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Although the treatment landscape has rapidly evolved over the last years, hepatocellular carcinoma (HCC) is one of the most lethal cancers. With recent advances, both immunotherapy and tyrosine kinase inhibitors (TKIs)-based chemotherapy constitute the standard treatment for advanced HCC. A systematic search of randomized clinical trials employing TKIs was performed in 17 databases, obtaining 25 studies evaluating the prognosis, tumor response, and presence of adverse events (AEs) related to TKIs in HCC. Overall effect sizes were estimated for the hazard ratios (HR) and odds ratios (OR) with 95% confidence interval (CI), either extracted or calculated with the Parmar method, employing STATA 16. Heterogeneity was assessed by Chi-square-based Q-test and inconsistency (I2) statistic; source of heterogeneity by meta-regression and subgroup analysis; and publication bias by funnel plot asymmetry and Egger's test. The research protocol was registered in PROSPERO (CRD42023397263). Meta-analysis revealed a correlation between survival and tumor response parameters and TKI treatment vs. placebo, despite detecting high heterogeneity. Combined TKI treatment showed a significantly better objective response rate (ORR) with no heterogeneity, whereas publication bias was only detected with time to progression (TTP). Few gastrointestinal and neurological disorders were associated with TKI treatment vs. placebo or with combined treatment. However, a higher number of serious AEs were related to TKI treatment vs. sorafenib alone. Results show positive clinical benefits from TKI treatment, supporting the approval and maintenance of TKI-based therapy for advanced HCC, while establishing appropriate strategies to maximize efficacy and minimize toxicity.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Inibidores de Proteínas Quinases , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Medição de Risco , Resultado do Tratamento , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêuticoRESUMO
OBJECTIVE: To compare various exercise modalities' efficacy on migraine frequency, intensity, duration, and disability. BACKGROUND: Exercise has been shown to be an effective intervention to reduce migraine symptoms and disability; however, no clear evidence exists regarding the most effective exercise modalities for migraine treatment. METHODS: A systematic review was performed in PubMed, PEDro, Web of Science, and Google Scholar. Clinical trials that analyzed the efficacy of various exercise modalities in addressing the frequency, intensity, duration, and disability of patients with migraine were included. Eight network meta-analyses based on frequentist (F) and Bayesian (B) models were developed to estimate the direct and indirect evidence of various exercise modalities. Standardized mean difference (SMD) and 95% confidence (CI) and credible intervals (CrI) were calculated for each treatment effect based on Hedge's g and p scores to rank the modalities. RESULTS: We included 28 studies with 1501 migraine participants. Yoga (F: SMD -1.30; 95% CI -2.09, -0.51; B: SMD -1.33; 95% CrI -2.21, -0.45), high-intensity aerobic exercise (F: SMD -1.30; 95% CI -2.21, -0.39; B: SMD -1.17; 95% CrI -2.20, -0.20) and moderate-intensity continuous aerobic exercise (F: SMD -1.01; 95% CI -1.63, -0.39; B: SMD -1.06; 95% CrI -1.74, -0.38) were significantly superior to pharmacological treatment alone for decreasing migraine frequency based on both models. Only yoga (F: SMD -1.40; 95% CI -2.41, -0.39; B: SMD -1.41; 95% CrI -2.54, -0.27) was significantly superior to pharmacological treatment alone for reducing migraine intensity. For diminishing migraine duration, high-intensity aerobic exercise (F: SMD -1.64; 95% CI -2.43, -0.85; B: SMD -1.56; 95% CrI -2.59, -0.63) and moderate-intensity continuous aerobic exercise (SMD -0.96; 95% CI -1.50, -0.41; B: SMD -1.00; 95% CrI -1.71, -0.31) were superior to pharmacological treatment alone. CONCLUSION: Very low-quality evidence showed that yoga, high- and moderate-intensity aerobic exercises were the best interventions for reducing migraine frequency and intensity; high- and moderate-intensity aerobic exercises were best for decreasing migraine duration; and moderate-intensity aerobic exercise was best for diminishing disability.
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Terapia por Exercício , Transtornos de Enxaqueca , Metanálise em Rede , Humanos , Transtornos de Enxaqueca/terapia , Terapia por Exercício/métodos , Avaliação de Resultados em Cuidados de SaúdeRESUMO
In the original publication [...].
