivars are important to manage this bug. The objective of this study was to evaluate the biological aspects of N. viridula fed on three sesame cultivars aiming to select possible resistance sources for integrated pest management (IPM) programs of this stinkbug. The experimental design used randomized blocks with three treatments and four replications, each with newly emerged N. viridula nymphs fed with sesame capsules of the cultivars BRS Anahí (T1), BRS Morena (T2) and BRS Seda (T3). Two to three green sesame capsules were supplied every two days per group of ten N. viridula nymphs as one replication until the beginning of the adult stage. Adults of this stinkbug were fed in the same manner as its nymphs but with mature sesame capsules until the end of the observations. Survival during each of the five instars and of the nymph stage of N. viridula with green sesame capsules was similar between cultivars, but the duration of the nymph stage was shorter with green capsules of the BRS Morena than with those of the BRS Anahí. The oviposition period, number of egg masses and eggs per female, and the percentage of nymphs hatched were higher with mature capsules of the sesame cultivar BRS Anahí and lower with the others. Nymphs did not hatch from eggs deposited by females fed mature seed capsules of the sesame cultivar BRS Morena, which may indicate a source of resistance against this stinkbug in this cultivar. The worldwide importance of N. viridula to sesame cultivation makes these results useful for breeding programs of this plant aiming to develop genotypes resistant to this bug. In addition, the BRS Morena is a cultivar already commercially available and can be recommended in places where there is a history of incidence of N. viridula, aiming to manage the populations of this pest.

The first confirmed outbreak of chikungunya reported in Timor-Leste, 2024.

Abstract: Timor-Leste is a mountainous, half-island nation with a population of 1.3 million, which shares a land border with Indonesia and is 550 km from Darwin, Australia. Since independence in 2002, Timor-Leste has achieved significant development; however, high levels of poverty remain. Chikungunya virus (CHIKV) is endemic in over 100 countries in Africa, Asia, Europe and in the Americas. It is transmitted by the bite of infected Aedes aegypti or Ae. albopictus mosquitoes, which are present in Timor-Leste and which contribute to annual rainy-season dengue virus (DENV) outbreaks. Symptomatic people typically suffer from acute onset of fever, usually accompanied by severe arthritis or arthralgia. Joint pain can be debilitating for several days, and may sometimes last for weeks, months or years. Unlike DENV infection which has significant mortality, most people recover completely. Between 2002 and 2023, there were 26 cases of CHIKV notified in Australia who acquired their infection in Timor-Leste; however, laboratory testing capability for CHIKV in Timor-Leste only became available in 2021 using polymerase chain reaction (PCR). The first locally diagnosed case was notified in November 2023. In January 2024, an outbreak of CHIKV was recognised in Timor-Leste for the first time, with 195 outbreak cases reported during 1-31 January 2024; all were PCR positive. There were no cases hospitalised, and no deaths. The median age of cases was 17 years (range 1-76 years); 51% were males. Cases were reported across the country; most (88/195) were from Dili, although the highest incidence was seen in the neighbouring municipality of Ermera (monthly incidence rate of 58.8 cases per 100,000 population). This first reported outbreak of CHIKV in Timor-Leste highlights the need for improved mosquito-borne illness control and response strategies, including minimising breeding sites and promoting early presentation for treatment and differential diagnosis from DENV, and consideration of the deployment of Wolbachia-infected mosquitoes, particularly as they have shown to reduce the transmission of CHIKV, DENV and Zika virus, all of which pose threats in Timor-Leste.

Pubic Osteomyelitis After Laparoscopic Simple Prostatectomy: Pubic Bone Resection With Partial Cystectomy.

