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Objective: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age., Methods: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated., Results: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days)., Conclusion: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference., Trial Registration Number: ClinicalTrials.gov number, NCT05403307 (https://classic., Clinicaltrials: gov/ct2/show/NCT05403307)., Competing Interests: Declaration of competing interest Rodrigues, Maltempi de Souza, Manfio, de Souza, Araujo, Cohen, Barbosa, Romeiro Silva, Sganzerla, Dias da Silva, Ferreira, Kunkel, Camargo, Sarturi, Guilhem, Oliveira, Lopes, Widmar, Barufi, Nunes da Silva, Gradia, Brandalize, Royer, Luiz, Baura, Abreu, and Poitevin report honoraria fee for working in this study from Hospital Moinhos de Vento. Rosa reports honoraria fee related to investigator activities from Pfizer, and research grants from Pfizer, MSD and Brazilian Ministry of Health. Falavigna reports honoraria fee related to investigator activities from Pfizer and MSD, consulting fees from Sanofi, Ultragenyx, Novartis, Alnylam, PTC and JCR, and honoraria for lectures from Janssen, Abbvie, Sanofi, Roche, Pfizer and Novartis.Valluri, Srivastava, Julião, Melone, Allen, Kyaw, Spinardi, Castillo, and McLaughlin are Pfizer empolyees. Kucharski, and Pedrotti have nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

This study evaluated the effects of broiler age (A) and levels of replacement (L) of control diet (CD) on the utilization of energy and nutrients of whole corn germ. 720 one-day-old broilers (b) were allocated at completely randomized design to six treatments and six replicates, in three assays: pre-starter (1-8 days, 10 b/cage), starter (15-22 days, 6 b/cage), and grower (28-35 days, 4 b/cage) phases. The treatments were: CD and four test diets (L): 100, 150, 200, 250, or 300 g kg-1 of the CD replaced by WCG levels. The data were adjusted to the response surface model. The stationary points for apparent energy metabolizable (AME) and AME corrected for nitrogen balance (AMEn) were: 4173 and 3591 kcal kg-1, respectively, and coefficients of gross energy (AMCGE), crude protein (AMCCP), dry matter (AMCDM), and ether extract (AMCEE) were: 49.3, 40.4, 72.6, and 61.3%, respectively; and Ileal digestibility coefficient of crude protein (IDCCP), dry matter (IDCDM), digestibility crude protein values (DCP), and digestibility dry matter value (DDM) were: 78.0, 57.96, 8.50, and 56.17%, respectively. The EP for AMEn was at 18 days of age, 28 g kg-1 WCG. There was a correlation between A and L on digestibility and metabolisability of nutrient's WCG.

Anoikis is a process of programmed cell death induced by the loss of cell/matrix interactions. In previous work, we have shown that the acquisition of anoikis resistance upregulates syndecan-4 (SDC4) expression in endothelial cells. In addition, SDC4 gene silencing by microRNA interference reverses the transformed phenotype of anoikis-resistant endothelial cells. Due to this role of SDC4 in regulating the behavior of anoikis-resistant endothelial cells, we have evaluated that the functional consequences of SDC4 silencing in the extracellular matrix (ECM) remodeling in anoikis-resistant rabbit aortic endothelial cells submitted to SDC4 gene silencing (miR-Syn4-Adh-1-EC). For this, we evaluated the expression of adhesive proteins, ECM receptors, nonreceptor protein-tyrosine kinases, and ECM-degrading enzymes and their inhibitors. Altered cell behavior was monitored by adhesion, migration, and tube formation assays. We found that SDC4 silencing led to a decrease in migration and angiogenic capacity of anoikis-resistant endothelial cells; this was accompanied by an increase in adhesion to fibronectin. Furthermore, after SDC4 silencing, we observed an increase in the expression of fibronectin, collagen IV, and vitronectin, and a decrease in the expression of integrin α5β1 and αvβ3, besides that, silenced cells show an increase in Src and FAK expression. Quantitative polymerase chain reaction and Western blot analysis demonstrated that SDC4 silencing leads to altered gene and protein expression of MMP2, MMP9, and HSPE. Compared with parental cells, SDC4 silenced cells showed a decrease in nitric oxide production and eNOS expression. In conclusion, these data demonstrate that SDC4 plays an important role in ECM remodeling. In addition, our findings represent an important step toward understanding the mechanism by which SDC4 can reverse the transformed phenotype of anoikis-resistant endothelial cells., (© 2024 International Federation for Cell Biology.)

Azoles are the main antifungal agents employed in clinical practice to treat invasive candidiasis. Nonetheless, their efficacy is limited by fungal resistance mechanisms, mainly the overexpression of efflux pumps. Consequently, candidiasis has a worrisome death rate of 75%. One potential strategy to overcome efflux-mediated resistance is to inhibit this process. Ailanthus altissima is a Chinese tree that produces several active substances, including altissimacoumarin D. Due to the low yield of its extraction and the need to search for new drugs to treat candidiasis, this study aimed to synthesize altissimacoumarin D and its analogues, as well as evaluating their ability to reverse the resistance phenotype of Candida albicans . Coumarin isofraxidin was prepared via total synthesis through a solvent-free Knoevenagel condensation as the key step. Isofraxidin and other commercially available coumarins were alkylated with prenyl or geranyl groups to yield the natural product altissimacoumarin D and seven analogues. The antifungal activity of the coumarins and their ability to reverse the fungal resistance phenotype were assessed using microbroth methodologies. Toxicity was evaluated using erythrocytes and an in silico prediction. All compounds improved the antifungal activity of fluconazole by inhibiting efflux pumps, and ACS47 and ACS50 were the most active. None of the coumarins were toxic to erythrocytes. In silico predictions indicate that ACS47 and ACS50 may be safe for human use. ACS47 and ACS50 are promising candidates when used as adjuvants in the antifungal therapy against C. albicans -resistant strains.

