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Objective: This study investigated the influence of photoinitiator types on degree of conversion (DC), rate of polymerization (RP), flexural strength (FS), flexural modulus (FM), and light transmittance (LT) of filled and unfilled light-curable resin cements through different thicknesses and shades of lithium disilicate ceramics., Methods: Lithium disilicate ceramic discs (IPS Emax Press, background [0.0], 0.5, 1.0, 2.0, 3.0, and 4.0 mm, shades A1 and BL3) were prepared. Experimental resin-based cements [TEGDMA/BisGMA (50/50 mass%)] were prepared using either camphorquinone (CQ)/amine (0.44/1.85 mol%) or TPO (0.44 mol%)], and a micro and nanofiller loads of nil (unfilled); 40/10 mass%; and 50/10 mass%). Resin cements (0.2 mm thick) were placed on the lower surface of the ceramic specimens and light-activated for 30 s from the upper surface using a Bluephase Style curing light (exitance at tip: 1236 mW/cm 2 ± 1.20). LT and distribution of irradiance through the ceramics were measured using a UV-vis spectrometer and a beam profile camera, respectively (n = 3). The DC and RP were measured in real-time using mid infrared spectroscopy in attenuated total reflectance (ATR) mode (n = 3). FS and FM were measured using a universal testing machine (n = 5). Statistical analyses were performed on LT, DC, RP, FS, and FM data using a general linear model, and supplementary ANOVA and post hoc Tukey multiple comparison test were also performed (α = .05)., Results: Thicknesses, shades, photoinitiator type, and fillers load significantly influenced the optical and mechanical characteristics of the resin-based materials (p < 0.05). The BL3 shade ceramic provided higher values of DC, RP, FS, FM, and LT compared with the A1 shade (p < 0.05). Increasing ceramic thickness decreased the properties of the resin-based materials (p < 0.05). Generally, TPO improved mechanical properties of the resin cement compared with CQ (p < 0.05)., Significance: The luting process of indirect restorations may be improved by using high molar absorptivity, more reactive, and more efficient photoinitiators such as TPO, as opposed to conventional CQ. The use of such initiator may allow the placement of thicker and more opaque indirect restorations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Develop a sustainable bovine hydroxyapatite dental ceramic with the addition of titanium dioxide (TiO 2 ) nanoparticles (5 % and 8 % by weight), analyzing the outcome of this addition to the microstructure, as well as its mechanical and chemical properties, in order to evaluate whether they satisfy the International Organization for Standardization (ISO) 6872:2015 for dental ceramics or not., Methods: Disks were obtained through uniaxial followed by isostatic pressing from bovine hydroxyapatite powder and TiO 2 nanoparticles and sintered at 1300ºC for 2 h. Three experimental groups were developed (HA, HA+5 %TiO 2 and HA+8 %TiO 2 ) and subjected to X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), indentation fracture (IF), biaxial flexural strength (BFS) and chemical solubility test., Results: XRD revealed, for HA group, the appearance of a peak corresponding to b-tricalcium phosphate (ß-TCP). For HA+ 5 %TiO 2 and HA+ 8 %TiO 2, the entire composition was converted into ß-TCP and calcium titanate (CaTiO 3 ). The SEM images showed a dense ceramic matrix and a uniform distribution of another phase in groups with TiO 2 nanoparticles. HA+ 5 %TiO 2 (1.40 ± 0.18 MPa.m 1/2 ) and HA+ 8 %TiO 2 (1.32 ± 0.18 MPa.m 1/2 ) showed significantly higher fracture toughness values than HA (0.67 ± 0.09 MPa.m 1/2 ). HA showed significantly higher characteristic stress (295.8 MPa) in comparison to groups with 5 % (235.1 MPa) and 8 % (214.4 MPa) TiO 2 nanoparticles. Differences were not observed between the Weibull modulus values. The solubility results indicated that all experimental ceramics were above the 2000 ug/cm 2 limit set by the ISO 6872:2015., Significance: This study proposed the development and characterization of a new ceramic for dental prosthesis made from HA extracted from bovine bones, with the intention of reusing these solids waste and transforming them into a sustainable and low-cost material. Although the experimental calcium phosphate ceramic with additions of 5 % and 8 % of TiO 2 achieved desirable mechanical properties, the chemical solubility values were very high., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although previous studies demonstrated that the ancestral lifestyle can enhance the metabolic health of offspring exposed to an obesogenic diet, the specific connections between these positive effects in redox state and telomere length are unknown. We investigated the impact of paternal resistance training (RT) on stress-responsive signaling and the pathways involved in telomere homeostasis in skeletal muscle. This investigation encompassed both the fathers and first-generation litter exposed to a long-term standard diet (24 weeks) and high fat diet (HFD). Wistar rats were randomized into sedentary or trained fathers (8 weeks of resistance training). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups: offspring of sedentary or trained fathers exposed to either a control diet or HFD. The gastrocnemius was prepared for reverse transcription-quantitative polymerase chain reaction, immunoblotting, ELISA, and electron paramagnetic resonance spectroscopy. RT upregulated shelterin mRNA levels and antioxidant protein, preserving muscle telomere in fathers. Conversely, HFD induced a disturbance in the redox balance, which may have contributed to the offspring telomere shortening from sedentary fathers. Pre-conceptional paternal RT downregulates Kelch-like ECH-associated protein 1 (Keap1) mRNA levels in the skeletal muscle of progeny exposed to HFD, driving an increase in Glutathione reductase mRNA levels, Sod1 and Catalase protein levels to mitigate ROS production. Also, paternal exercise upregulates α-Klotho protein levels, mediating antioxidative responses without altering shelterin mRNA levels and telomere length. We provide the first in-depth analysis that the offspring's redox state seems to be directly associated with the beneficial effects of paternal exercise., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Mycoplasma (M.) hyopneumoniae is a primary etiological agent of porcine enzootic pneumonia (PEP), a disease that causes significant economic losses to pig farming worldwide. Current commercial M. hyopneumoniae vaccines induce partial protection, decline in preventing transmission of this pathogen or inducing complete immunity, evidencing the need for improving vaccines against PEP. In our study, we aimed to test the effectiveness of the SBA-15 ordered mesoporous silica nanostructured particles as an immune adjuvant of a vaccine composed of M. hyopneumoniae strain 232 proteins encapsulated in SBA-15 and administered by intramuscular route in piglets to evaluate the immune responses and immune-protection against challenge. Forty-eight 24-day-old M. hyopneumoniae-free piglets were divided into four experimental groups with different protocols, encompassing a commercial vaccine against M. hyopneumoniae, SBA-15 vaccine, SBA-15 adjuvant without antigens and a non-immunized group. All piglets were challenged with the virulent strain 232 of M. hyopneumoniae. Piglets that received the SBA-15 and commercial vaccine presented marked immune responses characterized by anti-M. hyopneumoniae IgA and IgG antibodies in serum, anti-M. hyopneumoniae IgA antibodies in nasal mucosa and showed an upregulation of IL-17 and IL-4 cytokines and downregulation of IFN-γ in lungs 35 days post-infection. Piglets immunized with SBA-15 vaccine presented a reduction of bacterial shedding compared to piglets immunized with a commercial bacterin. In addition, piglets from SBA-15 adjuvant suspension group presented increased IL-17 gene expression in the lungs without involvement of Th1 and Th2 responses after challenge. These results indicated that SBA-15 vaccine induced both humoral and cell-mediated responses in the upper respiratory tract and lungs, first site of replication and provided protection against M. hyopneumoniae infection with a homologous strain with reduction of lung lesions and bacterial shedding. Finally, these results enhance the potential use of new technologies such as nanostructured particles applied in vaccines for the pig farming industry., 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. Published by Elsevier Ltd.)

