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The chemotherapeutic drug doxorubicin (DOX) has been widely used for treating solid tumors attributed to its antiproliferative effectiveness; however, its clinical use is limited due to side effects, including cardiotoxicity, myelosuppression, and drug resistance. Combining DOX with buthionine sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, showed promising results in overcoming these adverse effects, potentially reducing the required DOX dose while maintaining efficacy. The aim of the present study was to examine the effects of different concentrations of BSO and DOX, both individually and in combination, utilizing B16/F10 (murine melanoma), SNB-19 (human glioblastoma), S180 (murine sarcoma), and SVEC4-10 (murine endothelial) cell lines. Cell viability, migration, and clonogenicity were assessed using the following assays MTT, scratch, and colony formation. Antioxidant levels of GSH, as well as activities catalase (CAT), and superoxide dismutase (SOD) were measured. BSO alone exhibited minimal cytotoxic effects, while DOX alone reduced cell viability significantly. The combination of BSO+DOX decreased IC 50 values for most cell lines, demonstrating a synergistic effect, especially in B16/F10, S180, and SVEC4-10 cells. BSO+DOX combination significantly inhibited cell migration and clonogenicity compared to DOX alone. While GSH levels were decreased with BSO+DOX treatment activities of CAT and SOD increased following DOX administration but remained unchanged by BSO. These results suggest that BSO may be considered a valuable tool to improve DOX therapeutic efficacy, particularly in cases of chemotherapy-resistant tumors, as BSO enhances DOX activity while potentially reducing systemic chemotherapeutic drug toxicity.

This article presents a symmetrical reduced-size eight-element MIMO antenna array with high electromagnetic isolation among radiators. The array utilizes easy-to-build techniques to cover the n77 and n78 new radio (NR) bands. It is based on an octagonal double-negative metamaterial split-ring resonator (SRR), which enables a size reduction of over 50% for the radiators compared to a conventional disc monopole antenna by increasing the slow-wave factor. Additionally, due to the extreme proximity between the radiating elements in the array, the modal significance ( MS ) method was employed to identify which propagation modes had the most impact on the electromagnetic coupling among elements. This approach aimed to mitigate their effect by using an electromagnetic barrier, thereby enhancing electromagnetic isolation. The electromagnetic barriers, implemented with strip lines, achieved isolation values exceeding 20 dB for adjacent elements (<0.023 λ) and approaching 40 dB for opposite ones (<0.23 λ) after analyzing the surface current distribution by the MS method. The elements are arranged in axial symmetry, forming an octagon with each antenna port located on a side. The array occupies an area of 0.32 λ 2 at 3.5 GHz, significantly smaller than previously published works. It exhibits excellent performance for MIMO applications, demonstrating an envelope correlation coefficient ( ECC ) below 0.0001, a total active reflection coefficient ( TARC ) lower than -10 dB for various incoming signals with random phases, and a diversity gain ( DG ) close to 20 dB.

(1) Background: We examined the effect of the acute administration of olive oil (EVOO), linseed oil (GLO), soybean oil (SO), and palm oil (PO) on gastric motility and appetite in rats. (2) Methods: We assessed food intake, gastric retention (GR), and gene expression in all groups. (3) Results: Both EVOO and GLO were found to enhance the rate of stomach retention, leading to a decrease in hunger. On the other hand, the reduction in food intake caused by SO was accompanied by delayed effects on stomach retention. PO caused an alteration in the mRNA expression of NPY, POMC, and CART. Although PO increased stomach retention after 180 min, it did not affect food intake. It was subsequently verified that the absence of an autonomic reaction did not nullify the influence of EVOO in reducing food consumption. Moreover, in the absence of parasympathetic responses, animals that received PO exhibited a significant decrease in food consumption, probably mediated by lower NPY expression. (4) Conclusions: This study discovered that different oils induce various effects on parameters related to food consumption. Specifically, EVOO reduces food consumption primarily through its impact on the gastrointestinal tract, making it a recommended adjunct for weight loss. Conversely, the intake of PO limits food consumption in the absence of an autonomic reaction, but it is not advised due to its contribution to the development of cardiometabolic disorders.

Objective: The prevalent symptoms of severe dengue in pediatric patients are divided into three subgroups: severe plasma leakage, severe bleeding, and severe organ damage. In addition, the seasonal patterns of the disease and the outcomes of cure or death from dengue were evaluated., Methods: An epidemiological, observational, analytical, cross-sectional study was conducted with data from the Notifiable Disease Information System (SINAN - Sistema de Informação de Agravos de Notificação and DATASUS - Departamento de Informática do Sistema Único de Saúde) of the Ministry of Health from 2019 to 2020., Results: During the study period, 1,857 cases of severe dengue were observed in the pediatric age group, with the most common symptoms being respiratory failure, melena, hematemesis, and altered level of consciousness. The total proportion of patients hospitalized for severe dengue was 89.6%, and 51.2% of these patients died, corroborating the importance of early detection of the disease., Conclusion: Severe dengue is more prevalent during the seasonal period, with hot and humid characteristics owing to the mechanism involved in the viral cycle. The most prevalent symptoms of severe dengue in pediatric patients were respiratory failure alone, gastrointestinal bleeding, and altered level of consciousness. It is important to identify signs of severity for early intervention and a better prognosis, considering that death is closely related to a delayed diagnosis.

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1β, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.

The effect of calorie restriction, fasting, and ketogenic diets on the treatment of liver cancer remains uncertain. Therefore, we conducted a systematic review to evaluate the effect of restrictive diets on the development and progression of liver cancer in animal models. We did a meta-analysis using the Cochrane Collaboration's Review Manager software, with the random effects model and the inverse variance technique. We examined 19 studies that were conducted between 1983 and 2020. Of these, 63.2% investigated calorie restriction, 21.0% experimented with a ketogenic diet, and 15.8% investigated the effects of fasting. The intervention lasted anything from 48 h to 221 weeks. Results showed that restrictive diets may reduce tumor incidence and progression, with a significant reduction in the risk of liver cancer development. Thereby, our results suggest that putting limits on what you eat may help treat liver cancer in more ways than one., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest that pertain to this work. PROSPERO registration: CRD42021267023., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intermittent fasting (IF) and physical exercise (PE) have beneficial psychological and physiological effects, improving memory and anxiety-like behavior. However, the impact of this combination on brain electrophysiological patterns is unknown. We aimed to evaluate the behavior and parameters of a brain excitability-related phenomenon named cortical spreading depression (CSD) in young rats (31-87 days of life) submitted to IF and treadmill PE for eight weeks. Sixty-four male and female Wistar rats aged 24 days were randomized into control, IF, PE, and IF+PE groups. Behavioral tests (open field (OF), object recognition, and elevated plus maze (EPM)) were performed, and the CSD propagation features were recorded. IF caused behavioral responses indicative of anxiety (lower number of entries and time spent in the OF center and EPM open arms). IF also reduced the discrimination index for object recognition memory tests and increased the propagation velocity of CSD. PE rats displayed more entries into the OF center and lowered CSD propagation speed. Data suggest that IF worsens anxiety-like behavior and memory and accelerates CSD in young rats. In contrast, PE reverted the unfavorable effects of IF. The brain effects of IF and PE at younger ages are recommended for study.