The aim of this paper was to synthesize and characterize polymeric scaffolds of Chitosan/Xanthan/Hydroxyapatite-Graphene Oxide nanocomposite associated with mesenchymal stem cells for regenerative dentistry application. The chitosan-xanthan gum (CX) complex was associated with Hydroxyapatite-Graphene Oxide (HA-GO) nanocomposite with different Graphene Oxides (GO) concentration (0.5 wt%; 1.0 wt%; 1.5 wt%). The scaffolds characterizations were performed by X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Raman spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and contact angle. The mechanical properties were assessed by compressive strength. The in vitro bioactivity and the in vitro cytotoxicity test (MTT test) were analyzed as well. The data was submitted to the Normality and Homogeneity tests. In vitro Indirect Cytotoxicity assay data was statistically analyzed by ANOVA two-way, followed by Tukey's test (α = 0.05). Compressive strength and contact angle data were statistically analyzed by one-way ANOVA, followed by Tukey's test (α = 0.05). XRD showed the presence of Hydroxyapatite (HA) peaks in the structures CXHA, CXHAGO 0.5%,1.0% and 1.5%. FT-IR showed amino and carboxylic bands characteristic of CX. Raman spectroscopy analysis evidenced a high quality of the GO. In the TGA it was observed the mass loss associated with the CX degradation by depolymerization. SEM analysis showed pores in the scaffolds, in addition to HA incorporated and adhered to the polymer. Contact angle test showed that scaffolds have a hydrophilic characteristic, with the CX group the highest contact angle and CXHA the lowest ( p < 0.05). 1.0 wt% GO significantly increased the compressive strength compared to other compositions. In the bioactivity test, the apatite crystals precipitation on the scaffold surface was observed. MTT test showed high cell viability in CXHAGO 1.0% and CXHAGO 1.5% scaffold. CXHAGO scaffolds are promising for regenerative dentistry application because they have morphological characteristics, mechanical and biological properties favorable for the regeneration process.

Objective: To develop a chitosan-xanthan (CX) membrane associated with Hydroxyapatite (HA) and different concentrations of graphene oxide (GO)., Methodology: The CX complex was associated with the hydroxyapatite-graphene oxide (HAGO) nanocomposite in different concentrations. The experimental groups were:1) CX; 2) Chitosan-Xanthan/Hydroxyapatite (CXHA); 3) Chitosan-Xanthan/Hydroxyapatite-Graphene Oxide 0.5% (CXHAGO 0.5%); 4) CXHAGO 1.0%; 5) CXHAGO 1.5%. The membranes characterizations were performed by X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Raman spectroscopy, Scanning Electron Microscopy (SEM), Contact angle, Tensile Strength, in vitro Bioactivity and the in vitro Cell viability (MTT test). The data was submitted to the Normality and Homogeneity tests. In vitro Indirect Cytotoxicity assay data was statistically analyzed by two-way ANOVA and Tukey's test (α = 0.05). Tensile Strength and Contact Angle data were statistically analyzed by one-way ANOVA followed by Tukey's test (α = 0.05)., Results: XRD, FTIR and Raman spectroscopy confirmed the characteristic bands of the CX polymeric complex, the phosphate bands related to HA, and the presence of GO. SEM images demonstrated the non-porous and homogeneous surface of membranes. The contact angle test showed the hydrophilic characteristic of all membranes (p > 0.05). CX showed tensile strength significantly higher than other membranes. The apatite deposition was observed in all membranes after performing the bioactivity test. The cell viability of CXHAGO 1.0% and CXHAGO 1.5% was significantly higher than CX., Conclusion: The addition of HAGO reduced the mechanical strength of membranes, but improved its cell viability. It demonstrated the potential of CXHAGO membranes to be used in guided bone regeneration therapies., 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 © 2022. Published by Elsevier Ltd.)

This research aimed to produce, on a multigram scale, a new class of non-toxic, halogen- and metal-free antifouling agents from the abundant lecithin byproducts of industrial soybean oil extraction. Three glycerophospholipid analogues were prepared by a facile methanolysis of crude soybean lecithins and a subsequent solvent-free O-alkylation: lysoglycerophosphocholines (LGPCs) and its ether derivatives O -alkyl lysoglycerophosphocholines (ALPCs). As efficient antiproliferative agents, LGPCs and ALPCs are an eco-friendly alternative to current commercial antifoulants which possess significant toxicity to aquatic life. In situ immersion tests of coated stainless-steel nets with previously incorporated automotive paint products, LGPCs and ALPCs (1- O -octadecyl-2- O -acyl- sn -glycero-3-phosphocholine, ALPC18, and 1- O -hexadecyl-2- O -acyl- sn -glycero-3-phosphocholine, ALPC16), in an aquaculture reservoir in SP-Brazil revealed significant growth inhibition against macrofouling species, especially the epibiotic golden mussel ( Limnoperna fortunei ), when compared with the control. These results promise a more sustainable and ecologically innocuous approach to combating the biofouling phenomenon and the deeply concerning dissemination of the golden mussel which has provoked an economic crisis in the energy and aquaculture sectors., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Expression of the cell surface heparan sulfate proteoglycan syndecan-4 is dysregulated in breast cancer, the most frequent malignancy in women. High expression of syndecan-4 correlates with a worse survival in the subgroup of estrogen receptor negative and estrogen/progesterone-receptor negative patients. Aberrant expression of syndecan-4 in breast cancer involves both transcriptional and posttranscriptional mechanisms, including estrogen- and growth factor-dependent regulation, mutations in GAPVD1 , NUP153 , PDE4DIP , and RREB1 , as well as targeting by microRNAs. At the functional level, syndecan-4 plays an important role in various stages of breast cancer progression by interacting with ligands as diverse as plasma proteins, extracellular matrix proteins, growth factors, and surface receptors, as well as members of the integrin family. Mechanisms including integrin recycling, ectodomain shedding, and crosstalk with other syndecans expand the repertoire of syndecan-4 function. Through these interactions, syndecan-4 regulates cellular processes such as adhesion, migration, and invasion. Additional possible functions of syndecan-4 in cells of the microenvironment contribute to the complexity of its pathophysiology. Notably, syndecan-4 expression is modulated by drugs used in breast cancer treatment, such as trastuzumab and zoledronate. Overall, these findings mark syndecan-4 as a novel pathogenesis factor and promising target for therapeutic interventions in breast cancer.

Anoikis is a type of apoptosis that occurs in response to the loss of adhesion to the extracellular matrix (ECM). Anoikis resistance is a critical mechanism in cancer and contributes to tumor metastasis. Nitric oxide (NO) is frequently upregulated in the tumor area and is considered an important player in cancer metastasis. The aim of this study was to evaluate the effect of NO on adhesiveness, invasiveness, and migration of anoikis-resistant endothelial cells. Here, we report that anoikis-resistant endothelial cells overexpress endothelial nitric oxide synthase. The inhibition of NO release in anoikis-resistant endothelial cells was able to decrease adhesiveness to fibronectin, laminin, and collagen IV. This was accompanied by an increase in cell invasiveness and migration. Furthermore, anoikis-resistant cell lines displayed a decrease in fibronectin and collagen IV protein expression after L-NAME treatment. These alterations in adhesiveness and invasiveness were the consequence of MMP-2 up-regulation observed after NO release inhibition. The decrease in NO levels was able to down-regulate the activating transcription factor 3 (ATF3) protein expression. ATF3 represses MMP-2 gene expression by antagonizing p53-dependent trans-activation of the MMP-2 promoter. We speculate that the increased release of NO by anoikis-resistant endothelial cells acted as a response to restrict the MMP-2 action, interfering in MMP-2 gene expression via ATF3 regulation. The up-regulation of nitric oxide by anoikis-resistant endothelial cells is an important response to restrict tumorigenic behavior. Without this mechanism, invasiveness and migration potential would be even higher, as shown after L-NAME treatment.