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4-Nitroaniline (4NA) is a common organic pollutant that is released into the environment during the manufacture and processing of a wide variety of industrial products. This article describes the use of an emulsion liquid membrane process to remove 4NA from aqueous solutions using a type 1 facilitated transport mechanism. Optimization of the removal process was carried out by analyzing the efficiency of 4NA removal from the feed phase and the initial apparent feed/membrane fluxes and permeabilities under different experimental conditions. The kinetics of the removal process was analyzed using a simplified mass transfer model involving an empirical mass transfer coefficient calculated from experimental data, assuming that the concentrations of 4NA in the external aqueous phase and in the internal w/o emulsion are uniform. The results show that there is a very good fit between the experimental and model data and that the variation in the values of the overall mass transfer coefficients with the experimental conditions coincides with that of the removal efficiency mentioned above. The transport mechanism was studied by identifying the rate-controlling step of the removal process, using models described for adsorption processes, due to the strong parallelism between the transport mechanisms in adsorption and emulsion liquid membrane processes.
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OBJECTIVE: The goal of this study was to reach consensus about the best exercise prescription parameters, the most relevant considerations, and other recommendations that could be useful for prescribing exercise to patients with migraine. METHODS: This was an international study conducted between April 9, 2022 and June 30, 2022. An expert panel of health care and exercise professionals was assembled, and a 3-round Delphi survey was performed. Consensus was reached for each item if an Aiken V Validity Index ≥ 0.7 was obtained. RESULTS: The study included 14 experts who reached consensus on 42 items by the third round. The most approved prescription parameters were 30 to 60 minutes of exercise per session, 3 days per week of moderate-intensity continuous aerobic exercise, and relaxation and breathing exercises for 5 to 20 minutes every day. When considering an exercise prescription, initial exercise supervision should progress to patient self-regulation; catastrophizing, fear-avoidance beliefs, headache-related disability, anxiety, depression, physical activity baseline level, and self-efficacy could influence the patients' exercise participation and efficacy; and gradual exposure to exercise could help improve these psychological variables and increase exercise efficacy. Yoga and concurrent exercise were also included as recommended interventions. CONCLUSION: From the experts in the study, exercise prescriptions should be adapted to patients with migraine considering different exercise modalities, such as moderate-intensity aerobic exercise, relaxation, yoga, and concurrent exercise, based on the patients' preferences and psychological considerations, level of physical activity, and possible adverse effects. IMPACT: The consensus reached by the experts can help prescribe exercise accurately to patients with migraine. Offering various exercise modalities can improve exercise participation in this population. The evaluation of the patients' psychological and physical status can also facilitate the adaptation of the exercise prescription to their abilities and diminish the risk of adverse events.
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Transtornos de Enxaqueca , Yoga , Humanos , Técnica Delphi , Terapia por Exercício , Exercício FísicoRESUMO
The study of proteins with intrinsically disordered regions (IDRs) has emerged as an active field of research due to their intriguing nature. Although IDRs lack a well-defined folded structure, they play important functional roles in cells, following biological mechanisms different from those of the traditional structured proteins. Consequently, it has been necessary to re-design experimental and theoretical methods in order to face the challenges introduced by the dynamic nature of IDRs. In this work, we present an accurate and cost-effective method to study the conformational dynamics of IDRs based on the use of residue-local probabilistic expressions that characterize the conformational ensembles obtained from finite-temperature molecular dynamics (MD) simulations. It is shown that the good performance and the high convergence rates achieved with our method are independent of the IDR lengths, since the method takes advantage of the major influence of the identity and conformation of the nearest residue neighbors on the amino-acid conformational preferences to evaluate the IDR conformational ensembles. This allows us to characterize the conformational space of IDRs using a reduced number of probabilities which can be obtained from comparatively short MD simulations or experimental databases. To exemplify the usefulness of our approach, we present an application to directly detect Molecular Recognition Features (MoRFs) in an IDR domain of the protein p53, and to follow the time evolution of the thermodynamic magnitudes of this system during its exploration of the conformational space.
