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Objective: This study aims to assess the association between chronic pathologies and depressive and/or anxious disorders is high resulting in a reduction in the patient's quality of life., Patients and Methods: This is a prospective cross-sectional study with a descriptive and analytical design. Sociodemographic data and lifestyle habits were collected. Subsequently, the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Hospital Anxiety and Depression Scale (HADS) were applied. Results A total of 141 patients participated in the study, with a mean age of 45.78 (SD 16.01) years, of which 60.3% were female (n=85) and 39.7% were male (n=56). 58.9% had ulcerative colitis (UC) (n=83), and 41.1% had Crohn's disease (CD) (n=58). 16.5% of patients had a previous diagnosis of generalized anxiety disorder (GAD) and/or major depression (MD) (n=23). Regarding IBDQ scores, participants with anxiety had significantly lower mean scores in all IBDQ items (p<0.001), while the depression diagnosis obtained significantly lower mean values for systemic (p=0.015), emotional (p=0.001), and intestinal symptoms (p=0.005). Conclusion The results indicate that anxiety and depression negatively impact the quality of life of patients with IBD independently of the disease activity., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Exposure to pesticides, individually or in a mixture, in drinking water is one of the main sources of human contamination, which causes adverse effects on the reproductive system. Our study aimed to investigate, the effects of a 90-day exposure to low concentrations of glyphosate (GLY), atrazine (ATZ), and 2,4-dichlorophenoxyacetic acid (2,4-D), in commercial formulations, on morphological, molecular, and hormonal parameters of the ventral prostate of gerbils (Meriones unguiculatus). The animals were exposed via drinking water to individual concentrations of GLY: 700 μg/L, ATZ: 3 μg/L, and 2,4-D: 70 μg/L, as well as to their mixture (MIX). Our findings showed an increase in prostatic complex relative weight in ATZ-exposed animals. Stereological and morphometric techniques indicated an increase in the percentage and thickness of muscular stroma, following an increase in the amount of collagen and reticular fibers in the MIX group. Histopathological analysis showed a decrease in the incidence of epithelial atrophy, subepithelial inflammation, and microacini in the MIX. On the other hand, ATZ-exposed animals showed an increase in hyperplasia and total prostatic intraepithelial neoplasia (PIN). The expression of caspase-3 decreased and estrogen receptor alpha (ERα) increased in the 2,4-D and MIX. Western blotting showed an increase in estrogen receptor beta (ERβ) expression in MIX-exposed animals. Testosterone levels decreased in animals from the GLY, ATZ and 2,4-D groups. Our findings provide evidence that individual or combined exposure to herbicides causes hormonal imbalance and morphological alterations, besides favoring the incidence of proliferative lesions in the prostate, predisposing the gland to more severe injuries., 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 © 2024 Elsevier Ltd. All rights reserved.)

The study aimed to investigate the repercussions of androgen modulation on the adrenal cortex of male gerbils, focusing on the morphophysiology, proliferation, and cell death, as well as the expression of hormone receptors and steroidogenic enzymes. Mongolian gerbils (Meriones unguiculatus) were divided into three experimental groups: Control (C), Testosterone (T), animals received injections of testosterone cypionate and Castrated (Ct), animals underwent orchiectomy. The results showed that castration increased the zona fasciculata and promoted cell hypertrophy in all zones. Testosterone supplementation increased cell proliferation and cell death. Androgen modulation promoted an increase in AR, Erα, and ERβ. Castration promoted an increase in the CYP19, while decreasing 17βHSD enzymes. Testosterone supplementation, on the other hand, reduced CYP17 and increased CYP19 and 3βHSD enzymes. By analyzing the effects of androgen supplementation and deprivation, it can be concluded that testosterone is responsible for tissue remodeling in the cortex, regulating the rate of cell proliferation and death, as well as cell hypertrophy. Testosterone also modulate steroid hormone receptors and steroidogenic enzymes, consequently affecting the regulation, hormone synthesis and homeostasis of this endocrine gland., 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 © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the relationship between premenstrual disorders (PMD) and age, we analyzed the prevalence and severity of psycho-emotional and physical symptoms in a representative sample of Brazilian women., Methods: This observational and retrospective study analyzed data from Brazilian women aged 20-49 years from five regions of the country who reported premenstrual symptoms. Participants completed a premenstrual symptom screening questionnaire and self-reported the presence and severity of their symptoms. Among 23 104 women reporting does premenstrual symptoms, 38.91% (n = 8990) experienced PMD caused functional impairment. Finally, 5121 participants agreed to complete the adapted version of the screening questionnaire., Results: The age group distribution was 20-29 (46.7%), 30-39 (38.3%), and 40-49 years (15%). The most prevalent and severe physical symptom was acne/oily skin in participants aged 20-29 years and headache in women aged 30-49 years. Regarding psycho-emotional symptoms, the most prevalent was anxiety/tension in women aged 20-29 years and 40-49 years and irritability/anger in those aged 30-39 years. Irritability/anger was the most severe symptom in all groups., Conclusion: PMD significantly impacts the quality of life of Brazilian women with varying intensity. Physical symptoms associated with PMD vary with age, while psycho-emotional symptoms, particularly irritability/anger and anxiety, were intense in Brazilian women of reproductive age. These findings inform early diagnosis and individualized treatment approaches for PMD, addressing the needs of women., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Despite treatment advances through immunotherapies, including anti-PD-1/PD-L1 therapies, the overall prognosis of non-small cell lung cancer (NSCLC) patients remains poor, underscoring the need for novel approaches that offer long-term clinical benefit. This review examined the literature on the subject over the past 20 years to provide an update on the evolving landscape of dendritic cell-based immunotherapy to treat NSCLC, highlighting the crucial role of dendritic cells (DCs) in immune response initiation and regulation. These cells encompass heterogeneous subsets like cDC1s, cDC2s, and pDCs, capable of shaping antigen presentation and influencing T cell activation through the balance between the Th1, Th2, and Th17 profiles and the activation of regulatory T lymphocytes (Treg). The intricate interaction between DC subsets and the high density of intratumoral mature DCs shapes tumor-specific immune responses and impacts therapeutic outcomes. DC-based immunotherapy shows promise in overcoming immune resistance in NSCLC treatment. This article review provides an update on key clinical trial results, forming the basis for future studies to characterize the role of different types of DCs in situ and in combination with different therapies, including DC vaccines., 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 © 2024 Oliveira, Silva, Fernandes, Batah, Herrera, Cetlin and Fabro.)