Syndecan-4, a predicted target of the microRNA miR-140-3p, plays an important role in multiple steps of tumor progression and is the second most abundant heparan sulfate proteoglycan produced by breast carcinoma cell lines. To investigate the potential functional relationship of miR-140-3p and syndecan-4, MDA-MB-231, SKBR3, and MCF-7 breast cancer (BC) cells were transiently transfected with pre-miR-140-3p, syndecan-4 small interfering RNAJ, or control reagents, respectively. Altered cell behavior was monitored by adhesion, migration, and invasion chamber assays. Moreover, the prognostic value of syndecan-4 was assessed by Kaplan-Maier Plotter analysis of gene expression data from tumor samples of 4929 patients. High expression of syndecan-4 was associated with better relapse-free survival in the whole collective of BC patients, but correlated with a worse survival in the subgroup of estrogen receptor negative and estrogen/progesterone-receptor negative patients. miR-140-3p expression was associated with improved survival irrespective of hormone receptor status. miR-140-3p overexpression induced posttranscriptional downregulation of syndecan-4, as demonstrated by quantitative real-time PCR (qPCR), flow cytometry, and luciferase assays, resulting in decreased BC cell migration and matrigel invasiveness. Furthermore, miR-140-3p overexpression and syndecan-4 silencing increased the adhesion of BC to fibronectin and laminin. qPCR analysis demonstrated that syndecan-4 silencing leads to altered gene expression of adhesion-related molecules, such as fibronectin and focal adhesion kinase, as well as in the gene expression of the proinvasive factors matrix metalloproteinase 2 and heparanase (also known as HPSE). We conclude that syndecan-4 is a novel target of miR-140-3p that regulates BC cell invasiveness and cell-matrix interactions in the tumor microenvironment., (© 2021 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC.)

Cancer is an important cause of morbidity and mortality worldwide. Advances in research on the biology of cancer revealed alterations in several key pathways underlying tumorigenesis and provided molecular targets for developing new and improved existing therapies. Syndecan-4, a transmembrane heparan sulfate proteoglycan, is a central mediator of cell adhesion, migration and proliferation. Although several studies have demonstrated important roles of syndecan-4 in cell behavior and its interactions with growth factors, extracellular matrix (ECM) molecules and cytoskeletal signaling proteins, less is known about its role and expression in multiple cancer. The data summarized in this review demonstrate that high expression of syndecan-4 is an unfavorable biomarker for estrogen receptor-negative breast cancer, glioma, liver cancer, melanoma, osteosarcoma, papillary thyroid carcinoma and testicular, kidney and bladder cancer. In contrast, in neuroblastoma and colorectal cancer, syndecan-4 is downregulated. Interestingly, syndecan-4 expression is modulated by anticancer drugs. It is upregulated upon treatment with zoledronate and this effect reduces invasion of breast cancer cells. In our recent work, we demonstrated that the syndecan-4 level was reduced after trastuzumab treatment. Similarly, syndecan-4 levels are also reduced after panitumumab treatment. Together, the data found suggest that syndecan-4 level is crucial for understanding the changes involving in malignant transformation, and also demonstrate that syndecan-4 emerges as an important target for cancer therapy and diagnosis.

Heparan sulfate proteoglycans (HSPGs) play important roles in cancer initiation and progression, by interacting with the signaling pathways that affect proliferation, adhesion, invasion and angiogenesis. These roles suggest the possibility of various strategies of regulation of these molecules. In this review, we demonstrated that the anticancer drugs can regulate the heparan sulfate proteoglycans activity in different ways: some act directly in core protein, and can bind to a specific type of HSPG. Others drugs interact with glycosaminoglycans chains, and others can act directly in enzymes that regulate HSPGs levels. We also demonstrated that the HSPGs drug targets can be divided into four groups: monoclonal antibodies, antitumor antibiotic, natural products, and mimetics peptide. Interestingly, many drugs demonstrated in this review are approved by FDA and is used in cancer therapy (Food and Drug Administration) like trastuzumab, panitumumab, bleomycin and bisphosphonate zoledronic acid (ASCO) or are in clinical trials like codrituzumab and genistein. This review should help researchers to understand the mechanism of action of anticancer drugs existing and also may inspire the discovery of new drugs that regulate the heparan sulfate proteoglycans activity.

