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In this mini-review, we discuss the role of NF-κB, a proinflammatory transcription factor, in the expression of genes involved in inflammation, proliferation, and apoptosis pathways, and link it with prognosis of various human cancers, particularly non-small cell lung cancer (NSCLC). We and others have shown that NF-κB activity can be impacted by post-translational S-glutathionylation through reversible formation of a mixed disulfide bond between its cysteine residues and glutathione (GSH). Clinical data analysis showed that high expression of NF-κB correlated with shorter overall survival (OS) in NSCLC patients, suggesting a tumor promotion function for NF-κB. Moreover, NF-κB expression was associated with tumor stage, lymph node metastasis, and 5-year OS in these patients. NF-κB was over-expressed in the cytoplasm of tumor tissue compared to adjacent normal tissues. S-glutathionylation of NF-κB caused negative regulation by interfering with DNA binding activities of NF-κB subunits. In response to oxidants, S-glutathionylation of NF-κB also correlated with enhanced lung inflammation. Thus, S-glutathionylation is an important contributor to NF-κB regulation and clinical results highlight the importance of NF-κB in NSCLC, where NF-κB levels are associated with unfavorable prognosis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Danyelle M. Townsend reports financial support was provided by Medical University of South Carolina. DMT and ADB serve as Editors for Biomedicine and Pharmacotherapy., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Liposomes composed of a rigid bilayer have high plasma stability; however, they can be challenged in efficacy due to complications in releasing the encapsulated drug as well as being internalized by the tumor cell. On the other hand, fusogenic liposomes may fuse with the plasmatic membrane and release encapsulated material directly into the cytoplasm. In a previous study, fusogenic liposomes composed of alpha-tocopheryl succinate (TS) and doxorubicin (DOX) were developed (pHSL-TS-DOX). These stabilized tumor growth and reduced toxicity compared to a commercial formulation. In the present study, we investigated whether cellular uptake or DOX accumulation in the tumor could justify the better performance of the pHSL-TS-DOX formulation. Release, deformability, and DOX plasmatic concentration studies were also carried out. pHSL-TS-DOX showed an adequate release profile and demonstrated characteristics of a deformable formulation. Data from apoptosis, cell cycle, and nuclear morphology studies have shown that the induction of cell death caused by pHSL-TS-DOX occurred more quickly. Higher DOX cellular uptake and tumor accumulation were observed when pHSL-TS-DOX was administered, demonstrating better drug delivery capacity. Therefore, better DOX uptake as well as tumor accumulation explain the great antitumor activity previously demonstrated for this formulation., Competing Interests: Declaration of Competing Interest The authors, above cited, declare that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The World Health Organizations declaration of the COVID-19 pandemic was a milestone for the scientific community. The high transmission rate and the huge number of deaths, along with the lack of knowledge about the virus and the evolution of the disease, stimulated a relentless search for diagnostic tests, treatments, and vaccines. The main challenges were the differential diagnosis of COVID-19 and the development of specific, rapid, and sensitive tests that could reach all people. RT-PCR remains the gold standard for diagnosing COVID-19. However, new methods, such as other molecular techniques and immunoassays emerged. Also, the need for accessible tests with quick results boosted the development of point of care tests (POCT) that are fast, and automated, with high precision and accuracy. This assay reduces the dependence on laboratory conditions and mass testing of the population, dispersing the pressure regarding screening and detection. This review summarizes the advances in the diagnostic field since the pandemic started, emphasizing various laboratory techniques for detecting COVID-19. We reviewed the main existing diagnostic methods, as well as POCT under development, starting with RT-PCR detection, but also exploring other nucleic acid techniques, such as digital PCR, loop-mediated isothermal amplification-based assay (RT-LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and next-generation sequencing (NGS), and immunoassay tests, and nanoparticle-based biosensors, developed as portable instruments for the rapid standard diagnosis of COVID-19., Competing Interests: Conflict of interest statement The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aim: Amphotericin B (AmB) is an antileishmanial drug with high toxicity; however, this drawback might overcome by decreasing the AmB self-aggregation state. This work aimed at evaluating the influence of cholesterol on the aggregation state of AmB loaded in a nanoemulsion (NE-AmB) for the treatment of cutaneous leishmaniasis. NE-AmB (1, 4 and 8 mg/kg/day) was administered intravenously to animals infected by Leishmania major every 2 days for a total of five injections. Results: Ultraviolet-visible spectroscopy and circular dichroism studies demonstrated that cholesterol reduced AmB aggregation state in NE. NE-AmB was stable after 180 days, and its hemolytic toxicity was lower than that observed for the conventional AmB. NE-AmB administered intravenously into animals infected by Leishmania major at 8 mg/kg was capable of stabilizing the lesion size and reducing the parasitic load. Conclusion: These findings support the NE potential as a stable nanocarrier for AmB in the treatment of cutaneous leishmaniasis.