Drugs that act on α-adrenoceptors may contain morpholine and pyrimidinone heterocycles. The aim of this study was to synthesize a series of pyrimidinones (S6a-e and S8) and characterize their α-adrenoceptor activity. Cytotoxicity assays (MTT and LDH) were performed in A7r5 and HUVECs. Concentration-effect curves to phenylephrine (Phe) were performed in rat aortic rings in the presence of compounds S6a-e and S8 or vehicle. Nitric oxide (NO) production and NO stable metabolic products, nitrite and nitrate, expressed as total nitrogen oxides (NOx) were assessed in HUVECs by confocal microscopy with the DAF-2DA probe and by the Griess reaction, respectively. Molecular docking simulations were performed using the 6a compound and α 2A -adrenoceptor. In the evaluated conditions, the percentage of viable cells and the release of LDH were similar between control cells and cells exposed to the tested pyrimidinones. S6d, S6e, S8, and the positive control prazosin (but not S6a, S6b, and S6c) decreased Phe-induced contractions in endothelium-denuded aortic rings. S6a, S6b, and S6c decreased Phe-induced contractions in endothelium-intact aortic rings. The effect of S6a was abolished by L-NAME. NO production and NOx levels were inhibited in the presence of the α 2 receptor antagonist yohimbine and the NOS inhibitor L-NAME. The 6a docking simulation estimated that the mean binding free energy of the compound was lower than the estimated value for yohimbine. These data suggest that S6d, S6e, and S8 may be α 1 -adrenoceptor antagonists while S6a acts as an agonist of α 2 -adrenoceptors., Competing Interests: Declaration of competing interest The authors of the manuscript entitled “New morpholine-containing pyrimidinones act on alpha-adrenergic receptors” declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging., 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 © 2024 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to compare the DNA preservation capacity of buccal mucosa exfoliated cells when stored in different solutions under varying time and temperature conditions., Design: DNA preservation solutions, including Dimethyl sulphoxide disodium-EDTA-saturated NaCl (DESS), Tris-EDTA-NaCl-Tween20 buffer (TENT), Nucleic Acid Preservation Buffer (NAP), and phosphate-buffered saline (PBS), were prepared. Buccal mucosa cells from a single patient were collected, dispensed into these solutions, and stored at room temperature (RT) and 4 °C for 24 h, 72 h, 30 days, 90 days, and 180 days. DNA was extracted using the salting-out method and the QIAamp DNA Mini Kit. DNA concentration and purity were determined using the QuBit device and NanoDrop, while DNA integrity was assessed using the Agilent 4200 TapeStation system. The ability to amplify the IFNA primer was also evaluated by PCR., Results: The salting-out method yielded better concentration and purity results, with PBS, TENT, and DESS buffers demonstrating superior concentration values when stored at 4 °C, resulting in mean values exceeding 10 ng/μL for up to 30 days. DESS consistently exhibited the best integrity values over time for both temperature conditions. Amplification capacity was enhanced when samples were stored at 4 °C. When stored at RT, PBS achieved 100% amplification within 24 h. NAP yielded the poorest results., Conclusion: In the context of long-term preservation, the DESS buffer emerges as the most effective solution, maintaining requisite DNA quality and quantity standards for up to 30 days at RT and up to 3 months at 4 °C., 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 Ltd. All rights reserved.)

Edaphoclimatic conditions influence nitrous oxide (N 2 O) emissions from agricultural systems where soil biochemical properties play a key role. This study addressed cumulative N 2 O emissions and their relations with soil biochemical properties in a long-term experiment (26 years) with integrated crop-livestock farming systems fertilized with two P and K rates. The farming systems consisted of continuous crops fertilized with half of the recommended P and K rates (CCF1), continuous crops at the recommended P and K rates (CCF2), an integrated crop-livestock system with half of the recommended P and K rates (ICLF1), and an integrated crop-livestock at the recommended P and K rates (ICLF2). The ICLF2 may have promoted the greatest entry of carbon into the soil and positively influenced the soil's biochemical properties. Total carbon (TC) was highest in ICLF2 in both growing seasons. The particulate and mineral-associated fractions in 2016 and 2017, respectively, and the microbial biomass fraction in the two growing seasons were also very high. Acid phosphatase and arylsulfatase in ICLF1 and ICLF2 were highest in 2016. The soil properties correlated with cumulative N 2 O emissions were TC, total nitrogen (TN), particulate nitrogen (PN), available nitrogen (AN), mineral-associated organic carbon (MAC), and microbial biomass carbon (MBC). The results indicated that ICLF2 induces an accumulation of more stable organic matter (OM) fractions that are unavailable to the microbiota in the short term and result in lower N 2 O emissions.

Mining activities generate large quantities of wastes that significantly alter the biogeochemistry and ecological structure of entire river basins. Microbial communities that develop in these areas present a variety of survival and adaptation mechanisms. Knowing this diversity at the molecular level is strategic both for understanding adaptive processes and for identifying genomes with potential use in bioremediation and bioprospecting. In this work, prokaryotic and eukaryotic communities were evaluated by meta-taxonomics (16S and 18S amplicons) in sediments and water bodies impacted by acid mine drainage in an important coal mining area in southern Brazil. Five sampling stations were defined on a gradient of impacts (pH 2.7-4.25). Taxon diversity was directly proportional to pH, being greater in sediments than in water. The dominant prokaryotic phyla in the samples were Proteobacteria, Actinobacteria, Acidobacteria, OD1, Nitrospirae, and Euryarchaeota, and among the eukaryotes, algae (Ochrophyta, Chlorophyta, Cryptophyceae), fungi (Basidiomycota, Ascomycota, and Cryptomycota), and protists (Ciliophora, Heterolobosea, Cercozoa). The prokaryotic genera Leptospirillum, Acidithiobacillus, Acidiphilium, Thiomonas, Thermogymnomonas, and Acidobacterium, and the eukaryotic genera Pterocystis and Poteriospumella were associated with more acidic conditions and higher metal concentrations, while the prokaryotic genera Sediminibacterium, Gallionella Geothrix, and Geobacter were more abundant in transitional environments., (© 2023. The Author(s), under exclusive licence to Springer Nature Japan KK, part of Springer Nature.)

Ethiprole, a phenylpyrazole insecticide, has been increasingly used in the Neotropical region to control stink bug pests in soybean and maize fields. However, such abrupt increases in use may have unintended effects on non-target organisms, including those inhabiting freshwater ecosystems. Here, we evaluated the effects of acute (96 h) sublethal exposure to ethiprole (up to 180 μg/L, which is equivalent to 0.013% of the recommended field dose) on biomarkers of stress in the gills, liver, and muscle of the Neotropical fish Astyanax altiparanae. We further recorded potential ethiprole-induced effects on the structural histology of A. altiparanae gills and liver. Our results showed that ethiprole exposure increased glucose and cortisol levels in a concentration-dependent manner. Ethiprole-exposed fish also exhibited higher levels of malondialdehyde and greater activity of antioxidant enzymes, such as glutathione-S-transferase and catalase, in both gills and liver. Furthermore, ethiprole exposure led to increased catalase activity and carbonylated protein levels in muscle. Morphometric and pathological analyses of the gills revealed that increasing ethiprole concentration resulted in hyperemia and loss of integrity of the secondary lamellae. Similarly, histopathological analysis of the liver demonstrated higher prevalence of necrosis and inflammatory infiltrates with increasing ethiprole concentration. Altogether, our findings demonstrated that sublethal exposure to ethiprole can trigger a stress response in non-target fish species, which may lead to potential ecological and economic imbalances in Neotropical freshwater systems., 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 Ltd. All rights reserved.)

Purpose: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment., Methods: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days., Results: A total of 546 patients were included in the study. A KPS of <70 ( P = .021), the number of brain metastases ( P = .001), the lack of brain metastasectomy ( P = .006), and the lack of systemic therapies after BrRT ( P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 ( P < .001), the lack of brain metastasectomy ( P = .015), and the lack of systemic therapies after BrRT ( P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days., Conclusion: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.