The cell's resistance to cell death by adhesion loss to extracellular matrix (anoikis), contributes to tumor progression and metastasis. Various adhesion molecules are involved in the anoikis resistance, including the syndecan-4 (SDC4), a heparan sulfate proteoglycan (HSPG) present on the cell surface. Changes in the expression of SDC4 have been observed in tumor and transformed cells, indicating its involvement in cancer. In previous works, we demonstrated that acquisition of anoikis resistance resistance by blocking adhesion to the substrate up-regulates syndecan-4 expression in endothelial cells. This study investigates the role of SDC4 in the transformed phenotype of anoikis resistant endothelial cells. Anoikis-resistant endothelial cells (Adh1-EC) were transfected with micro RNA interference (miR RNAi) targeted against syndecan-4. The effect of SDC4 silencing was analyzed by real-time PCR, western blotting and immunofluorescence. Transfection with miRNA-SDC4 resulted in a sequence-specific decrease in syndecan-4 mRNA and protein levels. Furthermore, we observed a reduction in the number of heparan and chondroitin sulfate chains in the cell extract and culture medium. The SDC4 silencing led to downregulation of proliferative and invasive capacity and angiogenic abilities of anoikis-resistant endothelial cells. Compared with the parental cells (Adh1-EC), SDC4 silenced cells (SDC4 miR-Syn-4-1-Adh1-EC e miR-Syn-4-2-Adh1-EC) exhibited an increase in adhesion to collagen and laminin and also in the apoptosis rate. Moreover, transfection with miRNA-SDC4 caused a decrease in the number of cells in the S phase of the cell cycle. This is accompanied by an increase in the heparan sulfate synthesis after 12 h of simulation with fetal calf serum (FCS). SDC4 silencing cells are more dependent of growth factors present in the FCS to synthesize heparan sulfate than parental cells. Similar data were obtained for the wild-type cell line (EC). Our results indicated that downregulation of SDC4 expression reverses the transformed phenotype of anoikis resistant endothelial cells. These and other findings suggest that syndecan-4 is suitable for pharmacological intervention, making it an attractive target for cancer therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Trastuzumab (Tmab), an antibody for breast cancer, was incorporated in Langmuir monolayers with different lipidic compositions to investigate the drug action in lipidic interfaces of pharmaceutical interest. Tmab caused all lipid films to expand as confirmed with by surface pressure-area isotherm, proving its incorporation. It also affected the compressional and structural properties as observed by in-plane elasticity curves and polarization modulation reflection-absorption infrared spectroscopy (PM-IRRAS), respectively. Although Tmab did not change significantly the compressional modulus for dipalmitoylphosphatidylcholine (DPPC) monolayers, it decreased it for the mixtures of DPPC with cholesterol. In contrast, for dipalmitoylphosphoethanolamine (DPPE), Tmab increased the compressional modulus for both monolayers, pure DPPE or mixed with cholesterol. While Brewster Angle Microscopy showed discrete distinctive morphological patterns for the monolayers investigated, PM-IRRAS showed that Tmab caused an increased number of gauche conformers related to the CH 2 stretching mode for the lipid acyl chains, suggesting molecular disorder. Furthermore, the antibody kept the β-sheet structure of the polypeptide backbone adsorbed at the lipid monolayers although the secondary conformation altered according to the film composition at the air-water interface. As a result, the results suggest that the membrane lipid profile affects the adsorption of Tmab at lipid monolayers, which can be important for the incorporation of this drug in lipidic supramolecular systems like in liposomes for drug delivery and in biomembranes., Competing Interests: Declaration of Competing Interest I declare no conflict of interest of the above paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A chemoselective route for the synthesis of 1- O -alkylglycerols chimyl (1), batyl (2), and selachyl (3) is reported. These compounds can be naturally isolated from shark liver oil and the skin of animals such as stingrays and chimeras and exhibit potential anti-fouling activity. The synthetic approach developed in this work included two distinct methods of preparation. The first was based on solvent-free reactions catalyzed by onium quaternary salts (N and P) and ionic liquids; the second methodology was based on a series of one-pot reactions., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Trastuzumab (Tmab) is a monoclonal antibody administered as targeted therapy for HER2-positive breast cancer whose molecular interactions at the HER2 receptor microenvironment are not completely clarified yet. This paper describes the influence of Tmab in the molecular organization of films of biological-relevant molecules at the air water interface. For that, we spread components of tumorigenic and non-tumorigenic cells directly on the air-water interface. The physicochemical properties of the films were investigated with surface pressure-area isotherms and Brewster angle microscopy, and distinction between the cellular lines with higher or lower amount of HER2 could be detected based on the physicochemical properties of the interfacial films. The systems organized at the air-water interface were transferred to solid supports as Langmuir-Blodgett films and the nano-scale morphology investigated with atomic force microscopy. The overall results related to Tmab interacting with the films lead to the conclusion that Tmab tends to condense rich-HER2 films, causing irregular dimerization of the receptor protein, changing the membrane topography of the films, with formation of phases with different levels of reflectivity and aggregation morphology, and finally revealing that the interaction of the antibody with proteo-lipidic biointerfaces is modulated by the film composition. We believe that novel perspectives concerning the molecular interactions in the plasma membrane microenvironment through Langmuir monolayers can be obtained from this work in order to enhance the Tmab-based cancer therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Anoikis is a form of programmed cell death induced by loss of contact from neighboring cells or from their extracellular matrix (ECM). Many tumorigenic cells are anoikis resistant, facilitating cancer progression and metastasis. Trastuzumab is a monoclonal antibody used for the treatment of breast and gastric cell cancer, but its mechanism of action is not well elucidated and its target molecules not well defined. Heparan sulfate proteoglycans (HSPGs) and glycosaminoglycans (GAGs) play important roles in tumor development and in response of cancer cells to drugs. This study investigates the effect of trastuzumab on the expression of HSPGs and sulfated glycosaminoglycans (SGAGs) in anoikis-resistant endothelial cells. After trastuzumab treatment, endothelial cells resistant to anoikis show an increase in adhesion to fibronectin followed by a decrease in invasion, proliferation, and angiogenic capacity. In addition, a significant increase in the number of cells in the S phase of the cell cycle was also observed. In relation to HSPGs and SGAGs expression, we observed a decrease in syndecan-4 and perlecan expression, as well as in the heparan sulfate biosynthesis in anoikis-resistant endothelial cells after exposure to trastuzumab. Our results suggest that trastuzumab interacts with GAGs and proteoglycans of the cell surface and ECM and through this interaction controls cellular events in anoikis-resistant endothelial cells., (© 2019 Wiley Periodicals, Inc.)

Objective: to analyze aspects related to the increase or decrease of self-care in patients living with human immunodeficiency virus treated in a specialized outpatient service., Method: analytical cross-sectional study with 135 patients aged 18 and over, of both sexes, who are followed up on the service. The independent variables and outcomes were collected from the nursing consultation instrument, whose theoretical reference is the Orem's Theory. The data were analyzed by parametric approach. Relationships or differences were considered significant if p <0.05. The analysis was done with SPSS v21.0 software., Results: most participants were male (56.3%), with a mean age of 42.1 years. Patients who needed to conceal the diagnosis had less self-care (β = -0.72 (-1.38, -0.06), p <0.031). The chance of performing self-care decreased with increasing age (OR = 0.93 (0.89, 0.97), p <0.003). On the other hand, patients with a permanent partner had a higher chance of performing self-care (OR = 3.46 (1.27, 9.46), p <0.015)., Conclusion: aspects related to the increase or decrease of self-care in patients living with human immunodeficiency virus were evidenced. However, further studies are necessary to emphasize the analytical character of the self-care of these patients.

