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This work aimed to understand how lifelong exercise training promotes the remodelling of the immune system and prostate signalome in a rat model of PCa. Fifty-five male Wistar rats were divided into four groups: control sedentary, control exercised, induced PCa sedentary and induced PCa exercised. Exercised animals were trained in a treadmill for 53 weeks. Pca induction consisted on the sequential administration of flutamide, N-methyl-N-nitrosourea and testosterone propionate implants. Serum concentrations of C-reactive protein (CRP) and tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) were not different among groups. Peripheral levels of γδ T cells were higher in Pca exercised group than in the PCa sedentary group (p

3,4-Methylenedioxypyrovalerone (MDPV) is consumed worldwide, despite its potential to cause toxicity in several organs and even death. There is a recognized need to clarify the biological pathways through which MDPV elicits general and target-organ toxicity. In this work, a comprehensive untargeted GC-MS-based metabolomics analysis was performed, aiming to detect metabolic changes in putative target organs (brain, heart, kidneys and liver) but also in urine of mice after acute exposure to human-relevant doses of MDPV. Male CD-1 mice received binge intraperitoneal administrations of saline or MDPV (2.5 mg/kg or 5 mg/kg) every 2 h, for a total of three injections. Twenty-four hours after the first administration, target organs, urine and blood samples were collected for metabolomics, biochemical and histological analysis. Hepatic and renal tissues of MDPV-treated mice showed moderate histopathological changes but no significant differences were found in plasma and tissue biochemical markers of organ injury. In contrast, the multivariate analysis significantly discriminated the organs and urine of MDPV-treated mice from the control (except for the lowest dose in the brain), allowing the identification of a panoply of metabolites. Those levels were significantly deviated in relation to physiological conditions and showed an organ specific response towards the drug. Kidneys and liver showed the greatest metabolic changes. Metabolites related with energetic metabolism, antioxidant defenses and inflammatory response were significantly changed in the liver of MDPV-dosed animals, while the kidneys seem to have developed an adaptive response against oxidative stress caused by MDPV. On the other hand, the dysregulation of metabolites that contribute to metabolic acidosis was also observed in this organ. The heart showed an increase of fatty acid biosynthesis, possibly as an adaptation to maintain the cardiac energy homeostasis. In the brain, changes in 3-hydroxybutyric acid levels may reflect the activation of a neurotoxic pathway. However, the increase in metabolites with neuroprotective properties seems to counteract this change. Metabolic profiling of urine from MDPV-treated mice suggested that glutathione-dependent antioxidant pathways may be particularly involved in the compensatory mechanism to counteract oxidative stress induced by MDPV. Overall, this study reports, for the first time, the metabolic profile of liver, kidneys, heart, brain, and urine of MDPV-dosed mice, providing unique insights into the biological pathways of toxicity. Our findings also underline the value of toxicometabolomics as a robust and sensitive tool for detecting adaptive/toxic cellular responses upon exposure to a physiologically relevant dose of a toxic agent, earlier than conventional toxicity tests.

Oxaliplatin-based chemotherapy has been widely used to treat colorectal cancer. Here, we report a case of a 71-year-old man, former smoker (40 pack-years), with no history of relevant exposures such as occupational, environmental or drug exposure. The patient developed acute partial respiratory insufficiency concomitant with the eighth cycle of adjuvant chemotherapy with oxaliplatin and capecitabine for stage IIIA colorectal adenocarcinoma. After the exclusion of other causes, namely pulmonary thromboembolism, high-resolution chest computed tomography (CT) showed a usual interstitial pneumonia (UIP) pattern. After the discussion at the multidisciplinary meeting on interstitial lung diseases and considering the temporal association between clinical and imaging findings and chemotherapy treatment, along with exclusion of other potential causes, the most likely hypothesis was pulmonary fibrosis secondary to oxaliplatin. A literature review on this scope was also performed. We conclude that pulmonary fibrosis is a rare complication of oxaliplatin, but with the widespread use of oxaliplatin combinations in colorectal cancer, active assessment for interstitial lung disease is recommended.