Heavy metals are elements found into the environment mainly due to anthropogenic activities. Naturally occurring and higher released doses cause disorders in the prostate, which depends on appropriate hormonal regulation, and exposure to heavy metals may impair prostate homeostasis. The current work highlighted the main mechanisms of toxicity of different environmental heavy metal contaminants, such as aluminum, arsenic, cadmium, chromium, lead, mercury, and nickel, and their impacts found in the prostate morphophysiology of murine models. The repercussions triggered by heavy metals on the prostate include hormonal imbalance and oxidative damage, leading to morphological alterations, which can vary according to the chemical properties of each element, exposure time and concentration, and age. The information of altered biological pathways and its impacts on the prostate of exposed murines are related to human outcomes being useful in the real context of human exposure., 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 Inc. All rights reserved.)

Vaccines prevent numerous infectious diseases, including influenza. Despite their significant contribution to controlling influenza, vaccine coverage against this disease varies among health care workers. The Health Belief Model could thus help to understand the reasons why these workers accept (or not) the immunobiological. The aim of this study was to describe the main results of research performed on influenza vaccination among health care workers using the Health Belief Model. This is an integrative literature review. Data search took place in October 2020 in the PubMed database, with the following descriptors: "influenza vaccine"; "health professionals"; "Health Belief Model," and their synonyms. Eleven studies were included in this review. The main dimensions of the model (susceptibility, severity, benefits, and barriers) were more explored by the studies, and self-efficacy was the least studied dimension. Moreover, we observed a relationship between the theory's dimensions (susceptibility, severity, benefits, barriers, cues to action, and self-efficacy) and influenza vaccination in health care workers. In conclusion, this review identified profiles of beliefs for each dimension of the Health Belief Model, which has traditionally been an ally for determining refusal or acceptance of the influenza vaccine among health care workers., Competing Interests: Confilicts of interest: None

Numerous genotyping techniques based on different principles and with different costs and levels of resolution are currently available for understanding the transmission dynamics of brucellosis worldwide. We aimed to compare the population structure of the genomes of 53 Brazilian Brucella abortus isolates using eight different genotyping methods: multiple-locus variable-number tandem-repeat analysis (MLVA8, MLVA11, MLVA16), multilocus sequence typing (MLST9, MLST21), core genome MLST (cgMLST) and two techniques based on single nucleotide polymorphism (SNP) detection (parSNP and NASP) from whole genomes. The strains were isolated from six different Brazilian states between 1977 and 2008 and had previously been analyzed using MLVA8, MLVA11, and MLVA16. Their whole genomes were sequenced, assembled, and subjected to MLST9 MLST21, cgMLST, and SNP analyses. All the genotypes were compared by hierarchical grouping method based on the average distances between the correlation matrices of each technique. MLST9 and MLST21 had the lowest level of resolution, both revealing only four genotypes. MLVA8, MLVA11, and MLVA16 had progressively increasing levels of resolution as more loci were analyzed, identifying 6, 16, and 44 genotypes, respectively. cgMLST showed the highest level of resolution, identifying 45 genotypes, followed by the SNP-based methods, both of which had 44 genotypes. In the assessed population, MLVA was more discriminatory than MLST and was easier and cheaper to perform. SNP techniques and cgMLST provided the highest levels of resolution and the results from the two methods were in close agreement. In conclusion, the choice of genotyping technique can strongly affect one's ability to make meaningful epidemiological conclusions but is dependent on available resources: while the VNTR based techniques are more indicated to high prevalence scenarios, the WGS methods are the ones with the best discriminative power and therefore recommended for outbreaks investigation., 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. Published by Elsevier B.V.)

(1) Background: Stroke is one of the leading causes of disability. To identify the best treatment strategies for people with stroke (PwS), the aim of the current study was to compare the effects of training on a treadmill with functional electrical stimulation (TT-FES) with training on a treadmill (TT), and to analyze the effects of sequence of training on mobility and the parameters of walking ability. (2) Methods: Prospective, longitudinal, randomized and crossover study, in which 28 PwS were distributed into groups, namely the A-B Group (TT-FES followed by TT) and B-A Group (TT followed by TT-FES), using the foot drop stimulator, and were measured with functional tests. (3) Results: We found improved mobility, balance, non-paretic limb coordination, and endurance only in the group that started with TT-FES. However, sensorimotor function improved regardless of the order of training, and paretic limb coordination only improved in the B-A Group, but after TT-FES. These data indicate that the order of the protocols changed the results. (4) Conclusions: Although biomechanical evaluation methods were not used, which can be considered a limitation, our results showed that TT-FES was superior to isolated training on a treadmill with regard to balance, endurance capacity, and coordination of the non-paretic limb.

Objective: Peritoneal carcinomatosis (PC) indicates advanced stage cancer, which is generally associated with a poor outcome and a 6 to 12 months. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option for treating patients with primary PC, such as mesothelioma, or secondary PC, such as colorectal cancer (CRC) or pseudomixoma. Until recently, such patients were deemed untreatable. The purpose of this study was to assess the results of CRS + HIPEC in patients with PC. Postoperative complications, mortality and survival rates were evaluated according to the diagnosis., Results: Fifty-six patients with PC, undergoing full CRS + HIPEC between October 2004 and January 2020, were enrolled. The mortality rate was 3.8% and the morbidity rate was 61.5%. Complications were significantly higher in proportion to the duration of surgery (p<0.001). The overall survival rates, as shown in the Kaplan-Meyer curve, were respectively 81%, 74% and 53% at 12, 24 and 60 months. Survival rates according to each diagnosis for the same periods were 87%, 82% and 47% in patients with pseudomixoma, and 77%, 72% and 57% in patients with CRC (log-rank 0.371, p=0.543)., Conclusion: CRS with HIPEC is an option for pacients with primary or secondary PC. Although complication rates are high, a longer survival rate may be attained compared to those seen in previously published results; in some cases, patients may even be cured.

Background: A significant proportion of patients with non-small-cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICIs). Since metabolic reprogramming with increased glycolysis is a hallmark of cancer and is involved in immune evasion, we used 18 F-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET/CT) to evaluate the baseline glycolytic parameters of patients with advanced NSCLC submitted to ICIs, and assessed their predictive value., Methods: 18 F-FDG PET/CT results in the 3 months before ICIs treatment were included. Maximum standardized uptake values, whole metabolic tumor volume (wMTV), and whole-body total lesion glycolysis (wTLG) were evaluated. Cutoff values for high or low glycolytic categories were determined using receiver-operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were evaluated. Patients with a complete response and a matching group with resistance to ICIs underwent immunohistochemistry analysis. An unsupervised k-means clustering model integrating programmed cell death ligand 1 (PD-L1) expression, glycolytic parameters, and ICIs therapy was performed., Results: In all, 98 patients were included. Lower baseline 18 F-FDG PET/CT parameters were associated with responses to ICIs. Patients with low wMTV or wTLG had improved PFS and OS. High wTLG, strong tumor expression of glucose transporter-1, and lack of responses were significantly associated. Patients with low glycolytic parameters benefited from ICIs, regardless of chemotherapy. Conversely, those with high parameters benefited from the addition of chemotherapy. Patients with higher wTLG and lower PD-L1 were associated with progression and worse survival to ICIs monotherapy., Conclusions: Glycolytic metabolic profiles established through baseline 18 F-FDG PET/CT are useful biomarkers for evaluating ICI therapy in advanced NSCLC., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2022.)