Aim: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder in women. We investigate the effect of physical exercise on body composition, nutritional parameters, and oxidative stress in rats with PCOS., Methods: Female rats were into three groups: Control, PCOS, and PCOS + Exercise. PCOS was induced by letrozole (1 mg/kg via p.o.) for 21 days consecutively. Physical exercise was swimming, for 21 consecutive days, 1 h/day with 5 % load. In all groups, we assessed the nutritional and murinometric parameters, body composition, thermography, and oxidative stress in brown adipose tissue (BAT) and peri-ovarian adipose tissue (POAT)., Key Findings: In PCOS we observed an increase (P < 0.05) in body weight vs. the Control group. But, the PCOS + Exercise group prevent this weight gain (P < 0.05). The temperature in BAT, decrease (P < 0.05) in the PCOS group vs. Control group. PCOS + Exercise prevented this reduction (P < 0.05) in BAT temperature vs. PCOS groups. We observed decreases (P < 0.05) in Lee Index and BMI in POS + Exercise vs. PCOS group. In PCOS rats, we observed an increase (P < 0.05) in murinometric (SRWG, EI, and FE) and body composition parameters (TWB, ECF, ICF, and FFM) vs. the Control group. The PCOS + Exercise prevents (P < 0.05) these changes in all groups, compared with PCOS. Regarding the BAT, we observe an increase (P < 0.05) in MPO and MDA levels in the PCOS vs. Control group. PCOS + Exercise prevents (P < 0.05) these increases vs. the PCOS group., Significance: PCOS modifies body composition, and nutritional parameters, and induces changes in oxidative stress in BAT. Physical exercise prevented these alterations., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest, financial or otherwise., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Arthritis is a chronic disease that affects, approximately, 1 % of the total global population. It is characterized by chronic inflammation, accompanied in most of the cases of motor disability and sever pain. The main therapies available have high risk of failure and advanced treatments are scarce and highly cost. In this scenario, search for effective, safe and low-cost treatments is quite desirable. Methyl gallate (MG) is a plant-derived phenolic compound described to present remarkable anti-inflammatory effect in experimental models of arthritis. Thus, in this study we formulated nanomicelles of MG using Pluronic (F-127) as matrix and evaluated in vivo the pharmacokinetic, biodistribution and its effect in the mice model of zymosan-induced arthritis. The nanomicelles were formed with a size 126 nm. The biodistribution showed a ubiquitous tissue deposition with a renal excretion. The pharmacokinetics showed elimination half-life of 1.72 h and a clearance of 0.006 L/h. The oral pretreatment with nanomicelles containing MG (3.5 or 7 mg/kg) demonstrated a reduction in total leukocytes, neutrophils, and mononuclear cells from the inflammation site. The data supports the use of methyl gallate nanomicelles as an alternative drug for arthritis. DATA AVAILABILITY: All the data of this study are transparent., 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 © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance. Therefore, the aim was to assess whether bromelain supplementation exerts anti-inflammatory effects in adults., Methods: The systematic review was registered in PROSPERO (n° CRD42020221395), and the search was performed in MEDLINE, Scopus, Web of Science, and Cochrane Library. The terms used in the search were: "bromelains", "bromelain", "randomized clinical trial", and "clinical trial". Eligibility criteria were: randomized clinical trials with participants aged 18 years or over, of both sexes, who received supplementation with bromelain alone or in combination with other oral compounds, with an evaluation of inflammatory parameters as primary and secondary outcomes, published in English, Portuguese or Spanish., Results: 1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks. Markers associated with inflammation varied between studies, including IL-2, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ and MCP-1, PGE-2, CRP and fibrinogen. Eleven (11) participants experienced side effects, and two discontinued treatment in the studies. The reported adverse effects were mainly gastrointestinal but well tolerated., Conclusion: The general effect of bromelain supplementation on inflammation is inconsistent because of population heterogeneity, doses used, treatment duration, and parameters evaluated. The observed effects are punctual and isolated, and further standardization is needed to establish doses, supplementation time, and which type of inflammatory condition is indicated., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Robust evidence have shown diet or dietary components in playing a direct role on cancer chemoprevention such as breast cancer (BC), and also prevention against cancer therapy side effects. In this context, vitamin E isoforms have been associated with tumor suppression pathways, mainly related to proliferation, invasion, metastasis, tumor metabolism and chemoresistance., Objective: Therefore, we performed a systematic review with meta-analysis to assess the effects of vitamin E consumption and/or supplementation on breast cancer risk, treatment, and outcomes., Methods: The studies were selected in the electronic databases PubMed, Science Direct, Scopus and Web of Science., Results: A total of 22 articles were selected, which nine manuscripts we perform the meta-analysis. The summary effect estimate did not indicate any significant association between consumption versus non-consumption of total vitamin E and breast cancer risk. After assessing the effects of vitamin E supplementation on breast cancer risk, only two had data for comparison and vitamin E supplementation presented no impact on breast cancer risk. However, the summary effect estimate from the included studies indicated that vitamin E consumption was inversely associated with breast cancer recurrence in the control group. There are no significant results regarding dietary or supplemental vitamin E intake and BC risk reduction., Conclusion: Finally, regarding recurrence, survival, and mortality, the results indicated that vitamin E consumption was inversely associated with breast cancer recurrence, although no association was found for breast cancer mortality., Competing Interests: Declaration of competing interest The authors declare that there are no conflict of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to determine the oxidative/antioxidative effects, modulatory and selective potential of α-tocopherol (vitamin E) on antineoplastic drug-induced toxicogenetic damage. The toxicity, cytotoxicity and genotoxicity induced by antineoplastic agents cyclophosphamide (CPA) and doxorubicin (DOX) was examined utilizing as models Saccharomyces cerevisiae, Allium cepa , Artemia salina and human peripheral blood mononuclear cells (PBMCs) in the presence of α-tocopherol. For these tests, concentrations of α- tocopherol 100 IU/ml (67mg/ml), CPA 20 µg/ml, DOX 2 µg/ml were used. The selectivity of α-tocopherol was assessed by the MTT test using human mammary gland non-tumor (MCF10A) and tumor (MCF-7) cell lines. Data showed cytoplasmic and mitochondrial oxidative damage induced by CPA or DOX was significantly diminished by α-tocopherol in S. cerevisiae . In addition, the toxic effects on A. salina and cytotoxic and mutagenic effects on A. cepa were significantly reduced by α-tocopherol. In PBMCs, α-tocopherol alone did not markedly affect these cells, and when treated in conjunction with CPA or DOX, α-tocopherol reduced the toxicogenetic effects noted after antineoplastic drug administration as evidenced by decreased chromosomal alterations and lowered cell death rate. In human mammary gland non-tumor and tumor cell lines, α-tocopherol produced selective cytotoxicity with 2-fold higher effect in tumor cells. Evidence indicates that vitamin E (1) produced anti-cytotoxic and anti-mutagenic effects against CPA and DOX (2) increased higher selectivity toward tumor cells, and (3) presented chemoprotective activity in PBMCs.