Exercise training and regular physical activity have been mentioned as one of the non-pharmacological approaches to enhance breast cancer outcomes. Such evidence encourages health professionals to recommend it as an adjuvant in treatment conditions to improve cardiorespiratory fitness that, can increase the rate of completion of pharmacologic therapies, reduce cancer-related fatigue, and improve muscle strength and quality of life. Research results have highlighted a positive relationship between exercise and breast tumor outcomes, that seem to be dose dependent (the more activity the more protection) and can be mediated through several biological mechanisms. In this chapter, we intend to summarize the current knowledge about the effects of exercise in the regulation of metabolic and steroid hormones, tumor-related inflammation, and the attenuation of cancer-induced muscle wasting, highlighting the exercise designs that can prompt the best results. info:eu-repo/semantics/publishedVersion

The escalation of life expectancy is accompanied by an increase in the prevalence of age-related conditions, such as sarcopenia. Sarcopenia, a muscle condition defined by low muscle strength, muscle quality or quantity, and physical performance, has a high prevalence among the elderly and is associated to increased mortality. The neuromuscular system has been emerging as a key contributor to sarcopenia pathogenesis. Indeed, the age-related degeneration of the neuromuscular junction (NMJ) function and structure may contribute to the loss of muscle strength and ultimately to the loss of muscle mass that characterize sarcopenia. The present mini-review discusses important signaling pathways involved in the function and maintenance of the NMJ, giving emphasis to the ones that might contribute to sarcopenia pathogenesis. Some conceivable biomarkers, such as C-terminal agrin fragment (CAF) and brain-derived neurotrophic factor (BDNF), and therapeutic targets, namely acetylcholine and calcitonin gene-related peptide (CGRP), can be retrieved, making way to future studies to validate their clinical use.

Made available in DSpace on 2022-04-29T08:30:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-01 Purpose This study aimed to determine the role of mammalian target of rapamycin (mTORC1) activation and catabolic markers in resistance training's (RT) antiatrophy effect during cachexia-induced muscle loss. Methods Myofiber atrophy was induced by injecting Walker 256 tumor cells into rats exposed or not exposed to the RT protocol of ladder climbing. The role of RT-induced anabolic stimulation was investigated in tumor-bearing rats with the mTORC1 inhibitor rapamycin, and cross-sectional areas of skeletal muscle were evaluated to identify atrophy or hypertrophy. Components of the mTORC1 and ubiquitin-proteasome pathways were assessed by real-time polymerase chain reaction or immunoblotting. Results Although RT prevented myofiber atrophy and impaired the strength of tumor-bearing rats, in healthy rats, it promoted activated mTORC1, as demonstrated by p70S6K's increased phosphorylation and myofiber's enlarged cross-sectional area. However, RT promoted no changes in the ratio of p70S6K to phospho-p70S6K protein expression while prevented myofiber atrophy in tumor-bearing rats. Beyond that, treatment with rapamycin did not preclude RT's preventive effect on myofiber atrophy in tumor-bearing rats. Thus, RT's ability to prevent cancer-induced myofiber atrophy seems to be independent of mTORC1's and p70S6K's activation. Indeed, RT's preventive effect on cancer-induced myofiber atrophy was associated with its capacity to attenuate elevated tumor necrosis factor a and interleukin 6 as well as to prevent oxidative damage in muscles and an elevated abundance of atrogin-1. Conclusions By inducing attenuated myofiber atrophy independent of mTORC1's signaling activation, RT prevents muscle atrophy during cancer by reducing inflammation, oxidative damage, and atrogin-1 expression. Department of Physical Education State University of Londrina Department of Physical Education Universidade Estadual Paulista (UNESP) Presidente Prudente Federal University of Mato Grosso Graduate Program of Health Sciences Faculty of Medicine State University of Londrina Department of General Pathology University of Porto Ciafel Faculty of Sport Department of Physical Education Universidade Estadual Paulista (UNESP) Presidente Prudente

BACKGROUND: Evidence-Based Practice (EBP) is becoming increasingly important in Physical Therapy (PT). For proper designing, implementing, disseminating and evaluating EBP in PT, a valid and reliable questionnaire measuring attitudes, knowledge, behavior, prerequisites, and barriers related to EBP and guidelines is needed. One questionnaire that could be used to collect this information is the “EBP Questionnaire”, developed by Jette et al. 2003. However, to our knowledge, no Portuguese version or published study with the Portuguese PT population was performed using this questionnaire. OBJECTIVE: The aim of this study was to translate, cross-culturally adapt and validate the “EBP Questionnaire” to European Portuguese and for the PT population. Material and Methods: A draft version was pilot tested for content validity (n=17), and a revised version was tested for test-retest reliability (n=72). The percentage of agreement and the Kappa coefficients between the 2 tests were analyzed. Additionally, the internal consistency was calculated. RESULTS: The preliminary final version of the European Portuguese EBP questionnaire was well accepted (only the items 22, 23, 45-51 needed to be reviewed). The mean average percentage of agreement was 82% (ranged 58–97%), and the Kappa coefficients were 0.658 (ranged 0.336–0.844). In the internal consistency, the mean average Cronbach’s ? coefficients were 0.665 (ranged 0.365–0.879). CONCLUSION: The results suggested that this questionnaire can be a useful instrument for measuring self-reported beliefs, attitudes, knowledge, and behaviors related to EBP in the Portuguese PTs context.