This study compared the effects of aerobic physical training and estradiol (E2) replacement on central pathways involved with thermoregulation in ovariectomized rats. Rats were assigned to untrained ovariectomized treated with placebo (UN-OVX), untrained ovariectomized treated with E2 (E2-OVX), and trained ovariectomized (TR-OVX) groups. Tail skin temperature (TST), internal temperature (Tint), and basal oxygen consumption (VO 2 ) were recorded. Neuronal activity, brain expression of Kiss1, NKB and Prodyn, and central norepinephrine (NE) levels were measured. UN-OVX had the highest TST. Compared to UN-OVX rats, TR-OVX and E2-OVX had lower Fos expression in the paraventricular and arcuate (ARC) nuclei, and lower double labeling for Tyrosine Hydroxylase and Fos in the brainstem. Compared to UN-OVX, only TR-OVX group exhibited lower kisspeptin (Kiss1), neurokinin B (NKB), and prodynorphin expression in the ARC and higher central NE levels. Aerobic physical training before menopause may prevent the heat dissipation imbalance induced by reduction of E2, through central NE release, modulation of Kiss1, NKB and prodynorphin expression in neurons from ARC nucleus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Our study evaluated the oviposition behaviour of Anastrepha fraterculus (Wiedemann, 1830) and Ceratitis capitata (Wiedemann, 1824) in five fruit species. Apples, guavas, mangoes, peaches and tangerines were exposed to infestation for 6, 12 and 24 hours. Anastrepha fraterculus and C. capitata showed different oviposition behaviour in apples and tangerines and similar oviposition behaviour in guavas, mangoes and peaches. There was a positive correlation between infestation time and pupae/kg, as well as between pupae/fruit and the survival rate of the immature (pupal viability). In this study, we present discussions about the oviposition behaviour of flies and the host infestation index. This index can reflect the reproductive capacity that each fruit species offers for each fly species. Here, we see an adult recovery rate greater than 89% in the highest infestation index observed in guava (185 A. fraterculus per unit fruit) and peach (220 C. capitata per unit fruit). Understanding the reproductive capacity of each host can help with risk analysis and the management of fruit flies.

Previous studies have highlighted the positive effects of Estradiol (E2) replacement therapy and physical exercise on skeletal muscle during menopause. However, the comparison effects of exercise training (ET) and estradiol replacement therapy during menopause on skeletal muscle have not been investigated to date. This study aimed to compare the effects of endurance exercise training versus E2 replacement therapy on mitochondrial density, redox status, and inflammatory biomarkers in the skeletal muscle of ovariectomized rats. Thirty female Wistar rats (12-week-old) were randomly assigned into three groups: Untrained ovariectomized rats (UN-OVX, n = 10); untrained ovariectomized rats treated with estradiol replacement therapy (E2-OVX); and, trained ovariectomized rats (TR-OVX). After ovariectomy, the E2-OVX rats were treated subcutaneously with E2 (implanted Silastic® capsule containing 360 μg of 17β-estradiol/mL) while the TR-OVX group performed an exercise training protocol (50-70% of maximal running speed on a treadmill, 60 min/day, 5 days/week for 8 weeks). After euthanasia, the soleus muscle was processed for histological and biochemical evaluations. Only exercise prevented the reduction of maximal oxygen consumption and increased mechanical efficiency (ME). While mitochondrial muscle density, total antioxidant capacity (FRAP), catalase (CAT) activity, and interleukin 10 levels were higher in TR-OVX, only OVX-E2 presented higher CAT activity and lower interleukin 6 levels. Endurance exercise training compared with E2 replacement therapy maintains the aerobic capacity improving the ME of OVX rats. In addition, only endurance exercise training raises the skeletal muscle mitochondrial content and tends to balance the redox and inflammatory status in the skeletal muscle of OVX rats., (© 2022. The Author(s).)

Cancer cells harbor genomic instability due to accumulated DNA damage, one of the cancer hallmarks. At least five major DNA Damage Repair (DDR) pathways are recognized to repair DNA damages during different stages of the cell cycle, comprehending base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR), and non-homologous end joining (NHEJ). The unprecedented benefits achieved with immunological checkpoint inhibitors (ICIs) in tumors with mismatch repair deficiency (dMMR) have prompted efforts to extend this efficacy to tumors with HR deficiency (HRD), which are greatly sensitive to chemotherapy or PARP inhibitors, and also considered highly immunogenic. However, an in-depth understanding of HRD's molecular underpinnings has pointed to essential singularities that might impact ICIs sensitivity. Here we address the main molecular aspects of HRD that underlie a differential profile of efficacy and resistance to the treatment with ICIs compared to other DDR deficiencies., Competing Interests: LMC reports grants from Novartis and BMS. The remaining authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Silva, Wanderley and Colli.)