Osteomyelitis of the pubic symphysis presents a diagnostic challenge, characterized by symptoms of pubic pain and discomfort radiating to the groin, thigh, or hip. Post-prostate surgery occurrences are rare, with a propensity for cancer-related procedures. Conservative antibiotic therapy may prove insufficient, necessitating surgical intervention. This article details a unique case involving Pseudomonas aeruginosa infection, the second most prevalent pathogen. Despite the rarity of the diagnosis, particularly after a benign surgical procedure, timely intervention was hindered, leading to a delayed management course. The case involves a 69-year-old male with a history of benign prostatic hyperplasia who underwent laparoscopic simple prostatectomy. Post surgery, he developed recurrent urinary infection-related symptoms, leading to hospitalization. Diagnostic tools such as CT scans, MRI, and F-18-FDG-PET/CT scan played crucial roles in identifying the inflammatory process. Subsequent surgical debridement, pubic bone resection, and partial cystectomy, followed by an eight-week antibiotic course, led to a favorable recovery. Discussion emphasizes the rarity of pubic symphysis osteomyelitis, particularly after benign surgery, underscoring the importance of imaging and timely intervention. The presented case adds to the limited literature on post-prostatectomy osteomyelitis, emphasizing the need for heightened clinical awareness and consideration of rare complications even in routine surgical scenarios.

Anthropometric, Metabolic, and Endocrine Parameters as Predictors of Estimated Average Glucose and Other Biomarkers of Dysglycemia in Women with Different Phenotypes of Polycystic Ovary Syndrome.

The aim of the study was to evaluate the efficacy of anthropometric, metabolic, and endocrine abnormalities as predictors of estimated average glucose and other biomarkers of dysglycemia in women with different phenotypes of polycystic ovary syndrome (PCOS). This cross-sectional study included 648 women with PCOS and 330 controls. A single protocol of investigation was applied for all subjects. PCOS women were divided by phenotypes according to the Rotterdam criteria. Biomarkers of dysglycemia were considered dependent variables and anthropometric, lipid, and hormone alterations as independent variables using univariate and multivariate logistic regressions. Univariate logistic regression analysis, controlled for age and BMI, showed that many biomarkers of dysglycemia could be predicted by anthropometric, lipid, and endocrine variables. Multivariate logistic models showed that in non-PCOS women estimated average glucose (eAG) was predicted by lower TSH levels (OR=0.39; p=0.045); fasting glucose was predicted by increased T (OR=2.3). For PCOS, phenotype A, eAG was predicted by decreased HDL-C (OR=0.17, p=0.023) and high levels of free estradiol (OR=7.1, p<0.001). Otherwise, in PCOS, phenotype D, eAG was predicted by higher levels of HDL-C. The current study demonstrated that eAG was poorly predicted by anthropometric, lipid, and hormone parameters. Nevertheless, without adding significant benefits, it was comparable with other established markers of dysglycemia in women with different PCOS phenotypes.

Genomic and proteomic characterization of vB_SauM-UFV_DC4, a novel Staphylococcus jumbo phage.

Staphylococcus aureus is one of the most relevant mastitis pathogens in dairy cattle, and the acquisition of antimicrobial resistance genes presents a significant health issue in both veterinary and human fields. Among the different strategies to tackle S. aureus infection in livestock, bacteriophages have been thoroughly investigated in the last decades; however, few specimens of the so-called jumbo phages capable of infecting S. aureus have been described. Herein, we report the biological, genomic, and structural proteomic features of the jumbo phage vB_SauM-UFV_DC4 (DC4). DC4 exhibited a remarkable killing activity against S. aureus isolated from the veterinary environment and stability at alkaline conditions (pH 4 to 12). The complete genome of DC4 is 263,185 bp (GC content: 25%), encodes 263 predicted CDSs (80% without an assigned function), 1 tRNA (Phe-tRNA), multisubunit RNA polymerase, and an RNA-dependent DNA polymerase. Moreover, comparative analysis revealed that DC4 can be considered a new viral species belonging to a new genus DC4 and showed a similar set of lytic proteins and depolymerase activity with closely related jumbo phages. The characterization of a new S. aureus jumbo phage increases our understanding of the diversity of this group and provides insights into the biotechnological potential of these viruses. KEY POINTS: • vB_SauM-UFV_DC4 is a new viral species belonging to a new genus within the class Caudoviricetes. • vB_SauM-UFV_DC4 carries a set of RNA polymerase subunits and an RNA-directed DNA polymerase. • vB_SauM-UFV_DC4 and closely related jumbo phages showed a similar set of lytic proteins.