Objective The aim of this study was to investigate the effects of creatine supplementation on early stages of ethanol-induced hepatic damage. Methods Male Swiss mice were divided into three groups (n = 12/group): control (C), ethanol (E), and ethanol supplemented with creatine (EC). The control group received a diet containing 15.8% of total calories from proteins, 46.3% from carbohydrates, and 37.9% from lipids. The ethanol and ethanol and creatine groups received diets containing 15.8% of total calories from proteins, 16.2% from carbohydrates, and 34.5% from lipids; the remaining calories were obtained from the addition of 5% of 95% ethanol. Creatine (1%; weight/vol) was added to the diet of EC mice. After 14 and 28 d, six animals from each group were sacrificed, generating subdivisions in each group: C14 and C28, E14 and E28, EC14 and EC28. After sacrifice, the liver was removed, weighed, and prepared for histologic, biochemical, and molecular analysis, and blood was collected. Results Ethanol intake induced mild cell degeneration, liver damage, oxidative lesions, and inflammation. Surprisingly, ethanol intake combined with creatine exacerbated cell degeneration and fat accumulation, hepatic expression of genes related to ethanol metabolism, oxidative stress and inflammation, and promoted oxidative stress and elevated plasma alanine aminotransferase (P Conclusion Creatine supplementation associated with ethanol is able to interfere in the alcohol metabolism and oxidative stress and to exacerbate ethanol-induced hepatic damage. These new findings are opposite to those observed in several studies where protective effects of creatine in a wide variety of injury models, including non-alcoholic fatty liver disease, were described.

Although resistance exercise (RE) is now recognized as an adjuvant in cancer treatment because of its capacity to prevent muscle wasting, weakness, and cachexia, it is unknown whether RE can mitigate tumor development. Two solid adenocarcinoma models (Walker-256 and Ehrlich) were used to investigate the effects of RE on tumor cell proliferation, growth, and aggressiveness parameters in tumor-bearing animals' life span.Walker-256 tumor-bearing rats and Ehrlich tumor-bearing mice were subjected to RE, which consisted of climbing a ladder apparatus with loads tied to their tails. After 4 wk, animals were euthanized, and tumors were excised and assessed for tumor microenvironment evaluation such as cell proliferation and apoptosis determination, collagen deposit, and presence of malignant tumor morphology.Our data demonstrate that RE mitigated tumor growth and favored tumor end points such as lower Scarff-Bloom-Richardson histological grade tumor, denoting slow cell aberrant form and division, decreased tumor cell proliferation (evaluated by nucleus marked with antigen ki-67), and lower viable tumor area in both types of tumors studied. In addition, RE stimulated tumor microvessel density in Walker-256 tumor-bearing rats, but there was no change in their life span.RE may mitigate tumor growth and tumor malignancy parameters such as lower histopathological grade, assuming less nuclear pleomorphism and mitotic cells, smaller viable tumor area, and decreased tumor cell proliferation in both adenocarcinomas. In addition, RE induced tumor vascularization.

This research studies the application of a life cycle assessment (LCA) methodology to evaluate the environmental impacts of an improvement to traditional brick manufacture. This study case was carried out using realistic combustion gas measurements and experimental results. The traditional process and the addition of one or two hopper blower (HB) devices provided the three scenarios for this study, which were evaluated quantitatively using a set of metric indicators for potential impacts while applying a “cradle-to-gate” approach. A decreasing trend was observed for most values of the potential impact categories when the device was used. An opportunity to improve the traditional process by adding this device has been identified, as a reduction in the environmental impact categories has been observed. The study suggests that the LCA tool may be valuable for quantifying the environmental impacts of improvements in the processes.

