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Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Brazilian Journal of Biology is the property of Instituto Internacional de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Classical models of gene amplification envision chromosomally localized focal amplicons encompassing the immediate contiguous chromosomal regions flanking the driver gene. We present evidence that this is not the case for the HER2/neu amplicon in human breast cancer. Using a large panel of HER-2/neu positive cell lines, we observed that the HER- 2/neu amplicon is made up of DNA segments mapping at different positions along chromosome 17. Sub-regions were subsequently re-amplified with the creation of condensed array of shorter amplicons. In addition, we show involvement of other chromosomes. The massive inter and intra-chromosomal reshuffling associated with amplified HER-2/neu containing sequences not only shed new light on the mechanism of gene amplification in human cancer but also have significant clinical implications for developing new targeted therapies and for combating drug resistance in this important subtype of breast cancer. [ABSTRACT FROM AUTHOR]

Objective: Currently available contraceptive methods do not meet the needs of all users. We sought to explore preferences of potential end-users regarding an on-demand, non-hormonal female contraceptive currently under development, using a web-based survey., Study Design: We recruited respondents for an exploratory survey via web link on Amazon Mechanical Turk (MTurk). Individuals were eligible if they were 18-44 years of age, identified as cis-gender female, were English-speaking, not pregnant, and had used barrier contraception previously. Respondents provided demographic characteristics and a basic reproductive history. We then provided a brief description of the potential contraceptive. Respondents were asked about their interest in the proposed contraceptive and preferences for method attributes., Results: A total of 500 respondents completed the survey. Three-quarters of respondents were <35 years of age and 48.2% were currently using a barrier contraceptive method. Three-fourths of respondents (73.8%) expressed interest in using the contraceptive under development. The majority wanted the method to be small (≤2 inches), rod-shaped, and low cost (<$5 per use). More than half (59.4%) said it was important to be able to use the method without partners' knowledge. The most reported potential concerns were vaginal irritation (51.6%) and lack of effectiveness (46.4%). Sixty percent of respondents were confident they could use the method correctly., Discussion: Available contraceptive methods lack attributes preferred by some users. Development of new contraceptives frequently does not involve end-user input early in the development process. Individuals in this sample displayed interest in the proposed contraceptive and expressed preferences that can inform the further development of this method., Competing Interests: TM serves on a data safety monitoring board for phase 4 safety studies of Bayer contraceptive products. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor KN declared a past co-authorship with the author(s) MAT., (© 2023 Madden, Cohen, Paul, Hurley, Thomas and Pauletti.)