Purpose: To assess the validity of a Written Clinical Reasoning Prompt (WCRP) to help nursing students' clinical reasoning (CR)., Method: This is a methodological study of translation and cross-cultural adaptation into Brazilian Portuguese of instruments that aim to promote CR improvement, composed of (1) WCRP; (2) two case studies; (3) a questionnaire about students' perceptions during decision-making in case studies; (4) a scoring rubric for correcting case studies. For translation and cross-cultural adaptation, stages 1-8 of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Consortium Network were adopted. Agreement values among experts >80% and content validity coefficient (CVC) > 0.8 were considered satisfactory. For the pretest, a randomized clinical trial was carried out with 24 nursing students (intervention group, n = 14, using the WCRP to solve case studies; control group, n = 10, without using the WCRP)., Findings: The WCRP was translated and adapted into Brazilian Portuguese, requiring minimal adjustments to obtain agreement among the judges above 80% and CVC above 0.80. Regarding face validation, an adequate agreement was obtained in the assessment by students. There was no difference in the accuracy of nursing diagnoses between the intervention and control groups in the pretest., Conclusion: The WCRP was translated and adapted into Brazilian Portuguese and had adequate face and content validity estimates; however, there was no association with improving nursing students' diagnostic accuracy., Implications for Nursing Practice: The translated and adapted versions of all instruments into Brazilian Portuguese had adequate evidence of content and face validity. The use of WCRP was not associated with a significant improvement in nursing students' diagnostic accuracy. New studies with larger samples, a sample power of at least 80%, and a level of significance of 5% are needed., (© 2021 NANDA International, Inc.)

Side effects often limit the use of doxorubicin (DOX) in cancer treatment. We have recently developed a nanostructured lipid carrier (NLC) formulation for synergistic chemotherapy, encapsulating DOX and the anticancer adjuvants docosahexaenoic acid (DHA) and α-tocopherol succinate (TS). Hydrophobic ion-pairing with TS allowed a high DOX entrapment in the nanocarrier. In this work, we investigated the pharmacokinetics of this formulation after intravenous administration in mice. The first data obtained led us to propose synthesizing covalent DOX-TS conjugates to increase DOX retention in the NLC. We successfully conjugated DOX to TS via an amide or hydrazone bond. In vitro studies in 4T1 tumor cells indicated low cytotoxicity of the amide derivative, while the hydrazone conjugate was effective in killing cancer cells. We encapsulated the hydrazone derivative in a DHA-based nanocarrier (DOX-hyd-TS/NLC), which had reduced particle size and high drug encapsulation efficiency. The pH-sensitive hydrazone bond allowed controlled DOX release from the NLC, with increased drug release at acidic conditions. In vivo studies revealed that DOX-hyd-TS/NLC had a better pharmacokinetic profile than free DOX and attenuated the short-term cardiotoxic effects caused by DOX, such as QT prolongation and impaired left ventricular systolic function. Moreover, this formulation showed excellent therapeutic performance by reducing tumor growth in 4T1 tumor-bearing mice and decreasing DOX-induced toxicity to the heart and liver, demonstrated by hematologic, biochemical, and histologic analyses. These results indicate that DOX-hyd-TS/NLC may be a promising nanocarrier for breast cancer treatment., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects. Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like tumors, and be surface-functionalized for targeting purposes. Herein, we developed a folate-coated pH-sensitive liposome as a drug delivery system for IRN to reach improved tumor therapy without potential adverse events. Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug. Tumor tissue of IRN-containing groups presented large areas of necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional colorectal cancer treatment., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: The objective of this study was to develop and validate an educational video on nasopharyngeal and oropharyngeal suctioning., Background: The use of videos in nursing education can improve students' skills in performing procedures., Design: This was a methodological study., Methods: This study was performed in five steps: (1) development of the script for an educational video on nasopharyngeal and oropharyngeal suctioning; (2) content validation of the script by 10 nurse specialists; (3) development of the video; (4) content validation of the video by six nurse specialists; (5) cognitive testing by 51 nursing students regarding the understanding of the items, until the following requirements were met: (1) mean and median scores ≥4, with significant inter-rater agreement, according to the Wilcoxon test; (2) 95% confidence intervals >80 for the proportion of maximum scores, according to the binomial distribution. p values <0.05 were considered significant., Results: After four rounds of evaluation by the specialists, the script was considered validated. The video was considered validated after two rounds of evaluation by specialists and students (p < 0.001). The video addressed the following topics: concept, indications, contraindications, required materials, appropriate technique, nursing notes and complications., Conclusions: The video script was created by using the Storyboard technique and validated by specialist nurses using the Delphi technique. Nursing students watched, analyzed and understood the video which may support them to improve their technical skills of this procedure., (Copyright © 2021. Published by Elsevier Ltd.)