We investigate the effectiveness and safety of a novel magnetic hyperthermia (MHT) protocol, whereby a pretreatment with nontargeted magnetic nanoparticles (MNPs) is used to boost the subsequent ir...

Introduction: The purpose of this article was to develop and validate a scale to assess common knowledge about temporomandibular disorders (TMDs) in the general population, evaluate the status of TMDs knowledge in the Portuguese population, quantify the severity and prevalence of TMDs-related symptoms in the general population, and assess the association between TMDs-related symptoms’ severity and demographic, medical and oral associated factors. Materials and Methods: This study was an analytical cross-sectional survey design. The sample consisted of 2165 participants selected through a snowball sampling method. The participants completed an online questionnaire regarding social and demographic characteristics, medical history, oral habits, Fonseca’s Anamnestic Index, a scale about difficulties on impulsiveness control and also the TMDs knowledge scale developed. The psychometric properties of the scale developed was tested on a small number of participants (n = 210). The P value set was 0.05. Results: Concerning psychometric properties all items showed a moderate-to-strong positive association with the loading factor. The Cronbach’s alpha was 0.956, showing good reliability. TMDs knowledge was positive in 1295 participants (59.8%). Multivariate-adjusted odds showed that female gender, diagnosis of tension-type headache, migraine, anxiety, impulsiveness, facial trauma, and parafunctional habits increased the risk of developing TMDs (adjusted odds ratios from 1.84 to 49.38). Conclusion: The scale developed is psychometrically valid and reliable and the participants had an overall positive knowledge about TMDs. A high prevalence of TMDs-related symptoms among the Portuguese population was found and the associated factors were female gender, impulsiveness, tension-type headache, migraine, anxiety, facial trauma, and parafunctional habits.

Amanita phalloides is one of the most toxic mushrooms worldwide, being responsible for the majority of human fatal cases of mushroom intoxications. α-Amanitin, the most deleterious toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and renal failure. Herein, we used cyclosporine A after it showed potential to displace RNAP II α-amanitin in silico. That potential was not confirmed either by the incorporation of ethynyl-UTP or by the monitoring of fluorescent RNAP II levels. Nevertheless, concomitant incubation of cyclosporine A with α-amanitin, for a short period, provided significant protection against its toxicity in differentiated HepaRG cells. In mice, the concomitant administration of α-amanitin [0.45 mg/kg intraperitoneal (i.p.)] with cyclosporine A (10 mg/kg i.p. plus 2 × 10 mg/kg cyclosporine A i.p. at 8 and 12 h post α-amanitin) resulted in the full survival of α-amanitin-intoxicated mice, up to 30 days after the toxin's administration. Since α-amanitin is a substrate of the organic-anion-transporting polypeptide 1B3 and cyclosporine A inhibits this transporter and is a potent anti-inflammatory agent, we hypothesize that these mechanisms are responsible for the protection observed. These results indicate a potential antidotal effect of cyclosporine A, and its safety profile advocates for its use at an early stage of α-amanitin intoxications.

Background: Obesity is considered protective for bone mass, but this view has been progressively challenged. Menopause is characterized by low bone mass and increased adiposity. Our aim was to determine how visceral and bone marrow adiposity change following ovariectomy (OVX), how they correlate with bone quality and if they are influenced by physical activity. Methods: Five-month-old Wistar rats were OVX or sham-operated and maintained in sedentary or physically active conditions for 9 months. Visceral and bone marrow adiposity as well as bone turnover, femur bone quality and biomechanical properties were assessed. Results: OVX resulted in higher weight, visceral and bone marrow adiposity. Visceral adiposity correlated inversely with femur Ct.Th (r = −0.63, p &lt, 0.001), BV/TV (r = −0.67, p &lt, 0.001), Tb.N (r = −0.69, p &lt, 0.001) and positively with Tb.Sp (r = 0.58, p &lt, 0.001). Bone marrow adiposity also correlated with bone resorption (r = 0.47, p &lt, 0.01), bone formation rate (r = −0.63, p &lt, 0.01), BV/TV (r = −0.85, p &lt, 0.001), Ct.Th (r = −0.51, p &lt, 0.0.01), and with higher empty osteocyte lacunae (r = 0.39, p &lt, 0.05), higher percentage of osteocytes with oxidative stress (r = 0.64, p &lt, 0.0.01) and lower femur maximal stress (r = −0.58, p &lt, 0.001). Physical activity correlated inversely with both visceral (r = −0.74, p &lt, 0.01) and bone marrow adiposity (r = −0.92, p &lt, 0.001). Conclusions: OVX increases visceral and bone marrow adiposity which are associated with inferior bone quality and biomechanical properties. Physical activity could contribute to reduce adipose tissue and thereby improve bone quality.