Background: Incident reporting (IR) is one of the most used systems to gain knowledge of adverse events (AEs) and to identify sources of risk. During COVID-19 pandemic, several organizational changes have been implemented to respond adequately and effectively to the emergency; this required the suspension of most deferrable activities., Objective: The aim of this study is to investigate whether IR attitude of health workers has been reduced during the pandemic event., Method: A retrospective analysis was conducted at the Azienda Ospedale - Università di Padova (Italy), considering IR of years 2019 and 2020. To standardize the effects of the decrease in admissions, we considered the number of incidents per 1000 admissions., Results: Data shows that during the first (March-May 2020) and second waves (October-December 2020) of the COVID-19 pandemic there was a statistically significant reduction in the rate of IR for every 1000 admissions (P = 0.001-Wilcoxon test), especially for AEs and in COVID-19 units., Conclusion: This study shows a reduction in IR especially during the first and second pandemic waves of COVID-19 in year 2020. Education and training interventions could be fundamental to raise awareness of the importance of IR in health workers, as this could provide opportunities to understand what is impacting on safety in a particular healthcare context and enable continuous improvement., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The increased demand for pesticide-free foods has also increased the search for healthier and environmentally friendly alternatives in agriculture. Essential oils are known to possess natural antifungal properties, becoming a reliable alternative for commercial fungicides, especially for postharvest decay control. However, essential oils are volatile and photodegradable, which reduces their long-term activities. This work presents the development of a lemongrass essential oil-containing poly(lactic acid) nanocapsules. They have shown in vitro antifungal activity against Colletotrichum acutatum and Colletotrichum gloeosporioides with a MIC dosage of 0.1% (v/v) for both phytopathogens. In the in vivo assay with postharvest apples, the ones treated with encapsulated essential oil showed bitter rot lesions three times smaller than the ones treated with non-encapsulated essential oil, or in comparison to the apples in positive control. The methodology led to stable nanocapsules with spherical morphology, a mean diameter of 96.4 nm, and with an encapsulation efficiency of 99%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR) contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure delivery system complexed with the IGF-1 gene to treat the placenta. IGF-1 is a growth factor critical to achieving appropriate placental and fetal growth. Delivery of genes to a model of human trophoblast and mouse placenta was achieved using a diblock copolymer (pHPMA-b-pDMAEMA) complexed to hIGF-1 plasmid DNA under the control of trophoblast-specific promoters (Cyp19a or PLAC1). Transfection efficiency of pEGFP-C1-containing nanocarriers in BeWo cells and non-trophoblast cells was visually assessed via fluorescence microscopy. In vivo transfection and functionality was assessed by direct placental-injection into a mouse model of IUGR. Complexes formed using pHPMA-b-pDMAEMA and CYP19a-923 or PLAC1-modified plasmids induce trophoblast-selective transgene expression in vitro, and placental injection of PLAC1-hIGF-1 produces measurable RNA expression and alleviates IUGR in our mouse model, consequently representing innovative building blocks towards human placental gene therapies.

Novel aptamer-functionalized polyethylene glycol-polylactic acid (PEG-PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer's disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients.

The treatment of dementias, which are currently incurable pathologies, requires an approach to care that involves both the patients and their families. The effect of alternative interventions, besides the pharmacological approach, therefore warrants evaluation. In this paper, we describe one such intervention, which was provided by our home care team for Alzheimer's Disease. Patients were granted a three-month period of home care assistance, which included physical and cognitive rehabilitation as well as interventions on the home environment and the family, such as psychological support for the main caregivers. The assistance was provided in thrice-weekly sessions, each lasting six hours. Twenty-two patients (age 78.4±6.5 yrs), all of whom had received a diagnosis of probable AD, were enrolled. There was a statistically significant improvement in the NPI score (p = 0.004), Barthel index (p = 0.01), Tinetti's scale (p = 0.013) and CBI score (p = 0.016) at the end of the 3-month treatment period. The patients' caregivers also reported a significant improvement in the physical and social burden at the CBI at the end of the period of home care assistance (p = 0.026 and p = 0.006). In a further evaluation performed 3 months after the end of the treatment period, the beneficial effect previously observed in both patients and caregivers was no longer present.

Purpose: Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major target of anthracyclines. This study was designed to evaluate whether TOP2A gene alterations may predict incremental responsiveness to anthracyclines in some breast cancers., Methods: A total of 4,943 breast cancers were analyzed for alterations in TOP2A and HER2. Primary tumor tissues from patients with metastatic breast cancer treated in a trial of chemotherapy plus/minus trastuzumab were studied for amplification/deletion of TOP2A and HER2 as a test set followed by evaluation of malignancies from two separate, large trials for changes in these same genes as a validation set. Association between these alterations and clinical outcomes was determined., Results: Test set cases containing HER2 amplification treated with doxorubicin and cyclophosphamide (AC) plus trastuzumab, demonstrated longer progression-free survival compared to those treated with AC alone (P = .0002). However, patients treated with AC alone whose tumors contain HER2/TOP2A coamplification experienced a similar improvement in survival (P = .004). Conversely, for patients treated with paclitaxel, HER2/TOP2A coamplification was not associated with improved outcomes. These observations were confirmed in a larger validation set, where HER2/TOP2A coamplification was again associated with longer survival when only anthracycline-containing chemotherapy was used for treatment compared with outcome in HER2-positive cancers lacking TOP2A coamplification., Conclusion: In a study involving nearly 5,000 breast malignancies, both test set and validation set demonstrate that TOP2A coamplification, not HER2 amplification, is the clinically useful predictive marker of an incremental response to anthracycline-based chemotherapy. Absence of HER2/TOP2A coamplification may indicate a more restricted efficacy advantage for breast cancers than previously thought.