Low-grade chronic inflammation is one of the main disorders that characterize adipose tissue dysfunction in obesity and is an important element in the pathogenesis of several comorbidities. In this context, selenium is an essential micronutrient that exerts important anti-inflammatory functions, and the role of selenium in controlling inflammation associated with obesity is not well defined. Thus, this study aimed to evaluate the relationship between markers of the nutritional status of selenium and low-grade chronic inflammation in obese women. This cross-sectional study included 81 women aged between 18 and 50 years, who were divided into two groups according to body mass index (BMI): the obesity group (n = 38) and normal weight group (n = 43). Selenium intake was assessed by 3-day diet records. The plasma, erythrocyte, and urinary selenium concentrations were determined using inductively coupled plasma optical emission spectrometry. The analysis of serum cytokines interleukin (IL)-8, IL-1β, IL-6, IL-10, and tumor necrosis factor alpha (TNFα) was performed using flow cytometry. The results of this study revealed that the obese women had higher dietary intake of selenium than eutrophic women. However, obese participants showed decreased selenium concentrations in plasma and erythrocytes, in parallel with increased concentrations of selenium in the urine. Regarding the inflammatory parameters, obese women exhibited higher concentrations of IL-6 and lower concentrations of the cytokines IL-8, IL-1β, and TNFα than eutrophic women. In the binary logistic regression analysis, erythrocyte selenium was considered an independent predictor of the serum concentrations of cytokine IL-8 in obese women, reflecting the anti-inflammatory action of this micronutrient., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity., Objective: Therefore, this systematic review aimed to evaluate antitumor and chemopreventive activity of different vitamin E isoforms (tocopherols and tocotrienols) through in vitro and in vivo studies., Method: The systematic review was registered in PROSPERO (No. CRD4202126207) and the search was carried out in four electronic databases (PubMed, Science Direct, Scopus and Web of Science) in June 2021 by three independent reviewers. The search equation used was: "Supplementation" AND ("Vitamin E" OR Tocopherol OR Tocotrienol) AND "breast cancer" AND (chemotherapy OR therapy OR prevention). In vitro studies and animal models of breast cancer supplemented with tocopherol or tocotrienol vitamers, alone or in combination, were included., Results: The results revealed 8546 relevant studies that were initially identified in our search. After analysis, a total of 12 studies were eligible for this systematic review. All studies included animal models, and 5 of them also performed in vitro experiments on cancer cell lines. The studies performed supplementation with tocopherols, mixtures (tocopherols and tocotrienols) and synthetic vitamin E forms. There was an significant association of estradiol, dendritic cells and pterostilbene in combined therapy with vitamin E. Vitamin E delayed tumor development, reduced tumor size, proliferation, viability, expression of anti-apoptotic and cell proliferation genes, and upregulated pro-apoptotic genes, tumor suppressor genes and increased immune response. The effects on oxidative stress markers and antioxidant activity were conflicting among studies. Only one study with synthetic vitamin E reported cardiotoxicity, but it did not show vitamin E genotoxicity., Conclusion: In conclusion, vitamin E isoforms, isolated or associated, showed antitumor and chemopreventive activity. However, due to studies heterogeneity, there is a need for further analysis to establish dose, form, supplementation time and breast cancer stage., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objective: To test the reliability and validity of the Dutch Eating Behavior Questionnaire (DEBQ) in an online format in university students from low-income regions., Methods: We applied the questionnaire to a sample of 195 and 117 university students from a low-income region (Gini index of 0.56) to study validity and reliability, respectively. The DEBQ consists of 33 items on eating behavior in three dimensions/factors: emotional eating, restrained eating and external eating. The questionnaire was administered twice at 2-week intervals. We tested the reliability via temporal stability and internal consistency and construct validity via exploratory and confirmatory factor analysis., Results: For reliability, we identified an acceptable Spearman correlation coefficient (rho > 0.30 and p  < 0.05) and Cronbach's alpha ( α  ≥ 0.70) for all DEBQ items. In the exploratory analysis, we identified 6 factors representing a mix of original and additional factors, with an explained variance of 69.1%. In the confirmatory analysis with structural equation modeling, we observed better global model adjustment for the 6-factor model with the Tucker-Lewis index and comparative fit index closer to one, as well as root mean square error of approximation closer to zero than the original (3-factor) model. Using generalized structural equation modeling, we also observed a better fit in latent class modeling for the 6-factor model (AIC: 16990.67; BIC. 17874.38) than for the 3-factor model (AIC: 17904.09; BIC: 18342.67)., Conclusion: The online format of the DEBQ has acceptable reliability and validity for measuring eating behavior in university students from low-income regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 de Carvalho, Cardoso, Feuerstein, Sousa, Collese, Torres-Leal, Nascimento-Ferreira and De Moraes.)

Chronic low-grade inflammation may be associated with the development of chronic non-communicable diseases in young populations, often lasting to adulthood. Studies show that the diet is related to chronic inflammation. The Pro-inflammatory/Anti-inflammatory Food Intake Score (PAIFIS) is an indicator that measures the inflammatory potential of the diet, with the help of validated tools that assess food consumption. The validation of tools that assess inflammatory dietary patterns in young populations to produce valid and reliable results is essential to guide disease prevention strategies for adulthood., Methods: This study aimed to estimate the Pro-inflammatory/Anti-inflammatory Food Intake Score (PAIFIS) in children and adolescents in South America and to test its reliability and validity using a food frequency questionnaire (FFQ) and an inflammatory biomarker. This work consists of a validation study in a sample of children and adolescents conducted in South America (SAYCARE Study). The habitual consumption of food contributing to calculating the PAIFIS was obtained through an FFQ and 24 h Dietary Recall (24HDR). Reliability was tested using the FFQ (FFQ1 × FFQ2), using Spearman's correlation coefficient to estimate the agreement between measurements. The validity of the PAIFIS was tested using 24HDR and the inflammatory biomarker C-reactive protein (CRP) using Spearman's correlation and multilevel linear regression., Results: For children and adolescents, pro- and anti-inflammatory food groups showed Spearman's correlation coefficients ranging from 0.31 to 0.66, convergent validity ranging from 0.09 to 0.40, and criterion validity for a reliability range from -0.03 to 0.18. The PAIFIS showed Spearman's correlation coefficients for reliability ranging from 0.61 to 0.69, convergent validity from 0.16 to 0.23, and criterion validity from -0.03 to 0.24., Conclusion: The PAIFIS showed acceptable reliability, weak convergent validity, and weak criterion validity in children and adolescents.