The objective of this study is to propose the use of specific synthetic lipid as an active substance (biocide) in the control of harmful aquatic microorganisms, such as pathogens and non-indigenous species, transported in ships' ballast water. The biocide candidate, without metal or halogen components, was produced from a sub-product of the edible oil industry, the lecithin. Laboratory assays were conducted with phytoplankton, zooplankton, and marine bacteria to evaluate the efficiency of the biocide. The study also considers specific biocide's characteristics related to environmental risks, such as chemical composition, persistence, bioaccumulation, and toxicity. Results showed that, in the first 24 h of treatment, the biocide effectively reduced the concentration of the planktonic micro-organisms to very low levels. Additionally, a preliminary risk evaluation pointed that biocide candidate has a low residual toxicity, also a low potential for persistence and bioaccumulation in the environment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To evaluate the treatment of eroded dentin (Sensodyne Repair & Protect™, Er:YAG laser and combinations). The occlusal surfaces of 25 third molars were sectioned 1.5 mm in thickness. After an erosion cycle (5 min in demineralizing solution + 3 h in remineralizing solution; six cycles a day for 8 days), the samples were divided into five groups (n = 5): (E) erosion - control; (ES) erosion + Sensodyne Repair & Protect (NovaMin); (EL) erosion + Er:YAG laser (40 mJ, 10 Hz, 0.4 W, 50 μs, 3.1 J/cm 2 , 63 W/cm 2 ); (ELS) erosion + Er:YAG laser + Sensodyne; and (ESL) erosion + Sensodyne + Er:YAG laser. Following storage in ultrapure water (37 °C/14 days), the Ca/P ratio was evaluated by EDXRF and the morphology surfaces examined in SEM. The percentage of exposed dentin tubules was calculated. One-way analysis of variance and Tukey's test at 5% were used to treat the data. The Ca/P ratio was higher in E and ES groups. More exposed dentin tubules were found in E group and less exposed tubules were found in the ES group (p < 0.0001). When the toothpaste and laser were combined, the number of occluded dentin tubules was higher when laser was performed first (ELS). A positive effect was found when the laser and toothpaste were combined.

Introduction: Chagas disease represents an important health problem with socioeconomic impacts in many Latin-American countries. It is estimated that 20% to 30% of the people infected by Trypanosoma cruzi will develop chronic Chagas cardiomyopathy (CCC), which is generally accompanied by heart failure (HF). Cardiac resynchronization therapy (CRT) may be indicated for patients with HF and electromechanical dysfunctions., Objective: The primary endpoint of this study was to analyze the response to CRT in patients with CCC, while the secondary endpoint was to estimate the survival rates of CRT responder patients., Methods: This is an observational, cross-sectional and retrospective study. The records of 50 patients with CRT pacing devices implanted between June 2009 and March 2017 were analyzed. For statistical analyses, Pearson's correlation was used along with Student's t-test, and survival was analyzed using the Kaplan-Meier method. A P value of <0.05 was considered significant., Results: Out of 50 patients, 56% were male, with a mean age of 63.4±13.3 years and an average CRT duration of 61.2±21.7 months. The mean QRS duration was 150.12±12.4 ms before and 116.04±2.2 ms after the therapy (P<0.001). The mean left ventricular ejection fractions (LVEF) were 29±7% and 39.1±12.2% before and after CRT, respectively (P<0.001). A total of 35 (70%) patients had a reduction of at least one New York Heart Association (NYHA) functional class after six months of therapy (P=0.014). The survival rate after 72 months was 45%., Conclusion: This study showed clinical improvement and a nonsignificant survival rate in patients with CCC after the use of CRT.

Syndecans are heparan sulfate proteoglycans characterized as transmembrane receptors that act cooperatively with the cell surface and extracellular matrix proteins. Syn4 knockdown was performed in order to address its role in endothelial cells (EC) behavior. Normal EC and shRNA-Syn4-EC cells were studied comparatively using complementary confocal, super-resolution and non-linear microscopic techniques. Confocal and super-resolution microscopy revealed that Syn4 knockdown alters the level and arrangement of essential proteins for focal adhesion, evidenced by the decoupling of vinculin from F-actin filaments. Furthermore, Syn4 knockdown alters the actin network leading to filopodial protrusions connected by VE-cadherin-rich junction. shRNA-Syn4-EC showed reduced adhesion and increased migration. Also, Syn4 silencing alters cell cycle as well as cell proliferation. Moreover, the ability of EC to form tube-like structures in matrigel is reduced when Syn4 is silenced. Together, the results suggest a mechanism in which Syndecan-4 acts as a central mediator that bridges fibronectin, integrin and intracellular components (actin and vinculin) and once silenced, the cytoskeleton protein network is disrupted. Ultimately, the results highlight Syn4 relevance for balanced cell behavior., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix. Anoikis resistance is a critical mechanism in tumor metastasis. Cancer cells deregulate and adapt their metabolism to survive in the absence of adhesion, spreading metastases to distant organs. These adaptations include abnormal regulation of growth factor receptors activating prosurvival signaling pathways, such as the Ras/ERK and PI3K/Akt pathways, and extracellular matrix remodeling, leading to metastasis by an increase of invasiveness and inhibiting anoikis. This study investigates the possible involvement of ECM components and signaling pathways in the regulation of resistance to anoikis in endothelial cells (EC). Endothelial cells submitted to stressful conditions by blocking adhesion to substrate (anoikis resistance) display an up-regulation of Ras/ERK and PI3k/Akt pathways by high expression of Ras, ERK, PI3K (p110α) and Akt (Thr 308). After ERK and PI3K inhibiting, all EC-derived cell lines studied showed lower growth, a decrease in invasive potential and a higher rate of apoptosis. Furthermore, anoikis-resistant cell lines display a decrease in the expression of fibronectin, collagen IV and hyaluronic acid and an increase in the expression of laminin, perlecan, αv, β3, α5 and β1 integrins subunits, hyaluronidades 1, 2 and 3 and metalloproteinases 2 and 9. These results indicate that the acquisition of anoikis resistance induced remodeling of the extracellular matrix and overexpression of the PI3K/Akt and Ras/ERK pathway components. Acquisition of resistance to anoikis is a potentially crucial step in endothelial cell transformation.

Objective: To evaluate the level and the persistence of maternal antibodies in infants after maternal immunization with pneumococcal polysaccharide vaccine (Pn23V)., Methods: Pregnant women were assigned to two groups, during routine low-risk pre-natal visits. The first Group (VAC) received the Pn23V vaccine shortly after enrolment at 28 weeks or later, and the second Group (NO&#95;VAC) received no vaccine. To investigate the antibody persistence, we collected blood samples from the mothers after 1 month of delivery and from the infants at 1 and 6 months of age., Results: Antibody titers were measured for serotypes 1, 6B and 14. Geometric mean antibody concentrations of specific immunoglobulin G were significantly higher in the vaccinated group compared with unvaccinated controls for all three serotypes tested., Conclusion: Despite the antibody level's decline, at 6 months of age, proportions  >0.35 μg/ml remained higher in the infants of vaccinated mothers than controls for all three serotypes., (© The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this study was to assess the performance of resin cements when different curing modes are used, by evaluating the degree of conversion and bond strength to a ceramic substrate., Material and Methods: Three resin cements were evaluated, two dual-cured (Variolink II and RelyX ARC) and one light-cured (Variolink Veneer). The dual-cured resin cements were tested by using the dual activation mode (base and catalyst) and light-activation mode (base paste only). For degree of conversion (DC) (n=5), a 1.0 mm thick feldspathic ceramic disc was placed over the resin cement specimens and the set was light activated with a QTH unit. After 24 h storage, the DC was measured with Fourier transform infrared spectroscopy (FTIR). For microshear bond strength testing, five feldspathic ceramic discs were submitted to surface treatment, and three cylindrical resin cement specimens were bonded to each ceramic surface according to the experimental groups. After 24 h, microshear bond testing was performed at 0.5 mm/min crosshead speed until the failure. Data were submitted to one-way ANOVA followed by Tukey test (p<0.05). Scanning electron microscopy (SEM) was used for classifying the failure modes., Results: Higher DC and bond strength values were shown by the resin cements cured by using the dual activation mode. The Variolink II group presented higher DC and bond strength values when using light-activation only when compared with the Variolink Veneer group., Conclusion: The base paste of dual-cured resin cements in light-activation mode can be used for bonding translucent ceramic restorations of up to or less than 1.0 mm thick.