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Proteínas Intrinsicamente Desordenadas , Conformação Proteica , Proteínas Intrinsicamente Desordenadas/química , Simulação de Dinâmica Molecular , Probabilidade , AminoácidosRESUMO
Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1 and NRP2 are the receptors of multiple proteins involved in key signaling pathways associated with tumor progression. We aimed to systematically review all the available findings on their role in HCC. We searched the Scopus, Web of Science (WOS), PubMed, Cochrane and Embase databases for articles evaluating NRPs in preclinical or clinical HCC models. This study was registered in PROSPERO (CRD42022349774) and include 49 studies. Multiple cellular and molecular processes have been associated with one or both NRPs, indicating that they are potential diagnostic and prognostic biomarkers in HCC patients. Mainly NRP1 has been shown to promote tumor cell survival and progression by modulating several signaling pathways. NRPs mainly regulate angiogenesis, invasion and migration and have shown to induce invasion and metastasis. They also regulate the immune response and tumor microenvironment, showing a crucial interplay with the hypoxia response and microRNAs in HCC. Altogether, NRP1 and NRP2 are potential biomarkers and therapeutic targets, providing novel insight into the clinical landscape of HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neuropilinas/genética , Neuropilinas/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Transdução de Sinais , Biomarcadores , Biomarcadores Tumorais , Microambiente TumoralRESUMO
Despite pharmacological advances such as lenvatinib approval, therapeutic failure of hepatocellular carcinoma (HCC) remains a big challenge due to the complexity of its underlying molecular mechanisms. Neuropilin-1 (NRP1) is a co-receptor involved in several cellular processes associated to chemoresistance development. Since both the double-edged process of autophagy and hypoxia-derived response play crucial roles in the loss of therapeutic effectiveness, herein we investigated the interplay among NRP1, autophagy and hypoxia in development of lenvatinib resistance in HCC cell lines. We first analyzed NRP1 expression levels in human HCC samples from public databases, found significantly increased NRP1 expression in human HCC samples as well as its correlation with advanced tumor and metastasis stages. Among 3 HCC cell lines (HepG2, Huh-7 and Hep3B), Hep3B and Huh-7 cells showed significantly increased NRP1 expression levels and cell migration ability together with higher susceptibility to lenvatinib. We demonstrated that NRP1 gene silencing significantly enhanced the anticancer effects of lenvatinib on Hep3B and Huh-7 cells. Furthermore, lenvatinib suppressed NRP1 expression through promoting autophagy in Hep3B and Huh-7 cells; co-treatment with bafilomycin A1 attenuated the antitumor effects of lenvatinib, and NRP1 silencing prevented this loss of in vitro effectiveness of lenvatinib even in the presence of bafilomycin A1. In addition, exposure to a hypoxic microenvironment significantly decreased NRP1 expression through autophagy in Hep3B and Huh-7 cells. Under hypoxia, HIF-1α directly modulated NRP1 expression; HIF-1α silencing not only enhanced the anticancer effects of combined lenvatinib and hypoxia, but also prevented the loss of effectiveness caused by bafilomycin A1, highlighting the potential role of HIF-1α-derived hypoxia response in the adaptive cellular response to lenvatinib and promoting resistance acquisition by autophagy modulation. Overall, NRP1 may constitute a potential therapeutic target to prevent lenvatinib failure derived from a hypoxia-associated modulation of autophagy in advanced HCC.
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Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas , Neuropilina-1 , Humanos , Autofagia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neuropilina-1/genética , Neuropilina-1/metabolismoRESUMO
The molecule 4-aminophenol (4AP) is recognised as a serious environmental pollutant that enters the environment during the manufacture and processing of a variety of industrial processes and through the degradation of some pharmaceutical products. This paper describes a comparative study of 4AP removal from aqueous solutions by emulsion liquid membranes using acid and basic type 1-facilitated transports. The results are explained by analysing the stripping process through both the different relative acid/basic strength of the hydroxyl and amine groups of the 4AP molecule and the hydrogen-bonding capacity with water of the ionisation products generated by the reaction of 4AP with HCl or NaOH. To optimize the 4AP removal process, the influence of different experimental conditions (stripping agent concentration in the product phase, surfactant concentration in the membrane phase, stirring rate, feed phase/emulsion phase volume ratio, product phase/membrane phase volume ratio and emulsification rate and time) were studied. The kinetics of the removal process has been analysed by fitting the experimental results to first order, second order and the Behnajady and Avrami models. The Behnajady model presents an excellent fit, allowing to calculate both the initial removal rate and the maximal removal conversion. Optimal conditions of the removal process obtained through these parameters are in full agreement with those obtained from the experimental study.