Adrenoceptors are the receptors for catecholamines, adrenaline, and noradrenaline. They are divided in α (α 1 and α 2 ) and β (β 1 , β 2 and β 3 ). α 1 -adrenoceptors are subdivided in α 1A , α 1B and α 1D . Most tissues express mixtures of α 1 -adrenoceptors subtypes, which appear to coexist in different densities and ratios, and in most cases, their responses are probably due to the activation of more than one type. The three subtypes of α 1 -adrenoceptors are G-protein-coupled receptors (GPCR), specifically coupled to G q/11 . Additionally, the activation of these receptors may activate other signaling pathways or different components of these pathways, which leads to a great variety of possible cellular effects. The first clinically used α1 antagonist was Prazosin for Systemic Arterial Hypertension (SAH). It was followed by its congeners, Terazosin and Doxazosin. Nowadays, there are many classes of α-adrenergic antagonists with different selectivity profiles. In addition to SAH, the α 1 -adrenoceptors are used to treat Benign Prostatic Hyperplasia (BPH) and urolithiasis. This antagonism may be part of the mechanism of action of tricyclic antidepressants. Moreover, the activation of these receptors may lead to adverse effects such as orthostatic hypotension, similar to what happens with antidepressants and with some antipsychotics. Structure-activity relationships can explain, in part, how antagonists work and how selective they can be for each one of the subtypes. However, it is necessary to develop new molecules which antagonize the α 1 - adrenoceptors or make chemical modifications in these molecules to improve the selectivity and pharmacokinetic profile and/or reduce the adverse effects of known drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Endurance training prevents cardiac dysfunction induced by menopause, but to date, no studies compared the effects of endurance training prior to menopause versus estrogen replacement therapy during menopause on heart function of rats., Methods: Female Wistar rats aged three months were randomly assigned into three groups: Untrained ovariectomized rats (UN-OVX), untrained ovariectomized rats treated with estradiol (UN-OVX-E2), and ovariectomized rats previously exercised (EX-OVX). The endurance training protocol consisted of running on a treadmill at 60-70% of maximal aerobic capacity, 60 min per day, five days per week, for eight weeks. Estradiol replacement therapy consisted of silastic capsules containing the hormone for twelve days. After euthanasia, hearts were harvested, weighed and cardiac function was evaluated by the Langendorff technique., Results: Both cardiac contractility and relaxation indexes improved similarly in the EX-OVX and UN-OVX-E2 rats compared to UN-OVX., Conclusion: Our findings reveal similar beneficial effects between endurance training previously to menopause and estradiol replacement therapy during menopause on cardiac function of rats., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In-vitro effects of sub-lethal concentrations of malathion, phenanthrene (Phe) and cadmium (Cd) were tested on Chironomus sancticaroli larvae in acute bioassays by measuring biochemical and molecular parameters. Malathion was evaluated at 0.001, 0.0564 and 0.1006 mg L -1 ; Phe at 0.0025, 1.25 and 2.44 mg L -1 ; and Cd at 0.001, 3.2 and 7.4 mg L -1 . The recovery test carried out at the highest concentration of each compound showed that survival of larvae exposed to Phe ranged from 4% to 5%, while the effects of malathion and Cd were irreversible, not allowing the emergence of adults. Results showed that malathion and Cd inhibited AChE, EST-α and ES-β activities at the two highest concentrations. Phe at 0.0025, 1.25 and 2.44 mg L -1 ; and Cd at 3.2 and 7.4 mg L -1 inhibited glutathione S-transferase activity. Oxidative stress was exclusively induced by the lowest concentration of malathion considering SOD activity once CAT was unaffected by the stressors. Lipid peroxidation was registered exclusively by malathion at the two highest concentrations, and total hemoglobin content was only reduced by Cd at the two highest concentrations. The relationship among biochemical results, examined using the PCA, evidenced that malathion and Cd concentrations were clustered into two groups, while Phe only formed one group. Four hemoglobin genes of C. sancticaroli were tested for the first time in this species, with Hemoglobin-C being upregulated by malathion. The toxicity ranking was malathion > Phe > Cd, while biochemical and molecular results showed the order malathion > Cd > Phe. Our results highlight the importance of combining different markers to understand the effects of the diverse compounds in aquatic organisms., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Atrazine (ATZ) is among the most widely used herbicides in the world, and yet it has a potential to contaminate aquatic environments due to pesticide leaching from agricultural areas. In the Neotropical region, studies about the effects of this herbicide in native aquatic wildlife is scarce.Our study aimed at investigating the effects of a 30-day exposure to a commercial atrazine formulation on oxidative stress parameters, histopathology in testis and liver, and hormone levels in males and female of yellow-tailed tetra fish (Astyanax altiparanae). Adults were exposed to low but environmentally relevant concentrations of atrazine as follows: 0 (CTL-control), 0.5 (ATZ0.5), 1 (ATZ1), 2 (ATZ2) and 10 (ATZ10) μg/L. Our results showed decreased GST activity in gills in all groups of exposed animals and increased CAT activity in gills from the ATZ10 group. In the liver, there was an increase in lipid peroxidation in fish from ATZ1 and ATZ2 groups. Histological analysis of the liver showed increased percentage of sinusoid capillaries in ATZ2 fish, increased vascular congestion in ATZ1 and increased leukocyte infiltration in the ATZ10 group. Hepatocyte diameter analysis revealed a decrease in cell size in all groups exposed to ATZ, and a decrease in hepatocyte nucleus diameter in ATZ1, ATZ2 and ATZ10 groups. Endocrine parameters did not show significant changes following ATZ exposure, although an increase of triiodothyronine/thyroxine (T 3 /T 4 ) ratio was observed in ATZ2 fish. Our results provide evidence that even low, environmentally relevant concentrations of ATZ produced oxidative damage and histological alterations in adult yellow-tailed tetra., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

This work aimed to formulate and perform physicochemical and functional characterization of maltodextrin microcapsules containing ethanolic extract of stevia, rich in antioxidant compounds, encapsulated by a spray-drying process with two maltodextrins (DE10 and DE19). The powders were named M10 and M19, respectively. We analyzed the physicochemical parameters, antidiabetic activity, cytotoxicity, bioaccessibility of the compounds by in vitro digestion, as well as the structure of the microcapsules by scanning electron microscopy. Microcapsules showed higher solubility (∼35%), lower moisture content (∼29%), and the maltodextrin DE10 had higher efficiency as an encapsulating agent (87%) when compared to DE19 (76%) and showed well-defined spherical structures. The microencapsulation preserved the content of phenolic compounds and antioxidant activity present in the extract (7.2% and 87.5%, respectively). The bioaccessibility of these microencapsulated compounds and antioxidant activity were higher under different conditions of in vitro digestion (mouth, gastric, and intestinal conditions) and showed no cytotoxic effects. We identified 41 compounds (by UHPLC-MS/MS-Qtof) related to the nutritional benefits offered by stevia and the microencapsulation technique can be recommended to preserve bioactive compounds. PRACTICAL APPLICATION: Ethanol extract from stevia leaves contains antioxidant phytochemicals related to the nutritional benefits of stevia. However, this extract presents low solubility and consequently low bioaccessibility under in vitro digestion. The microencapsulation process protects the bioactive compounds of the different pH from digestion and improves the physical-chemical parameters of the extract, increasing its applicability as a possible food additive., (© 2020 Institute of Food Technologists®.)

The dogs' responses to training exercise are seldom monitored using physiological variables, and cardiac autonomic regulation (CAR) is a relevant determinant of endurance-training adaptation. There are studies in the literature establishing that regular exercise could interfere with CAR in dogs, measured by heart rate and vagal-derived indexes of heart-rate-variability (HRV). However, few studies were found using a prescribed training program based on the lactate threshold (LT) to determine HRV by a 24-h Holter analysis. The purpose of this study was to test whether an endurance-training program (ETP) guided individually by LT raises time-domain measures of HRV in healthy Beagle dogs. Twenty dogs were assigned to two groups: control (C) and trained (T). The dogs from group T underwent an incremental exercise test (IET) to determine their LT. Both LT and velocity corresponding to the LT (VLT) was determined by visual inspection. T group performed an eight-week endurance-training program consisting of treadmill runs set to 70-80% of the VLT. Next, dogs from the group T have submitted to IET again. The maximal velocities (Vmax) at which achieved by the trained dogs in both IETs were determined. The group S did not undergo IETs or ETP. HRV was determined by the 24-hour-Holter at rest, before and on the 2°, 4°, 6° and 8° training weeks. To examine the HR impact on HRV, standard HRV variables were normalized to prevailing HR. VLT and Vmax rose in group T, indicating an improvement of dogs' aerobic and anaerobic capacity. The normalized standard HRV indexes were relatively attenuated since these variables had a reduction in the degree of correlation concerning an average HR. The ETP resulted in decreased resting heart rate and increased time-domain indices, highlighting the log-transformed square root of the mean sum of the squared differences between R-R intervals (Ln rMSSD). The lactate-guided endurance-training program could lead to better parasympathetic cardiac modulation in Beagle dogs., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to analyse morphological and molecular (ITS region) characteristics for eight species of mites in the family Macrochelidae that are present in cattle manure in Brazil. Six of these species were already known in Brazil and, for five of these, both tools (morphology and phylogeny) were concordant regarding all the trees used. The species G. saprophila and M. scutatus were reported in the present study for the first time in Brazil. The data obtained in this study suggest that the molecular analysis corroborated the morphological identification in most species of macrochelids. The results also demonstrate the need to correlate identifications through dichotomous keys, by using phylogenetic studies to better distinguish cryptic species.