Cadmium selenide (CdSe) magic-sized quantum dots (MSQDs) are semiconductor nanocrystals with stable luminescence that are feasible for biomedical applications, especially for in vivo and in vitro imaging of tumor cells. In this work, we investigated the specific interaction of CdSe MSQDs with tumorigenic and non-tumorigenic cells using Langmuir monolayers and Langmuir-Blodgett (LB) films of lipids as membrane models for diagnosis of cancerous cells. Surface pressure-area isotherms and polarization modulation reflection-absorption spectroscopy (PM-IRRAS) showed an intrinsic interaction between the quantum dots, inserted in the aqueous subphase, and Langmuir monolayers constituted either of selected lipids or of tumorigenic and non-tumorigenic cell extracts. The films were transferred to solid supports to obtain microscopic images, providing information on their morphology. Similarity between films with different compositions representing cell membranes, with or without the quantum dots, was evaluated by atomic force microscopy (AFM) and confocal microscopy. This study demonstrates that the affinity of quantum dots for models representing cancer cells permits the use of these systems as devices for cancer diagnosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This experiment was conducted with the aim of estimating the ME requirements of free-range laying hens for maintenance, weight gain, and egg production. These experiments were performed to develop an energy requirement prediction equation by using the comparative slaughter technique and the total excreta collection method. Regression equations were used to relate the energy intake, the energy retained in the body and eggs, and the heat production of the hens. These relationships were used to determine the daily ME requirement for maintenance, the efficiency energy utilization above the requirements for maintenance, and the NE requirement for maintenance. The requirement for weight gain was estimated from the energy content of the carcass, and the diet's efficiency energy utilization was determined from the weight gain, which was measured during weekly slaughter. The requirement for egg production was estimated by considering the energy content of the eggs and the efficiency of energy deposition in the eggs. The requirement and efficiency energy utilization for maintenance were 121.8 kcal ME/(kg∙d)and 0.68, respectively. Similarly, the NE requirement for maintenance was 82.4 kcal ME/(kg∙d), and the efficiency energy utilization above maintenance was 0.61. Because the carcass body weight and energy did not increase during the trial, the weight gain could not be estimated. The requirements for egg production requirement and efficiency energy utilization for egg production were 2.48 kcal/g and 0.61, respectively. The following energy prediction equation for free-range laying hens (without weight gain) was developed: ME /(hen ∙ d) = 121.8 × W + 2.48 × EM, in which W = body weight (kg) and EM = egg mass (g/[hen ∙ d]).

Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonization of distant organs. Cell adhesion plays an important role in neoplastic transformation. Tumors produce several molecules that facilitate their proliferation, invasion and maintenance, especially proteoglycans. The syndecan-4, a heparan sulfate proteoglycan, can act as a co-receptor of growth factors and proteins of the extracellular matrix by increasing the affinity of adhesion molecules to their specific receptors. It participates together with integrins in cell adhesion at focal contacts connecting the extracellular matrix to the cytoskeleton. Changes in the expression of syndecan-4 have been observed in tumor cells, indicating its involvement in cancer. This study investigates the role of syndecan-4 in the process of anoikis and cell transformation. Endothelial cells were submitted to sequential cycles of forced anchorage impediment and distinct lineages were obtained. Anoikis-resistant endothelial cells display morphological alterations, high rate of proliferation, poor adhesion to fibronectin, laminin and collagen IV and deregulation of the cell cycle, becoming less serum-dependent. Furthermore, anoikis-resistant cell lines display a high invasive potential and a low rate of apoptosis. This is accompanied by an increase in the levels of heparan sulfate and chondroitin sulfate as well as by changes in the expression of syndecan-4 and heparanase. These results indicate that syndecan-4 plays a important role in acquisition of anoikis resistance and that the conferral of anoikis resistance may suffice to transform endothelial cells.

Objective: The nursing workload consists of the time spent by the nursing staff to perform the activities for which they are responsible, whether directly or indirectly related to patient care. The aim of this study was to evaluate the nursing workload in an adult intensive care unit at a university hospital using the Nursing Activities Score (NAS) instrument., Methods: A longitudinal, prospective study that involved the patients admitted to the intensive care unit of a university hospital between March and December 2008. The data were collected daily to calculate the NAS, the Acute Physiology and Chronic Health Evaluation (APACHE II), the Sequential Organ Failure Assessment (SOFA) and the Therapeutic Intervention Scoring System (TISS-28) of patients until they left the adult intensive care unit or after 90 days of hospitalization. The level of significance was set at 5%., Results: In total, 437 patients were evaluated, which resulted in an NAS of 74.4%. The type of admission, length of stay in the intensive care unit and the patients' condition when leaving the intensive care unit and hospital were variables associated with differences in the nursing workload. There was a moderate correlation between the mean NAS and APACHE II severity score (r=0.329), the mean organic dysfunction SOFA score (r=0.506) and the mean TISS-28 score (r=0.600)., Conclusion: We observed a high nursing workload in this study. These results can assist in planning the size of the staff required. The workload was influenced by clinical characteristics, including an increased workload required for emergency surgical patients and patients who died.