Background: In Brazil, there are no instruments available to measure the presence, frequency, severity and distress related to heart failure (HF) symptoms., Aims: To adapt the Symptom Status Questionnaire - HF (SSQ-HF) into Brazilian Portuguese and to examine the content validity of the adapted version., Methods: The instrument was translated, back-translated and evaluated by an expert committee for semantic, idiomatic, cultural, and conceptual equivalences. An agreement ≥80% was considered adequate. The adapted version was evaluated by both an expert committee (n = 9) for clarity, theoretical relevance and practical relevance (acceptable content validity coefficient (CVC): ≥0.70), and by a patient committee regarding understanding (n = 40)., Results: The adapted version obtained 100% agreement regarding the equivalences. The total instrument CVC was 0.99. All patients understood the items., Conclusion: The SSQ-HF-Brazilian version has satisfactory evidence of equivalence and content validity. Additional psychometric tests are deemed to confirm that the instrument can be used in Brazil., Competing Interests: Declaration of Competing Interest We declare that we have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ibuprofen, a non-steroidal anti-inflammatory drug, inhibits the activity of cyclooxygenase enzyme, leading to reduction in Prostaglandin E 2 (PGE 2 ) production. Due to the importance of PGE 2 in promoting the brain masculinization in male fetus, this study aimed to evaluate the effects of in utero and lactational exposure to ibuprofen and their late repercussions on reproductive parameters in male rats. Pregnant rats were exposed to ibuprofen (10, 30 or 60 mg/kg) or vehicle (control group) per gavage daily from gestational day 15 to day 21 after birth, and late reproductive effects were assessed during the sexual development and in the reproductive adult life in the male offspring. Males exposed to ibuprofen had a decrease in body weight and anogenital distance, as well as a delay in the ages of testicular descent and preputial separation. In adulthood, there was a decrease in the Leydig cells nuclei volume, testosterone levels and percentage of normal sperm morphology. All animals exposed to ibuprofen presented male copulatory behavior, however, in the presence of another male, they also presented a female-typical behavior. Maternal exposure to ibuprofen during the sensitive windows of brain development adversely impacted the reproductive parameters of male rats, suggesting an incomplete masculinization of the hypothalamus., 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 Inc. All rights reserved.)

Conventional chemotherapy regimens have limitations due to serious adverse effects. Targeted drug delivery systems to reduce systemic toxicity are a powerful drug development platform. Encapsulation of antitumor drug(s) in thermosensitive nanocarriers is an emerging approach with a promise to improve uptake and increase therapeutic efficacy, as they can be activated by hyperthermia selectively at the tumor site. In this review, we focus on thermosensitive nanosystems associated with hyperthermia for the treatment of cancer, in preclinical and clinical use.

Background: Studies have shown the efficacy of videos used in isolation to retain knowledge, acquire skills, and establish students' self-confidence. A few studies have investigated the efficacy of videos associated with simulations, while none of these studies have addressed bed bathing, one of the first procedures learned by nursing students., Objective: To test the efficacy of a video-assisted bed bath simulation on improving the performance of psychomotor skills of undergraduate nursing students., Design: A randomized clinical trial., Setting: A Teaching Skills and Simulation Center at a Federal University in Brazil., Participants: All students regularly enrolled in the second year of the nursing undergraduate program at a Federal University, aged 18 years old, who had never performed a bed bath and had attended a theoretical class addressing the procedure (n = 56)., Methods: The students were randomized into two groups: the Control group (n = 28) simulated a bed bath with the instructions of a tutor, while the Intervention group (n = 28) watched a video during the bed bathing simulation, under the supervision of a tutor. The performance of students concerning bed bathing was assessed twice (before and after the simulation) using a previously validated instrument., Results: The psychomotor skills of both groups significantly improved in the second assessment, and the Intervention group scored higher (p = 0.003)., Conclusions: The use of a video during bed bath simulations was efficacious for improving the performance of psychomotor skills of undergraduate nursing students., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Breast cancer is a health problem worldwide with high incidence and mortality rates. It is well known that the development of more sensitive and specific diagnostic methods is of great importance since an early diagnosis is essential to successfully treat tumors. Lapachol is a natural compound, belonging to the naphthoquinone group that has been widely used in traditional medicine to treat various illnesses, including cancer. The aim of this study was to evaluate technetium-99m ( 99m Tc) labeled lapachol as an imaging probe for breast cancer identification., Methods: To achieve this purpose, lapachol was labeled with 99m Tc, radiochemical purity and in vitro stability were determined. Blood clearance, in healthy mice, and biodistribution, in 4T1 tumor-bearing mice, were also evaluated., Results: Lapachol was successfully labeled with 99m Tc, with high values of radiochemical yield (95.9±3.4%). In vitro stability showed that the radiolabeled complex remained stable for up to 24h, with values above 90% for both saline and plasma (95.6±3.6% and 96.4±1.7%, respectively). The radiolabeled complex decays in a biphasic manner, with a half-life of distribution and elimination equal to 3.3 and 50.0min, respectively. Biodistribution and scintigraphic images showed high uptake in organs of excretion (kidneys, liver, and intestine). It could be also noted that tumor uptake was higher than the muscle at all time points. Tumor-to-muscle ratio reaches ∼4.5 at 24h after administration., Conclusion: These findings suggest that 99m Tc-lapachol can be a potential diagnostic agent for breast tumors., (Copyright © 2019 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