Insulin resistance (IR) is a key risk factor for chronic metabolic diseases, but its laboratory diagnosis is still costly; thus, the triglyceride-glucose (TyG) index has been proposed as a surrogate method. Our aim was to provide a detailed analysis of cutoffs and test the hypothesis that the TyG index would present reasonable performance parameters for IR screening. This is a cross-sectional study with baseline data from 12,367 eligible participants of both sexes (aged 35-74 years) from the Brazilian Longitudinal Study of Adult Health. TyG correlation and agreement with the Homeostasis Model Assessment for Insulin Resistance were analyzed. Positive and negative predictive values (PV+, PV-) and likelihood ratio (LR+, LR-) were calculated. A moderate positive correlation between TyG and Homeostasis Model Assessment for Insulin Resistance was observed (Pearson r = 0.419). The area under the receiver operating characteristic curve of TyG for IR diagnosis was 0.742 and the optimal cutoff was 4.665, reaching a kappa agreement value of 0.354. For this cutoff, a PV+ of 59.3% and PV- of 76.0%, as well as an LR+ of 2.07 and LR- of 0.45 were obtained. Alternatively, because high sensitivity is desired for screening tests, selecting a lower cutoff, such as 4.505, increases the PV- to 82.1%, despite decreasing the PV+ to 50.8%. We conclude that TyG has important performance limitations for detecting IR, but that it may still be reasonably useful to help screening for IR in adults because it can be calculated from low-cost routine blood tests., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Among the central features of Alzheimer's disease (AD) progression are altered levels of the neuropeptide somatostatin (SST), and the colocalisation of SST-positive interneurons (SST-INs) with amyloid-β plaques, leading to cell death. In this theoretical review, I propose a molecular model for the pathogenesis of AD based on SST-IN hypofunction and hyperactivity. Namely, hypofunctional and hyperactive SST-INs struggle to control hyperactivity in medial regions in early stages, leading to axonal Aβ production through excessive presynaptic GABAB inhibition, GABAB1a/APP complex downregulation and internalisation. Concomitantly, excessive SST-14 release accumulates near SST-INs in the form of amyloids, which bind to Aβ to form toxic mixed oligomers. This leads to differential SST-IN death through excitotoxicity, further disinhibition, SST deficits, and increased Aβ release, fibrillation and plaque formation. Aβ plaques, hyperactive networks and SST-IN distributions thereby tightly overlap in the brain. Conversely, chronic stimulation of postsynaptic SST2/4 on gulutamatergic neurons by hyperactive SST-INs promotes intense Mitogen-Activated Protein Kinase (MAPK) p38 activity, leading to somatodendritic p-tau staining and apoptosis/neurodegeneration - in agreement with a near complete overlap between p38 and neurofibrillary tangles. This model is suitable to explain some of the principal risk factors and markers of AD progression, including mitochondrial dysfunction, APOE4 genotype, sex-dependent vulnerability, overactive glial cells, dystrophic neurites, synaptic/spine losses, inter alia. Finally, the model can also shed light on qualitative aspects of AD neuropsychology, especially within the domains of spatial and declarative (episodic, semantic) memory, under an overlying pattern of contextual indiscrimination, ensemble instability, interference and generalisation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Arterial pressure (Pa) regulation is essential to adequately distribute nutrients to metabolizing tissues, remove wastes and avoid lesions associated with hypertension. In vertebrates, short-term Pa regulation is achieved through the baroreflex, which elicits inversely proportional changes in heart rate (f H ) and vascular resistance to restore Pa. The cardiac limb of this reflex has been reported in all vertebrate groups studied to date: teleosts, amphibians, snakes, lizards, crocodiles, birds and mammals - which led to the suggestion that the baroreflex is an ancient trait present in all vertebrate species. However, it is not clear whether more basal groups of vertebrates, such as cyclostomes, elasmobranchs and chondrosteans, manifest baroreflex regulation of f H . Thus, the aim of this study was to determine whether the white sturgeon (Acipenser transmontanus; Chondrostei: Acipenseridae) exhibits a cardiac baroreflex. To do so, we induced Pa perturbations through injections of phenylephrine, sodium nitroprusside (SNP) and saline solution (hypervolemia), and examined possible f H baroreflex responses. We also investigated whether f H responses triggered by fright and chemoreflex were present in this species, in order to confirm the potential of sturgeon to perform reflexive cardiac adjustments. The findings indicate that A. transmontanus exhibits reflex bradycardia in response to fright and chemoreceptor stimulation, illustrating its capacity for short-term cardiac regulation. However, this species does not display baroreflex control of f H across its physiological range. This dissociation suggests that while the nervous and cardiovascular systems of A. transmontanus are primed for rapid reflex responses, a cardiac baroreflex mechanism remains absent., 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.)

Objective: The aim of this study was to investigate the association between dietary patterns and biochemical markers related to diabetes mellitus (DM): glucose, insulin, glycated hemoglobin (HbA1c), and homeostasis model assessment of insulin resistance index from 35 454 Brazilian adolescents 12 to 17 y of age., Methods: Dietary patterns were derived using factor analysis by the principal components method. The data originated from the school-based study ERICA (Study of Cardiovascular Risk in Adolescents) carried out between 2013 and 2014. Linear regression models analyzed the associations., Results: Three dietary patterns were found: traditional Brazilian, bread and coffee, and Western. An inverse association was found in young girls between the traditional Brazilian pattern and fasting glucose (β = -0.76; P = 0.005) and HbA1c in the second and third tertiles (β = -0.04; P = 0.002; β = -0 .06; P < 0.001), and the Western pattern with HbA1c (β = -0.02; P = 0.035). In boys, a positive association was found between the second tertile of the dietary pattern and insulin (β = 0.48; P = 0.009) and homeostasis model assessment of insulin resistance index (β = 0.11; P = 0.012)., Conclusions: This study showed that the traditional Brazilian pattern was inversely associated with blood glucose and HbA1c values in girls. Furthermore, the data suggest that there is an important difference between boys and girls in the association of dietary patterns and the markers used., 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.)

In SARSCoV-2 infections, excessive activation of the immune system dramatically elevates reactive oxygen species levels, harms cell structures, and directly increases disease severity and mortality. We aimed to evaluate whether plasma oxidative stress biomarker levels could predict mortality in adults admitted with Coronavirus Disease 2019 (COVID-19), considering potential confounders. We conducted a cohort study of 115 adults (62.1 ± 17.6 years, 65 males) admitted to a Brazilian public hospital for severely symptomatic COVID-19. Serum levels of α-tocopherol, glutathione, superoxide dismutase, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, and advanced oxidation protein products were quantified at COVID-19 diagnosis using real-time polymerase chain reaction. Serum levels of α-tocopherol, glutathione, superoxide dismutase, and advanced oxidation protein products differed significantly between survivors and non-survivors. Serum glutathione levels below 327.2 μmol/mL were associated with a significant risk of death in COVID-19 patients, even after accounting for other factors (adjusted hazard ratio = 3.12 [95% CI: 1.83-5.33])., 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.)

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice submitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The gut has been suggested as the first organ to be affected by unbalanced diets contributing to the obesogenic process. This study aimed to test a short time-course exposition model to a known pro- or anti-inflammatory enriched fatty diet to understand the early gut alterations. Male mice were exposed to the chow diet (CT), high-fat (HF) diet, or a high-fat diet partially replaced on flaxseed oil (FS), rich in omega-3 (ω3), for 14 days. HF and FS increased the total body weight mass compared with the CT group, but FS reduced the epididymal fat depot compared to HF. The bioinformatics from mice and human databases showed the Zo1-Ocln-Cldn7 tight junctions as the main protein-triad. In the ileum, the HF diet has increased IL1β transcript and IL1β, TNFα, and CD11b proteins, but reduced the tight junctions (Zo1, Ocln, and Cld7) compared to the CT group. Despite the FS diet being partially efficient in protecting the ileum against inflammation, the tight junctions were increased, compared to the HF group. The GPR120 and GPR40 receptors were unaffected by diets, but GPR120 was colocalized on the surface of ileum macrophages. The short period of a high-fat diet was enough to start the obesogenic process, ileum inflammation, and reduce the tight junctions. Flaxseed oil did not protect efficiently against dysmetabolism. Still, it increased the tight junctions, even without alteration on inflammatory parameters, suggesting the protection against gut permeability during early obesity development., Competing Interests: Conflict of Interests The authors have declared that no competing interests exist., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Physical training is a potent therapeutic approach for improving mitochondrial health through peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) signaling pathways. However, comprehensive information regarding the physical training impact on PGC-1α in the different physiological systems with advancing age is not fully understood. This review sheds light on the frontier-of-knowledge data regarding the chronic effects of exercise on the PGC-1α signaling pathways in rodents and humans. We address the molecular mechanisms involved in the different tissues, clarifying the precise biological action of PGC-1α, restricted to the aged cell type. Distinct exercise protocols (short and long-term) and modalities (aerobic and resistance exercise) increase the transcriptional and translational PGC-1α levels in adipose tissue, brain, heart, liver, and skeletal muscle in animal models, suggesting that this versatile molecule induces pleiotropic responses. However, PGC-1α function in some human tissues (adipose tissue, heart, and brain) remains challenging for further investigations. PGC-1α is not a simple transcriptional coactivator but supports a biochemical environment of mitochondrial dynamics, controlling physiological processes (primary metabolism, tissue remodeling, autophagy, inflammation, and redox balance). Acting as an adaptive mechanism, the long-term effects of PGC-1α following exercise may reflect the energy demand to coordinate multiple organs and contribute to cellular longevity., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to investigate the involvement of Brazilian adolescents in home cooking, estimating its associations with sex and socioeconomic status., Methods: This cross-sectional study involved a probabilistic sample of 14- to 19-y-olds enrolled in 29 public schools in the municipality of Juiz de Fora, MG, Southeast Brazil (n = 835). To assess involvement in home cooking, a 12-question questionnaire was used. The content was based on the Brazilian Food Guide, which encourages the acquisition, development, and sharing of culinary skills. Pearson's χ test and Poisson regression models were carried out, without and with adjustments., Results: Most of the adolescents did not usually participate in meal planning (61%), and in the choice/purchase of food and culinary ingredients (67%). Boys were less likely to know how to cook "from scratch", positively self-evaluate their culinary skills, enjoy cooking, wish to learn more about cooking and meal preparation, and to participate frequently in the planning and preparation of meals. Belonging to a lower socioeconomic status represented a greater probability of preparing meals alone for the family., Conclusions: We verified an alarming prevalence of adolescents with behaviors unaligned with Brazilian Food Guide recommendations; that is, most of them, especially boys, were not involved in home cooking. Adolescence may present a window of opportunity for the development of culinary skills, resulting in long-term benefits for the population's diet quality. Furthermore, to change a historical pattern that overloads women's daily lives, it is necessary to encourage, from an early age, the presence of boys in the kitchen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