Background: Knee osteoarthritis ( k OA) is a common chronic disease that induces changes in redox status and inflammatory biomarkers, cell death, and motor impairment. Aerobic training can be a non-pharmacological alternative to prevent the progression of the disease., Objective: To evaluate the effects of an 8 weeks moderate-intensity treadmill aerobic training program on redox status and inflammatory biomarkers and motor performance in k OA-like changes induced by monosodium iodoacetate (MIA) in rats., Methods: Twenty-seven rats were randomly divided into three groups: SHAM; induced k OA (OA); and induced k OA + aerobic training (OAE). Motor performance was evaluated by the number of falls on rotarod test, the total time of displacement and the number of failures on a 100 cm footbridge. Data for cytokines and histology were investigated locally, whereas plasma was used for redox status biomarkers., Results: The OA group, compared to the SHAM group, increased 1.13 times the total time of displacement, 6.05 times the number of failures, 2.40 times the number of falls. There was also an increase in cytokine and in thiobarbituric acid reactive substances (TBARS) (IL1β: 5.55-fold, TNF: 2.84-fold, IL10: 1.27-fold, IL6: 1.50-fold, TBARS: 1.14-fold), and a reduction of 6.83% in the total antioxidant capacity (FRAP), and of 35% in the number of chondrocytes. The aerobic training improved the motor performance in all joint function tests matching to SHAM scores. Also, it reduced inflammatory biomarkers and TBARS level at values close to those of the SHAM group, with no change in FRAP level. The number of falls was explained by IL1β and TNF (58%), and the number of failures and the total time of displacement were also explained by TNF (29 and 21%, respectively)., Conclusion: All findings indicate the efficacy of moderate-intensity aerobic training to regulate inflammatory biomarkers associated with improved motor performance in induced k OA-like changes, thus preventing the loss of chondrocytes., (Copyright © 2019 Martins, Mendonça, Aguiar, Fonseca, Santos, Tossige-Gomes, Melo, Oliveira, Leite, Camargos, Ferreira, Coimbra, Poortmans, Oliveira, Silva, Domingues, Bernardo-Filho and Lacerda.)

Background: Chronic obstructive pulmonary disease (COPD) leads to peripheral and respiratory muscle dysfunctions. Nowadays, inspiratory muscle training can be geared toward strength or endurance gains. This study aims to investigate the effects of an inspiratory muscle training (IMT) protocol using different therapeutic modalities to be implemented in pulmonary rehabilitation programs. The effects of IMT on exercise capacity were considered as the primary endpoint, and the effects of IMT on inspiratory muscle function, health-related quality of life, and daily physical activity level were considered as the secondary outcomes., Methods: This study is a blinded-investigator randomized controlled clinical trial. Sixty subjects will be randomly allocated into three groups: (1) pulmonary rehabilitation (PR) associated with inspiratory muscle training without any load (PRWIMT), (2) PR associated with inspiratory muscle training with a linear load (PRIMTLL), and (3) PR associated with inspiratory muscle training with isocapnic voluntary hyperpnea (PRIMTIVH). The protocol will be performed 5 days a week (3 days with supervision) for 10 weeks. The study will assess anthropometric data, lung function, respiratory muscle strength, and functional capacity by the Incremental Shuttle Walking Test and the Six-Minute Walk Test, lung volumes during the submaximal endurance test, peripheral muscle strength of the upper and lower limbs, dyspnea, and quality of life related to health, before and after the training protocol. Normality will be tested using the Kolmogorov-Smirnov test, and variables will be compared by two-way analysis of variance. The significance level was set at p < 0.05. Ethics approval was obtained from the Institutional Ethics Committee in Research (1.663.411). The study results will be disseminated through presentation at specific scientific conferences and publication in peer-reviewed journals., Discussion: The different IMT protocols used in our study will be able to guide respiratory therapists to understand and to include in conventional PR programs the most effective respiratory muscle training type in subjects with COPD., Trial Registration: Brazilian Clinical Trials Registry, RBR-94v6kd . Registered on 11 March 2017.

OBJECTIVE To determine whether the lactate threshold of dogs could be determined by a visual method and to assess the extent of agreement and bias among treadmill velocities for the lactate threshold as determined by visual (LTv) and polynomial (LTp) methods, glucose threshold as determined by visual (GTv) and polynomial (GTp) methods, and heart rate deflection point (HRdp) as a method for estimating the aerobic capacity of dogs. ANIMALS 18 healthy adult Beagles. PROCEDURES Each dog underwent a standardized incremental treadmill exercise test once. The test ended when the dog began to show signs of fatigue. Plasma lactate and glucose concentrations and heart rate (HR) were plotted against exercise intensity (treadmill velocity) for the duration of the test, and the LTv, GTv, and HRdp were determined visually. The LTp and GTp were determined by means of a second-order polynomial function. One-way ANOVA, Pearson correlation, Bland-Altman analyses, and ordinary least products regression were used to assess the extent of agreement and bias among the various threshold velocities. RESULTS Mean velocity did not differ significantly among the thresholds evaluated. There was a strong positive correlation between the LTv velocity and the velocity for GTv (r = 0.91), LTp (r = 0.96), GTp (r = 0.94), and HRdp (r = 0.95). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that LTv could be determined for dogs undergoing intense exercise on a treadmill, and the treadmill velocity corresponding to the LTv was associated with the velocity for the other hallmarks of endurance. Thus, that method may be useful for prescription and evaluation of conditioning programs for dogs.

Background/aim: Post-operative radiation therapy (PORT) is associated with improvement in loco-regional control and survival rates in early breast cancer. However, the evidence of benefit in patients after treatment with neoadjuvant chemotherapy (NAC) is poor. We aimed to assess the impact of the type of surgery in the PORT plan and the role of the PORT fields in clinical outcomes in breast cancer patients who had undergone NAC followed by surgery., Materials and Methods: We performed a retrospective analysis of all non-metastatic breast cancer patients treated between 2008 and 2014 at our institution who had received NAC and PORT., Results: A total of 528 women were included of whom 396 were submitted to mastectomy or nipple-sparing/skin-sparing mastectomy. Most (92.8%) of the patients had locally advanced disease (clinical stage IIB to IIIC). All patients underwent irradiation for breast or chest wall. Most patients received PORT to the supraclavicular and axillary (levels II and III) nodes (87.1% and 86.4% for breast-conserving surgery and 95.1% and 93.8% for mastectomy and nipple-sparing/skin-sparing mastectomy, respectively). Irradiation of level I axillary and internal mammary nodes was uncommon. The disease-free survival and overall survival rates at 3 years were 72% and 85%, respectively. There were no statistically significant differences in clinical outcomes according to the use of nodal irradiation., Conclusions: After NAC, most patients received irradiation of the breast/chest wall and axillary and supraclavicular nodes. In this setting, PORT to breast/chest wall with or without regional nodal irradiation was safe and effective, with acceptable disease-free and overall survival rates reported in this high-risk population.