The use of nanotechnological products is increasing steadily. In this scenario, the application of nanotechnology in food science and as a technological platform is a reality. Among the several applications, the main use of this technology is for the development of foods and nutraceuticals with higher bioavailability, lower toxicity, and better sustainability. In the health field, nano-nutraceuticals are being used as supplementary products to treat an increasing number of diseases. This review summarizes the main concepts and applications of nano-nutraceuticals for health, with special focus on treating cancer and inflammation., Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-022-00338-7., (© The Author(s) under exclusive licence to Sociedade Brasileira de Farmacognosia 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Breast cancer (BC) diagnosis has been associated with significant risk factors, including family history, late menopause, obesity, poor eating habits, and alcoholism. Despite the advances in the last decades regarding cancer treatment, some obstacles still hinder the effectiveness of therapy. For example, chemotherapy resistance is common in locally advanced or metastatic cancer, reducing treatment options and contributing to mortality. In this review, we provide an overview of BC metabolic changes, including the impact of restrictive diets associated with chemoresistance, the therapeutic potential of the diet on tumor progression, pathways related to metabolic health in oncology, and perspectives on the future in the area of oncological nutrition., Competing Interests: Conflicts of Interest The authors declare no conflicts of interest in this work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The 3 branched-chain AA (BCAA), Val, Leu, and Ile, are essential AA used by tissues as substrates for protein synthesis and energy generation. In addition, BCAA are also involved in modulating cell signaling pathways, such as nutrient sensing and insulin signaling. In our previous study, dietary BCAA supplementation was shown to improve protein synthesis and glucose homeostasis in transition cows. However, a more detailed understanding of the changes in metabolic pathways associated with an increased BCAA availability is desired to fine-tune nutritional supplementation strategies. Multiparous Holstein cows (n = 20) were enrolled 28 d before expected calving and assigned to either the BCAA treatment (n = 10) or the control group (n = 10). Cows assigned to BCAA were fed 550 g/d of rumen-protected BCAA mixed with 200 g/d of dry molasses from calving until 35 DIM, whereas the cows assigned to the control were fed only 200 g/d of dry molasses. Serum samples were collected on d 10 before expected calving, as well as on d 4 and d 21 postpartum. Milk samples were collected on d 14 postpartum. From a larger cohort, we selected 20 BCAA-supplemented cows with the greatest plasma urea nitrogen concentration, as an indicator for greater BCAA availability, for the metabolomics analysis herein. Serum and milk samples were subjected to a liquid chromatography-mass spectrometry-based assay, detecting and measuring the abundance of 241 serum and 211 milk metabolic features, respectively. Multivariable statistical analyses revealed that BCAA supplementation altered the metabolome profiles of both serum and milk samples. Increased abundance of serum phosphocholine and glutathione and of milk Val, Ile, and Leu, and decreased abundance of milk acyl-carnitines were associated with BCAA supplementation. Altered phosphocholine and glutathione abundances point to altered hepatic choline metabolism and antioxidant balance, respectively. Altered milk acyl-carnitine abundances suggest changes in mammary fatty acid metabolism. Dietary BCAA supplementation was associated with a range of alterations in serum and milk metabolome profiles, adding to our understanding of the role of BCAA availability in modulating dairy cow protein, lipid, and energy metabolism on a whole-body level and how it affects milk composition., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Introduction: Obesity and its comorbidities are increasingly prevalent in Latin America, with a more rapid growth in individuals with lower income. The composition of movement behaviors within a 24 h period may have important implications for obesity, metabolic and mental health in cross-sectional data. However, a longitudinal study is needed to confirm the findings from the primarily cross-sectional evidence. The COVID-19 pandemic has been associated with cardiometabolic outcomes and has impeded healthy behavior., Objectives: The first objective is to evaluate the time elapsed since the diagnosis of not meeting 24 h movement guidelines and the potential subsequent onset of metabolic syndrome in undergraduate students from low-income regions within 4 years of follow up. The second objective is to test the association between 24 h movement, mental wellbeing, eating behaviors, and abdominal obesity in the period of this pandemic., Methods: The 24 h movement behavior and metabolic syndrome (24 h-MESYN) study is a multicentre cohort study that will include participants from two Brazilian cities within the 2022-2025 period to asses the first objective, and also a nested case-control study at the baseline will be carried out to evaluate the second objective. Previously, we conducted a feasibility study in the academic year of 2021 to assessing the psychometric properties of subjective tools, refine our study protocol, and adjust the epidemiological conditions of the cohort's subsequent phases (like as prevalence of exposure of interest, sampling process, and study adherence). Statistical tests as Cohen's kappa agreement; factorial analysis; logistic, Poisson and linear regression; and Kaplan-Meier analysis will be performed, in accordance with the objectives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nascimento-Ferreira, Marin, Abrão Ferreira, Oliveira, Bandeira, Silva Sousa, Miranda de Sousa, de Almeida Cardoso, Conceição da Silva, Rosa, de Carvalho, Pereira de Carvalho Silva, Franco, Torres-Leal, Barbosa de Carvalho and Ferreira de Moraes.)

Redox imbalance can lead to irreversible damages to biological functions. In this context, rutin stands out for its antioxidant potential. The objective of this study was to evaluate the acute and chronic effect of rutin on the hepatic redox imbalance. The study was performed according to three different protocols. First, healthy male Swiss mice were divided into two groups: control and rutin, the second of which received chronic oral supplementation of rutin (10 mg/kg). The second involved evaluation of the generation of reactive oxygen species (ROS) by HepG2 cells, incubated or not with rutin (20 and 40  μ g/mL) for 3 h. The final protocol involved assessment of the acute effect of rutin (10 mg/kg) in mice with oxidative stress induced by 2,2'-azobis(2-methylpropionamidine) dihydrochloride (ABAP). After the in vivo treatments, the livers were collected to analyze the oxidative damage by thiol, and the antioxidant defense by catalase, superoxide dismutase, and glutathione peroxidase. In the HepG2 cells, the following probes were employed to assess the ROS production: dichlorofluorescein, MitoSOX, dihydroethidium, and Amplex Red. Rutin administered chronically improved the antioxidant defense in healthy animals, and when administered acutely both inhibited the increased production of ROS in HepG2 cells and improved the redox imbalance parameters in mice with induced oxidative stress. This study suggests rutin as a protective agent for restoration of hepatic redox homeostasis in redox injury induced by ABAP in Swiss mice and HelpG2 cells.

Objective: To evaluate the association among embryonic morphological parameters, clinical factors and euploid blastocyst formation., Methods: This prospective cohort study included 422 blastocysts from 135 patients who had undergone preimplantation genetic analysis after intracytoplasmic sperm injection (ICSI)., Results: Of 422 blastocysts, 200 (47.4%) were euploid and 222 (52.6%) aneuploid. Women aged older than 38 years were more likely to develop aneuploid embryos (OR: 3.4, CI: 2.2-5.4, p<0.001). Poor ovarian reserve (OR: 3.3, p<0.001), increased male age (39.0 versus 40.7, p=0.019), and decrease in sperm percentage with normal morphology (2.5% vs. 1.9%, p=0.047) were associated with aneuploidy. Type C trophectoderm (TE) and type C inner cell mass were associated with a high risk of embryo aneuploidy, with OR of 4.1 (CI: 2.2-7.7, p<0.001) and 1.7 (CI: 1.01-3.0, p=0.048), respectively. Logistic regression analysis revealed maternal age and type C TE as the main risk factors for aneuploidy. Among combinations of factors, the best marker for the risk of aneuploidy was maternal age older than 38 years, combined with a type-C embryo with trophectoderm, which showed a positive predictive value of 88.6% and a specificity of 97.5%., Conclusions: Trophectoderm and type-C inner cell mass are the main embryo risk factors for aneuploidy, explaining approximately 71% and 60% of the risk, respectively. Among clinical factors, advanced maternal and paternal age (older than 38 and 36 years, respectively), antral follicles (<5), and a low percentage of sperm with normal morphology increased the risk of embryonic aneuploidy.