Current cancer therapies are successfully increasing the lifespan of cancer patients. Nevertheless, cardiotoxicity is a serious chemotherapy-induced adverse side effect. Doxorubicin (DOX) and mitoxantrone (MTX) are cardiotoxic anticancer agents, whose toxicological mechanisms are still to be identified. This study focused on DOX and MTX’s cardiac mitochondrial damage and their molecular mechanisms. As a hypothesis, we also sought to compare the cardiac modulation caused by 9 mg/kg of DOX or 6 mg/kg of MTX in young adult mice (3 months old) with old control mice (aged control, 18–20 months old) to determine if DOX- and MTX-induced damage had common links with the aging process. Cardiac homogenates and enriched mitochondrial fractions were prepared from treated and control animals and analyzed by immunoblotting and enzymatic assays. Enriched mitochondrial fractions were also characterized by mass spectrometry-based proteomics. Data obtained showed a decrease in mitochondrial density in young adults treated with DOX or MTX and aged control, as assessed by citrate synthase (CS) activity. Furthermore, aged control had increased expression of the peroxisome proliferator-activated receptor γ coactivator 1 α (PGC1α) and manganese superoxide dismutase (MnSOD). Regarding the enriched mitochondrial fractions, DOX and MTX led to downregulation of proteins related to oxidative phosphorylation, fatty acid oxidation, amino acid metabolic process, and tricarboxylic acid cycle. MTX had a greater impact on malate dehydrogenase (MDH2) and pyruvate dehydrogenase E1 component subunit α (PDHA1). No significant proteomic changes were observed in the enriched mitochondrial fractions of aged control when compared to young control. To conclude, DOX and MTX promoted changes in several mitochondrial-related proteins in young adult mice, but none resembling the aged phenotype.

Orthodontic treatment acts through the application of forces and/or by stimulating and redirecting the functional forces within the craniofacial complex. Considering the interrelationship between craniomandibular and craniocervical systems, this intervention may alter craniocervical posture. Thus, our aim is to (a) compare craniocervical posture, hyoid bone position, and craniofacial morphology before, after, and also in the contention phase at least one year after the orthodontic treatment, in patients with temporomandibular disorders and (b) to verify whether the presence of condylar displacement, the skeletal class, or the facial biotype interferes with the abovementioned outcomes. To do so an observational, analytical, longitudinal, and retrospective design study was carried out. A non-probabilistic convenience sampling method was applied. The sample consisted of clinical records of patients diagnosed with temporomandibular disorders in order to compare pre-orthodontic treatment with post-orthodontic treatment (n = 42) and contention phase data (n = 26). A cephalometric analysis of several variables was performed. The p-value was set as 0.05. When the pre- and post-orthodontic treatment data were analyzed, there were statistically significant changes in variables concerning craniocervical posture (CV angle, C0-C1, and AA-PNS) and also concerning hyoid bone position (C3-Rgn). When pre- and post-orthodontic treatment and contention phase data were analyzed the variables concerning craniocervical posture (C0-C1, CVT/Ver, NSL/OPT, NSL/CVT, NSL/Ver, OPT/CVT, OPT/Ver) and facial biotype had statistically significant changes. This allowed us to conclude that in the sample studied, there were significant differences regarding hyoid bone position (pre- versus post-orthodontic treatment) and craniocervical posture (pre- versus post-orthodontic versus contention), with the craniocervical posture being prone to return to basal values. The presence of condylar displacement was found to significantly increase the H-H1 distance in the three moments of evaluation. Facial biotype was found to significantly increase the NSL/Ver angle on hypodivergent compared to hyperdivergent in the contention phase.