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Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and colorectal cancer (CRC) are two of the most frequent and deadly tumors with a complex pharmacological framework. Here, we assessed the prognostic, diagnostic and clinicopathological value of NRP1 in liver cancer and CRC patients. We searched PubMed, Scopus, Web of Science, Embase and Cochrane Library databases for articles evaluating the NRP1 correlation with survival parameters, tumor development or clinicopathological features. Hazard ratios and odds ratios with 95% confidence intervals were extracted or estimated by Parmar method and pooled to evaluate the overall effect size with STATA 16 software. Heterogeneity was analyzed by chi-square-based Q test and I2 statistic, along with meta-regression and subgroup analysis, and publication bias was assessed by funnel plot asymmetry and Egger's test. The study protocol was registered in PROSPERO (CRD42022307062). NRP1 overexpression was significantly correlated with lower survival in liver cancer patients and with tumor development in hepatocarcinoma patients, and was strongly correlated with an increased risk of vascular invasion in liver cancer and metastasis in CRC and liver tumors. These results support the role of NRP1 as a potential and useful biomarker in both types of cancer.
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The presence of pharmaceutical products, and their metabolites, in wastewater has become a focus of growing environmental concern. Among these pharmaceutical products, ibuprofen (IBU) is one of the most consumed non-steroidal anti-inflammatory drugs and it can enter the environment though both human and animal consumption, because it is not entirely absorbed by the body, and the pharmaceutical industry wastewater. Nanofiltration has been described as an attractive process for the treatment of wastewater containing pharmaceutical products. In this paper, the modification of a polysulfone nanofiltration membrane by coating with graphene oxide (GO) and reduced graphene oxide (RGO) has been carried out. The morphology and elemental composition of the active layer of unmodified and modified membranes were analyzed by scanning electronic microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX), respectively. Initial characterization membranes was carried out, studying their water permeability coefficient and their permeate flux and rejection coefficients, at different applied pressures, using magnesium chloride solutions. The behavior of both pristine and coated membranes against ibuprofen solutions were analyzed by studying the permeate fluxes and the rejection coefficients at different pressures and at different contaminant concentrations. The results have shown that both GO and RGO coated membranes lead to higher values of ibuprofene rejection than that of uncoated membrane, the latter being the one that presents better results in the studies of permeability, selectivity, and fouling.
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Hepatic fibrosis is a reversible response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by excessive deposition of extracellular matrix resulting in liver dysfunction and cirrhosis. Melatonin (N-acetyl-5-methoxytryptamine), the main product secreted by the pineal gland, is a multitasking indolamine with important physiological functions such as anti-inflammatory and antioxidant actions, modulation of circadian rhythms, and immune system enhancement. Among the numerous biological activities of melatonin, its antifibrotic effects have received increasingly more attention. In this study, we performed a systematic review of publications of the last 10 years evaluating the mechanisms of action of melatonin against liver fibrosis. The study protocol was registered at PROSPERO (CRD42022304744). Literature research was performed employing PubMed, Scopus, and Web of Science (WOS) databases, and after screening, 29 articles were included. Results from the selected studies provided denoted the useful actions of melatonin on the development, progression, and evolution of liver fibrosis. Melatonin antifibrotic effects in the liver involved the reduction of profibrogenic markers and modulation of several cellular processes and molecular pathways, mainly acting as an antioxidant and anti-inflammatory agent. In addition, the indolamine influenced different molecular processes, such as hepatocyte apoptosis, modulation of autophagy and mitophagy, restoration of circadian rhythms, and modulation of microRNAs, among others. Although some limitations have been found regarding variability in the study design, the findings here summarized display the potential role of melatonin in ameliorating the development of liver fibrosis and its possible progression to liver cirrhosis and hepatocarcinoma.
