Cognitive impairments associated with chemotherapy in women with breast cancer: a meta-analysis and meta-regression.

Chemotherapy is one of the most widely used treatments for breast cancer (BC). However, there is evidence of side effects like cognitive changes related to the chemotherapy treatment. The aim of the study was not only to summarize the existing evidence on the relationship between chemotherapy and cognitive performance in women with BC but also to identify additional consequences and aspects associated with these impairments. We conducted a systematic review with meta-analysis and meta-regression to present updated information on the matter. We retrieved data from the databases PubMed, Web of Science, PsycINFO, CINAHL, and Scopus. Twenty studies comprising over 2,500 women were examined and the results indicated that chemotherapy can compromise cognition in women with BC (-1.10 OR [95%CI: -1.81 to -0.74], P<0.01), with working memory (-0.49 OR [95%CI: -0.85 to -0.13], P=0.03) being the most affected among the domains. Furthermore, additional data indicated that cognitive impairment is most likely amid women with BC having a lower education level (Q=4.85, P=0.02). Our results suggested that chemotherapy affects cognitive functions in women with BC, and certain characteristics can worsen the deterioration. A comprehensive study of women with breast cancer and existing predictors contributes to optimized personal journeys, elevated life prospects, and advanced care that can also aid prognosis and therapeutic approaches.

Cognitive impairments associated with chemotherapy in women with breast cancer: a meta-analysis and meta-regression

Chemotherapy is one of the most widely used treatments for breast cancer (BC). However, there is evidence of side effects like cognitive changes related to the chemotherapy treatment. The aim of the study was not only to summarize the existing evidence on the relationship between chemotherapy and cognitive performance in women with BC but also to identify additional consequences and aspects associated with these impairments. We conducted a systematic review with meta-analysis and meta-regression to present updated information on the matter. We retrieved data from the databases PubMed, Web of Science, PsycINFO, CINAHL, and Scopus. Twenty studies comprising over 2,500 women were examined and the results indicated that chemotherapy can compromise cognition in women with BC (-1.10 OR [95%CI: -1.81 to -0.74], P<0.01), with working memory (-0.49 OR [95%CI: -0.85 to -0.13], P=0.03) being the most affected among the domains. Furthermore, additional data indicated that cognitive impairment is most likely amid women with BC having a lower education level (Q=4.85, P=0.02). Our results suggested that chemotherapy affects cognitive functions in women with BC, and certain characteristics can worsen the deterioration. A comprehensive study of women with breast cancer and existing predictors contributes to optimized personal journeys, elevated life prospects, and advanced care that can also aid prognosis and therapeutic approaches.

Resveratrol-Loaded Lipid Nanocarriers Are Internalized By Endocytosis in Yeast.

Different positive pharmacological effects have been attributed to the natural product resveratrol (RSV), including antioxidant, antiaging, and cancer chemopreventive properties. However, its low bioavailability and rapid metabolic degradation has led to the suspicion that many of the biological activities of this compound observed in vitro may not be attainable in humans. To improve its bioavailability and pharmacokinetic profile, attempts have been made to encapsulate RSV into lipid-based nanocarrier systems. Here, the dioctadecyldimethylammonium bromide (DODAB):monoolein (MO) liposomal system (1:2) loaded with RSV revealed appropriate characteristics for drug release purposes: reduced size for cellular uptake (157 ± 23 nm), stability up to 80 days, positive surface charge (ζ ≈ +40 mV), and a controlled biphasic release of RSV from the lipid nanocarriers over a period of almost 50 h at pH 5.0 and 7.4. Moreover, the encapsulation efficiency of the nanocarrier ranged from 70% to 92% and its RSV loading capacity from 9% to 14%, when [RSV] was between 100 and 200 µM. The partition coefficient ( Kp) of RSV between lipid and aqueous phase was log Kp = 3.37 ± 0.10, suggesting moderate to high lipophilicity of this natural compound and reinforcing the lipid nanocarriers' suitability for RSV incorporation. The thermodynamic parameters of RSV partitioning in the lipid nanocarriers at 37 °C (Δ H = 43.76 ± 5.68 kJ mol-1; Δ S = 0.20 ± 0.005 kJ mol-1; and Δ G = -18.46 ± 3.48 kJ mol-1) reflected the spontaneity of the process and the establishment of hydrophobic interactions. The cellular uptake mechanism of the RSV-loaded nanocarriers labeled with the lipophilic fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was studied in the eukaryotic model system Saccharomyces cerevisiae. Thirty minutes after incubation, yeast cells readily internalized nanocarriers and the spots of blue fluorescence of DPH clustered around the central vacuole in lipid droplets colocalized with the green fluorescence of the lipophilic endocytosis probe FM1-43. Subsequent studies with the endocytosis defective yeast deletion mutant ( end3Δ) and with the endocytosis inhibitor methyl-ß-cyclodextrin supported the involvement of an endocytic pathway. This novel nanotechnology approach opens good perspectives for medical applications.