There is evidence that central cholinergic stimulation increases heat dissipation in normotensive rats besides causing changes on the cardiovascular system via modulation of baroreceptors activity. However, the contribution of the central cholinergic system on thermoregulatory responses and its relationship with cardiovascular adjustments in spontaneously hypertensive rats (SHRs), an animal model of reduced baroreceptor sensitivity and thermoregulatory deficit, has not been completely clarified. Therefore, the aim of this study was to verify the involvement of the central cholinergic system in cardiovascular and thermoregulatory adjustments in SHRs. Male Wistar rats (n = 17) and SHRs (n = 17) were implanted with an intracerebroventricular cannula for injections of 2 µL of physostigmine (phy) or saline solution. Tail temperature (T tail ), internal body temperature (T int ), systolic arterial pressure (SAP), heart rate (HR) and metabolic rate were registered during 60 min while the animals remained at rest after randomly receiving the injections. The variability of the SAP and the HR was estimated by the fast Fourier transform. Phy treatment began a succession of cardiovascular and thermoregulatory responses that resulted in increased SAP, reduced HR and increased T tail in both Wistar and SHRs groups. The magnitude of these effects seems to be more intense in SHRs, since the improvement of heat dissipation reflected in T int . Taken together, these results provide evidence that hypertensive rats present greater cardiovascular and thermoregulatory responses than normotensive rats after central cholinergic stimulation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: and Purpose: Post-operative radiation therapy (PORT) is usually indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy (NAC) and surgery. However, the optimal timing to initiation of PORT is currently unknown., Material and Methods: We retrospectively evaluated data from patients with BC who received PORT after NAC and surgery at our institution from 2008 to 2014. Patients were categorized into three groups according to the time between surgery and PORT: <8 weeks, 8-16 weeks and >16 weeks., Results: A total of 581 patients were included; 74% had clinical stage III. Forty-three patients started PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks after surgery was associated with better disease-free survival (DFS) (<8 weeks versus 8-16 weeks: HR 0.33; 95% CI 0.13-0.81; p = 0.02; <8 weeks versus >16 weeks: HR 0.38; 95% CI 0.15-0.96; p = 0.04) and better overall survival (OS) (<8 weeks versus 8-16 weeks: HR 0.22; 95% CI 0.05-0.90; p = 0.036; <8 weeks versus >16 weeks: HR 0.28; 95% CI 0.07-1.15; p = 0.08)., Conclusion: PORT started up to 8 weeks after surgery was associated with better DFS and OS in locally-advanced BC patients submitted to NAC. Our findings suggest that early initiation of PORT is critically important for these patients. However, the low numbers of patients and events in this study prevent us from drawing firm conclusions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A thermostable variant of the mesophilic xylanase A from Bacillus subtilis (BsXynA-G3&#95;4x) contains the four mutations Gln7His, Gly13Arg, Ser22Pro, and Ser179Cys. The crystal structure of the BsXynA-G3&#95;4x has been solved, and the local environments around each of these positions investigated by molecular dynamics (MD) simulations at 328K and 348K. The structural and MD simulation results were correlated with thermodynamic data of the wild-type enzyme, the 4 single mutants and the BsXynA-G3&#95;4x. This analysis suggests that the overall stabilizing effect is entropic, and is consistent with solvation of charged residues and reduction of main-chain flexibility. Furthermore, increased protein-protein hydrogen bonding and hydrophobic interactions also contribute to stabilize the BsXynA-G3&#95;4x. The study revealed that a combination of several factors is responsible for increased thermostability of the BsXynA-G3&#95;4x; (i) introduction of backbone rigidity in regions of high flexibility, (ii) solvation effects and (iii) hydrophobic contacts., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The marine environment constitutes an extraordinary resource for the discovery of new therapeutic agents. In the present manuscript we studied the effect of 3 different sponge derived guanidine alkaloids, crambescidine-816, -830, and -800. We show that these compounds strongly inhibit tumor cell proliferation by down-regulating cyclin-dependent kinases 2/6 and cyclins D/A expression while up-regulating the cell cyclin-dependent kinase inhibitors -2A, -2D and -1A. We also show that these guanidine compounds disrupt tumor cell adhesion and cytoskeletal integrity promoting the activation of the intrinsic apoptotic signaling, resulting in loss of mitochondrial membrane potential and concomitant caspase-3 cleavage and activation. The crambescidin 816 anti-tumor effect was fnally assayed in a zebrafish xenotransplantation model confirming its potent antitumor activity against colorectal carcinoma in vivo.Considering these results crambescidins could represent promising natural anticancer agents and therapeutic tools.

Background: The purpose of the study was to characterize the epidemiological profile and average time on the waiting list of patients undergoing an urgent corneal transplantation (CT) in a referral center in the state of Rio Grande do Norte, northeastern Brazil., Methods: This cross-sectional study included cases of urgent corneal transplants performed in a referral center from January 2010 to December 2014. Data were collected between January and March 2015., Results: Seventy-four cases of emergency CT were analyzed. Of these, 69.4% were male, over the age range from 8 to 92 years. There were 38 transplants occurring in the right eye, 55.4% with tectonic purpose, 25.7% with optical purpose, and 18.9% therapy purpose. The main indications for patient inclusion in an emergency were the perforation (52.7%) and corneal ulcer unresponsive to medical treatment (33.8%). Interstitial keratitis was the most common diagnosis (74.3%), responsible for all prioritized cases in line for corneal ulcer unresponsive to treatment. The average length of the waiting line to perform the urgent CT was 9.03 days., Conclusions: In this study, there was a predominance of male patients and patients >50 years old, which corroborates the results of other studies with similar results. Perforation was the main indication to include the patient on the urgency list (52.7%). There is a need for further research to improve public health policies on the process of corneal transplantation as well as raising awareness of the importance of organ donation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Sub-chronic effects of ecologically relevant concentrations of cadmium (Cd) were evaluated in the catfish Rhamdia quelen. The fish were exposed to Cd (0, 0.1, 1, 10 and 100μgL(-1)) for 15 days. Bioconcentration was observed in the liver of fish exposed to 10 and 100μgL(-1) of cadmium. The liver glutathione S-transferase activity decreased at 0.1 and 1μgL(-1) and increased at 100μgL(-1) and lipoperoxidation increased in all tested concentrations. Fish exposed to 0.1, 1 and 100µgL(-1) Cd presented increase in hepatic lesion index. In the kidney, the catalase activity and LPO reduced in all exposed groups. The gluthatione peroxidase, etoxiresorufin-O-deethylase activities and metallothionein increased at the highest concentration of Cd, but the level of reduced glutathione decreased. The genotoxicity was observed at 0.1 and 100μgL(-1). Neurotoxicity was not observed. The results showed that low concentrations (range of μgL(-1)) of Cd caused hepato-, nephro- and hematological alterations in this freshwater fish species., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This study aimed to compare the direct medical costs of renal transplantation and renal replacement therapies, specifically hemodialysis and peritoneal dialysis, from the perspective of the Brazilian Unified National Health System (SUS). Renal replacement therapies costs were based on data published in the literature. Cost items for kidney transplant were identified in a private hospital based on procedure codes used for charging the SUS, and other items were taken from the literature. In the four years covered by the study, cadaver kidney transplant generated per-patient savings of BRL 37,000 and BRL 74,000 compared to hemodialysis and peritoneal dialysis, respectively. Savings were even greater with living donor kidney transplant: BRL 46,000 and BRL 82,000 compared to hemodialysis and peritoneal dialysis, respectively. This result, together with survival and quality-of-life analyses, characterizes kidney transplant as the best clinical and financial alternative, thus supporting public policies for organ transplants in Brazil.