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Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Melatonina/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Humanos , Cirrose Hepática/patologia , Melatonina/administração & dosagem , Melatonina/metabolismoRESUMO
OBJECTIVE: This study aimed to investigate the effect of auriculotherapy on the intensity of physical and mood Premenstrual syndrome (PMS) symptoms. DESIGN: Single-blind randomized, placebo-controlled clinical trial. SETTING: Federal University of Parana, Curitiba, Brazil. INTERVENTION: Ninety-one women were randomly assigned to Auriculotherapy (AG), Placebo (PG), and Control (CG) groups. The intervention was 8 weeks long, done once per week. At each session in AG the microneedles were placed in seven points related to PMS symptoms (Anxiety; Endocrine; Muscle relaxation; Analgesia; Kidney; Shen Men; and Sympathetic). At PG the microneedles also were placed in seven points but unrelated to PMS symptoms (Tonsils; Vocal cords; Teeth; Eyes; Allergy; Mouth; and External nose). MAIN OUTCOME MEASURES: Assessments of PMS symptoms (Premenstrual Syndrome Screening Tool), musculoskeletal pain (Nordic Musculoskeletal Questionnaire), anxiety (Beck Anxiety Inventory), and quality of life (WHOQOL-Bref) were done at baseline, before the 5th session, after program completion, and a month follow-up. RESULTS: The AG and PG showed significantly lower scores of PMS symptoms, musculoskeletal pain, and anxiety. On the quality of life and follow-up analysis, the significance was observed only in PG. CONCLUSION: Auriculotherapy can be used as adjunctive therapy to reduce the physical and mood PMS symptoms.
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Auriculoterapia , Síndrome Pré-Menstrual , Método Duplo-Cego , Feminino , Humanos , Síndrome Pré-Menstrual/tratamento farmacológico , Qualidade de Vida , Método Simples-CegoRESUMO
Emulsion liquid membranes have been successfully used for the removal of different types of organic and inorganic pollutants by means of carrier-mediated transport mechanisms. However, the models that describe the kinetics and transport of such mechanisms are very complex due to the high number of model parameters. Starting from an analysis of the similarity between the elemental mechanisms of carrier-mediated transport in liquid membranes and of transport in adsorption processes, this paper presents an experimental analysis of the possibility of applying kinetic and mechanistic models developed for adsorption to carrier-mediated transport in emulsion liquid membranes. We study the removal of a target species, in this case, Cu(II), by emulsion liquid membranes containing membrane phase solutions of benzoylacetone (carrier agent), Span 80 (emulsifying agent) and kerosene (diluent), and hydrochloric acid as a stripping agent in the product phase. The experimental results fit the pseudo-second-order adsorption kinetic model, showing good relationships between the experimental and model parameters. Although both Cu(II) diffusion through the feed/membrane interface boundary layer and complex Cu-benzoylacetone diffusion through the membrane phase controls Cu(II) transport, it is the former step that mainly controls the transport process.
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Lutein is mainly supplied by dietary fruit and vegetables, and they are commonly jointly assessed in observational and interventional studies. Lutein bioavailability and health benefits depend on the food matrix. This study aimed to assess the effect of dietary intervention with lutein-rich fruit or vegetables on lutein status markers, including serum and faecal concentrations (by high pressure liquid chromatography), dietary intake (24 h recalls ×3), and macular pigment optical density (MPOD) and contrast threshold (CT) as visual outcomes. Twenty-nine healthy normolipemic subjects, aged 45-65 y, consumed 1.8 mg lutein/day supplied from fruits (14 subjects, 500 g/day of oranges, kiwi and avocados) or vegetables (15 subjects, 180 g/day of green beans, pumpkin, and sweet corn) for four weeks. Serum lutein concentration increased by 37%. The effect of the food group intervention was statistically significant for serum lutein+zeaxanthin concentration (p = 0.049). Serum α- and ß-carotene were influenced by food type (p = 0.008 and p = 0.005, respectively), but not by time. Serum lutein/HDL-cholesterol level increased by 29% (total sample, p = 0.008). Lutein+zeaxanthin/HDL-cholesterol increased, and the intervention time and food group eaten had an effect (p = 0.024 and p = 0.010, respectively) which was higher in the vegetable group. The MPOD did not show variations, nor did it correlate with CT. According to correlation matrixes, serum lutein was mainly related to lutein+zeaxanthin expressed in relation to lipids, and MPOD with the vegetable group. In faecal samples, only lutein levels increased (p = 0.012). This study shows that a relatively low amount of lutein, supplied by fruit or vegetables, can have different responses in correlated status markers, and that a longer intervention period is needed to increase the MPOD. Therefore, further study with larger sample sizes is needed on the different responses in the lutein status markers and on food types and consumption patterns in the diet, and when lutein in a "pharmacological dose" is not taken to reduce a specific risk.