Lipid-based Nanocarriers for siRNA Delivery: Challenges, Strategies and the Lessons Learned from the DODAX: MO Liposomal System.

The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a diversity of nanocarriers has been described, liposomes continue to be one of the most attractive siRNA vehicles due to their relatively low toxicity, facilitated siRNA complexation, high transfection efficiency and enhanced pharmacokinetic properties. This review focuses on RNAi as a therapeutic approach, the challenges to its application, namely the nucleic acids' delivery process, and current strategies to improve therapeutic efficacy. Additionally, lipid-based nanocarriers are described, and lessons learned from the relation between biophysical properties and biological performance of the dioctadecyldimethylammonium:monoolein (DODAX: MO) system are explored. Liposomes show great potential as siRNA delivery systems, being safe nanocarriers to protect nucleic acids in circulation, extend their half-life time, target specific cells and reduce off-target effects. Nevertheless, several issues related to delivery must be overcome before RNAi therapies reach their full potential, namely target-cell specificity and endosomal escape. Understanding the relationship between biophysical properties and biological performance is an essential step in the gene therapy field.

Structural dynamics and physicochemical properties of pDNA/DODAB:MO lipoplexes: effect of pH and anionic lipids in inverted non-lamellar phases versus lamellar phases.

Dioctadecyldimethylammonium bromide (DODAB):Monoolein (MO) lipoplexes have mainly been studied within the range of high molar ratios of DODAB, with noticeable transfection efficiencies in the Human Embryonic Kidney (HEK, a.k.a. 293T) cell line. In this work, we intend to study the effect of high MO content on the structure and physicochemical properties of pDNA/DODAB:MO lipoplexes to achieve some correlation with their transfection efficiency. Static/Dynamic Light Scattering and Cryo-TEM imaging were used to characterize the size/morphology of DNA/DODAB:MO lipoplexes at different DODAB:MO contents (2:1, 1:1, 1:2) and charge ratios (CRs) (+/-). Nile Red fluorescence emission was performed to detect changes in microviscosity, hydration and polarity of DNA/DODAB:MO systems. Lipoplexes stability at physiological pH values and in the presence of anionic lipids was evaluated by Förster Resonance Energy Transfer (FRET). Physicochemical/structural data were complemented with transfection studies in HEK cells using the ß-galactosidase reporter gene activity assay. This work reports the coexistence of multilamellar and non-lamellar inverted phases in MO-richer lipoplexes (DODAB:MO 1:2 and 1:4), leading to transfection efficiencies comparable to those of multilamellar (DODAB-richer) lipoplexes, but at higher charge ratios [CR (+/-)=6.0] and without dose-effect response. These results may be related to the structural changes of lipoplexes promoted by high MO content.

DODAB:monoolein-based lipoplexes as non-viral vectors for transfection of mammalian cells.