The tumor vessel network has been investigated as a precursor of an inhospitable tumor microenvironment, including its repercussions in tumor perfusion, oxygenation, interstitial fluid pressure, pH, and immune response. Dysfunctional tumor vasculature leads to the extravasation of blood to the interstitial space, hindering proper perfusion and causing interstitial hypertension. Consequently, the inadequate delivery of oxygen and clearance of by-products of metabolism promote the development of intratumoral hypoxia and acidification, hampering the action of immune cells and resulting in more aggressive tumors. Thus, pharmacological strategies targeting tumor vasculature were developed, but the overall outcome was not satisfactory due to its transient nature and the higher risk of hypoxia and metastasis. Therefore, physical exercise emerged as a potential favorable modulator of tumor vasculature, improving intratumoral vascularization and perfusion. Indeed, it seems that regular exercise practice is associated with lasting tumor vascular maturity, reduced vascular resistance, and increased vascular conductance. Higher vascular conductance reduces intratumoral hypoxia and increases the accessibility of circulating immune cells to the tumor milieu, inhibiting tumor development and improving cancer treatment. The present paper describes the implications of abnormal vasculature on the tumor microenvironment and the underlying mechanisms promoted by regular physical exercise for the re-establishment of more physiological tumor vasculature.

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Purpose: Prostate cancer is a major cause of cancer-related death in males worldwide and, in addition to impairing prostate function, also causes testicular adaptations. In this study, we aim to investigate the preventive effect of exercise training on PCa-induced testicular dysfunction. Methods: As a model, we used fifty Wistar Unilever male rats, randomly divided in four experimental groups. Prostate cancer was chemically and hormonally induced in two groups of animals (PCa groups). One control group and one PCa group was submitted to moderate intensity treadmill exercise training. Fifty weeks after the start of the training the animals were sacrificed and sperm, prostate, testis and serum were collected and analyzed. Sperm concentration and morphology, and testosterone serum levels were determined. In addition, histological analyses of the testes were performed, and testis proteomes and metabolomes were characterized. Results: We found that prostate cancer negatively affected testicular function, manifested as an arrest of spermatogenesis. Oxidative stress-induced DNA damage, arising from reduced testis blood flow, may also contribute to apoptosis of germ cells and consequential spermatogenic impairment. Decreased utilization of the glycolytic pathway, increased metabolism of ketone bodies and the accumulation of branched chain amino acids were also evident in the PCa animals. Conversely, we found that the treadmill training regimen activated DNA repair mechanisms and counteracted several metabolic alterations caused by PCa without impact on oxidative stress. Conclusions: These findings confirm a negative impact of prostate cancer on testis function and suggest a beneficial role for exercise training in the prevention of prostate cancer-induced testis dysfunction. published

Objective The purpose of this study was to determine the skin pressure needed to promote the macroscopic deformation of the asymptomatic patellar tendon and to verify if the pressure is associated with the individual’s characteristics. Methods A descriptive laboratory study was performed with a convenience sample of 18 young, voluntary, and asymptomatic individuals of both sexes. A progressively increasing pressure was applied on the skin over the patellar tendon, through an instrument designed to perform and control the pressure upon an ultrasound probe; data were recorded and analyzed by 2 blind investigators. All statistical analyses were conducted considering α = 0.05. Results The average pressure needed to promote a macroscopic deformation of the patellar tendon was 1.12 ± 0.37 kg/cm2. Female sex and age were inversely but not significantly associated with the pressure performed. Sports practice, weight, height, body mass index, muscle mass, and subcutaneous thickness were positively but not significantly associated with the pressure executed. Conclusion The average pressure needed to promote the macroscopic deformation of the patellar tendon was 1.12 ± 0.37 kg/cm2, which was not influenced by the characteristics of the participants.

Methylphenidate (MPH) is a first-line stimulant drug to treat attention deficit hyperactivity disorder (ADHD). Overdiagnosis of ADHD and MPH abuse lead to serious concerns about the possible long-term adverse consequences of MPH in healthy children and adolescents. We aimed to evaluate MPH effects in adolescent male Wistar rats (postnatal day 40) using an oral dose scheme (2 daily MPH doses 5 mg/kg in a 5% sucrose solution, 5 h apart, for 7 days) that mimics the therapeutic doses given to human adolescents. Twenty-four hours after the last MPH administration, rats were sacrificed and brain areas [cerebellum, prefrontal cortex (PFC), hippocampus, and striatum], peripheral organs (liver, heart, and kidneys), and blood were collected for biochemical and histological analysis. MPH treatment did not alter rats’ body temperature or weight, neither food or water intake throughout the experiment. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) significantly increased in the PFC and hippocampus of MPH-treated rats, meanwhile protein carbonylation remained unchanged in the brain. In the heart, the GSH/GSSG ratio and GSH levels were significantly increased, with decreased GSSG, while histology revealed significant damage, namely interstitial edema, vascular congestion, and presence of a fibrin-like material in the interstitial space. In the kidneys, MPH treatment resulted in extensive necrotic areas with cellular disorganization and cell infiltration, and immunohistochemistry analysis revealed a marked activation of nuclear factor-ĸB. This study showed that clinically relevant oral MPH doses improve the GSH redox status in the brain and heart, but evoke heart and kidney tissue damage to adolescent rats.