It is known that long-term high-fat diet (HF) feeding drastically affects the adipose tissue, contributing to metabolic disorders. Recently, short-term HF consumption was shown to affect different neuronal signaling pathways. Thus, we aimed to evaluate the inflammatory effects of a short-term HF and whether a diet containing omega-3 fatty acid fats from flaxseed oil (FS) has protective effects. Mice were divided into three groups for 3 d, according to their diets: Control group (CT), HF, or FS for 3 d. Lipid profiles were assessed through mass spectrometry and inflammatory markers by RT-qPCR and Western blotting. After short-term HF, mice increased food intake, body weight, adiposity, and fasting glucose. Increased mRNA content of Ccl2 and Tnf was demonstrated in the HF compared to CT in mesenteric adipose tissue. In the liver, TNFα protein was higher in the HF group than in CT, followed by a decreased polyunsaturated fatty acids tissue incorporation in HF. On the other hand, the consumption of FS reduced food intake and fasting glucose, as well as increased omega-3 fatty acid incorporation in MAT and the liver. However, short-term FS was insufficient to control the early inflammation triggered by HF in MAT and the liver. These data demonstrated that a 3-d HF diet is enough to damage glucose homeostasis and trigger inflammation. In contrast, short-term FS protects against increased food intake and fasting glucose but not inflammation in mice., Competing Interests: Declaration of competing interests The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although the 5 times stand-to-sit test (5TSST) is indicated for screening for muscle weakness in older adults, its validity is based only on the correlation with quadriceps muscle strength or with the muscle strength of a few muscle groups of the lower limbs. Thus, the objective of the present study was to verify whether in independent older women, the 5TSST can really estimate global muscle strength, considering the sum of muscle strength of the trunk, hip, knee and ankle, which are important for functional activities., Methods: 119 independent older women participated in this cross-sectional study, undergoing the 5TSST and an isometric muscle strength assessment of the trunk, hip, knee and ankle, using an isokinetic dynamometer. The accuracy of the 5TSST for the discrimination of older women with reduced global muscle strength was evaluated by the ROC curve., Results: The ROC curve showed that the 5TSST may discriminate older women with reduced global muscle strength with moderate accuracy (AUC = 0.783; 95 % CI = 0.681-0.886; p < 0.001). The 5TSST score with the best accuracy (sensitivity: 80.0 % and specificity: 61.8 %) to evaluate global muscle strength was 11.64 s., Conclusion: 5TSST can be used to identify reduced global muscle strength in independent older women, standing out as an accessible tool for the screening of muscle weakness., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

6-Nitrodopamine (6-ND) is a novel catecholamine that is released from human umbilical cord vessels and Chelonoidis carbonaria aortic rings. The synthesis/release of 6-ND is inhibited by either pre-incubation of the vessels with the nitric oxide (NO) synthase inhibitor L-NAME or by mechanical removal of the endothelium. 6-ND causes powerful vasorelaxation, acting as a potent and selective dopamine D 2 -like receptor antagonist. Basal release of 6-ND from Panterophis guttatus endothelium intact and denuded aortic rings was quantified by LC-MS/MS. In order to evaluate the interaction of 6-ND with other catecholamines, aortic rings were suspended vertically between two metal hooks in 10-mL organ baths containing Krebs-Henseleit's solution and attached to isometric transducers. Endothelium intact aortic rings presented basal release of 6-ND, which was significantly reduced by previous incubation with L-NAME (100 μM). In endothelin-1 (3 nM) pre-contracted endothelium intact aortic rings, 6-ND (10pM-1 μM) and the dopamine D 2 -receptor antagonist L-761,626 (10 pM-1 μM) induced concentration-dependent relaxations, which were not affected by incubation with L-NAME but greatly reduced in endothelium-removed aortic rings. 6-ND (0.1-1 μM) produced significant rightward shifts of the concentration-response curves to dopamine in L-NAME pre-treated endothelium-intact (pA 2 7.01) rings. Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND (1 μM). The EFS-induced contractions of L-NAME pre-treated endothelium-intact aortic rings were significantly inhibited by incubation with 6-ND (1 μM). The results indicate that 6-ND released from Pantherophis guttatus aortic rings is coupled to NO release and represents a new mechanism by which NO can modulate vascular reactivity independently of cGMP production., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Non-alcoholic fatty liver disease (NAFLD) has a growing epidemiologic and economic burden. It is associated with Western diet (WD) patterns, and its pathogenesis involves metabolic disorders (obesity, dyslipidemia, hyperglycemia, and diabetes) and gut dysbiosis, features that are usually neglected or not reproduced by most animal models. Thus, we established a 6-mo WD-induced NAFLD mouse model associated with metabolic disorder, investigating its main features at the gut microbiome-liver-adipose tissue axis, also evaluating the correlations of gut dysbiosis to the other disease outcomes., Methods: Male C57 BL6 mice received a high-fat (30% lard and 0.2% cholesterol, ∼57% calories) and sucrose-rich (20%) chow, and a high-sugar solution (23.1 and 18.9 g/L of D-fructose and D-glucose) for 6 mo., Results: The model featured high serum cholesterol levels, glucose intolerance, and hyperinsulinemia. WD intervention resulted in extensive macro/microvesicular liver steatosis and pericellular fibrosis-resembling human disease-accompanied by hepatic stellate cell activation and CD68+ macrophage infiltration, increased protein levels of proinflammatory p65-nuclear factor-κB, interleukin-6 and tumor necrosis factor-α, with decreased antioxidant regulator Nrf2. Mice showed clear obesity with adipocyte hypertrophy, and CD68+macrophage/mast cell infiltration in adipose tissue while a reduction in number of goblet cells was also observed in the small intestine. Moreover, the pyrosequencing of the 16 S ribosomal RNA of gut cecal content showed decreased bacterial diversity, enriched Firmicutes and Proteobacteria, decreased Bacteroidetes and Fusobacteria, and increased ratio of Firmicutes to Bacteroidetes. Bacteroidetes and Bacteroides had the highest number of significant correlations with liver-adipose tissue axis outcomes. In silico analysis of gut microbiome in NAFLD obese patients revealed a depletion in Bacteroides, which also correlated to disease outcomes., Conclusion: This mice model gathered suitable phenotypical alterations in gut-liver-adipose tissue axis that resembled NAFLD associated with metabolic disorders in humans and may be considered for preclinical investigation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The human Respiratory Syncytial Virus (hRSV) is the main causative agent of acute respiratory infections (ARI), such as pneumonia and bronchiolitis. One of the factors that lead to success in viral replication is the interaction of the M2-2 protein with the ribosomal complex. This interaction is responsible for the phase change of viral activity, acting as an inhibitor or inducer of viral replication, according to the concentration of mRNA. Based on the importance of M2-2 gene and protein have to viral physiology, we performed here evaluations of genetic diversity, phylogenetic reconstructions, phylodynamics, and selection test. Our results suggested an alternative way of classifying this virus in clades A and B, based on a new phylogenetic marker, the M2-2 gene. Therefore, our study is the first one to investigate the dynamics of the evolutionary diversification process of hRSV from the perspective of the M2-2 viral gene. In our study was also identified that the M2-2 gene is under the effect of purifying selection originated by population genetic bottlenecks. Therefore, the M2-2 gene demonstrated an interesting potential to be applied in evolutionary studies involving hRSV, recovering phylogenetic signals and traits of natural selection under the evolution of this virus., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To explore the effect of adding different percentages of nanostructured silver vanadate decorated with silver nanoparticles (β-AgVO 3 ) to dental porcelains, evaluating the antimicrobial activity and the influence on the mechanical properties., Methods: Thirty-six specimens were made, for each concentration, control group, 0.5%, 1%, 2.5% and 5%, using two commercial brands: IPS InLine and Noritake Cerabien ZR. For the analysis of mechanical properties, the Vickers microhardness test and the roughness test were performed. For the antimicrobial analysis, the XTT and CFU assays were performed., Results: There was a statistically significant difference between groups for mechanical and microbiological analyses., Significance: The modification of dental porcelains, with the incorporation of β-AgVO 3 , influenced the mechanical properties of the material and demonstrated antimicrobial activity at certain concentrations., (Copyright © 2022 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