Bracken (Pteridium aquilinum) is a carcinogenic plant whose main toxin, ptaquiloside, causes cancer in farm and laboratory animals. Ptaquiloside contaminates underground waters as well as meat and milk from bracken-grazing animals and is a suspected human carcinogen. A better understanding of the underlying mechanisms of carcinogenesis can be achieved by studying the early stages of this process. Unfortunately, most research on ptaquiloside has focused on the late, malignant, lesions, so the early changes of ptaquiloside-induced carcinogenesis remain largely unknown. This study aims to characterize early-stage ptaquiloside-induced urinary bladder lesions both morphologically and immunohistochemically. 12 male CD-1 mice were administered 0.5 mg ptaquiloside intraperitoneally, weekly, for 15 weeks, followed by 15 weeks without treatment. 12 control animals were administered saline. Bladders were tested immunohistochemically for antibodies against a cell proliferation marker (Ki-67), and two cell adhesion markers (E-cadherin and β-catenin). Two exposed animals died during the work. Six ptaquiloside-exposed mice developed low-grade and two developed high grade urothelial dysplasia. No lesions were detected on control animals. Significantly, increased (p < 0.05) Ki-67 labeling indices were found on dysplastic urothelium from ptaquiloside-exposed mice, compared with controls. No differences were found concerning E-cadherin and β-catenin expression. Early-stage ptaquiloside-induced urothelial lesions show increased cell proliferation but there is no evidence for reduced intercellular adhesiveness, though this may be a later event in tumor progression., (Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.)

Carrageenans have unique properties in the pharmaceutical and food industries that involve interactions with lipid interfaces, which may be accessed if surface chemistry techniques are employed. The interaction between three different types of carrageenans with dipalmitoylphosphatidylcholine (DPPC) was investigated using Langmuir monolayers as biointerface models. With a combination of data on Surface Pressure-Area Isotherms and Polarization Modulation Infrared Reflection-Absorption Spectroscopy (PM-IRRAS), the effect of different fractions on DPPC monolayers was compared by considering the chemical and structural differences as well as the anticoagulant activity of each fraction. Thus, a model is proposed in which carrageenans can encompass interactions that are maximized due to geometrical adaptations on behalf of the interactions between polysaccharide sulfate groups and lipid polar heads., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Investigating the role of drugs whose pharmaceutical activity is associated with cell membranes is fundamental to comprehending the biochemical processes that occur on membrane surfaces. In this work, we examined the action of 1,4-naphthoquinone in lipid Langmuir monolayers at the air-water interface, which served as a model for half of a membrane, and investigated the molecular interactions involved with tensiometry and vibrational spectroscopy. The surface pressure-area isotherms exhibited a noticeable shift to a lower area in relation to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dihexadecanoyl-sn-glycero-3-phospho-l-serine (DPPS) lipid monolayers, which indicated a disruption of the monolayer structure and solubilisation of the lipids towards the aqueous subphase. To better correlate to the action of this drug in biological membrane events, cell cultures that represented tumorigenic and non-tumorigenic cells were spread onto the air-water interface, and 1,4-naphthoquinone was then incorporated. While only slight changes were observed in the non-tumorigenic cells upon drug incorporation, significant changes were observed in the tumorigenic cells, on which the organisation of the Langmuir monolayers was disrupted as evidenced by tensiometry and vibrational spectroscopy. This work then shows that this drug interacts preferentially for specific surfaces. In simplified models, it has a higher effect for the negative charged DPPS rather than the zwitterionic DPPC; and for complex cell cultures, 1,4-naphthoquinone presents a more significant effect for that representing tumorigenic cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Although several histopathological and clinical features of canine mammary gland tumours have been widely studied from a prognostic standpoint, considerable variations in tumour individual biologic behaviour difficult the definition of accurate prognostic factors. It has been suggested that the malignant behaviour of tumours is the end result of several alterations in cellular physiology that culminate in tumour growth and spread. Accordingly, the aim of this study was to determine, using a multivariable model, the independent prognostic value of several immunohistochemically detected tumour-associated molecules, such as MMP-9 and uPA in stromal cells and Ki-67, TIMP-2 and VEGF in cancer cells., Results: Eighty-five female dogs affected by spontaneous malignant mammary neoplasias were followed up for a 2-year post-operative period. In univariate analysis, tumour characteristics such as size, mode of growth, regional lymph node metastases, tumour cell MIB-1 LI and MMP-9 and uPA expressions in tumour-adjacent fibroblasts, were associated with both survival and disease-free intervals. Histological type and grade were related with overall survival while VEGF and TIMP-2 were not significantly associated with none of the outcome parameters. In multivariable analysis, only a MIB-1 labelling index higher than 40% and a stromal expression of MMP-9 higher than 50% retained significant relationships with poor overall and disease-free survival., Conclusions: The results of this study indicate that MMP-9 and Ki-67 are independent prognostic markers of canine malignant mammary tumours. Furthermore, the high stromal expressions of uPA and MMP-9 in aggressive tumours suggest that these molecules are potential therapeutic targets in the post-operative treatment of canine mammary cancer.

Investigating the role of proteoglycans associated to cell membranes is fundamental to comprehend biochemical process that occurs at the level of membrane surfaces. In this paper, we exploit syndecan-4, a heparan sulfate proteoglycan obtained from cell cultures, in lipid Langmuir monolayers at the air-water interface. The monolayer served as a model for half a membrane, and the molecular interactions involved could be evaluated with tensiometry and vibrational spectroscopy techniques. Polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) employed in a constant surface pressure regime showed that the main chemical groups for syndecan-4 were present at the air-water interface. Subsequent monolayer decompression and compression showed surface pressure-area isotherms with a large expansion for the lipid monolayers interacting with the cell culture reported to over-express syndecan-4, which was also an indication that the proteoglycan was inserted in the lipid monolayer. The introduction of biological molecules with affinity for syndecam-4, such as growth factors, which present a key role in biochemical process of cell signaling, changed the surface properties of the hybrid film, leading to a model, by which the growth factor binds to the sulfate groups present in the heparan sulfate chains. The polypeptide moiety of syndecan-4 responds to this interaction changing its conformation, which leads to lipid film relaxation and further monolayer condensation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To immunohistochemically evaluate matrix metalloproteinase (MMP)-9 expression in benign and malignant mammary gland tumors (MMTs) in dogs and relate expression to prognostic factors and patient outcome., Animals: 118 female dogs with naturally occurring mammary gland tumors and 8 dogs without mammary gland tumors., Procedures: 24 benign mammary gland tumors and 94 MMTs (1/affected dog) were obtained during surgical treatment; control mammary gland tissue samples were collected from unaffected dogs after euthanasia for reasons unrelated to the study. Tumors were evaluated for proliferation, invasive growth, histologic grade, and metastatic capacity; expression of MMP-9 was determined immunohistochemically, and its relationship with clinical and histologic findings was investigated. For dogs with MMTs, follow-up continued for 2 years; data were used to compute overall survival time and disease-free interval and construct survival curves., Results: MMTs had significantly higher MMP-9 expression in stromal cells and in neo-plastic cells than did the benign neoplasms. Stromal MMP-9 expression was also higher in highly proliferative tumors and in tumors with invasive growth, high histologic grade, and metastatic capacity. Furthermore, tumors from patients with shorter overall survival times and disease-free intervals had higher expression of MMP-9 in stromal cells., Conclusions and Clinical Relevance: In dogs with MMTs, level of MMP-9 expression by stromal cells was related to factors of poor prognosis and shorter overall survival times and disease-free intervals. These results suggested that MMP-9 produced by tumor-adjacent stromal cells contributed to MMT progression in female dogs and that assessment of MMP-9 expression may be a valuable prognostic factor.