This study aimed to evaluate the effects of the extracted oil of Acrocomia aculeata pulp in preventing or mitigating the reproductive toxicity induced by cyclophosphamide (CP) in male rats. Adult male rats were segregated into seven groups that received vehicle, 100 mg/kg/day of CP, or 10 mg/kg/day of β-carotene or 3 or 30 mg/kg/day of A. aculeata oil co-administered with CP. A. aculeata oil exhibited a high content of β-carotene. CP treatment induced reproductive toxicity in the animals, as it changed the reproductive organs weight, hormone levels, sperm counts and testicular histology. In contrast, co-administration of A. aculeata improved CP-induced alterations in these parameters. A. aculeata oil also increased the gene Ckit expression and normalised the antioxidant enzymes levels which were changed by CP. The A. aculeata oil is capable of protecting the male reproductive system from the adverse effects of CP, possibly by acting as an antioxidant and increasing the Ckit gene expression., (© 2018 Blackwell Verlag GmbH.)

Background: Dental caries is considered a multifactorial disease, in which microorganisms play an important role. The diet is decisive in the biofilm formation because it provides the necessary resources for cellular growth and exopolysaccharides synthesis. Exopolysaccharides are the main components of the extracellular matrix (ECM). The ECM provides a 3D structure, support for the microorganisms and form diffusion-limited environments (acidic niches) that cause demineralization of the dental enamel. Streptococcus mutans is the main producer of exopolysaccharides. Candida albicans is detected together with S. mutans in biofilms associated with severe caries lesions. Thus, this study aimed to determine the effect of tt-farnesol and myricetin topical treatments on cariogenic biofilms formed by Streptococcus mutans and Candida albicans., Methods: In vitro dual-species biofilms were grown on saliva-coated hydroxyapatite discs, using tryptone-yeast extract broth with 1% sucrose (37 °C, 5% CO 2 ). Twice-daily topical treatments were performed with: vehicle (ethanol 15%, negative control), 2 mM myricetin, 4 mM tt-farnesol, myricetin + tt-farnesol, myricetin + tt-farnesol + fluoride (250 ppm), fluoride, and chlorhexidine digluconate (0.12%; positive control). After 67 h, biofilms were evaluated to determine biofilm biomass, microbial population, and water-soluble and -insoluble exopolysaccharides in the ECM., Results: Only the positive control yielded a reduced quantity of biomass and microbial population, while tt-farnesol treatment was the least efficient in reducing C. albicans population. The combination therapy myricetin + farnesol + fluoride significantly reduced water-soluble exopolysaccharides in the ECM (vs. negative control; p < 0.05; ANOVA one-way, followed by Tukey's test), similarly to the positive control., Conclusions: Therefore, the combination therapy negatively influenced an important virulence trait of cariogenic biofilms. However, the concentrations of both myricetin and tt-farnesol should be increased to produce a more pronounced effect to control these biofilms.

Fipronil is an insecticide widely used in agriculture, veterinary medicine and public health that has recently been listed as a potential endocrine disrupter. In the present study we evaluated the effects of perinatal exposure to fipronil during the period of sexual brain differentiation and its later repercussions on reproductive parameters in male rats. Pregnant rats were exposed (via gavage) to fipronil (0.03, 0.3 or 3mgkg -1 ) from Gestational Day 15 until Postnatal Day 7. Fipronil exposure did not compromise the onset of puberty. In adulthood, there was no effect on organ weight or sperm production. Furthermore, there were no adverse effects on the number of Sertoli cells per seminiferous tubule, testicular and epididymal histomorphometry or histopathology or expression patterns of androgen receptor in the testis. Similarly, no changes were observed in the sexual behaviour or hormone levels. However, in rats exposed to fipronil, changes in sperm motility were observed, with a decrease in motile spermatozoa and an increase in non-mobile spermatozoa, which can compromise sperm quality in these rats. Perinatal exposure to fipronil has long-term effects on sperm parameters, and the epididymis can be a target organ. Additional studies should be undertaken to identify the mechanisms by which fipronil affects sperm motility.

Background: No previous study has investigated the predictive risk factors of the nursing diagnosis of risk for decreased cardiac output after coronary artery bypass grafting (CABG)., Aims: This study aimed to identify the predictive risk factors of the nursing diagnosis of risk for decreased cardiac output after CABG., Methods: This was a prospective cohort study performed at a cardiac university hospital in São Paulo, Brazil and 257 adult patients undergoing CABG were included. Potential risk factors for low cardiac output in the immediate post-operative period were investigated using the patients' medical records. Univariate analysis and logistic regression were used to identify the predictive risk factors of decreased cardiac output. The area under the receiver operating characteristic curve was calculated as a measure of accuracy. The variables that could not be analysed through logistic regression were analysed through Fisher's exact test., Results: One hundred and ninety-five patients had low cardiac output in the immediate post-operative period. The predictive risk factors included age ⩾60 years, decreased left ventricle ejection fraction, not using the radial artery graft, positive fluid balance and post-operative arrhythmia that differed from the pre-operative arrhythmia. This model predicted the outcome with a sensitivity of 62.9%, a specificity of 87.2% and an accuracy of 81.5%. The variables analysed through Fisher's exact test included heart failure, re-exploration and bleeding-related re-exploration., Conclusions: The predictive risk factors for the nursing diagnosis of risk for decreased cardiac output after CABG were found. These results can be used to direct nurses in patient monitoring, staff training and nursing team staffing.