We conducted mosquito-based Zika virus surveillance in São Paulo State, Brazil from 2015 to 2018. We found 81 pools positive for Aedes aegypti and one pool positive for Aedes albopictus. Infection rates were highest in the summer. Areas with human Zika cases also had clusters of Zika-positive mosquitoes., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to investigate the effect of Chronic Noncommunicable Diseases (CNCDs) on the onset or increase in sleep problems during the COVID-19 pandemic period. The role of the report of sadness or nervousness during the pandemic was also evaluated as a mediator of this association. Data from a behavior survey during COVID-19, conducted in Brazil with 45,161 people (18 years old or older), from April 24 to May 24, 2020, were used. The outcome variable was the onset or increase in sleep problems, and the exposure variable was the presence of CNCDs. The adjusted Odds Ratio of the association between CNCDs and sleep was estimated, and a mediation analysis was performed to test the effect of the report of sadness or nervousness on this association, using the Karlson Holm Breen method. The increase in sleep problems was reported by 44.9% of the population, and 33.9% reported at least one CNCD. The chance of sleep problems was higher among people with diabetes (1.34; 1.05-1.71), hypertension (1.26; 1.06-1.50), and with coronary heart diseases (1.36; 1.13-1.65) or respiratory diseases (1.42; 1.04-1.93). Compared to people without CNCDs, individuals with at least one CNCD had a 36% greater chance of impaired sleep (1.36; 1.19-1.55). The report of sadness or nervousness explained 45.1% of the association between CNCD and sleep. Our findings alert us to care for the emotional state and sleep of chronic patients during the waves of the COVID-19 pandemic, and indicate the need for sleep monitoring in this population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The mechanisms by which a high-fat diet (HFD) promotes non-alcoholic fatty liver disease (NAFLD) appear to involve liver mitochondrial dysfunction and redox imbalance. The functional loss of the enzyme NAD(P) + transhydrogenase, a main source of mitochondrial NADPH, results in impaired mitochondrial peroxide removal, pyruvate dehydrogenase inhibition by phosphorylation, and progression of NAFLD in HFD-fed mice. The present study aimed to investigate whether pharmacological reactivation of pyruvate dehydrogenase by dichloroacetate attenuates the mitochondrial redox dysfunction and the development of NAFLD in NAD(P) + transhydrogenase-null (Nnt -/- ) mice fed an HFD (60% of total calories from fat). For this purpose, Nnt -/-  mice and their congenic controls (Nnt +/+ ) were fed chow or an HFD for 20 weeks and received sodium dichloroacetate or NaCl in the final 12 weeks via drinking water. The results showed that HFD reduced the ability of isolated liver mitochondria from Nnt -/- mice to remove peroxide, which was prevented by the dichloroacetate treatment. HFD-fed mice of both Nnt genotypes exhibited increased body and liver mass, as well as a higher content of hepatic triglycerides, but dichloroacetate treatment attenuated these abnormalities only in Nnt -/- mice. Notably, dichloroacetate treatment decreased liver pyruvate dehydrogenase phosphorylation levels and prevented the aggravation of NAFLD in HFD-fed Nnt -/- mice. Conversely, dichloroacetate treatment elicited moderate hepatocyte ballooning in chow-fed mice, suggesting potentially toxic effects. We conclude that the protection against HFD-induced NAFLD by dichloroacetate is associated with its role in reactivating pyruvate dehydrogenase and reestablishing the pyruvate-supported liver mitochondrial capacity to handle peroxide in Nnt -/- mice., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: Mitochondria play a central role in the host response to viral infection and immunity, being key to antiviral signaling and exacerbating inflammatory processes. Mitochondria and Toll-like receptor (TLR) have been suggested as potential targets in SARS-CoV-2 infection. However, the involvement of TLR9 in SARS-Cov-2-induced endothelial dysfunction and potential contribution to cardiovascular complications in COVID-19 have not been demonstrated. This study determined whether infection of endothelial cells by SARS-CoV-2 affects mitochondrial function and induces mitochondrial DNA (mtDNA) release. We also questioned whether TLR9 signaling mediates the inflammatory responses induced by SARS-CoV-2 in endothelial cells., Experimental Approach: Human umbilical vein endothelial cells (HUVECs) were infected by SARS-CoV-2 and immunofluorescence was used to confirm the infection. Mitochondrial function was analyzed by specific probes and mtDNA levels by real-time polymerase chain reaction (RT-PCR). Inflammatory markers were measured by ELISA, protein expression by western blot, intracellular calcium (Ca 2+ ) by FLUOR-4, and vascular reactivity with a myography., Key Results: SARS-CoV-2 infected HUVECs, which express ACE2 and TMPRSS2 proteins, and promoted mitochondrial dysfunction, i.e. it increased mitochondria-derived superoxide anion, mitochondrial membrane potential, and mtDNA release, leading to activation of TLR9 and NF-kB, and release of cytokines. SARS-CoV-2 also decreased nitric oxide synthase (eNOS) expression and inhibited Ca 2+ responses in endothelial cells. TLR9 blockade reduced SARS-CoV-2-induced IL-6 release and prevented decreased eNOS expression. mtDNA increased vascular reactivity to endothelin-1 (ET-1) in arteries from wild type, but not TLR9 knockout mice. These events were recapitulated in serum samples from COVID-19 patients, that exhibited increased levels of mtDNA compared to sex- and age-matched healthy subjects and patients with comorbidities., Conclusion and Applications: SARS-CoV-2 infection impairs mitochondrial function and activates TLR9 signaling in endothelial cells. TLR9 triggers inflammatory responses that lead to endothelial cell dysfunction, potentially contributing to the severity of symptoms in COVID-19. Targeting mitochondrial metabolic pathways may help to define novel therapeutic strategies for COVID-19., (Copyright © 2021. Published by Elsevier Inc.)

Using tolerant genotypes and the correct use of fertilizers can mitigate the negative effect of elevated Cu levels in the growing medium. In this context, the study aimed to evaluate the effects of excess Cu in the root system and the effectiveness of phosphorus (P) in minimizing the phytotoxicity of Cu in three genotypes: IAC 572 [(Vitis riparia x V. rupestris) x V. caribaea], Magnolia (V. rotundifolia) and Paulsen 1103 (V. berlandieri x V. rupestris). The plants were grown in nutrient solutions and were supplemented with the following treatments: 0.3 μM Cu (Control), 60 μM Cu (Cu) and 60 μM Cu and 62 mg L -1 P (Cu + P). Root samples were sectioned for microscopy analyses, and the shoot lengths, shoot and root dry matter, relative growth rates (RGR) and tissue nutrient contents were also evaluated. The roots of the genotypes that were cultivated with high Cu concentrations produced greater numbers of branches and larger diameters, except for Magnolia genotype that was cultivated in a Cu + P solution, which had an organization similar to the control. Excess Cu caused accumulations of phenolic compounds and decreased shoot lengths, dry matter and RGR in the genotypes. In the treatments with excess Cu, there were increases in this element in the tissues, but P decreased the metal concentrations in Magnolia roots. Therefore, Cu accumulations alter the root system development patterns, growth parameters and tissue nutrient contents in the studied genotypes. Magnolia has a higher tolerance and is also the only genotype for which the use of P has been shown to be effective., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