The recent therapeutic progress in multiple myeloma (MM) has led to the introduction of novel and highly potent drug classes. Daratumumab was the first CD38-targeting antibody showing to be effective and safe in MM patients as monotherapy and in combination regimens, which led to its rapid implementation in clinical practice. Considering that treatment discontinuation for drug-related adverse events can impact patients' quality of life and outcomes, the treatment decision should consider different factors and be weighted for each patient individually. Here, we aimed to guide clinicians using daratumumab treatment for MM by addressing practical real-world considerations based on an expert panel of Portuguese hematologists. Carefully following the recommendations mentioned in daratumumab's SmPC, and of those from other drugs used in combination regimens, along with ensuring a good communication with all healthcare professionals involved, is critical to prevent any complications arising from treatment. The risk of infection should be assessed for all patients under treatment with daratumumab and patients should be educated on the potential adverse events. Recommendations on prophylaxis and vaccination should be considered to avoid infections, and delays in the planned therapeutic schedule may be required to prevent adverse consequences of hematological toxicity. Daratumumab treatment is effective and feasible in patients with renal impairment, although careful patient monitoring and a frequent communication with the Nephrology department are of the utmost importance. Sharing clinical practice plays an important role in medical education by allowing to maximize treatment efficacy and minimize its safety risks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Geraldes, Neves, Chacim and da Costa.)

Background: A food frequency questionnaire (FFQ) for South American children and adolescents was developed, but its validity for assessing dietary iron intake has not been evaluated., Objective: To evaluate the validity of the FFQ and 24-hour dietary recalls (24h-DR) for assessing dietary iron intake in children and adolescents., Design: The South American Youth/Child Cardiovascular and Environmental study is a multicenter observational study, conducted in five South American cities: Buenos Aires (Argentina), Lima (Peru), Medellin (Colombia), Sao Paulo, and Teresina (Brazil). The FFQ assessed dietary intake over the previous 3 months, and the 24h-DR was completed three times (2 weekdays and 1 weekend day) with a minimum 5-day interval between recalls. Blood samples were collected to assess serum iron, ferritin, and hemoglobin levels., Participants and Setting: Data of 99 children (aged 3 to 10 years) and 50 adolescents (aged 11 to 17 years) from public and private schools were collected during 2015 to 2017., Main Outcome Measures: Dietary iron intake calculated from the FFQ (using the sum of daily iron intake in all food/food groups) and 24h-DR (mean of 3 days using the multiple source method)., Statistical Analyses Performed: Dietary iron intake in relation to blood biomarkers were assessed using Spearman rank correlations adjusted for sex, age, and total energy intake, and the quadratic weighted κ coefficients for agreement., Results: Spearman correlations showed very good coefficients (range = 0.78 to 0.85) for the FFQ in both age groups; for the 24h-DR, the coefficients were weak in children and adolescents (range = 0.23 to 0.28). The agreement ranged from 59.9% to 72.9% for the FFQ and from 63.9% to 81.9% for the 24h-DR., Conclusion: The South American Youth/Child Cardiovascular and Environmental study FFQ exhibited good validity to rank total dietary iron intake in children and adolescents, and as well as the 24h-DR, presented good strength of agreements when compared with serum iron and ferritin levels., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Malaria is the most common parasitic disease around the world, especially in tropical and sub-tropical regions. This parasitic disease can have a rapid and severe evolution. It is transmitted by female anopheline mosquitoes. There is no reliable vaccine or diagnostic test against malaria; instead, Artesunate is used for the treatment of severe malaria and Artemisinin is used for uncomplicated falciparum malaria. However, these treatments are not efficient against severe malaria and improvements are needed. Primaquine (PQ) is one of the most widely used antimalarial drugs. It is the only available drug to date for combating the relapsing form of malaria. Nevertheless, it has severe side effects. Particle drug-delivery systems present the ability to enhance the therapeutic properties of drugs and decrease their side effects. Here, we report the development of Polymeric Primaquine Microparticles (PPM) labeled with 99mTc for therapeutic strategy against malaria infection. The amount of primaquine encapsulated into the PPM was 79.54%. PPM presented a mean size of 929.47 ± 37.72 nm, with a PDI of 0.228 ± 0.05 showing a homogeneous size for the microparticles and a monodispersive behavior. Furthermore, the biodistribution test showed that primaquine microparticles have a high liver accumulation. In vivo experiments using mice show that the PPM treatments resulted in partial efficacy and protection against the development of the parasite compared to free Primaquine. These results suggest that microparticles drug delivery systems of primaquine could be a possible approach for malaria prevention and treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene that has emerged as an important player in the regulation of energy metabolism in peripheral tissues. However, its role in the hypothalamus has not been explored. Herein, we show that the genetic inhibition of SIRT3 in the hypothalamic arcuate nucleus (ARC) induced a negative energy balance and improvement of several metabolic parameters. These effects are specific for POMC neurons, because ablation of SIRT3 in POMC, but not in AgRP neurons, decreased body weight and adiposity, increased energy expenditure and brown adipose tissue (BAT) activity, and induced browning in white adipose tissue (WAT). Notably, the depletion of SIRT3 in POMC neurons caused these effects in male mice fed a chow diet but failed to affect energy balance in males fed a high fat diet and females under both type of diets. Overall, we provide the first evidence pointing for a key role of SIRT3 in POMC neurons in the regulation of energy balance., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

A vertical subsuperficial tidal flow constructed wetland (TFCW) operated under flooded time (FT) variation, was evaluated in the removal of carbonaceous, nitrogenous, and phosphorous matter from urban stream water. The TFCW downflow (117 L) was filled with bricks (44% porosity) and vegetated with Althernanthera philoxeroides (32 plants m -2 ). The TFCW was operated under different flooded times - Stage A (48 h), B (36 h), C (24 h), and D (12 h), organic loading rates of 19.58-43.83 gCOD m -2 d -1 , 3.68-6.94 gTN m -2 d -1 and 0.93-2.00 gTP m -2 d -1 and volumetric load rates of 46.8, 58.5, 78.0 and 11.7 L d -1 . No significant differences were observed in the removal efficiencies to Chemical Oxygen Demand (COD 66 to 94%), Total Ammonia Nitrogen (TAN 58 to 87%), and Total Nitrogen (TN 53 to 78%) among the stages, and nitrate concentrations lower than 6 mg L -1 in the effluent. High Total Phosphorus removal was obtained in FT of 48 h (TP 79%). Total phosphorus loading rate was a limiting factor in TP removal, which reduced along with the reduction of FT. The nitrifying community was present over time since ammonia-oxidizing bacteria (Nitrosospira) and nitrite-oxidizing bacteria (Nitrobacter and Nitrospira) were identified in operational stages with variation in relative abundance, but TAN removal efficiency did not show significant differences. There was no change in the denitrifying community structure, indicating that FT did not influence the TN removal. A. philoxeroides was responsible for phytoextraction of 2.1% of TN and 2.7% of TP from the total removed by TFCW. TN removal (65%) was attributed to adsorption in the filtering material and microbial metabolism during the rest time. The findings of this study suggest FT of 12 h to remove COD and TN, and equal to or higher than 48 h to remove TP., Competing Interests: Declaration of competing interest This statement is to certify that all Authors have seen and approved the manuscript being submitted. We have no conflict of interest to declare. We warrant that the article is the Author's original work. We warrant that the article has not received prior publication and is not under consideration for publication elsewhere. On behalf of all Co-Authors, the corresponding Author shall bear full responsibility for the submission. We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This research has not been submitted for publication nor has it been published in whole or in part elsewhere. We attest to the fact that all Authors listed on the title page have contributed significantly to the work, have read the manuscript and attest to the validity and legitimacy of the data and its interpretation, and agree to its submission to the Science of the Total Environment. All authors agree that the author list is correct in its content and order that no modification to the author list can be made without the formal approval of the Editor-in-Chief, and all authors accept that the Editor-in-Chief's decisions over acceptance or rejection or in the event of any breach in the Ethics in publishing and Policies and Ethics in the Science of the Total Environment. No additional authors will be added post submission, unless editors receive agreement from all authors and detailed information is supplied as to why the author list should be amended., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments., Methods: PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs., Results: The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced., Conclusion: This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.