Purpose: About 65% to 70% of melanomas harbor a mutation in v-raf murine sarcoma viral oncogene homolog B1 (BRAF) that causes the steady-state activation of extracellular signal-regulated kinase (ERK). We sought to investigate the efficacy of PLX4032 (BRAF inhibitor) to identify patterns/predictors of response/resistance and to study the effects of BRAF in melanoma., Experimental Design: Well-characterized melanoma cell lines, including several with acquired drug resistance, were exposed to PLX4032. Growth inhibition, phosphosignaling, cell cycle, apoptosis, and gene expression analyses were performed before and after exposure to drug., Results: Using a growth-adjusted inhibitory concentration of 50% cutoff of 1 microM, 13 of 35 cell lines were sensitive to PLX4032, 16 resistant, and 6 intermediate (37%, 46%, and 17% respectively). PLX4032 caused growth inhibition, G(0)/G(1) arrest, and restored apoptosis in the sensitive cell lines. A BRAF mutation predicted for but did not guarantee a response, whereas a neuroblastoma RAS viral oncogene homolog mutation or wild-type BRAF conferred resistance. Cells with concurrent BRAF mutations and melanocortin 1 receptor germ line variants and/or a more differentiated melanocyte genotype had a preferential response. Acquired PLX4032 resistance reestablishes ERK signaling, promotes a nonmelanocytic genotype, and is associated with an increase in the gene expression of certain metallothioneins and mediators of angiogenesis., Conclusions: PLX4032 has robust activity in BRAF mutated melanoma. The preclinical use of this molecule identifies criteria for its proper clinical application, describes patterns of and reasons for response/resistance, and affords insight into the role of a BRAF mutation in melanoma.

In breast cancer, recent studies suggest that the value of HER2 for predicting response to anthracycline-based chemotherapy may be more likely related to the concomitant amplification of the TOP2A gene. Here, we study the association between HER2 or TOP2A status and response to anthracycline-based preoperative chemotherapy and explore the interaction between HER2 or TOP2A status and intense dose-dense (IDD) chemotherapy. HER2 and TOP2A gene alterations were quantified by fluorescence in situ hybridization in primary tumor core biopsies from 373 high-risk primary breast cancer patients (tumors >/=3 cm or inflammatory) that received an IDD or conventionally scheduled anthracycline-based preoperative chemotherapy. HER2 was amplified in 94/350 tumors (27%) of which 40/94 (46%) demonstrated TOP2A amplification, and 17/94 (18%) TOP2A deletions. TOP2A gene alterations were not found in HER2 non-amplified cases. HER2 amplification was associated with a significantly higher pathologic complete response (pCR) rate only when TOP2A was co-amplified (30% vs. 11%, P = 0.002), but not when deleted (13% vs. 11%, P = 0.755), or normal (14% vs. 11%, P = 0.578) compared to HER2 non-amplified tumors. In multivariate analysis, TOP2A amplification (odds ratio [OR] 3.04, P = 0.021), but not HER2 amplification (OR 1.74, P = 0.170) was associated with a significantly higher pCR rate. No interaction was observed between HER2 or TOP2A status and IDD chemotherapy. TOP2A gene amplification may define a subset of HER2-amplified breast cancers that are responsible for the markedly improved chemosensitivity seen in HER2-positive breast cancer. However, added benefit of IDD chemotherapy itself was not associated with HER2 or TOP2A status.