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Fezes/química , Frutas/química , Luteína/sangue , Pigmento Macular/sangue , Verduras/química , Biomarcadores/sangue , Carotenoides/sangue , Dieta , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Zeaxantinas/sangueRESUMO
INTRODUCTION: The dietary carotenoids lutein (L) and zeaxanthin (Z) are transported in the bloodstream by lipoproteins, sequestered by adipose tissue, and eventually captured in the retina where they constitute macular pigment. There are no L&Z dietary intake recommendations nor desired blood/tissue concentrations for the Spanish general population. Our aim was to assess the correlation of L&Z habitual dietary intake (excluding food supplements), resulting serum concentrations and lipid profile with macular pigment optical density (MPOD) as well as the contrast sensitivity (CT), as visual outcome in normolipemic subjects (n = 101) aged 45-65. METHODS: MPOD was measured by heterochromatic flicker photometry, serum L&Z by HPLC, the dietary intake by a 3-day food records and CT using the CGT-1000-Contrast-Glaretester at six stimulus sizes, with and without glare. RESULTS: Lutein and zeaxanthin concentrations (median) in serum: 0.361 and 0.078 µmol/L, in dietary intake: 1.1 mg L+Z/day. MPOD: 0.34du. L+Z intake correlates with their serum concentrations (rho = 0.333, p = 0.001), which in turn correlates with MPOD (rho = 0.229, p = 0.000) and with fruit and vegetable consumption (rho = 0.202, p = 0.001), but not with lutein+zeaxanthin dietary intake. MPOD correlated with CT, with and without glare (rho ranges: -0.135, 0.160 and -0.121, -0.205, respectively). MPOD predictors: serum L+Z, L+Z/HDL-cholesterol (ß-coeficient: -0.91±0.2, 95%CI: -1.3,-0.5) and HDL-cholesterol (R2 = 15.9%). CT predictors: MPOD, mainly at medium and smaller visual angles (corresponding to spatial frequencies for which sensitivity declines with age) and gender (ß-coefficients ranges: -0.95,-0.39 and -0.13,-0.39, respectively). CONCLUSION: A higher MPOD is associated with a lower ratio of L+Z/HDL-cholesterol and with a lower CT (higher contrast sensitivity). The HDL-cholesterol would also act indirectly on the CT improving the visual function.
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Sensibilidades de Contraste/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Pigmento Macular/metabolismo , HDL-Colesterol/metabolismo , Dieta , Suplementos Nutricionais , Feminino , Ofuscação , Voluntários Saudáveis , Humanos , Lipídeos/sangue , Lipoproteínas/metabolismo , Luteína/administração & dosagem , Macula Lutea/efeitos dos fármacos , Macula Lutea/metabolismo , Masculino , Pessoa de Meia-Idade , Retina/efeitos dos fármacos , Retina/metabolismo , Visão Ocular/efeitos dos fármacos , Zeaxantinas/administração & dosagemRESUMO
In this paper, we describe the removal of cephalosporin C (CPC) from aqueous solutions by adsorption onto activated olive stones (AOS) in a stirred tank. For comparative purposes, several experiments of adsorption onto commercial granular activated carbon were carried out. A quantum study of the different species of cephalosporin C that, depending on the pH, exist in aqueous solution pointed to a favorable mass transfer process during adsorption. Activated olive stones were characterized by SEM, EDX and IR techniques and their pHzc was determined. A 10-3 M HCl cephalosporin C solution has been selected for the adsorption experiments because at the pH of that solution both electrostatic and hydrogen bond interactions are expected to be established between the adsorbate and the adsorbent. The adsorption process is best described by the Freundlich isotherm model and the pseudo-second-order kinetic model, while the adsorption mechanism is mainly controlled by film diffusion. Under the conditions studied, the adsorption process is of a physical nature, endothermic and spontaneous. Comparison of the adsorption results obtained in this paper with those of other authors shows that the efficiency of AOS is 20% of that of activated carbon but 65% higher than that of the XAD-2 adsorbent. Considering its low price, abundance, easy accessibility and eco-compatibility, the use of activated olive stones as adsorbents for the removal of emerging pollutants from aqueous solutions represents an interesting possibility from both the economic and the environmental points of view.