In this study, chitosan nanoparticles were used to encapsulate antioxidant rosmarinic acid, Salvia officinalis (sage) and Satureja montana (savory) extracts as rosmarinic acid natural vehicles. The nanoparticles were prepared by ionic gelation using chitosan and sodium tripolyphosphate (TPP) in a mass ratio of 7:1, at pH 5.8. Particle size distribution analysis and transmission electron microscopy (TEM) confirmed the size ranging from 200 to 300 nm, while surface charge of nanoparticles ranged from 20 to 30 mV. Nanoparticles demonstrate to be safe without relevant cytotoxicity against retina pigment epithelium (ARPE-19) and human cornea cell line (HCE-T). The permeability study in HCE monolayer cell line showed an apparent permeability coefficient Papp of 3.41±0.99×10(-5) and 3.24±0.79×10(-5) cm/s for rosmarinic acid loaded chitosan nanoparticles and free in solution, respectively. In ARPE-19 monolayer cell line the Papp was 3.39±0.18×10(-5) and 3.60±0.05×10(-5) cm/s for rosmarinic acid loaded chitosan nanoparticles and free in solution, respectively. Considering the mucin interaction method, nanoparticles indicate mucoadhesive proprieties suggesting an increased retention time over the ocular mucosa after instillation. These nanoparticles may be promising drug delivery systems for ocular application in oxidative eye conditions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Context: Nanotechnology can be applied to deliver and protect antioxidants in order to control the oxidative stress phenomena in several chronic pathologies. Chitosan (CS) nanoparticles are biodegradable carriers that may protect antioxidants with potent biological activity such as rosmarinic acid (RA) in Salvia officinalis (sage) and Satureja montana (savory) extracts for safe and innovative therapies., Objective: Development and characterization of CS nanoparticles as a stable and protective vehicle to deliver RA for medical applications using natural extracts as sage and savory., Materials and Methods: Antioxidant-CS based nanoparticles were prepared by ionic gelation with sodium tripolyphosphate (TPP), at pH 5.8 with a mass ratio of 7:1 (CS:TPP), with a theoretical antioxidant-CS loading of 40-50%. The nanoparticles were then characterized by different methods such as photon correlation spectroscopy, laser Doppler anemometry, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR), high-performance liquid chromatographic (HPLC), association efficiency, and antioxidant activity., Results and Discussion: Individual and small sizing nanoparticles, around 300 nm, were obtained. SEM confirmed smooth and spherical nanoparticles after freeze-drying. No chemical interactions were found between antioxidants and CS, after encapsulation, by DSC and FTIR. The association efficiency was 51.2% for RA (with 40% loading) and 96.1 and 98.2% for sage and savory nanoparticles, respectively (both with 50% loading). Antioxidant activity values were higher than 0.0348 eq [Asc. Ac.] g/L/g extract and 0.4251 µmol/eq Trolox/g extract., Conclusion: The extracts under study are promising vehicles for RA drug delivery in CS nanocarriers.

A versatile and metal-free approach for the synthesis of carbocycles and of heterocycles bearing seven- and eight-membered rings is described. The strategy is based on ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (PhI(OH)OTs). Reaction conditions can be easily adjusted to give ring expansion products bearing different functional groups. A route to medium-ring lactones was also developed.

There are few instruments available in Brazil for obtaining data on dental erosion among adults. For this reason, the interview entitled "A Survey on Hong Kong People's Dietary Behavior in Relations to Acid Erosion", published in English, was considered for translation. The aim of this study was to perform a cross-cultural adaptation and content validation for the Brazilian population. After obtaining the author's permission, the interview underwent several stages: translation, back translation, review by a bilingual person and a committee of experts, administration of the English instrument and of the Portuguese version to a bilingual group, and pretesting in a convenience sample of 50 adults. The interview was translated and adapted to the Portuguese language and the Brazilian culture. The analysis of the data revealed that the interview was easy to apply, conduct and understand; therefore, it was considered viable and capable of being used in different studies.

Background: No clear evidence is available in the literature regarding the acute effect of different styles of music on cardiac autonomic control., Objectives: The present study aimed to evaluate the acute effects of classical baroque and heavy metal musical auditory stimulation on Heart Rate Variability (HRV) in healthy men., Patients and Methods: In this study, HRV was analyzed regarding time (SDNN, RMSSD, NN50, and pNN50) and frequency domain (LF, HF, and LF / HF) in 12 healthy men. HRV was recorded at seated rest for 10 minutes. Subsequently, the participants were exposed to classical baroque or heavy metal music for five minutes through an earphone at seated rest. After exposure to the first song, they remained at rest for five minutes and they were again exposed to classical baroque or heavy metal music. The music sequence was random for each individual. Standard statistical methods were used for calculation of means and standard deviations. Besides, ANOVA and Friedman test were used for parametric and non-parametric distributions, respectively., Results: While listening to heavy metal music, SDNN was reduced compared to the baseline (P = 0.023). In addition, the LF index (ms(2) and nu) was reduced during exposure to both heavy metal and classical baroque musical auditory stimulation compared to the control condition (P = 0.010 and P = 0.048, respectively). However, the HF index (ms(2)) was reduced only during auditory stimulation with music heavy metal (P = 0.01). The LF/HF ratio on the other hand decreased during auditory stimulation with classical baroque music (P = 0.019)., Conclusions: Acute auditory stimulation with the selected heavy metal musical auditory stimulation decreased the sympathetic and parasympathetic modulation on the heart, while exposure to a selected classical baroque music reduced sympathetic regulation on the heart.

The aims of this study were to evaluate the effects of the addition of metabolic precursors and polydimethylsiloxane (PDMS) as an oxygen carrier to cultures of Bacillus subtilis BL53 during the production of γ-PGA. Kinetics analyses of cultivations of different media showed that B. subtilis BL53 is an exogenous glutamic acid-dependent strain. When the metabolic pathway precursors of γ-PGA synthesis, L-glutamine and a-ketoglutaric acid, were added to the culture medium, production of the biopolymer was increased by 20 % considering the medium without these precursors. The addition of 10 % of the oxygen carrier PDMS to cultures caused a two-fold increase in the volumetric oxygen mass transfer coefficient (kLa), improving γ-PGA production and productivity. Finally, bioreactor cultures of B. subtilis BL53 adopting the combination of optimized medium E, added of glutamine, α-ketoglutaric acid, and PDMS, showed a productivity of 1 g L(-1) h(-1) of g-PGA after only 24 h of cultivation. Results of this study suggest that the use of metabolic pathway precursors glutamine and a-ketolgutaric acid, combined with the addition of PDMS as an oxygen carrier in bioreactors, can improve γ-PGA production and productivity by Bacillus strains .