Objective: To construct conceptual and operational definitions for the defining characteristics (DCs) and related factors (RFs) of the nursing diagnosis (ND) ineffective health management for people with chronic heart failure., Method: Conceptual and operational definitions for the DC and RF were based on studies found in an integrative literature review in the databases Latin American Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature, and MEDLINE by using the key words Nursing diagnosis, Heart Failure, and Patient Cooperation in different combinations., Results: Conceptual and operational definitions for all the DCs and RFs were constructed., Conclusions and Implications for Practice: The definitions will facilitate in the identification of ND in clinical practice in patients with heart failure, future research on ND validation, and education in undergraduate courses., (© 2015 NANDA International, Inc.)

Introduction: Acid nucleic aptamers are RNA or DNA oligonucleotides capable of binding to a target molecule with high affinity and selectivity. These molecules are promising tools in nuclear medicine. Many aptamers have been used as targeting molecule of radiopharmaceuticals in preclinical studies. (1→3)-β-D-glucans are the main structural cell wall components of fungi and some bacteria. In the present study two radiolabeled (1→3)-β-D-glucan aptamers (seq6 and seq30) were evaluated to identity infectious foci caused by fungal or bacterial cells., Methods: Aptamer labeling with 99m Tc was performed by the direct method and biodistribution studies were accomplished in Swiss mice (n=6) infected in the right thigh muscle with Staphylococcus aureus or Candida albicans. A 99m Tc radiolabeled library consisting of oligonucleotides with random sequences was used as control., Results: There was a higher uptake of 99m Tc radiolabeled aptamers in the infected thigh than in the left thigh muscle (non-infected) in the S. aureus infected animals. The target/non-target ratios were 3.17±0.22 for seq6 and 2.66±0.10 for seq30. These ratios were statistically higher than the value (1.54±0.05) found for the radiolabeled library (control). With regard to biodistribution, no statistical difference was verified between aptamers and control uptakes in the infection foci in the C. albicans infected animals. The target/non-target ratios were 1.53±0.03, 1.64±0.12 and 1.08±0.02 for radiolabeled library, seq6 and seq30, respectively. Scintigraphic imaging of infected foci using radiolabeled aptamers was possible only for S. aureus infected mice., Conclusions: Seq6 and seq30 aptamers proved to be inefficient for diagnosis of C. albicans infection. Nevertheless, their applicability for diagnosis of S. aureus and other bacterial infections by scintigraphy should be further explored., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Therapeutic agents used in chemotherapy have low specificity leading to undesired severe side effects. Hence, the development of drug delivery systems that improve drug specificity, such as liposome moieties, is an alternative to overcome chemotherapy limitations and increase antitumor efficacy. In this study, the biodistribution profile evaluation of pH-sensitive long-circulating liposomes (SpHL) containing [ 99m Tc]DOX in 4T1 tumor-bearing BALB/c mice is described., Procedures: [ 99m Tc]DOX was radiolabeled by direct method. Liposomes were prepared and characterized. [ 99m Tc]DOX was encapsulated into liposomes by freezing and thawing. Circulation time for SpHL-[ 99m Tc]DOX was determined by measuring the blood activity from healthy animals. Biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 24 h after injection., Results: Blood levels of the SpHL-[ 99m Tc]DOX declined in a biphasic manner, with an α half-life of 14.1 min and β half-life of 129.0 min. High uptake was achieved in the liver and spleen, due to the macrophages captured. Moreover, tumor uptake was higher than control tissue, resulting in high tumor-to-muscle ratios, indicating higher specificity for the tumor area., Conclusion: [ 99m Tc]DOX was successfully encapsulated in liposomes. Biodistribution indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. In summary, these results showed the higher accumulation of SpHL-[ 99m Tc]DOX in the tumor area, suggesting selective delivery of doxorubicin into tumor.

Versican expression promotes tumor growth by destabilizing focal cell contacts, thus impeding cell adhesion and facilitating cell migration. It not only presents or recruits molecules to the cell surface, but also modulates gene expression levels and coordinates complex signal pathways. Previously, we suggested that the interaction between versican and human epidermal growth factor receptors may be directly associated with tumor aggressiveness. Thus, the expression of EGFR and HER-2 in these neoplasms may contribute to a better understanding of the progression mechanisms in malignant mammary tumors. The purpose of this study was to correlate the gene and protein expressions of EGFR and HER2 by RNA In Situ Hybridization (ISH) and immunohistochemistry (IHC), respectively, and their relationship with the versican expression in carcinomas in mixed tumors and carcinosarcomas of the canine mammary gland. The results revealed that EGFR mRNA expression showed a significant difference between in situ and invasive carcinomatous areas in low and high versican expression groups. Identical results were observed in HER-2 mRNA expression. In immunohistochemistry analysis, neoplasms with low versican expression showed greater EGFR immunostaining in the in situ areas than in invasive areas, even as the group presenting high versican expression displayed greater EGFR and HER-2 staining in in situ areas. Significant EGFR and HER-2 mRNA and protein expressions in in situ carcinomatous sites relative to invasive areas suggest that these molecules play a role during the early stages of tumor progression.