DNA/Cationic liposome complexes (lipoplexes) have been widely used as non-viral vectors for transfection. Neutral lipids in liposomal formulation are determinant for transfection efficiency using these vectors. In this work, we studied the potential of monoolein (MO) as helper lipid for cellular transfection. Lipoplexes composed of pDNA and dioctadecyldimethylammonium bromide (DODAB)/1-monooleoyl-rac-glycerol (MO) at different molar ratios (4:1, 2:1 and 1:1) and at different cationic lipid/DNA ratios were investigated. The physicochemical properties of the lipoplexes (size, charge and structure), were studied by Dynamic Light Scattering (DLS), Zeta Potential (ζ) and cryo-transmission electron microscopy (cryo-TEM). The effect of MO on pDNA condensation and the effect of heparin and heparan sulphate on the percentage of pDNA release from the lipoplexes were also studied by Ethidium Bromide (EtBr) exclusion assays and electrophoresis. Cytotoxicity and transfection efficiency of these lipoplexes were evaluated using 293T cells and compared with the golden standard helper lipids 1,2-dioleoyl-sn-glycero-3-hosphoethanolamine (DOPE) and cholesterol (Chol) as well as with a commercial transfection agent (Lipofectamine™ LTX). The internalization of transfected fluorescently-labeled pDNA was also visualized using the same cell line. The results demonstrate that the presence of MO not only increases pDNA compactation efficiency, but also affects the physicochemical properties of the lipoplexes, which can interfere with lipoplex-cell interactions. The DODAB:MO formulations tested showed little toxicity and successfully mediated in vitro cell transfection. These results were supported by fluorescence microscopy studies, which illustrated that lipoplexes were able to access the cytosol and deliver pDNA to the nucleus. DODAB:MO-based lipoplexes were thus validated as non-toxic, efficient lipofection vectors for genetic modification of mammalian cells. Understanding the relation between structure and activity of MO-based lipoplexes will further strengthen the development of these novel delivery systems.

Characterization of monoolein-based lipoplexes using fluorescence spectroscopy.

Lipoplexes are commonly used as delivery systems in vitro and in vivo, the role of a neutral lipid as helper being of extreme importance in these systems. Cationic liposomes composed of dioctadecyldimethylammonium bromide (DODAB) with monoolein (MO) as a helper, at different molar ratios (1:2; 1:1 and 1:0.5) were prepared, and subsequently titrated to DNA. The structural and physicochemical properties of the lipid/DNA complexes were assessed by ethidium bromide (EtBr) exclusion, 90 degrees static light scattering (90 degrees SLS) assays and fluorescence resonance energy transfer (FRET). In EtBr exclusion assays, the steady-state fluorescence spectra of EtBr were decomposed into the sum of two lognormal emissions, emanating from two different environments--H(2)O and DNA, and the effect of charge ratio (+/-) was observed. 90 degrees SLS assays gave an important contribution, detecting size variations in systems with different MO fractions on the lipoplexes. In FRET assays, 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine (DPH-HPC) was used as donor and EtBr as acceptor. The DNA component previously calculated by EtBr exclusion, was used to determine the energy transfer efficiency, as an indirect measurement of the lipoplexes structural and physicochemical properties. Our results demonstrate that the inclusion of monoolein in the cationic liposomes formulation significantly modifies the rate of DNA complexation, being DODAB:MO (1:1) the system with higher DNA condensation efficiency.

The effect of lens wear on refractive index of conventional hydrogel and silicone-hydrogel contact lenses: a comparative study.

PURPOSE: The purpose of this work was to evaluate the ability of four silicone-hydrogel contact lenses (galyfilcon A, balafilcon A, lotrafilcon A and lotrafilcon B) to retain their equilibrium water content before and after wear, through measurements of refractive index and compare with that of a conventional disposable hydrogel contact lens (etafilcon A). METHODS: The refractive indices of 115 contact lenses were measured using an automated refractometer (CLR 12-70, Index Instruments, Cambridge, U.K.) before and after a schedule of daily wear by 58 patients for 30 days in the case of silicone-hydrogel lenses and 15 days for the conventional contact lenses. RESULTS: In the silicone-hydrogel contact lenses the changes on the refractive indices were not statistically significant, however after being worn the refractive index of the conventional etalfilcon A hydrogel contact lens increased significantly (p<0.001). CONCLUSION: The results presented here show that after being worn the silicone-hydrogel contact lens, show more capacity to retain or to reach their initial equilibrium water content than conventional hydrogel contact lenses. This suggests that the silicone-hydrogel contact lenses are less susceptible to spoilation over time maintaining its biocompatibility and contributing to the clinical success of lens performance.