Isolation and Characterization of the Acadevirus Members BigMira and MidiMira Infecting a Highly Pathogenic Proteus mirabilis Strain.

Proteus mirabilis is an opportunistic pathogen and is responsible for more than 40% of all cases of catheter-associated urinary tract infections (CAUTIs). Healthcare-associated infections have been aggravated by the constant emergence of antibiotic-resistant bacterial strains. Because of this, the use of phages to combat bacterial infections gained renewed interest. In this study, we describe the biological and genomic features of two P. mirabilis phages, named BigMira and MidiMira. These phages belong to the Acadevirus genus (family Autographiviridae). BigMira and MidiMira are highly similar, differing only in four missense mutations in their phage tail fiber. These mutations are sufficient to impact the phages' depolymerase activity. Subsequently, the comparative genomic analysis of ten clinical P. mirabilis strains revealed differences in their antibiotic resistance profiles and lipopolysaccharide locus, with the latter potentially explaining the host range data of the phages. The massive presence of antimicrobial resistance genes, especially in the phages' isolation strain P. mirabilis MCS, highlights the challenges in treating infections caused by multidrug-resistant bacteria. The findings reinforce BigMira and MidiMira phages as candidates for phage therapy purposes.

Extraperitoneal robot-assisted radical prostatectomy with the Hugo™ RAS system: initial experience of a tertiary center with a high background in extraperitoneal laparoscopy surgery.

PURPOSE: The Hugo™ RAS system is a novel robotic platform with innovative features. However, there are currently no available data on extraperitoneal robot-assisted radical prostatectomy (RARP) performed using this system. The objective of this study is to describe the surgical setup and assess the safety and feasibility of the extraperitoneal approach in robotic radical prostatectomy with the Hugo™ RAS system. METHODS: Sixteen consecutive patients diagnosed with localized prostate cancer underwent extraperitoneal RARP ± lymph node dissection at our institution, between March and May 2023. All RARP procedures were performed extraperitoneal with a modular four-arm configuration. The focus was to describe the operative room setup, trocar placement, tilt and docking angles and evaluate the safety and feasibility of this approach with this robotic platform. Secondary outcomes recorded included, total operative time, console time, estimated bleeding, intra- and postoperative complications, and length of stay after surgery. A descriptive analysis was conducted. RESULTS: We report on the first sixteen cases of extraperitoneal robot-assisted radical prostatectomy performed with the new Hugo™ RAS system. All procedures were completed, without the need for conversion or placement of additional ports. No intraoperative complications or major technical failures that would prevent the completion of surgery were recorded. The median operative time was 211 min (IQR 180-277), and the median console time was 152 min (IQR 119-196). The mean docking time was 4.6 min (IQR 4.1-5.2). The median estimated blood loss and the median time to remove the vesical catheter were 200 mL (IQR 150-400) and 8 days (IQR 7-8), respectively. The median length of stay was 2 days (IQR 2-2). Only one minor complication was registered in the first 30 days. CONCLUSION: This study provides evidence of the safety and feasibility of the extraperitoneal approach in RARP with the Hugo™ RAS system. The description of the surgical setup in terms of trocar placement, arm-cart disposition, tilt and docking angles offers valuable information for surgeons interested in adopting this surgical approach with the Hugo™ RAS platform.

Characteristics and prognosis of young breast cancer patients treated in a public comprehensive cancer centre in Brazil: A retrospective cohort study.