Purpose: To identify the possible defining characteristics (DCs) and related factors of the nursing diagnosis (ND) decreased cardiac tissue perfusion., Methods: Cross-sectional study using medical charts of adults admitted to an emergency department with the chief complaint of chest pain in a hospital in São Paulo, Brazil., Findings: DCs identified: crushing chest pain, elevated markers of myocardial necrosis, ischemic electrocardiogram changes, sweating, nausea, and vomiting. Related factors identified: interruption of arterial blood flow and coronary spasm., Conclusion: This ND was clinically identified due to significant differences in the DCs of patients with and without the diagnosis., Practice Implications: The clinical indicators identified in this study can be the starting point for the DCs for this ND., (© 2015 NANDA International, Inc.)

Objective: To propose new criteria for expert selection for validation studies in nursing in Brazil., Methods: (a) Literature review on terms related to expertise and criteria for expert selection; and (b) development of new consensus criteria for expert selection and consensus building., Results: Definitions for the terms novice, advanced beginner, competent, proficient, and expert were found. In the second phase, criteria to rank the experts (junior, senior, and master) were developed and validated according to a score of 5-20., Conclusion and Implications for Nursing Practice: The new criteria valued clinical experience over academic experience. The use of these criteria by researchers in the country should reduce uncertainties, difficulties, and limitations imposed by the modification/current adaptation of already existing criteria., (© 2015 NANDA International, Inc.)

Purpose: Pancreatic cancer is the fourth most common cause of cancer-related death in the USA. This is mainly because of the chemoresistance of this type of tumor; thus, the development of novel therapeutic modalities is needed., Methods: Long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP) were administered systemically into pancreatic tumor-bearing mice for a period of 14 days. The antitumor efficacy and toxicity of this new treatment method on the basis of cisplatin-loaded liposomes was compared with the classical free-CDDP method. Tc-HYNIC-βAla-bombesin(7-14) tumor uptake and histopathologic findings were used to monitor and compare the two treatment modalities., Results: The antitumor activity of SpHL-CDDP treatment was shown by (a) decrease in tumor volume, (b) development of tumor necrotic areas, and (c) decrease in Tc-HYNIC-βAla-bombesin(7-14) tumor uptake. Toxicity was evaluated by the development of inflammation and necrotic areas in the kidneys, liver, spleen, and intestine: toxic effects were greater with free-CDDP than SpHL-CDDP., Conclusion: SpHL-CDDP showed significant antitumor activity in pancreatic cancer-bearing mice, with lower toxicity in comparison with free-CDDP.

Background: Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with (99m)Tc., Methods: Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with (99m)Tc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2 (.) 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05)., Results: Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol(.)L(-1) (S. aureus) and 10.10 μmol(.)L(-1) (E. coli). Thus, only the latter was radiolabeled with (99m)Tc. The radiochemical purity analysis of LyeTx I-K-HYNIC-(99m)Tc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2 (.) 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n = 3). However, RP-HPLC data suggested (99m)Tc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA)., Conclusions: The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

Background: Bleeding-related re-exploration is a life-threatening complication after cardiac surgery. Nurses must be aware of important risk factors for this complication so that their assessment, monitoring and evaluation activities can be prioritized, focused and anticipated., Aims: To identify the predictive factors for bleeding-related re-exploration after cardiac surgery and to describe the sources of postoperative bleeding., Methods: This is a prospective cohort study at a tertiary cardiac school-hospital in São Paulo/SP, Brazil. Adult patients (n=323) submitted to surgical correction of acquired cardiac diseases were included. Potential risk factors for bleeding-related re-exploration within the 24 hours following admission to the intensive care unit were investigated in the patients' charts. A univariate analysis and a multiple analysis through logistic regression were conducted to identify the outcome predictors. The area under the receiver-operating characteristic curve was calculated as a measure of accuracy considering the cut-off points with the highest sensitivity and specificity., Results: The univariate factors significantly associated with bleeding-related re-exploration were a lower preoperative platelet count, a lower number of bypasses in coronary artery bypass surgery and postoperatively, a lower body temperature, infusion of lower intravenous volume, a higher positive end-expiratory pressure during mechanical ventilation and transfusion of blood products. The independent predictors of bleeding-related re-exploration included postoperative red blood cell transfusion, and transfusion of fresh frozen plasma, platelet or cryoprecipitate units. These predictors had a sensitivity of 87.5%, a specificity of 99.28% and an accuracy of 97.93%., Conclusions: Blood product transfusion postoperatively is an independent predictor of bleeding-related re-exploration. Surgical errors prevailed as sources of bleeding., (© The European Society of Cardiology 2015.)