Reatividade em ambiente de contenção móvel: uma nova metodologia para avaliar o temperamento bovino / Animal reactivity in a mobile cage: a new methodology to access bovine temperament

Descreve-se uma nova metodologia para medir o temperamento dos bovinos por meio da reatividade, obtida por um dispositivo eletrônico que quantifica o número e a intensidade dos movimentos do animal em ambiente de contenção móvel, numa escala de 1 a 9.999 pontos. A reatividade foi comparada a características determinadas por outros dois métodos tradicionais para quantificar o temperamento bovino: a velocidade de fuga e o escore de temperamento. Foram utilizados 610 bovinos da raça Nelore, com média de idade de 467 dias e provenientes de dois rebanhos. As observações da reatividade não se ajustaram às distribuições normal, Poisson e binomial negativa. A padronização e as transformações logarítmicas neperianas e na base 10 não foram eficientes para adequar os dados à distribuição normal. Os animais avaliados para a característica apresentaram grande variabilidade fenotípica, com reatividade média de 534±447 pontos na escala original, mediana 442 pontos, moda 372 pontos, variação de 1 a 2.218 pontos e coeficiente de variação de 84 por cento. A correlação de classificação de resíduos encontrada entre reatividade e escore de temperamento variou de 0,75 a 0,85 (P<0,001) e foi superior em valores absolutos às correlações entre reatividade e velocidade de fuga e entre velocidade de fuga e escore de temperamento. A nova metodologia é eficiente para quantificar o temperamento de animais da raça Nelore e possui vantagens em relação às características velocidade de fuga e escore de temperamento. A obtenção da reatividade animal é rápida, prática, objetiva e segura para quem a faz, além de apresentar grande variabilidade fenotípica.

This paper describes a new methodology to access bovine temperament using it's reactivity eletronically measured as the intensity and count of movements in a mobile cage, using a scale from 1 to 9,999 points. The new trait, reactivity, was compared to two other traditional methods, flying speed and temperament scores. Six hundred and ten contemporary Nellores, with average age of 467 days and from two herds were used. Reactivity data did not fit Normal nor Poisson nor Negative Binomial Distibutions. Standartized reactivity data, neperian and base 10 log reactivity transformations were not successful in adjusting data to normal distribution. Reactivity presented large phenotipic variation, with average in the original scale of 534±447 points, median of 442, mode 372, range from 1 to 2,218 points and variation coefficient of 84 percent. Residual rank correlation between reactivity and temperament score vary from .75 to .85 (P<.001), and were larger than the ones between reactivity and flight speed and between flight speed and temperament score. The new methodology is efficient in measuring temperament of Nellore cattle and it has advantages in relation to the traits flight speed and temperament score. The measure of reactivity is easy, fast to get and safe to record. In addition, this trait presents large variability.

Effect of pH on the control release of microencapsulated dye in lecithin liposomes. II.

The objective of our work has been the microencapsulation of dyes with lecithin from soybean, with the formation of liposomes, as a substitute for synthetic auxiliaries so as to improve the quality of the effluent. Current scenarios promote the disintegration and leakage of the liposomes, such as, changes in temperature, pH, and the use of surfactants. Since dyeing process is a mix of all these parameters, we pretended to study each one separately. Changes in pH at constant temperature induce a release of dye similar with changes in temperature. In acid conditions, we found a very fast initial dye release which doesn't occur in basic conditions. Using carboxyfluorescein, as a pH fluorescence probe, we concluded that the liposome membrane doesn't protect the liposome interior from changes on the external pH.

Effect of temperature and surfactant on the control release of microencapsulated dye in lecithin liposomes. I.

The objective of our work has been the microencapsulation of dyes with lecithin from soybean, with the formation of liposomes, as a substitute for synthetic auxiliaries so as to improve the quality of the effluent. Current scenarios promote the disintegration and leakage of the liposomes, such as, changes in temperature, pH and the use of surfactants. Since dyeing process is a mix of all these parameters, we pretended to study each one separately. Rhodamine 6G fluorescence is known to be concentration quenched through the formation of non-fluorescent dimmers and, additionally, through the energy transfer from rhodamine monomer to these dimmers (Baptista ALF, Coutinho PJG, Real Oliveira MECD, Gomes JINR. Proceedings of 13th International Symposium of Surfactants, SIS 2000, Gainesville, USA, 2000). The temperature, the surfactant and pH induce a release of the encapsulated dye resulting in rhodamine dilution and consequently alterations in the dimerization/binding equilibrium. The experimental spectra indicate that rhodamine binds almost completely to liposomes. The decomposition of the rhodamine fluorescence spectra allowed us to determine the percentage of released dye during a simulated dyeing process, and allowed us to conclude that the dimerization process occurs mainly at the inner interfaces. The amount of dye released induced by temperature changes was greater in the presence of surfactant.