BACKGROUND: The incidence of breast cancer among women under 41 years old varies worldwide, with higher rates observed in developing countries. These young women often face later-stage diagnoses. In this study, we examine a cohort of young women who were treated for breast cancer in São Paulo, Brazil. METHODS: We conducted a retrospective cohort study involving women under 41 years old. Our objective was to describe patient and treatment characteristics, with the main outcomes being overall and disease-free survival. Our analysis explored the associations between age of menarche, history of breastfeeding, use of hormonal contraceptives, and age at diagnosis. RESULTS: Our study included 493 patients with a mean follow-up of 62.8 months. The mean age of the patients was 34.6 (SD=4.19). Of the patients, 68% presented with locally advanced disease, and 19.27% were metastatic at the time of diagnosis. We observed significant associations between age of menarche and age at diagnosis (p = 0.0096), as well as age at diagnosis and breastfeeding (p = 0.0232). Chemotherapy was administered to 92.91% of the patients as part of their treatment, while 27.2% were eligible for breast-conserving surgery. During the follow-up period, 153 patients died, with disease progression being the cause of death in 73.2% of cases. The median survival time for the entire cohort is still under review, while the metastatic patients at diagnosis had a median survival time of 28.64 months (95%CI 20.21-40.89). CONCLUSION: Our findings highlight significant associations between late-stage diagnosis and overall and disease-free survival in this patient age group. Given that the majority of patients present with locally advanced breast cancer, it is crucial to implement strategies that promote early-stage diagnosis and improve survival rates.

Measurement of extracapsular extension in sentinel lymph node as a possible predictor of residual axillary disease in breast cancer.

BACKGROUND: The presence of Extracapsular Extension (ECE) in the Sentinel Lymph Node Biopsy (SLNB) is still a doubt in the literature. Some studies suggest that the presence of ECE may be related to a greater number of positive axillary lymph nodes which could impact Disease Free Survival (DFS) and Overall Survival (OS). This study searches for the clinical significance of the ECE. METHODS: Retrospective cohort comparing the presence or absence of ECE in T1-2 invasive breast cancer with positive SLNB. All cases treated surgically at the Cancer Institute of the State of São Paulo (ICESP) between 2009 and 2013 were analyzed. All patients with axillary disease in SLNB underwent AD. OUTCOMES: Identify the association between the presence and length of ECE and additional axillary positive lymph nodes, OS and DFS between both groups. RESULTS: 128 patients with positive SLNB were included, and 65 had ECE. The mean metastasis size of 0.62 (SD = 0.59) mm at SLNB was related to the presence of ECE (p < 0.008). The presence of ECE was related to a higher mean of positive sentinel lymph nodes, 3.9 (± 4.8) vs. 2.0 (± 2.1), p = 0.001. The median length of follow-up was 115 months. The OS and DFS rates had no differences between the groups. CONCLUSION: The presence of ECE was associated with additional positive axillary lymph nodes in this study. Therefore, the OS and DFS were similar in both groups after 10 years of follow-up. It is necessary for additional studies to define the importance of AD when SLNB with ECE.

The Chemical Space of Marine Antibacterials: Diphenyl Ethers, Benzophenones, Xanthones, and Anthraquinones.

The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse family of compounds that have been isolated from different marine microorganisms. Within the different polyketides, benzophenones, diphenyl ethers, anthraquinones, and xanthones have shown promising antibacterial activity. In this work, a dataset of 246 marine polyketides has been identified. In order to characterize the chemical space occupied by these marine polyketides, molecular descriptors and fingerprints were calculated. Molecular descriptors were analyzed according to the scaffold, and principal component analysis was performed to identify the relationships among the different descriptors. Generally, the identified marine polyketides are unsaturated, water-insoluble compounds. Among the different polyketides, diphenyl ethers tend to be more lipophilic and non-polar than the remaining classes. Molecular fingerprints were used to group the polyketides according to their molecular similarity into clusters. A total of 76 clusters were obtained, with a loose threshold for the Butina clustering algorithm, highlighting the large structural diversity of the marine polyketides. The large structural diversity was also evidenced by the visualization trees map assembled using the tree map (TMAP) unsupervised machine-learning method. The available antibacterial activity data were examined in terms of bacterial strains, and the activity data were used to rank the compounds according to their antibacterial potential. This potential ranking was used to identify the most promising compounds (four compounds) which can inspire the development of new structural analogs with better potency and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.