Aim: More sensitive and accurate imaging approaches for early detection and therapy monitoring of lung tumours are needed to ameliorate prognosis and outcome. Lung tumours are known to overexpress receptors for bombesin-like peptides. However, thus far, no study has demonstrated the potential role of bombesin-like peptides in identifying A549 lung tumour cells in xenograft animal models. Thus, we evaluate the feasibility of Tc-HYNIC-βAla-Bombesin(7-14) as an imaging probe in lung cancer., Methods and Results: Xenograft lung tumours were implanted in nude mice and evaluated by histopathological analysis. Tumours were easily visualized by Tc-HYNIC-βAla-Bombesin(7-14) within 30 days after inoculation of the A549 cell line into mice. Scintigraphic images showed high tumour-to-background ratio., Discussion: The data obtained in this study indicate that Tc-HYNIC-βAla-Bombesin(7-14) may be useful as an imaging probe to detect A549 lung cancer cells. To our knowledge, this is the first time that this specific radiocompound has been used to visualize non-small-cell lung cancer A549 in mice. Further translational research in humans is required to establish the potential role of this radiocompound in clinical practice.

Diflubenzuron (DFB), an insecticide and acaricide insect growth regulator, can be used in agriculture against insect predators and in public health programs, to control insects and vectors, mainly Aedes aegypti larvae. Due to the lack of toxicological assessments of this compound, the objective of the present study was to evaluate the toxicological effects of subacute exposure to the DFB insecticide in adult male rats. Adult male rats were exposed (gavage) to 0, 2, 4, or 8 mg/kg of DFB for 28 days. No clinical signs of toxicity were observed in the DFB-treated animals of the experimental groups. However, there was an increase in serum levels of alanine aminotransferase in the group that received 8 mg/kg/DFB/day and urea at doses of 4 and 8 mg/kg/DFB/day, without altering other biochemical or hematological parameters. The subacute exposure to the lowest dose of DFB caused significant decrease in testis weight, daily sperm production, and in number of sperm in the epididymis in relation to the control group. However, no alterations were observed in the sperm morphology, testicular, epididymis, liver and kidney histology, or testosterone levels. These findings unveiled the hazardous effects of DFB on male reproduction after the subacute exposure and special attention should be addressed to the effects of low doses of this pesticide., (© 2014 Wiley Periodicals, Inc.)

Objective: Early diagnosis of malignant tumors is essential to successfully plan a radical and curative approach. In this study we describe the direct radiolabeling of doxorubicin (DOX) at physiological pH to identify murine breast tumor (4T1 cells)-bearing BALB/c mice., Materials and Methods: Technetium-99m (99mTc) DOX was prepared by adding 99mTc-pertechnetate to a PBS (pH 7.4) solution containing DOX in the presence of stannous chloride. Radiochemical purity and in-vitro stability were determined. The circulation time of 99mTc-DOX was determined by measuring blood radioactivity in healthy animals. Scintigraphic images and biodistribution studies were carried out in tumor-bearing mice at 1, 4, and 8 h after injection., Results: The 99mTc-DOX complex showed high radiochemical purity (99.27 ± 0.34%) and in-vitro stability until 8 h. Tc-DOX levels in blood declined in a biphasic manner, with an α half-life of 4.5 min and a β half-life of 277.2 min. High uptake was achieved in kidneys, liver, and spleen, because of the drug elimination routes. Moreover, tumor uptake was higher than that of control tissue, resulting in high tumor-to-muscle ratios., Conclusion: DOX was successfully labeled with 99mTc-pertechnetate and showed high stability. Biodistribution and scintigraphic studies indicated high tumor-to-muscle ratios in breast tumor-bearing BALB/c mice. These results suggested the feasibility of 99mTc-DOX as a functional agent in tumor diagnosis.

Objective: To identify factors associated with excessive bleeding (ExB) after cardiac surgery in adults., Background: Excessive bleeding after cardiac surgery must be anticipated for implementation of timely interventions., Methods: A prospective cohort study with 323 adults requiring open-chest cardiac surgery. Potential factors associated with ExB were investigated through univariate analysis and logistic regression. The accuracy of the relationship between the independent variables and the outcome was depicted through the receiver-operating characteristic (ROC) curve., Results: The factors associated with ExB included gender, body mass index (BMI), preoperative platelet count, intraoperative heparin doses and intraoperative platelet transfusion. The ROC curve cut-off points were 26.35 for the BMI; 214,000 for the preoperative platelet count, and 6.25 for intraoperative heparin dose. This model had an accuracy = 77.3%, a sensitivity = 81%, and a specificity = 62%., Conclusions: Male gender, BMI, preoperative platelet count, dose of intraoperative heparin >312.5 mg without subsequent platelet transfusion, are factors associated with ExB., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Fipronil, a phenylpyrazole insecticide, is used in agriculture, veterinary medicine, and public health. Because this insecticide is considered a potential endocrine disruptor, the aim of this study was to examine the influence of perinatal exposure to fipronil on neonatal female reproductive system development. Pregnant rats were exposed (via gavage) daily to fipronil (0.03, 0.3, or 3 mg/kg) from gestational day 15 to day 7 after birth, and effects on the reproductive functions assessed on postnatal day (PND) 22. No signs of maternal toxicity were observed during daily treatment with fipronil. Perinatal exposure to the highest dose of fipronil (3 mg/kg) delayed the age of vaginal opening (VO) and first estrus without markedly affecting the anogenital distance (AGD). Further, exposure to 0.3 mg/kg fipronil produced a significantly shorter estrus cycle and reduced number of cycles during the period of evaluation. However, the other reproductive parameters analyzed, including fertility, hormone levels, sexual behavior, and histology of ovaries and uterus, displayed no marked alterations. In this experimental model, fipronil interfered with development of neonatal female reproductive system as evidenced by delay in VO and estrus cycle alterations without apparent significant effects on fertility. Further studies are needed to identify the mechanisms of action associated with the observed female reproductive system changes.