6-nitrodopamine (6-ND) is released from rat isolated vas deferens and modulates electrical-field stimulation (EFS) contractions of the rat isolated epididymal vas deferens (RIEVD) via a specific receptor which is blocked by tricyclic antidepressants. Here, the effects of selective α 1 -adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline and EFS were investigated. Doxazosin and tamsulosin (3-10 nM) caused significant rightward shifts of the concentration-response curve to 6-ND, but had no effect on dopamine-, noradrenaline- and adrenaline-induced contractions. Alfuzosin (10 nM) produced rightward shifts on concentration-response curves to all catecholamines. Silodosin (10 nM) and terazosin (100 nM) displaced to the right the noradrenaline, dopamine and adrenaline curves, but higher concentrations of both antagonists (100 and 300 nM, respectively) were required to displace the 6-ND curves. The EFS-induced contractions were significantly inhibited only at the concentrations that the α 1 -adrenergic receptor antagonists caused rightward shifts on the 6-ND concentration-response curves. The inhibition of EFS-induced contractions by doxazosin (10 nM), tamsulosin (10 nM), alfuzosin (10 nM), silodosin (100 nM) and terazosin (300 nM), were not observed in RIEVD obtained from animals chronically treated with L-NAME. This work demonstrates that α 1 -adrenoceptor antagonists act as 6-ND receptor antagonists in RIEVD, opening the possibility that many actions previously attributed to noradrenaline could be due to 6-ND antagonism. In addition, blockade of the 6-ND receptors by both tricyclic antidepressants and α 1 -adrenergic receptor antagonists may represent the common mechanism of action responsible for their therapeutic use in the treatment of premature ejaculation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Telmisartan (TELM) is an angiotensin II (Ang II) type 1 receptor (Agtr1) antagonist, with partial agonism for Pparg, and has been shown to affect bone metabolism. Therefore, the aim of this study was to investigate the effects of TELM in the in vitro osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSC) from spontaneously hypertensive rats (SHRs). BMSC were obtained from male SHR, and the osteogenic medium (OM) was added to the cells concomitantly with TELM (0.005, 0.05, and 0.5 μM). Undifferentiated BMSC, in control medium (CM), showed an increased viability, while the addition of OM reduced this parameter, and TELM did not show cytotoxicity in the concentrations used. BMSC in OM had an alkaline phosphatase (ALP) activity peak at d10, which decreased at d14 and d21, and TELM reduced ALP at d10 in a dose-dependent manner. Mineralization was observed in the OM at d14, which intensified at d21, but was inhibited by TELM. Agtr1b was increased in the OM, and TELM inhibited its expression. TELM reduced Opn, Ocn, and Bsp and increased Pparg expression, and at the higher concentration TELM also increased the expression of adipogenic markers, Fabp4 and Adipoq. In addition, TELM 0.5 μM increased Irs1 and Glut4, insulin and glucose metabolism markers, known to be regulated by Pparg and to be related to adipogenic phenotype. Our data shows that TELM inhibited the osteogenic differentiation and mineralization of SHR BMSC, by favoring an adipogenic prone phenotype due to Pparg upregulation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

6-nitrodopamine (6-ND) is released from human umbilical cord vessels and modulates vascular reactivity by acting as a dopamine antagonist. Here we investigate whether 6-ND is released by the rat isolated vas deferens and its effect on this tissue. Dopamine, noradrenaline, adrenaline and 6-ND levels were quantified in rat isolated vas deferens by LC-MS-MS. Electric-field stimulation (EFS) and concentration-response curves to 6-ND, noradrenaline, dopamine and adrenaline were performed in the absence and in the presence (30 min) of L-NAME, SCH-23390, haloperidol, PG-01037, sonepiprazole, desipramine, clomipramine, amitriptyline, cyclobenzaprine, carbamazepine, maprotiline, paroxetine, oxcarbazepine and ketanserin in the rat isolated epididymal vas deferens (RIEVD). Basal releases of 6-ND and noradrenaline were detected from the rat isolated vas deferens. 6-ND release was reduced by tissue incubation with L-NAME and from the vas deferens obtained from L-NAME-treated rats. SCH-23390 caused leftward shifts on concentration-response curves to 6-ND without affecting dopamine- or EFS-induced RIEVD contractions. Haloperidol, PG-01037 and sonepiprazole caused significant rightward shifts on concentration-response curves to dopamine but had no effect on either the 6-ND or EFS-induced RIEVD contractions. The tricyclic compounds desipramine, clomipramine, amitriptyline, cyclobenzaprine and carbamazepine induced rightward shifts on 6-ND concentration-response curve but did not reduce the noradrenaline, dopamine and adrenaline contractile responses. They also reduced the EFS-induced RIEVD contractions in control but not in tissues obtained from L-NAME-treated animals. Maprotiline, oxcarbazepine, paroxetine and ketanserin had no effect in either 6-ND or EFS-induced RIEVD contractions. Thus, 6-ND modulates RIEVD contractility, and desipramine, clomipramine, amitriptyline, cyclobenzaprine and carbamazepine act as selective 6-ND receptor antagonists., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This work studied three emerging approaches to improve the convective drying (50 °C, 0.8 m/s) of celery. Celery slices of 2 mm thick were pretreated for 5 min using ultrasound (32 W/L, 40 kHz), vacuum (75 kPa vacuum pressure) and ethanol (99.8% v/v, as drying accelerator) applied individually or in combination. To evaluate individual effects of ultrasound and vacuum, the treatments were also performed with distilled water or air medium, respectively. Moreover, the cavitational level was characterized in each condition. Drying kinetics was evaluated tending into account the drying time required by each treatment and the Page's model parameters. In addition, microstructural effects and shrinkage were evaluated. As results, ethanol combined with ultrasound significantly improved drying kinetics reducing drying time by around 38%. However, vacuum pretreatment did not affect drying kinetics even in combination with ethanol and/or ultrasound. Microstructural evaluation did not evidence cell disruption, suggesting changes in intercellular spaces, pores and/or cell wall permeability. The use of ethanol and vacuum showed a greater effect on shrinkage after pretreatment and after drying, respectively. In conclusion, at the studied conditions, the drying acceleration by vacuum and ultrasound is lower compared to the effect produced using ethanol., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Dengue, Zika and Chikungunya viruses represent a serious public health problem. No evidence is available on the efficacy of repellents commercially available in Brazil. This systematic review assessed the efficacy and safety of products containing repellents commercially available in Brazil for protection against bites from Aedes aegypti and Aedes albopictus., Methods: We performed a systematic review using the CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science, AMED, LILACS and Scopus databases. Randomized clinical trials and non-randomized clinical trials comparing topical repellent products registered with the Brazilian Health Surveillance Agency were included. Main outcomes of interest investigated were adverse effects, percentage repellency and protection time against bites. Pairs of reviewers selected the studies, extracted the data and evaluated the risk of bias., Results: Sixteen studies were included. No adverse effects were reported by the studies. Against Ae. aegypti: protection time using DEET (10% and 20%-spray) was similar to IR3535 (10% and 20%-spray) and longer than citronella (5%-spray). DEET (25%-solution) had longer protection time than eucalyptus (25%-solution), while DEET (20%-lotion) had longer protection time than citronella (10%-lotion). There was no difference in protection time between herbal repellents. DEET (7% and 15%- spray) had higher percentage repellency compared to both icaridin (7%-spray) and IR3535 (20%-spray). Against Ae. albopictus: DEET (15%-spray) had a similar protection time to icaridin (20%-spray), but longer than citronella (10%-spray)., Conclusion: DEET proved more effective than the other synthetic and natural repellents marketed in Brazil for protecting against bites from the mosquito species investigated. All repellents studied exhibited satisfactory safety profile., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant spinocerebellar ataxia caused by pathological expansion of CAG trinucleotide repeats in the ATN1 gene. Most cases were described in patients from Japanese ancestry who presented with adult-onset progressive cerebellar ataxia associated with cognitive impairment, choreoathetosis and other movement disorders. DRPLA has been rarely described in Brazilian patients., Methods: We performed a retrospective observational multicentric study including six different Neurology Centers in Brazil. All patients with genetically confirmed diagnosis of DRPLA had their medical records evaluated and clinical, genetic and neuroimaging features were analyzed., Results: We describe of eight Brazilian patients (5 male, 3 female) from four nuclear families with genetically confirmed DRPLA. The most common neurological features included cerebellar ataxia (n = 7), dementia (n = 3), chorea (n = 2), psychiatric disturbances (n = 2), progressive myoclonic epilepsy (n = 2) and severe bulbar signs (n = 1). Progressive myoclonic epilepsy was observed in two juvenile-onset cases before 20-year. A large CAG trinucleotide length was observed in the two juvenile-onset cases and genetic anticipation was observed in all cases. Neuroimaging studies disclosed cerebellar atrophy (n = 6), as well as brainstem and cerebellar atrophy (n = 2) and leukoencephalopathy (n = 1)., Conclusion: The patients described herein reinforce that clinical features of DRPLA are highly influenced by age of onset, genetic anticipation and CAG repetition lengths. There is a large complex spectrum of neurological features associated with DRPLA, varying from pure cerebellar ataxia to dementia associated with other movement disorders (myoclonus, choreoathetosis). DRPLA is an unusual cause of cerebellar ataxia and neurodegeneration in Brazilian patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Glioblastoma multiforme (GBM) is the most common primary brain cancer. GBM has aggressive development, and the pharmacological treatment remains a challenge due to GBM anatomical characteristics' (the blood-brain barrier and tumor microenvironment) and the increasing resistance to marketed drugs, such as temozolomide (TMZ), the first-line drug for GBM treatment. Due to physical-chemical properties such as short half-life time and the increasing resistance shown by GBM cells, high doses and repeated administrations are necessary, leading to significant adverse events. This review will discuss the main molecular mechanisms of TMZ resistance and the use of functionalized nanocarriers as an efficient and safe strategy for TMZ delivery. GBM-targeting nanocarriers are an important tool for the treatment of GBM, demonstrating to improve the biopharmaceutical properties of TMZ and repurpose its use in anti-GBM therapy. Technical aspects of nanocarriers will be discussed, and biological models highlighting the advantages and effects of functionalization strategies in TMZ anti-GBM activity. Finally, conclusions regarding the main findings will be made in the context of new perspectives for the treatment of GBM using TMZ as a chemotherapy agent, improving the sensibility and biological anti-tumor effect of TMZ through functionalization strategies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Circular stepped-plates are often chosen to generate continuous waves in air due to their transmission efficiency, directive radiation patterns and capability to generate high-intensity airwave emission. Such features can be suitable for an acoustic radiator intended for the generation of harmonic radiation force, if the narrow bandwidth of the piezoelectric power transducer is not an obstacle to the application. This force has been used as the excitation source in noncontact modal analysis of mechanical devices, since it offers some advantages over the traditional impact method and the use of shakers. In this study, a directional stepped-plate ultrasonic device driven by a bolt-clamped Langevin-type transducer is used to excite the first flexural mode of a clamped-free beam by means of harmonic radiation force. The harmonic component was generated using an amplitude-modulated electrical input signal. The radiator design was done by solving a parametric optimization problem of finding a plate with the desired vibrational behavior using the genetic algorithm. Finite element analysis was used to obtain the dynamic behavior of the device and the airwave propagation was modeled using linear acoustic theory. Modal and harmonic analyses were conducted to obtain some of the electroacoustic parameters of the transducer. The acoustic field generated by the prototype is estimated by solving the Rayleigh integral and the obtained results are compared to experimental measurements., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Negative emotions can influence food intake. Leptin (an anorectic hormone) levels may change in response to psychological stressors. This study aimed to explore the relationship between leptin and food intake triggered by negative emotions in overweight women. Two groupswere studied: normal weight women (n = 21) and overweight women (n = 23). Both groups were exposed to videos to stimulate negative and neutral emotions followed by application ofthe Subjetive Analog Scale. Plasma leptin levels were evaluated before and after exposure to the videos. Subsequently, a brunch containing sweet and salty foods was offered to simulatea high food availability environment. Results show that when exposed to negative emotions there was an increase in food intake (normal weight: p=.010 / overweight: p=.005). There was no change in plasma leptin levels in normal weightand overweight women. Negative emotions promotedan increase in energy intake in both groups. The results reinforce the integration of biopsychosocial aspects involving emotions and food intake., (Copyright © 2021. Published by Elsevier Inc.)