Doxorubicin (DOX) is a topoisomerase II inhibitor commonly used in the treatment of several types of cancer. Despite its efficacy, DOX can potentially cause fatal adverse effects, like cardiotoxicity. This work aimed to assess the role of inflammation in DOX-treated infant and adult mice and its possible link to underlying cardiotoxicity. Two groups of CD-1 male mice of different ages (infants or adults) were subjected to biweekly DOX administrations, to reach a cumulative dose of 18.0 mg/kg, which corresponds approximately in humans to 100.6 mg/m2 for infants and 108.9 mg/m2 for adults a clinically relevant dose in humans. The classic plasmatic markers of cardiotoxicity increased, and that damage was confirmed by histopathological findings in both groups, although it was higher in adults. Moreover, in DOX-treated adults, an increase of cardiac fibrosis was observed, which was accompanied by an increase in specific inflammatory parameters, namely, macrophage M1 and nuclear factor kappa B (NF-κB) p65 subunit, with a trend toward increased levels of the tumor necrosis factor receptor 2 (TNFR2). On the other hand, the levels of myeloperoxidase (MPO) and interleukin (IL)-6 significantly decreased in DOX-treated adult animals. In infants, a significant increase in cardiac protein carbonylation and in the levels of nuclear factor erythroid-2 related factor 2 (Nrf2) was observed. In both groups, no differences were found in the levels of tumor necrosis factor (TNF-α), IL-1β, p38 mitogen-activated protein kinase (p38 MAPK) or NF-κB p52 subunit. In conclusion, using a clinically relevant dose of DOX, our study demonstrated that cardiac effects are associated not only with the intensity of the inflammatory response but also with redox response. Adult mice seemed to be more prone to DOX-induced cardiotoxicity by mechanisms related to inflammation, while infant mice seem to be protected from the damage caused by DOX, possibly by activating such antioxidant defenses as Nrf2.

Background Diagnosing and monitoring of children with respiratory disorders is often challenging. Respiratory sounds (RS) are simple, non-invasive and universally available measures that are directly related to movement of air, within the tracheobronchial tree. Thus, RS may be valuable indicators of respiratory health, their characteristics in the paediatric population are scattered in the literature and not systematized. Aim Systematically review the different acoustic RS properties in healthy children and in children with different respiratory disorders. Methods: MEDLINE, EMBASE, AMED and CINHAL databases were searched on Sept 2020. One author extracted data and two independently assessed the quality of the articles using the National Heart Lung and Blood Institute quality assessment tool. Results Twenty-eight studies were included with a total 2032 participants (44% with a respiratory condition, such as asthma, bronchiolitis, cystic fibrosis, presence of wheezing and non-specified low respiratory tract infections). A high heterogeneity in the procedures, outcomes and outcome measures used was found. Healthy participants showed lower values of F50 (from 194 ± 26 to 521 ± 18Hz) than those with asthma (from 140 ± 8 to 769 ± 85Hz) or bronchiolitis (from 100 to 80Hz). F50 tend to increase with provocation tests (136 ± 9 to 909 ± 81Hz) and decrease with treatments (128 ± 6 to 781 ± 57Hz). Wheeze rates ranged from 0 to 24.7 ± 25% on asthmatic participants. Crackles findings ranged from 6% on people with recurrent wheezing to 30.8% in middle lobe atelectasis. Conclusion RS show different acoustic properties in healthy children vs with different respiratory disorders and thus may be useful in the diagnostic and monitoring on paediatrics. published