Purpose: Considering the COVID-19 pandemic, vitamin D is a target of research and speculation. Lockdown or home isolation reduces sunlight exposition and increases the risk of vitamin D deficiency. Special attention is needed for older people at risk of both severe forms of COVID-19 and vitamin D deficiency. This review aims to highlight the association of vitamin D and COVID-19 in two instances, the direct influence of vitamin D on the immune system, and the indirect risks for other vitamin D deficiency-related diseases, such as musculoskeletal properties in older persons., Methods: We performed a narrative review., Results: Whether vitamin D deficiency is associated with COVID-19 poor prognosis, and if vitamin D supplementation may improve the post-infection outcomes is still unclear. In any case, the pandemic generates indirect burden, such as the sequence: home isolation, low sunlight exposition, vitamin D deficiency, and fragility fractures., Conclusion: Therefore, it is time to debate how to optimize vitamin D status in older people, especially during the COVID-19 pandemic., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021.)

This review systematically investigated observational studies in humans that evaluated the dietary intake of branched-chain amino acids (BCAA) and its association with insulin resistance. A search implemented through the electronic databases of PubMed, Scopus, and Web of Science. The evaluation of insulin resistance or the risk of developing insulin resistance in humans were the variables of interest in the search for articles. After using the selection criteria, three studies included in this review. The Food Frequency Questionnaire (FFQ) was the instrument used to evaluate the diet in all of the selected studies. Overall, 1940 studies identified and three thoroughly reviewed. We found only one study with positive effects of BCAA on insulin resistance; the other two reviewed studies did not demonstrate positive effects of the dietary intake of BCAA, individually or the sum of three amino acids on variables of interest. In this sense, the associations between BCAA and insulin resistance are inconsistent, potentially due to other longitudinal outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Non-Biological Complex Drugs (NBCDs) are complex non-biological drugs comprised of large high molecular weight molecules and, often, nanoparticular structures (including liposomes and block-copolymer micelles). In the case of NBCDs, the entire complex is the active pharmaceutical ingredient and its properties cannot be fully characterized by physicochemical analysis. Moreover, the manufacturing process is fundamental in creating the correct originator product. The same is true for generic versions of the product. A recent appraisal of approval procedures for NBCDs "follow-on products" approved in Europe shows a diversity of regulatory pathways. In fact, three different abridged application procedures, under European legislation, were used: the generic application procedure of Article 10(1), the hybrid application procedure of Article 10(3), and the biosimilar application procedure of Article 10(4). Three informed consent applications via Article 10(c) from innovator companies of glatiramer acetate and sevelamer carbonate were submitted shortly after the approval of the first follow-on products. Furthermore, a number of "well-established use" applications [via Article 10(a)] were approved for iron sucrose and iron dextran complexes. In order to protect patients from the increased risks of NBCD products and NBCD follow-on products, two complementary approaches should be considered: (i) improving the regulatory procedures and their guidance documents within the pre-registration phase, and (ii) not considering interchangeability whenever clinical data is not available. With regards to the latter, the need for adequate safety and efficacy data might also include risk management programmes within post-approval pharmacovigilance actions. This, however, would depend on a risk appraisal that must be considered for individual medicinal products, based on the nature of the submitted relevant set of safety/efficacy data., (Copyright © 2020 Gaspar, Silva-Lima, Magro, Alcobia, da Costa and Feio.)

Purpose: The diagnosis of multiple myeloma (MM) has a significant impact on patients. This study analyzed the mediating role of patients' unmet needs in the relationship between psychological morbidity/social support and quality of life (QoL)., Methods: This study included 213 patients with MM recruited from the outpatient medical oncology and clinical hematology services from five hospitals. Patients who meet the study criteria were referred by physicians and invited to participate in the study by the researcher. All participants answered the following questionnaires: Hospital Anxiety and Depression Scale, Satisfaction with Social Support Scale, Short-Form Survivor Unmet Needs Survey, and The European Organization for Research and Treatment of Cancer's Multiple Myeloma Module. Descriptive statistics, bivariate correlations, and structural equation modeling were performed to analyze the data., Results: The indirect effect of psychological morbidity on patients' future perspectives (MYFP) was partially mediated by information unmet needs (INF), while the indirect effect of psychological morbidity on treatment side effects (MYSE) was partially mediated by relationship and emotional unmet needs (REH). In turn, the indirect effect of psychological morbidity on disease symptoms (MYDS) was fully mediated by REH. Social support had an indirect effect on MYDS and MYSE fully mediated by REH., Conclusion: Intervention programs tailored to promote MM patients' QoL should specifically address information and emotional needs, raising awareness and training health professionals, caregivers, and family members to attend  MM patients' unmet needs.

Studies have shown synergistic and independent effects of leucine and resveratrol (RSV) as possible therapeutic agents to ameliorate metabolic disorders. Thus, the objective of this study was to investigate the effects of supplementation with leucine and RSV, alone and in combination, on metabolic changes in white adipose tissue of neonatally STZ-induced diabetic rats. After weaning, the rats were treated with trans-resveratrol (0.6 mg/kg/dose) and/or leucine (1.35 mg/kg/dose) administered orally. The animals were euthanized at age 16 weeks for blood analyses. Subcutaneous (SC), periepididymal (PE) and retroperitoneal (RP) fat pads were weighed. Adipocytes from PE and RP pads were isolated for morphometric analysis. Long-term supplementation with RSV promoted adiposity recovery, prevented hypoinsulinemia and improved the metabolic profile of the diabetic rats. However, some of these effects were impaired when RSV was associated with leucine. The diabetic rats supplemented with leucine alone showed no significant improvement in metabolic disorders.

Introduction: Allogeneic stem cell transplantation is an established procedure for a variety of diseases of the hematopoietic system. Our transplant program started in 1987 and since then advances have been made in the care of patients undergoing transplantation. We conducted a study to evaluate whether the changes implemented over time have improved the outcomes of transplantation., Material and Methods: We analyzed changes in patients, cell source, transplantation and outcome among 682 consecutive patients receiving their first transplant between 1987 and 2016. We compared overall survival, progression-free survival, the incidence of nonrelapse mortality and relapse in 10-year cohorts over the three decades of the study., Results: The median age of transplanted patients, the use of peripheral blood and unrelated donors all increased very significantly. There was an increase in the number of high-risk patients when comparing the first decade with the two subsequent ones. The 3-year non-relapse mortality decreased significantly from 29% to 20% (p = 0.045), while the overall survival, progression free survival and cumulative incidence of relapse remained stable., Discussion: Allogeneic hematopoietic stem cell transplantation has evolved considerably since its introduction in clinical practice. In the present study, we evaluated how these changes affected our practice along 30 years of activity and compared the results with those published in the literature., Conclusion: Despite increasing age, higher risk patients and the increasing use of unrelated donors our results show a continuous significantly reduced non-relapse mortality, with stable overall survival, progression free survival and relapse rate.