Purpose: The aim of this study was to evaluate the ability of phytate radiolabeled with technetium-99m (Tc-phytate) to identify inflammatory processes., Materials and Methods: Radiolabeling efficiency analyses were carried out by thin-layer chromatography on silica gel strips, yielding a radiochemical purity of 92%. In addition, the partition coefficient of Tc-phytate, obtained in a mixture of n-octanol/water (1 : 1), showed hydrophilic features of the radiopharmaceutical. After Tc-phytate was administered into the tail vein of healthy and inflammation focus-bearing rats, induced, in the right tight, by zymosan suspension at 5% (w/v), blood clearance evaluation was performed and showed a short plasma half-life (2.7 min). In the inflammation focus-bearing rats, Tc-phytate scintigraphic images were obtained at 2, 4, and 8 h after radiotracer injection., Results: A significant radiopharmaceutical uptake was found in mononuclear phagocyte system organs (liver and spleen) and in the inflammation focus (compared with contralateral muscle). Histopathological analysis showed an intense mononuclear infiltration in the inflamed muscle, suggesting that macrophages may be responsible for the greater radiotracer uptake in the inflamed site. Furthermore, the target-to-nontarget ratio (%ID/g of inflamed muscle-to-%ID/g of control muscle ratio) obtained by scintigraphic images performed at 2 h after the radiotracer injection was 10.24±3.49, remaining without any significant difference at 4 and 8 h., Conclusion: Inflammation focus was evident in the scintigraphic images from 2 to 8 h after Tc-phytate administration, suggesting that this radiopharmaceutical could be a potential alternative to identify inflamed regions.

Along with anti-cancer drug delivery researches, many efforts have been done to develop new tracers for diagnostic applications. Based on advances in molecular imaging, nanoparticles can be used to visualize, characterize and measure biological process at molecular and cellular level. Therefore, the purpose of this study was to synthesize, characterize and radiolabeled mesoporous silica nanoparticles (MSNs) for in vivo applications. The nanoparticles were synthesized, functionalized with 3-aminopropyltriethoxysilane (APTES) and then, anchored with diethylenetriaminepentaacetic acid (DTPA). Particles were physicochemical characterized by elemental analysis (CHN), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and zeta potential, and were morphologically characterized by scanning electron microscopy (SEM), low-angle X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. Results indicate that functionalization process was successfully achieved. Next, functionalized silica nanoparticles were radiolabeled with technetium-99m showing high radiochemical yields and high radiolabeled stability. These findings allow the use of the particles for in vivo applications. Biodistribution and scintigraphic images were carried out in healthy mice in order to determine the fate of the particles. Results from in vivo experiments showed high uptake by liver, as expected due to phagocytosis. However, particles also showed a significant uptake in the lungs, indicated by high lung-to-non-target tissue ratio. In summary, taking into account the great potential of these silica mesoporous structures to carry molecules this platform could be a good strategy for theranostic purposes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Once administered intravenously, technetium-99m (99mTc)-labeled phytate binds to calcium in the serum and behaves as a nanoparticle. On the basis of the high permeability of the tumor vasculature, 99mTc-phytate is expected to leak and accumulate specifically in inflammatory cells. The aim of this study was to evaluate the potential of 99mTc-phytate in assessing the degree of inflammation in Ehrlich solid tumors in mice., Materials and Methods: 99mTc-phytate was prepared by adding pertechnetate to a solution containing phytic acid and stannous chloride. The blood half-life of this particle following intravenous injection was determined using blood samples from healthy animals, whereas its size was measured by photon correlation spectroscopy. Scintigraphic imaging and biodistribution studies were carried out in tumor-bearing mice at 30 min and 2 h after injection., Results: The average size of the particles was in the range of 200 nm, suggesting that they are capable of passively passing through fenestrations in tumor vessels, which are 200-2000 nm in size. The blood half-life for 99mTc-phytate was found to be 2.1 min, a result that is in agreement with previous studies. Data from tumor-bearing mice showed high tumor uptake at 2 h after 99mTc-phytate administration. As a result, a high tumor-to-muscle ratio was achieved (T/M = 25.9 ± 7.54)., Conclusion: These findings indicate that 99mTc-sodium phytate has promising properties for identifying the type of tumor. This approach will have significant implications for characterizing tumor biology and treatment of malignant lesions.