This study aimed to determine the effect of a single bout of resistance exercise at different intensities on the mobilization of circulating EPCs over 24 hours in women. In addition, the angiogenic factors stromal cell-derived factor 1 (SDF-1α), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1-alpha (HIF-1α) and erythropoietin (EPO) were measured as potential mechanisms for exercise-induced EPCs mobilization. Thirty-eight women performed a resistance exercise session at an intensity of 60% (n = 13), 70% (n = 12) or 80% (n = 13) of one repetition maximum. Each session was comprised of three sets of 12 repetitions of four exercises: bench press, dumbbell curl, dumbbell squat, and standing dumbbell upright row. Blood was sampled at baseline and immediately, 6 hours, and 24 hours post-exercise. Circulating EPC and levels of VEGF, HIF-1α and EPO were significantly higher after exercise (P

Objective: The aim of the present systematic review and meta-analysis is to know, based on the available randomized controlled trials, if the non-surgical and non-pharmacological interventions commonly used for knee osteoarthritis (OA) patients are effective and which are the most effective ones. Material and Methods: RCTs were identified through electronic databases respecting the following terms to guide the search strategy: PICO (Patients – Humans with knee OA; Intervention – Non-surgical and non-pharmacological interventions; Comparison – Pharmacological, surgical, placebo, no intervention, or other non-pharmacological/non-surgical interventions; Outcomes – Pain, physical function and patient global assessment). The methodological quality of the selected publications was evaluated using the PEDro and GRADE scales. Additionally, a meta-analysis was performed using the RevMan. Only studies with similar control group, population characteristics, outcomes, instruments and follow-up, were compared in each analysis. Results: Initially, 52 RCTs emerge however, after methodological analysis, only 39 had sufficient quality to be included. From those, only 5 studies meet the meta-analysis criteria. Exercise (especially resistance training) had the best positive effects on knee OA patients. Pulsed Electromagnetic Fields and Moxibustion showed to be the most promising interventions from the others. Balance Training, Diet, Diathermy, Hydrotherapy, High Level Laser Therapy, Interferential Current, Mudpack, Neuromuscular Electrical Stimulation, Musculoskeletal Manipulations, Shock Wave Therapy, Focal Muscle Vibration, stood out, however more studies are needed to fully recommend their use. Other interventions did not show to be effective or the results obtained were heterogeneous. Conclusions: Exercise is the best intervention for knee OA patients. Pulsed Electromagnetic Fields and Moxibustion showed to be the most promising interventions from the others options available.

Iron oxide nanoparticles (ION) are gaining importance as diagnostic and therapeutic tool of central nervous system diseases. Although oleic acid-coated ION (O-ION) have been described as stable and biocompatible, their potential neurotoxicity was scarcely evaluated in human nervous cells so far. The primary aim of this work was to assess the molecular and cellular effects of O-ION on human astrocytes (A172 cells) under different experimental conditions. An extensive set of cyto- and genotoxicity tests was carried out, including lactate dehydrogenase release assay, cell cycle alterations, and cell death production, as well as comet assay, γH2AX assay, and micronucleus (MN) test, considering also iron ion release capacity and alterations in DNA repair ability. Results showed a moderate cytotoxicity related to cell cycle arrest and cell death promotion, regardless of serum presence. O-ION induced genotoxic effects, namely primary DNA damage, as detected by the comet assay and H2AX phosphorylation, but A172 cells were able to repair this particular damage because no chromosome alterations were found (confirmed by MN test results). Accordingly, no effects on the DNA repair ability were observed. The presence of serum proteins did not influence O-ION toxicity. Iron ions released from the O-ION surface seemed not to be responsible for the cytotoxic and genotoxic effects observed. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc. Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia. Grant Number: ED481B 2016/190‐0 Fundação para a Ciência e a Tecnologia. Grant Number: SFRH/BD101060/2014 Deputación Provincial da Coruña. Grant Number: 2019000011550 Ministerio de Educación, Cultura y Deporte. Grant Number: PRX19/00353 Xunta de Galicia. Grant Number: ED431B 2019/02 This work was funded by Xunta de Galicia (ED431B 2019/02). Vanessa Valdiglesias was supported by a Xunta de Galicia postdoctoral fellowship (ED481B 2016/190-0), B. Laffon by a Ministerio de Educación, Cultura y Deporte fellowship (PRX19/00353), Natalia Fernández-Bertólez by a Deputación Provincial da Coruña fellowship (2019000011550), and Fátima Brandao by the Portuguese Foundation for Science and Technology (SFRH/BD101060/2014). Authors would also like to acknowledge COST Action CA15132 “The comet assay as a human biomonitoring tool (hCOMET).” info:eu-repo/semantics/publishedVersion