Merkel cells carcinoma is a rare cutaneous neoplasia. Studies revealed an increase in the occurrence from 0.15 to 0.44 cases for every 100.000 inhabitants between 1986 and 2001. Around 50% of the patients, eventually, develop systemic disease, being the most common sites the liver, the bones and the brain. The etiology is still unknown. The present study presents a new case of Merkel cells carcinoma in extremity, treated with local resection and adjuvant radiotherapy.

Bracken (Pteridium aquilinum) has long been known to cause cancer in farm and laboratory animals. Ptaquiloside, a norsesquiterpene glycoside found in bracken, is considered its main carcinogenic toxin and is capable of inducing tumours in a variety of organ systems, but especially in the urinary bladder, depending on the animal species, the administration route employed and the duration of exposure. In the present study, 12 male CD-1 mice were intraperitoneally administered with 0.5 mg ptaquiloside weekly for 15 weeks, followed by 15 weeks without any treatment. Twelve animals used as controls were administered the vehicle solution (phosphate buffered saline). Two exposed animals died during the experimental work. On necropsy, blood and tissue samples (brain, eyes, thymus, heart, lungs, liver, digestive system, spleen, bladder, kidney, adrenal gland, urinary bladder, sexual accessory glands, testes, muscle, skin and femur) were collected for histological analysis. Leukograms were prepared from blood smears and total WBC counts obtained with a Neubauer chamber. Flow cytometry was used to assess blood T-(CD3(+)) and B-(CD19(+))-lymphocytes, medullary granulocytic (CD11b(+)/Ly-6G(-), CD11b(+)/Ly-6G(+)) and lymphocytic (CD19(+)/IgM(-), CD19+/IgM(+)) populations and thymic lymphoid (CD4(+), CD8(+), CD4(+)/CD8(+)) populations. Lymphoproliferative lesions were analysed immunohistochemically using antibodies against CD45R and CD3. All of the 10 surviving mice developed a lymphoproliferative malignancy. Lymphoproliferative disease was characterized by multifocal B-(CD45(+)/CD3(-))-lymphocytic renal (10/10 animals) and hepatic (2/10 animals) invasion, splenic white pulp hyperplasia (10/10) together with a significant increase in circulating B-(CD19(+))-lymphocytes and the appearance of circulating dysplastic lymphoid cells. Eight out of 10 ptaquiloside-exposed animals developed urothelial dysplasia (six low-grade dysplasia and two high-grade dysplasia). No lesions were detected in control mice. These results show that ptaquiloside is capable of inducing malignant transformation in mice and provide an in-depth characterisation of lymphoproliferative lesions. Furthermore, the urinary bladder is shown to be a target organ for this toxin in mice as well as in other animal species., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Context: Brain metastases are common complications of cancer. Magnetic resonance imaging (MRI), the main diagnostic imaging method in these cases, rarely shows cystic images., Case Report: The patient was a 45-year-old woman who had had severe headache for a month that was refractory to medication, and had previously had breast cancer, which had been treated. The MRI showed the criteria for neurocysticercosis. Since there was no improvement with clinical treatment, we chose to excise the lesions. Histopathological analysis showed an epithelioid malignant neoplasm., Conclusion: From immunohistochemical analysis, it was concluded that this was a metastasis of breast carcinoma. Even when the MRI is not characteristic of cerebral metastasis, this hypothesis needs to be ruled out in patients with a previous history of cancer.

The current work aimed to identify the source of an oil spill off the coast of Maranhão, Brazil, in September 2005 and effect a preliminary geochemical survey of this environment. A combination of bulk analytical parameters, such as carbon isotope (δ(13)C) and Ni/V ratios, and conventional fingerprinting methods (High Resolution Gas Chromatography and Mass Spectrometry) were used. The use of bulk methods greatly speeded source identification for this relatively unaltered spill: identification of the likely source was possible at this stage. Subsequent fingerprinting of biomarker distributions supported source assignment, pointing to a non-Brazilian oil. Steranes proved the most useful biomarkers for sample correlation in this work. Distribution patterns of environmentally more resilient compound types, such as certain aromatic structures, proved inconclusive for correlation, probably in view of their presence in the background., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The histopathological and clinical aspects of canine mammary tumours (CMTs) have been widely studied, but the variation in the biological behaviour of these neoplasms hampers the identification of prognostic factors. Sustained angiogenesis has been suggested to be one of the most important factors underlying tumour growth and invasion. This process involves the action of several growth factors including vascular endothelial growth factor (VEGF). The present study characterizes the relationship between immunohistochemical expression of VEGF and gross (e.g. size and tissue fixation) and microscopical (e.g. type, growth, necrosis, lymphoid infiltration, lymph node metastasis, histological grade and proliferation index) features of CMTs. Forty-eight benign and 64 malignant CMTs were evaluated. Statistical analysis failed to show a significant relationship between VEGF expression and the pathological features, suggesting that VEGF expression occurs in both benign and malignant tumours and is independent of histological type, proliferation, tissue invasion or local metastatic capacity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: To validate the psychometric properties of the Brazilian version of the 2007 Youth Risk Behavior Survey (YRBS) questionnaire., Methods: The original version of the 2007 YRBS was translated into Portuguese and back-translated into English. The questionnaire versions were analyzed by a committee of experts. The committee used semantic, idiomatic, cultural and conceptual equivalences as criteria of analysis. The final version of the translated 2007 YRBS questionnaire was administered in two occasions, with an interval of two weeks, in a sample of 873 high school students of both sexes, in the city of Londrina, Southern Brazil, to identify the psychometric properties. Test-retest reliability was analyzed by calculating the Kappa index of agreement and prevalence rate of each type of risk behavior when application was repeated. Chi-square test was used to identify statistical differences between the first and second questionnaire applications., Results: After minor changes identified in the translation process, the committee of experts concluded that the Portuguese version of the 2007 YRBS showed semantic, idiomatic, cultural and conceptual equivalences. Significant differences between the prevalence rates of both applications were found in 23.4% of items. The identification of 91% of items with moderate-to-substantial Kappa index of agreement and mean value of this index of 68.6% indicated the quality of psychometric properties of the Portuguese version of the 2007 YRBS., Conclusions: The translation, cross-cultural adaptation and psychometric qualities of the 2007 YRBS questionnaire were satisfactory, thus enabling its application in epidemiological studies in Brazil.