We investigated the antiophidic properties of isohemigossypolone (ISO), a naphthoquinone isolated from the outer bark of the Pachira aquatic Aubl. The inhibition of phospholipase A 2 , coagulant, fibrinogenolytic, hemorrhagic and myotoxic activities induced by Bothrops pauloensis venom (Pb) was investigated. For this, we use samples resulting from the incubation of Pb with ISO in different concentrations (1:1, 1:5 and 1:10 w/w), we also evaluated the condition of treatment using ISO after 15 min of venom inoculation. The activities of phospholipase A 2 , coagulant, fibrinogenolytic, hemorrhagic and myotoxic induced by the B. pauloensis venom were significantly inhibited when the ISO was pre-incubated with the crude venom. For in vivo neutralization tests, the results were observed even when the ISO was applied after 15 min of inoculation of the venom or metalloprotease (BthMP). Also, to identify the inhibition mechanism, we performed in silico assays, across simulations of molecular coupling and molecular dynamics, it was possible to identify the modes of interaction between ISO and bothropic toxins BmooMPα-I, Jararacussin-I and BNSP-7. The present study shows that naphthoquinone isohemigossypolone isolated from the P. aquatica plant inhibited part of the local and systemic damage caused by venom proteins, demonstrating the pharmacological potential of this compound in neutralizing the harmful effects caused by snakebites., (Copyright © 2021 Elsevier Inc. All rights reserved.)

All vertebrates have baroreflexes that provide fast regulation of arterial blood pressure (P A ) to maintain adequate tissue perfusion and avoid vascular lesions from excessive pressures. The baroreflex is a negative feedback loop, where altered P A results in reciprocal changes in heart rate (f H ) and systemic vascular conductance to restore pressure. In terrestrial environments, gravity usually leads to blood pooling in the lower body reducing venous return, cardiac filling, cardiac output and P A . Conversely, in aquatic environments, the hydrostatic pressure of surrounding water mitigates blood pooling and prevents vascular distensions. In this context, we aimed to test the hypothesis that vertebrate species that were exposed to gravity-induced hemodynamic disturbances throughout their evolutionary histories have a more effective barostatic reflex than those that were not. We examined the cardiac baroreflex of fish that perform (Clarias gariepinus and Hoplerythrinus unitaeniatus) and do not perform (Hoplias malabaricus and Oreochromis niloticus) voluntary terrestrial sojourns, using pharmacological manipulations of P A to characterize reflex changes in f H using a four-variable sigmoidal logistic function (i.e. the "Oxford technique"). Our results revealed that amphibious fish exhibit higher baroreflex gain and responsiveness to hypotension than strictly aquatic fish, suggesting that terrestriality and the gravitational circulatory stresses constitute a relevant driving force for the evolution of a more effective baroreflex in vertebrates. We also demonstrate that strictly aquatic teleosts have considerable baroreflex gain, supporting the view that the baroreflex is an ancient cardiovascular trait that appeared before vertebrates colonized the gravity-dominated realm of land., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To investigate the influence of different surface treatments on biaxial flexure strength, roughness, and surface topography of lithium silicate/disilicate-based ceramics., Methods: 225 discs (∅: 12 mm; 1.2 mm - ISO 6872) were made from three ceramics: IPS e.max CAD (LD - Ivoclar Vivadent), Suprinity (LSS - Vita) and Celtra Duo (LSC - Dentsply). The samples were randomly divided into 5 groups (n = 15): no treatment (C); 10% hydrofluoric acid + silane (HF); sandblasting Al 2 O 3 + silane (SB); silicatization + silane (SC); and self-etching ceramic primer (SEP). After surface treatment, a resin cement layer was applied to the disc surface (RelyX U200, 3M ESPE), mechanical cycled (1.2 × 10 6 cycles, 50 N, 3.8 Hz) and submitted to biaxial flexural strength test (1 mm/min, 1000 Kgf). Roughness, EDS and SEM were also performed. Data were analyzed by one-way ANOVA, Tukey test (5%) and Weibull., Results: ANOVA revealed that the "surface treatment" factor was significant for all ceramics (p < 0.05). The groups LD-HF (289.30 ± 40) LD-SEP (298. 87 ± 53.29), LSC-HF (195.51 ± 42.12), LSS-HF (269.58 ± 27.07) and LSS-SEP (207.45 ± 28.63) presented significantly higher biaxial flexure strength than respective control groups, except for the LSC-SEP (165.41 ± 33.86), which was statistically similar to the control. The Weibull modulus was significantly higher for the LD-SB, LSC-SC groups. Additionally, the LD-SB, LSC-SC and LSS-HF groups showed higher roughness compared to the other treatments., Significance: HF etching followed by silanization and self-etching ceramic primer are the most suitable surface treatments for lithium silicate/disilicate-based glass-ceramics., (Copyright © 2020 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