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Olea , Poluentes Químicos da Água , Adsorção , Cefalosporinas , Carvão Vegetal , Concentração de Íons de Hidrogênio , Cinética , Soluções , TermodinâmicaRESUMO
Protein folding evolves by exploring the conformational space with a subtle balance between enthalpy and entropy changes which eventually leads to a decrease of free energy upon reaching the folded structure. A complete understanding of this process requires, therefore, a deep insight into both contributions to free energy. In this work, we clarify the role of entropy in favoring the stabilization of folded structures in polyalanine peptides with up to 12 residues. We use a novel method referred to as K2V that allows us to obtain the potential-energy landscapes in terms of residue conformations extracted from molecular dynamics simulations at conformational equilibrium and yields folding thermodynamic magnitudes, which are in agreement with the experimental data available. Our results demonstrate that the folded structures of the larger polyalanine chains are stabilized with respect to the folded structures of the shorter chains by both an energetic contribution coming from the formation of the intramolecular hydrogen bonds and an entropic contribution coming from an increase of the entropy of the solvent with approximate weights of 60 and 40%, respectively, thus unveiling a key piece in the puzzle of protein folding. In addition, the ability of the K2V method to provide the enthalpic and entropic contributions for individual residues along the peptide chain makes it clear that the energetic and entropic stabilizations are basically governed by the nearest neighbor residue conformations, with the folding propensity being rationalized in terms of triads of residues.
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Dobramento de Proteína , Entropia , Ligação de Hidrogênio , Conformação Proteica em alfa-Hélice , TermodinâmicaRESUMO
Pertraction of Co(II) through novel supported liquid membranes prepared by ultrasound, using bis-2-ethylhexyl phosphoric acid as carrier, sulfuric acid as stripping agent and a counter-transport mechanism, is studied in this paper. Supported liquid membrane characterization through scanning electron microscopy, energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy shows the impregnation of the microporous polymer support by the membrane phase by the action of ultrasound. The effect on the initial flux of Co(II) of different experimental conditions is analyzed to optimize the transport process. At these optimal experimental conditions (feed phase pH 6, 0.5M sulfuric acid in product phase, carrier concentration 0.65M in membrane phase and stirring speed of 300 rpm in both phases) supported liquid membrane shows great stability. From the relation between the inverse of Co(II) initial permeability and the inverse of the square of carrier concentration in the membrane phase, in the optimized experimental conditions, the transport resistance due to diffusion through both the aqueous feed boundary layer (3.7576×104 s·m-1) and the membrane phase (1.1434×1010 s·m-1), the thickness of the aqueous feed boundary layer (4.0206×10-6 m) and the diffusion coefficient of the Co(II)-carrier in the bulk membrane (4.0490×10-14 m2·s-1) , have been determined.
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O surgimento do novo coronavírus exigiu a readaptação de diversos sistemas pertencentes à sociedade. Neste contexto, houve a necessidade da reestruturação dos fluxos de grande parte dos serviços de saúde. O presente relato de experiência descreve as ações adotadas pela Farmácia do Paraná (2ª RSM) para minimizar os impactos da pandemia aos pacientes e funcionários. Foram adotadas medidas de caráter administrativo, organizacional e estrutural, incluindo alterações nos processos de dispensação de medicamentos, nas renovações de cadastro e na busca ativa por usuários elegíveis ao serviço "Remédio em Casa". No panorama inicial da estratégia foi possível verificar um incremento no envio de medicamentos via SEDEX, refletindo em uma redução na quantidade de atendimentos presenciais. Tais ações, realizadas de maneira coordenada, contribuem para a redução do risco de contágio e exposição à Covid-19, refreando o avanço da contaminação e reforçando a importância das medidas de isolamento social. (AU)
The emergence of the new coronavirus required the readaptation of several social systems. In this context, there was a need to restructure flows of many health services. This experience report describes the actions adopted by "Pharmacy of Paraná" (2nd RSM) to minimize the impacts of the pandemic on patients and employees. Administrative, organizational, and structural measures were adopted, including changes in drug dispensing processes, registration renewals, and active search for eligible users of the "Remedies at Home" service. In the initial scenario of the strategy, there was an increase in sending medication via "SEDEX", which reduces the amount of inperson care. These actions, carried out in a coordinated manner, reduce the risk of contagion and exposure to Covid-19, curbing contamination and reinforcing the importance of social isolation measures. (AU)