Obesity and overweight in children and adolescents is increasing rapidly worldwide; however, scarce data have been reported from South America countries. With the purpose of assessing hyperlipidemia, insulin resistance and chronic inflammation, the evaluation of blood biomarkers such as glucose, lipoproteins and chronic inflammation proteins is required. In the context of the SAYCARE study, in children and adolescents (3 to 18 years) from seven South American cities, our aim was to assess the impact of pre analytical conditions on different biomarkers evaluated in 474 fresh serum samples, in different country centers. We also evaluated the stability according to time and frozen storage within this study across the concordance of the results obtained from the 49 blood samples measured in three different centers. Significant correlations as well as concordance were observed in TG, Total-C, HDL-C and glucose between Buenos Aires and São Paulo. The samples evaluated in Teresina and São Paulo presented similar results, with exception of total cholesterol. We observed acceptable concordance between Buenos Aires vs São Paulo and Teresina vs São Paulo, suggesting that samples could be processed in each of these centers. This concordance is a consequence of the strict pre analytical conditions previously established in the SAYCARE study.

This cohort study evaluated the fate of sound surfaces and inactive non-cavitated (INC) and active non-cavitated (ANC) caries lesions in a population-based sample of South Brazilian adolescents, in answer to the question: "Is lesion activity assessment a reliable criterion to diagnose a patient's caries activity?" A total of 801 schoolchildren were examined at baseline (aged 12 years) and after a mean time interval of 2.5 years. Data collection included a questionnaire and clinical examination. Patients were classified as caries-free (patients without any lesion), caries-inactive (patients with only inactive lesions), and caries-active (patients with at least one active lesion). The primary outcome was caries progression (presence of cavity, underlying dentin shadow, filling, or extraction at the follow-up exam). Negative binomial regression models were used to estimate the risk for caries progression. The main predictor variable was status of the surface at baseline: sound, INC, or ANC. Progression rates of 1.0, 9.0, and 12.6% were found for sound surfaces, INC, and ANC, respectively. INC (incidence risk ratio [IRR] 5.37, 95% CI 4.22-6.83) and ANC (IRR 4.96, 95% CI 3.43-7.17) had greater risk for caries progression than sound surfaces. Similar risks for progression were found for ANC and INC (IRR 0.92, 95% CI 0.64-1.32). Progression rates were 0.6, 1.1, and 2.2% for caries-free, caries-inactive, and caries-active individuals, respectively (p < 0.05). The risk for caries progression of sound surfaces was higher among caries-active adolescents (caries-free: IRR 2.78, 95% CI 1.63-4.72; caries-inactive: IRR 2.19, 95% CI 1.65-2.90). Caries-inactive patients behaved similarly to caries-free individuals (IRR 1.27, 95% CI 0.73-2.20). This study demonstrated the possibility of defining a patient's caries activity profile based on lesion features., (© 2020 S. Karger AG, Basel.)

Objective: The purpose of this study was to analyse the reliability and validity of a semi-quantitative FFQ to assess food group consumption in South American children and adolescents., Design: The SAYCARE (South American Youth/Child cARdiovascular and Environmental) study is an observational, multicentre, feasibility study performed in a sample of 3- to 18-year-old children and adolescents attending private and public schools from six South American countries. Participants answered the FFQ twice with a two-week interval and three 24-h dietary recalls. Intraclass and Spearman's correlations, weighted Cohen's kappa (κw), percentage of agreement and energy-adjusted Pearson's correlation coefficients were calculated., Setting: Seven cities in South America (Buenos Aires, Lima, Medelin, Montevideo, Santiago, Sao Paulo and Teresina)., Subjects: A sample of 200 children and 244 adolescents for reliability analyses and 252 children and 244 adolescents for validity analyses were included., Results: Depending on the food group, for children and adolescents, reliability analyses resulted in Spearman's coefficients from 0·47 to 0·73, intraclass correlation coefficients from 0·66 to 0·99, κw coefficients from 0·35 to 0·63, and percentage of agreement between 72·75 and 83·52 %. In the same way, validity analyses resulted in Spearman's coefficients from 0·17 to 0·37, energy-adjusted Pearson's coefficients from 0·17 to 0·61, κw coefficients from 0·09 to 0·24, and percentages of agreement between 45·79 and 67·06 %., Conclusion: The SAYCARE FFQ achieved reasonable reliability and slight-moderate validity for almost all food groups intakes. Accordingly, it can be used for the purpose of ranking the intake of individuals within a population.

Linaclotide is a synthetic peptide approved by the FDA for the treatment of constipation-predominant irritable bowel syndrome and chronic constipation. Linaclotide binds and activates the transmembrane receptor guanylate cyclase 2C (Gucy2c). Uroguanylin (UGN) is a 16 amino acid peptide that is mainly secreted by enterochromaffin cells in the duodenum and proximal small intestine. UGN is the endogenous ligand of Gucy2c and decreases body weight in diet-induced obese (DIO) mice via the activation of the thermogenic program in brown adipose tissue. Therefore, we wanted to evaluate whether oral linaclotide could also improve DIO mice metabolic phenotype. In this study, we have demonstrated that DIO mice orally treated with linaclotide exhibited a significant reduction of body weight without modifying food intake. Linaclotide exerts its actions through the central nervous system, and more specifically, via Gucy2c receptors located in the mediobasal hypothalamus, leading to the activation of the sympathetic nervous system to trigger the thermogenic activity of brown fat stimulating energy expenditure. These findings indicate for first time that, in addition to its effects at intestinal level to treat irritable bowel syndrome with constipation and chronic constipation, linaclotide also exerts a beneficial effect in whole body metabolism., (© 2020 S. Karger AG, Basel.)