The treatment of a complex temporomandibular disorder (TMD), such as disk displacement with reduction (DDR) associated with arthralgia and myalgia, may depends on understanding the impairments in muscle function. The aim of this study was to investigate the behavior of the anterior temporalis, masseter and sternocleidomastoid muscles in the time and frequency domains during chewing in patients with chronic painful TMD-DDR using electromyographic (EMG) analysis. Thirty-three patients who met the diagnostic criteria for TMD and 32 volunteers without TMD (control group) underwent clinical examination, chewing pattern classification and EMG analysis. For the EMG analyses, the side of habitual unilateral chewing, as determined by the chewing pattern classification, was selected for recording; in cases of bilateral chewing, the recording side was randomly selected. The EMG-EMG coherence function and EMG-EMG transfer function (gain and phase) values were obtained at the first chewing frequency peak, and the working-side masseter signal was used as a reference in the analyses of the other muscles. Compared to the control group, the TMD group showed a longer chewing stroke duration (P = 0.01) as well as changes in the coactivation and coordination strategies of the jaw muscles, evidenced by greater relative energy expenditure (P< 0.01) and impaired differential recruitment (P< 0.05) and coherence (P< 0.01). Delays in peak and temporal asynchrony occurred in the jaw and neck muscles (P< 0.05). Patients with chronic painful TMD-DDR during chewing presented changes in the jaw and neck muscles, with more compromised function of the former, which are specific to chewing., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1β, tumor necrosis factor-α and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 μg/day, i.art.), Hp given orally (20 μg/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i.p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive mono-arthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 μg/knee) or p.o. (20 μg/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P < 0.05). In parallel, the AIA-injected ipsilateral knee joints reach a peak of swelling 24 h after AIA induction, which persisted over the next four days in relation to PBS-injected rats or contralateral knee joints. There was a significant but not dose-dependent inhibitory effect produced by all dosages and routes of Hp treatments on AIA-induced knee joint swelling (P < 0.05). In addition, the increased synovial levels of MPO activity, total leukocytes number and IL-6, but not IL-1β, were significantly reduced by the lower i.art. dose of Hp. In conclusion, these results successfully demonstrate that Hp may represent a novel therapeutic strategy to treat RA, an effect which is unrelated to the proinflammatory actions of the neuropeptides CGRP and SP., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ultrasound was combined with ethanol to improve different aspects of carrot convective drying, evaluating both processing and product quality. The ultrasound in water treatment resulted in cellular swelling and small impact on texture. Differently, the ultrasound in ethanol and ethanol treatments modified both carrot microstructure (cell wall modifications of parenchymatic tissue) and macrostructure (shrinkage and resistance to perforation). Pre-treatments with ultrasound in ethanol and ethanol improved the drying kinetics, reducing the processing time (~50%) and the energy consumption (42-62%). These pre-treatments also enhanced rehydration, whose initial rate and water retention were higher than the control. In addition, the carotenoid content was preserved after drying, for all the treatments. Any impact on shrinkage was observed. A mechanistic discussion, based on structural modification (microstructure and macrostructure) and physical properties of water and ethanol, was provided. As conclusion, this work not only described positive aspects of combining the technologies of ultrasound and ethanol as pre-treatments to convective drying, but also proposed mechanisms to explain the phenomena., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Modern lifestyles, including lack of physical activity and poor nutritional habits, are driving the rapidly increasing prevalence of obesity and type 2 diabetes. Increased levels of free fatty acids (FFAs), particularly saturated FFAs, in obese individuals have been linked to pancreatic β-cell failure. This process, termed lipotoxicity, involves activation of several stress responses, including ER stress and oxidative stress. However, the molecular underpinnings and causal relationships between the disparate stress responses remain unclear. Here we employed transgenic mice, expressing a genetically-encoded cytosolic H 2 O 2 sensor, roGFP2-Orp1, to monitor dynamic changes in H 2 O 2 levels in pancreatic islets in response to chronic palmitate exposure. We identified a transient increase in H 2 O 2 levels from 4 to 8 h after palmitate addition, which was mirrored by a concomitant decrease in cellular NAD(P)H levels. Intriguingly, islets isolated from NOX2 knock-out mice displayed no H 2 O 2 transient upon chronic palmitate treatment. Furthermore, NOX2 knockout rescued palmitate-dependent impairment of insulin secretion, calcium homeostasis and viability. Chemical inhibition of NOX activity protected islets from palmitate-induced impairment in insulin secretion, however had no detectable impact upon the induction of ER stress. In summary, our results reveal that transient NOX2-dependent H 2 O 2 production is a likely cause of early palmitate-dependent lipotoxic effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aberrant microRNA expression implicates on hepatocellular carcinoma (HCC) development. Conversely, coffee consumption reduces by ~40% the risk for fibrosis/cirrhosis and HCC, while decaffeinated coffee does not. It is currently unknown whether these protective effects are related to caffeine (CAF), or to its combination with other common and/or highly bioavailable coffee compounds, such as trigonelline (TRI) and chlorogenic acid (CGA). We evaluated whether CAF individually or combined with TRI and/or CGA alleviates fibrosis-associated hepatocarcinogenesis, examining the involvement of miRNA profile modulation. Then, male C3H/HeJ mice were submitted to a diethylnitrosamine/carbon tetrachloride-induced model. Animals received CAF (50 mg/kg), CAF+TRI (50 and 25 mg/kg), CAF+CGA (50 and 25 mg/kg) or CAF+TRI+CGA (50, 25 and 25 mg/kg), intragastrically, 5×/week, for 10 weeks. Only CAF+TRI+CGA combination reduced the incidence, number and proliferation (Ki-67) of hepatocellular preneoplastic foci while enhanced apoptosis (cleaved caspase-3) in adjacent parenchyma. CAF+TRI+CGA treatment also decreased hepatic oxidative stress and enhanced the antioxidant Nrf2 axis. CAF+TRI+CGA had the most pronounced effects on decreasing hepatic pro-inflammatory IL-17 and NFκB, contributing to reduce CD68-positive macrophage number, stellate cell activation, and collagen deposition. In agreement, CAF+TRI+CGA upregulated tumor suppressors miR-144-3p, miR-376a-3p and antifibrotic miR-15b-5p, frequently deregulated in human HCC. CAF+TRI+CGA reduced the hepatic protein levels of pro-proliferative EGFR (miR-144-3p target), antiapoptotic Bcl-2 family members (miR-15b-5p targets), and the number of PCNA (miR-376a-3p target) positive hepatocytes in preneoplastic foci. Our results suggest that the combination of most common and highly bioavailable coffee compounds, rather than CAF individually, attenuates fibrosis-associated hepatocarcinogenesis by modulating miRNA expression profile., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Running is a modality that has a large number of adepts, including women. Therefore, it is important to understand how sportswear can help women, with special attention to the breast movement. The aim of this study was to analyse the effect of different combinations of breast support and footwear on the breast movement during walking and running. Twenty women performed treadmill walking (5 km/h) and running (7 and 10 km/h) combining different footwear (barefoot, minimalist, and traditional) and breast support conditions (bare breast, everyday bra, and sports bra). Three-dimensional data from breast and trunk markers were tracked for 10 stride cycles. Relative breast displacement was calculated and derived for velocity. An interaction effect was observed between support, footwear, and speed conditions. The bare breast conditions presented differences from the other conditions in the majority of the kinematic variables, presenting higher breast displacement and velocity values. On the other hand, the sports bra conditions presented the lowest values for the kinematics variables. In the vertical component of breast displacement during running (10 km/h) we verified that the sports bra presented reductions of 56% and 43% in relation to the bare breast and everyday bra conditions, respectively. Despite this, no differences were found between footwear within each breast support condition. A sports bra is efficient to decrease breast movement. In addition, neither of the tested footwear was able to decrease these movements., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