Purpose: To evaluate the efficacy and safety of docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2 (HER2) -positive, locally advanced breast cancer (LABC)., Patients and Methods: Forty-eight patients with immunohistochemistry-confirmed HER2-positive LABC or inflammatory breast cancer received 12 weeks of docetaxel, cisplatin, and trastuzumab with filgrastim, followed by surgery, adjuvant doxorubicin and cyclophosphamide, and locoregional radiotherapy with or without tamoxifen. The primary end point was pathologic complete response (pCR) in breast., Results: Baseline mean tumor size was 9.2 cm (range, 4 to 32 cm). pCR occurred in breast in 11 patients (23%; 95% CI, 12% to 37%) and breast and axilla in eight patients (17%; 95% CI, 8% to 30%). pCR rates in breast (HER2 positive, seven of 30 patients, 23% v HER2 negative, four of 18 patients, 22%; P > .05) and breast and axilla (four of 30 patients, 13% v four of 18 patients, 22%, respectively; P > .05) were similar regardless of HER2 status by fluorescence in situ hybridization (FISH). At a median follow-up time of 43 months, 4-year progression-free survival (PFS) rate was 81% (95% CI, 64% to 90%); overall survival (OS) rate was 86% (95% CI, 71% to 94%). In patients with pCR in breast and axilla, PFS and OS rates were 100% (95% CI, inestimable). In patients without pCR, PFS rate was 76% (95% CI, 57% to 88%; P = .15, log-rank test), and OS rate was 83% (95% CI, 66% to 92%; P = .21). Survival rates were similar regardless of FISH status. There were only two grade 4 adverse events., Conclusion: Twelve weeks of docetaxel, cisplatin, and trastuzumab is clinically active and leads to excellent survival in patients with large, HER2-positive tumors.

Background: HER-2/neu overexpression appears to be associated with improved response to anthracycline-based chemotherapy, but its association with response to taxane-based chemotherapy is unclear. In this retrospective subset analysis of patients with metastatic breast cancer enrolled in a randomized treatment trial, we investigated the response of patients with known HER-2/neu status to treatment with taxane-based epirubicin-paclitaxel (ET) chemotherapy compared with treatment with epirubicin-cyclophosphamide (EC) chemotherapy., Methods: HER-2/neu status (positive [i.e., HER-2/neu amplification] or negative [i.e., no HER-2/neu amplification]) of archival specimens of primary tumors from 297 patients with metastatic breast cancer was determined by use of fluorescence in situ hybridization. Associations between HER-2/neu status and the efficacy of randomly assigned chemotherapy (ET versus EC) were investigated. All statistical tests were two-sided., Results: Patients with HER-2/neu-positive tumors had a statistically significantly greater objective response rate than patients with HER-2/neu-negative tumors to treatment with ET (76% versus 50%, respectively; P =.005) but not to treatment with EC (46% versus 33%; P =.130). The objective response rate associated with ET was greater than that associated with EC for both HER-2/neu-positive tumors (76% versus 46%; P =.004) and HER-2/neu-negative tumors (50% versus 33%; P =.002). However, the improvement in the objective response rate associated with ET, compared with that associated with EC, was greater for patients with HER-2/neu-positive tumors (adjusted odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.48 to 8.92; P=.005) than for patients with HER-2/neu-negative tumors (adjusted OR = 1.92, 95% CI = 1.01 to 3.64; P=.046). Among patients with HER-2/neu-positive tumors, those who received ET had better progression-free survival and overall survival than those who received EC (for progression-free survival, adjusted relative risk [RR] = 0.65, 95% CI = 0.42 to 1.02; P=.062; for overall survival, adjusted RR = 0.60, 95% CI = 0.36 to 1.02; P=.059). However, among patients with HER-2/neu-negative tumors, those who received ET and those who received EC had similar progression-free survival and overall survival., Conclusions: HER-2/neu amplification does not adversely influence response to first-line chemotherapy with either ET or EC. Furthermore, a taxane-containing regimen such as ET may provide a preferential benefit to patients with HER-2/neu-positive tumors.