Synthesis, characterization, antioxidant and antiparasitic activities new naphthyl-thiazole derivatives.

In this work, 13 thiosemicarbazones (1a - m) and 16 thiazoles (2a - p) were obtained, which were properly characterized by spectroscopic and spectrometric techniques. The pharmacokinetic properties obtained in silico revealed that the derivatives are in accordance with the parameters established by lipinski and veber, showing that such compounds have good bioavailability or permeability when administered orally. In assays of antioxidant activity, thiosemicarbazones showed moderate to high antioxidant potential when compared to thiazoles. In addition, they were able to interact with albumin and DNA. Screening assays to assess the toxicity of compounds to mammalian cells revealed that thiosemicarbazones were less toxic when compared to thiazoles. In relation to in vitro antiparasitic activity, thiosemicarbazones and thiazoles showed cytotoxic potential against the parasites Leishmania amazonensis and Trypanosoma cruzi. Among the compounds, 1b, 1j and 2l stood out, showing inhibition potential for the amastigote forms of the two parasites. As for the in vitro antimalarial activity, thiosemicarbazones did not inhibit Plasmodium falciparum growth. In contrast, thiazoles promoted growth inhibition. This study shows in a preliminary way that the synthesized compounds have antiparasitic potential in vitro.

Programmed cell death-1 and its ligands: Current knowledge and possibilities in immunotherapy.

Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.

Larger dlPFC and vmPFC grey matter volumes are associated with high adherence to the Mediterranean diet: A cross-sectional study in older adults.

Dietary self-control is associated with inter-individual differences in neuroanatomy. Yet, whether such inter-individual differences are also associated with healthier dietary patterns is yet to be determined. In this cross-sectional study, a total of 100 northern Portuguese older community-dwellers were assessed with regards to i) the adherence to a healthy dietary eating pattern - the Mediterranean diet (MedDiet), and ii) grey matter density (GMD) of brain regions associated with valuation and dietary self-regulation, the ventromedial (vmPFC) and dorsolateral prefrontal cortex (dlPFC), through voxel-based morphometry. Healthy food choices were ascertained through the Mediterranean Diet Adherence Screener (MEDAS) where higher scores indicated greater adherence to the MedDiet. Voxel-based morphometry showed that greater grey matter density in the dlPFC and vmPFC associated with a higher adherence to the MedDiet. These results replicate previous links between dietary decision-making measured under laboratory conditions and the neuroanatomy of the brain's valuation and self-control system. Importantly, they shed new light on the potential relevance of inter-individual differences in the neuroanatomy of these two brain regions for adhering to healthier dietary patterns in everyday life.

Vitamin D and in vitro fertilization: a systematic review.

PURPOSE: Vitamin D (VD) action on calcium is well known, but its other properties, particularly in the human reproductive system, are not completely understood. This review aims at assessing the relationship between serum VD levels and IVF results. METHODS: A systematic review was carried out using MEDLINE, EMBASE, LILACS, Google scholar, the CAPES journal portal, and the Cochrane Library, as well as the descriptors "vitamin D" and "fertilization in vitro." The review was conducted by two authors following the PRISMA recommendations between September 2021 and February 2022. RESULTS: Eighteen articles were selected. Five of them showed a positive correlation between serum VD levels and IVF results, 12 lacked any association, and 1 exhibited a negative correlation. The 3 studies that assessed VD in the follicular fluid found a positive correlation between the serum and follicular levels. Non-Hispanic White patients seemed to suffer the consequence of vitamin D deficiency more than Asian patients. In one study alone in the VD-deficient group, there was a larger number of natural killer (NK) cells, B cells, a greater proportion of helper T cells/cytotoxic T cells (Th/Tc), and an association with a smaller number of mature oocytes. CONCLUSION: The association between serum VD levels and the post-IVF pregnancy rate is uncertain. However, VD levels might be more relevant in the White than in the Asian ethnicity and in the number of aspiration follicles, and they could act in the immune system having an impact both on embryo implantation and on pregnancy.