TRB3, a mammalian homolog of Drosophila tribbles, plays an important role in multiple tissues and it has been implicated in stress response regulation and metabolic control. However, the role of hepatic TRB3 and its relationship with endoplasmic reticulum stress (ER stress) during aging has not been elucidated. Thus, the present study aimed to explore the association of aging with TRB3 and ER stress on the hepatic glucose production in Wistar rats. We found the TRB3 protein content to be higher in livers of old rats (27 months) compared to young (3 months) and middle-aged (17 months) rats. The increased content of hepatic TRB3 of the old rats was associated with insulin resistance (decreased protein kinase B (Akt) and Forkhead Box O1 (FoxO1) phosphorylation) and increased enzymes of gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase)). Moreover, aging was associated with activation of the endoplasmic reticulum stress pathway-related molecules, with an increase in phosphorylation of Inositol-requiring enzyme 1 (p-IRE1α), the protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), eukaryotic translation initiation factor-α (p-eIF2α), binding immunoglobulin protein (BiP), and the C/EBP homologous protein (CHOP) contents in rats. These molecular changes resulted in increased liver glucose production in response to the pyruvate challenge and hyperglycemia of the old rats. In conclusion, our results suggested that, by interfering with insulin signaling in the liver, TRB3 was associated with ER stress and increased hepatic glucose production in aging rats., Competing Interests: Declaration of competing interest The authors of this study have no competing interests to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Exposure to fungicide ziram (zinc dimethyldithiocarbamate) has been associated with increased incidence of Parkinson's disease (PD). We recently demonstrated that the intranasal (i.n.) administration of sodium dimethyldithiocarbamate (NaDMDC, a more soluble salt than ziram) induces PD-like behavioral and neurochemical alterations in mice. We now investigated the putative neuroprotective effects of melatonin on behavioral dificits and neurochemical alterations induced by i.n. NaDMDC. Melatonin treatment (3, 10 or 30 mg/kg, i.p.) was given 1 h before NaDMDC administration (1 mg/nostril) during 4 consecutive days and we evaluated early (up to 7 days) and late (up to 35 days) NaDMDC-induced behavioral and neurochemical alterations. Melatonin treatment protected against early motor and general neurological impairments observed in the open field and neurological score of severity, respectively, and late deficits in rotarod test. Melatonin prevented the NaDMDC-induced alterations in the striatal tyrosine hydroxylase immunocontent. Melatonin also protected against increased levels of oxidative stress markers (4-hydroxynonenal and 3-nitrotyrosine) in the striatum, as well as the NaDMDC-induced increase of 4-hydroxynonenal and TNF, markers of oxidative stress and inflammation, respectively, in the olfactory bulb. These results further detail the mechanisms underlying NaDMDC toxicity and demonstrate the neuroprotective effects of melatonin against the neuronal damage induced by NaDMDC., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Several models of environmental enrichment and physical exercise have been used to explore the experience effects on brain functions and plasticity, mainly in adult animals. In order to examine the early influence of these stimuli on developing brain, the present study used calcium-binding protein parvalbumin as neuroplastic marker in the hippocampal formation of male Wistar rats subjected to environmental enrichment or physical exercise from postnatal days 21 to 60 (P21-P60). In our study, no significant difference in hippocampal expression and distribution of parvalbumin was found between enriched and control rats. However, a significant increase in parvalbumin protein expression as well as in the number of neurons stained with parvalbumin was observed in the hippocampal formation of rats submitted to daily treadmill exercise when compared to the control rats. The hippocampal region with the highest number of parvalbumin neurons in exercised rats was Cornus of Amon 2 e 3 (CA2/CA3). These findings indicate that developing brain may be differentially sensitive to environmental stimulation models. Specifically, our results show that hippocampal expression and distribution of parvalbumin in developing rats may be more influenced by exercise than by enriched environment. The mechanisms are not yet known., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest. All authors read and approved the final manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine the physico-mechanical properties of a high viscosity glass ionomer cement (GIC) reinforced with TiO 2 nanotubes (TiO 2 -nt)., Methods: TiO 2 -nt was incorporated into the GIC powder components (Ketac Molar EasyMix™) in concentrations of 0% (control group), 3%, 5%, 7% by weight. Compressive strength (n = 10/group), three point bending for flexural strength (n = 18/group), microshear bond strength to dentin and failure mode (n = 20/group), and surface roughness and weight loss before and after brushing simulation (30,000 cycles) (n = 8/group) were evaluated. Data were submitted to Shapiro-Wilk, ANOVA, Tukey and Chi-square tests (α ≤ 0.05)., Results: Addition of 5% of TiO 2 -nt into GIC presented the highest values for compressive strength and differed from the control, 3% and 7% groups (p = 0.023). There were no significant differences in flexural strength (p = 0.107) and surface roughness before and after the dental brushing (p = 0.287) among the groups. GIC added with 5% TiO 2 -nt showed the lowest weight loss values (p = 0.01), whereas the control, 3% or 5% TiO 2 -nt groups presented similar microshear bond strength values (p ≥ 0.05). The 5% TiO 2 -nt group featured higher microshear bond strength than the 7% TiO 2 -nt group (p = 0.034). Cohesive in material was the most representative failure mode for all groups., Significance: The incorporation of TiO 2 -nt did not affect GIC's adhesiveness to dentin, but improved its compressive strength at 5%. Furthermore, TiO 2 -nt decreased the percentage of weight loss after GIC's surface wear., (Copyright © 2020 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

New antifungals are increasingly needed due to the emergence of resistant fungal strains. Traditional antifungal assays are laborious and require significant amounts of samples. The present work presents a new proposal to evaluate antifungal activity and antagonism among fungal species, based on experiments of fungal culture and co-culture, 1 H NMR profile of fungal culture extracts and chemometrics. In order to develop the work, six axenic cultures of fungi that infested fruits (Fusarium guttiforme, Pestalotiopsis diospyri, Phoma caricae-papayae, Colletotrichum horii, Phytophthora palmivora, and C. gloeosporioides), and co-cultures of all possible combination among them were performed (totalizing 63 experiments). All fungal extracts were evaluated by 1 H NMR followed by Principal Component Analyses (PCA) in order to determine spectral dissimilarity among the extracts. Results showed that 1 H NMR data evaluated by PCA were capable to predict both antagonism and antifungal activity. Traditional antifungal in vitro assays of active and inactive extracts were also performed in order to prove the prediction made by PCA. The obtained data showed that the approach is an outstanding tool to simultaneously obtain and evaluate bioactive compounds because: it was able to predict the activity of five different extracts in a collection of sixty-three, which would be much more difficult and time consuming if applied randomly; most important antifungal extracts are indicated by PCA; hundreds of traditional in vitro assays are avoid; and, the method is very time and money saving., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the association of leptin rs7799039 and adiponectin rs2241766 gene polymorphisms on daily sleep duration in 4-5-year-old children., Methods: Data were obtained from the Predictors of Maternal and Infant Excess Body Weight - PREDI Study, a cohort study conducted in Joinville - Brazil. The current study is a cross-sectional study, which was carried out in the homes of the participants between July 2016 and August 2017. Total sleep time was self-reported by the mothers. The average total sleep time was classified according to the recommendation of the National Sleep Foundation for children aged 3-5 years: ≥10 or <10 h of sleep/day. Genotyping analysis was performed in blood samples by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique., Results: Of the 216 children included in the study, 167 (77.3%) and 49 (22.7%) had ≥10 and <10 h of sleep/day, respectively. There was a significant decrease in the average total sleep time as the number of risk alleles of the two polymorphisms increased (LEP: GG = 11 h18, GA = 10 h42, AA = 10 h15; ADIPOQ: TT = 11 h00, TG + GG = 10 h28). Interaction analysis showed a progressive increase in the odds of children sleeping <10 h/day at preschool age with an increasing number of risk alleles of the LEP and ADIPOQ polymorphisms (OR = 7.44, 95%CI, 2.45-22.55)., Conclusions: We found a progressive increase in the odds of 4-5 year old children sleeping less than 10 h/day as the number of risk alleles of the LEP-rs7799039 and ADIPOQ-rs2241766 polymorphisms increased, even after adjustment for other maternal and child characteristics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

It has been suggested that eccentric contraction (EC) is associated with increases in serially arranged sarcomeres (sarcomerogenesis), while concentric contraction (CC) has been associated with serial sarcomeres decrease. Sarcomerogenesis following EC is thought to be a protective muscle adaptation, preventing muscle injury in future eccentric exercise bouts (repeated bout effect). However, the mechanisms underlying sarcomerogenesis in EC remain unknown, and the sarcomerogenic responses observed in response to EC and CC are contradictory. We measured sarcomere length, sarcomere length uniformity, serial sarcomere number, and fascicle length in gastrocnemius medialis, tibialis anterior, vastus medialis and vastus lateralis in sedentary (SED) mice, and in mice following protocols of moderate uphill (TRU) and downhill (TRD) training and uphill (OTU) and downhill (OTD) overtraining. We found pain sensitivity after the first bout of EC exercise on TRD and OTD followed by a normalized sensory response after four weeks of training, indicating a repeated bout effect. However, these findings were not associated with sarcomerogenesis, as serial sarcomere numbers did not increase in TRD and OTD skeletal muscle samples compared to controls (SED). However, we found a decrease in serial sarcomere number in VL and TA in OTU group mice, which was associated with a decrease in fascicle length and no change of sarcomere length at the tested joint configuration. We conclude that excessive concentric muscle contraction (OTU group mice), leads to a decrease in serial sarcomere number, while moderate or excessive eccentric training, did not result in sarcomerogenesis, as reported in the literature., (Copyright © 2019 Elsevier Ltd. All rights reserved.)