The chronic use of Dexamethasone (Dex) induced hyperglycemia and insulin resistance. On the other hand, physical exercise attenuates the symptoms induced by Dex in many physiological systems. However, the effect of the exercise on the changes in gastric motility induced by dexamethasone remains unknown. We hypothesized that low-intensity aerobic exercise modulates the metabolic effects induced by Dex-treatment by modifying the gastrointestinal function and feeding behavior in rats. Male rats were distributed into the following groups: Control (Ctrl), Dex (1.0 mg/kg, i.p.), Exercise (Ctrl + Exercise 5%) and (Dex1.0 + Exercise 5%). The exercise protocol was swimming for 5 consecutive days. We assessed the murinometric and nutritional indices, food intake, blood glucose by (ipGTT) and the gastric emptying rate of a liquid test meal were assessed in all rats. We observed a significant decrease (p < .05) in the gastric emptying in Dex1.0 group in relation to Ctrl group. The exercise prevented decrease in the gastric emptying (p < .05) in Dex1.0 + EX5% group when compared with Dex1.0 groups. The Dex1.0 group induced a significantly increase (p < .05) in glycaemia vs Ctrl group. The hyperglycemia was improving (p < .05) in the Dex1.0 + Ex5% compared with Dex1.0 groups. We observed a positive correlation (p < .05, and r = 0.7065) between gastric retention vs glycaemia in the Dex1.0 groups. The Dex1.0 reduced (p < .05) the body weight and altered body composition, promoting hypophagia. IL-6 increased (p < .05) at gastric fundus in Ex5% compared with Ctrl groups. In conclusion, the use of Dex1.0 decreases gastric emptying, promotes hyperglycemia and modifies feeding behavior. The low-intensity exercise prevents hyperglycemia, thus improving gastric dysmotility without improving the anthropometric parameters., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Graphene is one of the crystalline forms of carbon, along with diamond, graphite, carbon nanotubes, and fullerenes, and is considered as a revolutionary and innovating product. The use of a graphene-based nanolabels is one of the latest and most prominent application of graphene, especially in the field of diagnosis and, recently, in loco radiotherapy when coupled with radioisotopes. However, its biological behavior and mutagenicity in different cell or animal models, as well as the in vivo functional activities, are still unrevealed. In this study we have developed by a green route of synthesizing graphene quantum dots (GQDs) and characterized them. We have also developed a methodology for direct radiolabeling of GQDs with radioisotopes.Finally; we have evaluated in vivo biological behavior of GQDs using two different mice models and tested in vitro mutagenicity of GQDs. The results have shown that GQDs were formed with a size range of 160-280 nm, which was confirmed by DRX and Raman spectroscopy analysis, corroborating that the green synthesis is an alternative, environmentally friendly way to produce graphene. The radiolabeling test has shown that stable radiolabeled GQDs can be produced with a high yield (>90%). The in vivo test has demonstrated a ubiquitous behavior when administered to healthy animals, with a high uptake by liver (>26%) and small intestine (>25%). Otherwise, in an inflammation/VEGF hyperexpression animal model (endometriosis), a very peculiar behavior of GQDs was observed, with a high uptake by kidneys (over 85%). The mutagenicity test has demonstrated A:T to G:C substitutions suggesting that GQDs exhibits mutagenic activity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Pancreatic Polypeptide-secreting tumor of the distal pancreas (PPoma) is a rare, difficult and indolent type of cancer with a survival rate of 5-year in only 10% of all cases. The PPoma is classified as a neuroendocrine tumor (NET) not functioning that overexpresses SSTR 2 (somatostatin receptor subtype 2). Thus, in order to improve the diagnosis of this type of tumor, we developed nanoparticulate drug carriers based on poly-lactic acid (PLA) polymer loaded with octreotide and radiolabeled with Technetium-99 m ( 99m Tc)., Methods: PLA/PVA octreotide nanoparticles were developed by double-emulsion technique. These nanoparticles were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and radiolabeled with 99mTc by the direct via forming 99m Tc-PLA/PVA octreotide nanoparticles. The safety of these nanosystems was evaluated by the MTT cell toxicity assay and their in vivo biodistribution was evaluated in xenografted inducted animals., Results: The results showed that a 189 nm sized nanoparticle were formed with a PDI of 0,097, corroborating the monodispersive behavior. These nanoparticles were successfully radiolabeled with 99mTc showing uptake by the inducted tumor. The MTT assay corroborated the safety of the nanosystem for the cells., Conclusion: The results support the use of this nanosystem ( 99m Tc-PLA/PVA octreotide nanoparticles) as imaging agent for PPoma. Graphical Abstract Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma) Radiolabeled Nanoparticles for Imaging.

Background and objective : The assessment of physical fitness has become a necessary issue in epidemiological studies, since a reduction in fitness is directly associated with early mortality. Therefore, the development of simple, accurate, and inexpensive methods is necessary to measure physical fitness. This study aimed to determine the reliability and validity of the criteria and constructs of the International Fitness Scale (IFIS), Portuguese version, in Brazilian pediatric populations. Methods : A total of 190 children aged 3-10 years and 110 adolescents aged 11-17 years were enrolled in an observational study of reliability and validity. For reliability, the participants completed a questionnaire twice (with an interval of 15 days). To test the criterion validity, we analyzed the agreement between the questionnaire and physical tests (20-m shuttle run test, handgrip strength, standing long jump tests, 4 × 10-m shuttle run test, and back-saver sit and reach test), and the construct validity was estimated by agreement between the questionnaire and high blood pressure. The reliability was analyzed by kappa coefficients. The agreement between the testing and retesting of the questionnaire was evaluated by kappa coefficients. We applied a 2 × 2 table to estimate the specificity, sensitivity, and accuracy of the questionnaire. Results : The mean age of the children was 6.7 years ( n = 190), and for the adolescents it was 14.6 years ( n = 110). The questionnaire reliability showed an almost perfect score (κ ≥ 0.93 in children and κ ≥ 0.88 in adolescents). The questionnaire showed moderate criterion validity (κ ≥ 0.40 in children and adolescents) as well as moderate construct validity (κ ≥ 0.40) in the components of general conditioning, cardiorespiratory capacity, muscular strength, and speed/agility in children and in the components of cardiorespiratory capacity, muscle strength, and speed/agility in adolescents. The questionnaire was a sensitive method for measuring physical fitness. Conclusions : The Portuguese version of the IFIS is a reliable and valid method for measuring physical fitness in pediatric populations.

In this study, we developed, characterized, and tested in vivo polymeric nanoparticle of ethambutol labeled with 99mTc as nanoradiopharmaceutical for early diagnosis of tuberculosis by single-photon emission computed tomography, also as a therapeutic choice. Nanoparticles were developed by double emulsification. All characterization tests were performed, as scanning electron microscopy and dynamic light scattering. The labeling process with 99mTc was performed using the direct labeling process. In vitro and in vivo assays were performed with animals and cells. The results showed that a spherical ethambutol nanoparticle with a size range of 280-300 nm was obtained. The stability test showed that the nanoparticles were well labeled with 99mTc (> 99.1%) and keep labeled over 24 h. The biodistribution assay showed that almost 18% of the nanoparticles were uptake by the lung in infected mice (male C57Bl/6) with Mycobacterium bovis BCG (4 × 10 5  CFU/cavity), corroborating its use as a nanodrug for tuberculosis imaging. The results for the cell assay corroborate its therapeutical effect. We developed and efficiently tested a new nanodrug that can be used for both imaging and therapy of tuberculosis, acting as a novel nanotheranostic.

Background Adolescents having early puberty (EP) are more likely to have obesity and increased cardiometabolic and inflammatory markers and atherosclerosis risk. We aimed to assess the indirect and mediated effects of leptin and adiposity on the relation between EP and cardiometabolic and inflammatory markers in European adolescents. Methods A sample of 511 adolescents with EP (12.5-17.5 years) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study was studied. To assess whether leptin levels and adiposity mediate the relation between EP and several biomarkers, linear regression models for mediation analyses were performed. Results EP was positively associated with the atherogenic index (Ath-I) (β=0.174; 95%CI 0.029-0.265) and negatively associated with the C-reactive protein (CRP) (β=-0.284; 95%CI -0.542 to -0.028) in girls. These associations were fully mediated by leptin levels (9.5%) and adiposity (44%), respectively. Moreover, EP has indirect effects on the apolipoprotein A-1 (ApoA-1) levels through adiposity in girls (for body mass index [BMI], β=0.014; 95%CI 0.005-0.028, and for waist circumference [WC], β=0.011; 95%CI 0.003-0.024), and on ApoA-1 (β=0.012; 95%CI 0.004-0.025), apolipoprotein B (ApoB) (β=-0.004; 95%CI -0.011 to -0.0004) and CRP (β=-0.265; 95%CI -0.819 to -0.047) through abdominal fat in boys. Conclusions Leptin levels and adiposity seem to play an important indirect and mediation role in the association between EP and cardiometabolic and inflammatory markers in adolescents. Weight control should be recommended in order to control the impaired cardiometabolic and inflammatory status arising in early pubertal adolescents.