Hormonal and Metabolic Factors Influence the Action of Progesterone on the Endometrium of Women with Polycystic Ovary Syndrome.

Hormonal and metabolic factors may influence endometrial quality and interfere with the action of progesterone. Therefore, the aim of our study was to address this issue. Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care centre. All subjects underwent endometrial biopsy (EB) in the follicular phase of the cycle prior to treatment. Thereafter, they were treated with micronized progesterone (400 mg/day × 10 days intravaginally) from days 14-28 of the next cycle. A second EB was performed between days 21-24 of the cycle (the second phase). The metabolic and hormonal serum levels were evaluated during the implantation window. EB samples were analysed using light microscopy for histomorphometric analysis. The endometrium of women with Polycystic Ovarian Syndrome (PCOS) in the second phase demonstrated a uniform surface epithelium with less leukocyte infiltration and an absence of apoptotic figures compared to the control group. (p < 0.021). The thickness of the surface epithelium in the second phase of the PCOS group correlated positively with free and bioavailable testosterone values. The number of stromal cells increases with increasing insulin levels. Our results suggest that histomorphometric abnormalities of the endometrium persist and are linked to androgen and insulin levels despite progesterone supplementation in PCOS.

Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery: randomized controlled trial (BREAST-MRI trial).

BACKGROUND: Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. METHODS: A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0-III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. RESULTS: 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR = 0.72; 95% CI 0.12-4.28; p = 0.7) and an OS of 95.3% in the MRI group versus 96.3% in the control group (HR = 1.37 95% CI 0.59-3.19; p = 0.8). Surgical management changed in 21 ipsilateral breasts in the MRI group; 21 (8.3%) had mastectomies versus one in the control group. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (RR = 1.002; 95% CI 0.57-1.75; p = 0.85). CONCLUSION: Preoperative MRI increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates.

Could be FOXO3a, miR-96-5p and miR-182-5p useful for Brazilian women with luminal A and triple negative breast cancers prognosis and target therapy?

FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs.

Nodes of the default mode network implicated in the quality of empathic responses: A clinical perspective of the empathic response

The ability to empathize with another person's inner experience is believed to be a central element of our social interactions. Previous research has focused on cognitive (e.g., theory of mind) and emotional (e.g., emotional contagion) empathy, and less on behavioral factors (i.e., the ability to respond empathically). Recent studies suggest that the Default Mode Network (DMN) mediates individual variability in distinct empathy-related behaviors. However, little is known about DMN activity during actual empathic responses, understood in this study as the ability to communicate our understanding of the others’ experience back to them. This study used an empathy response paradigm with 28 participants (22-37 years old) to analyze the relationship between the quality of empathic responses to 14 empathy-eliciting vignettes and patterns of attenuation in the DMN. Overall, the results suggest that high levels of empathic response, are associated with sustained activation of the DMN when compared with lower levels of empathy. Our results demonstrate that the DMN becomes increasingly involved in empathy-related behavior, as our level of commitment to the other's experience increases. This study represents a first attempt to understand the relation between the capacity for responding in a supportive way to others’ needs and the intra-individual variability of the pattern of the DMN attenuation. Here we underline the critical role that the DMN plays in high-level social cognitive processes and corroborate the DMN role in different psychiatric disorders associated with a lack of empathy. (AU)