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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.

AIMS Excessively intense physical training can compromise the functionality of the immune system and contribute to the appearance of symptoms associated with overtraining syndrome (OTS). The aim of this study was to analyze the splenic morphological changes in Wistar rats submitted to demanding training. METHODS The animals were randomly assigned to 2 groups; control group (CG) and exercise group (EG), animals in the EG group were sacrificed after 1 (EG1) and 3 weeks (EG3) of training. The animals were stimulated to run on the treadmill (-20o; from 25m/min, with a progressive increase of 1.25m/minute at each session; 1 hour/day) 6 days/ week. Body weight, food intake, appearance of hair, behavior and ability of animals to perform the imposed work were assessed during the protocol. The spleen was collected for histological analysis and immunohistochemical identification of CD4+ T lymphocytes and CD8+ T cells and NF-kB transcription factor. RESULTS The protocol did not induce OTS, however, decreases were observed in areas of white pulp in EG3 in relation to the other groups. The training induced a decrease in splenic CD4+ T cells with an increase in CD8+T cells. The training increased the expression of NF-κB P65 compared to sedentary animals. CONCLUSIONS In conclusion, even without manifestation of OTS, strenuous physical training, alter the histological and immunological structures of the spleen, suggesting in part a compromise in the functionality of the immune system.

Muscle wasting is one of the major health problems in older adults and is traditionally associated to sarcopenia. Nonetheless, muscle loss may also occur in older adults in the presence of cancer, and in this case, it is associated to cancer cachexia. The clinical management of these conditions is a challenge due to, at least in part, the difficulties in their differential diagnosis. Thus, efforts have been made to better comprehend the pathogenesis of sarcopenia and cancer cachexia, envisioning the improvement of their clinical discrimination and treatment. To add insights on this topic, this review discusses the current knowledge on key molecular players underlying sarcopenia and cancer cachexia in a comparative perspective. Data retrieved from this analysis highlight that while sarcopenia is characterized by the atrophy of fast-twitch muscle fibers, in cancer cachexia an increase in the proportion of fast-twitch fibers appears to happen. The molecular drivers for these specificmuscle remodeling patterns are still unknown; however, among the predominant contributors to sarcopenia is the age-induced neuromuscular denervation, and in cancer cachexia, the muscle disuse experienced by cancer patients seems to play an important role. Moreover, inflammation appears to be more severe in cancer cachexia. Impairment of nutrition-related mediators may also contribute to sarcopenia and cancer cachexia, being distinctly modulated in each condition.

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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Introduction: Benefits of regular physical exercise were demonstrated as preventive and coadjuvant nonpharmacological anticancer therapy. However, the role of exercise in modulating prostate cancer behavior has yet to be established. Methods: Prostate tumors were induced in C57BL/6 male mice (n = 28) by subcutaneous inoculation of a suspension of murine androgen-independent RM1 cells (1.5 × 105 cells/500 μL phosphate-buffered saline) in the dorsal region. Mice were randomly allocated into 2 study groups: sedentary tumor-induced (n = 14) and exercised tumor-induced (n = 14). Exercise consisted of voluntary running in wheeled cages. Mice (n = 7 per group) were sacrificed either 14 or 28 days after cell inoculation to evaluate tumor weight and percentage of area occupied by immunohistochemistry stained cells for Ki-67 and TdT-mediated dUTP-biotin nick end labeling, used as surrogate markers of cell proliferation and apoptosis, respectively. Results: Compared with sedentary tumor-induced mice, the tumors developed by exercised tumor-induced mice were significantly smaller at 14 days (0.17 [0.12] g vs 0.48 [0.24] g, P P P Conclusion: These results suggest that regular voluntary running inhibits prostate cancer cell growth by reducing cell proliferation and enhancing apoptosis.

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

Mitoxantrone (MTX) is used to treat several types of cancers and to improve neurological disability in multiple sclerosis. Unfortunately, cardiotoxicity is a severe and common adverse effect in MTX-treated patients. Herein, we aimed to study early and late mechanisms of MTX-induced cardiotoxicity using murine HL-1 cardiomyocytes. Cells were exposed to MTX (0.1, 1 or 10 µM) during short (2, 4, 6, or 12 h) or longer incubation periods (24 or 48 h). At earlier time points, (6 and 12 h) cytotoxicity was already observed for 1 and 10 µM MTX. Proteomic analysis of total protein extracts found 14 proteins with higher expression and 26 with lower expression in the cells exposed for 12 h to MTX (pH gradients 4-7 and 6-11). Of note, the expression of the regulatory protein 14-3-3 protein epsilon was increased by a factor of two and three, after exposure to 1 and 10 µM MTX, respectively. At earlier time-points, 10 µM MTX increased intracellular ATP levels, while decreasing media lactate levels. At later stages (24 and 48 h), MTX-induced cytotoxicity was concentration and time-dependent, according to the MTT reduction and lactate dehydrogenase leakage assays, while caspase-9, -8 and -3 activities increased at 24 h. Regarding cellular redox status, total glutathione increased in 1 µM MTX (24 h), and that increase was dependent on gamma-glutamylcysteine synthetase activity. Meanwhile, for both 1 and 10 µM MTX, oxidized glutathione was significantly higher than control at 48 h. Moreover, MTX was able to significantly decrease proteasomal chymotrypsin-like activity in a concentration and time-independent manner. In summary, MTX significantly altered proteomic, energetic and oxidative stress homeostasis in cardiomyocytes at clinically relevant concentrations and our data clearly demonstrate that MTX causes early cardiotoxicity that needs further study.

Objectives This study aimed to analyze the effect of creatine (Cr) supplementation on tumor microenvironment, evaluating the parameters of tumor aggressiveness. Methods Sixteen male Wistar rats were randomly assigned to 2 groups (n = 8/group): Tumor-bearing (T) and tumor-bearing supplemented with Cr (TCr). Cr supplementation was provided in drinking water for a total of 21 d. After 11 d of Cr supplementation (TCr group) or water (T group), Walker-256 tumor cells were inoculated subcutaneously in the right flank of all rats, which kept receiving Cr supplementation (TCr group) or water (T group) for 10 more days. The total period of the experiment was 21 d. Results Tumor weight corresponded with approximately 3.5% ± 0.9% of animal body weight in the T group. Cr supplementation did not accelerate tumor growth or increase tumor size. The histopathological analysis demonstrated the presence of nuclear pleomorphisms and atypical nuclei, with the presence of low-differentiated tumor cells, in both groups. Cr supplementation did not alter apoptosis and cell proliferation markers, nor tumor capsule thickness and viable tumor area. Conclusions Cr supplementation in Walker-256 tumor-bearing rats did not induce significant changes in tumor development, and did not interfere with the parameters of tumor aggressiveness, such as the level of cell differentiation and proliferation.

Signal transduction is essential for skeletal muscle functionality, a highly plastic tissue able to respond to mechanical and chemical stimuli by altering its metabolism, size and myogenic status. Several signaling pathways involving membrane and nuclear receptors, and secondary messengers as Ca2+, cAMP, inositol triphosphate (IP3) and diacylglycerol (DAG), contribute to such plasticity. The contribution of these transduction systems to muscle remodeling is well characterized; however, their input depends on several issues such as type of muscle (slow-twitch or fast-twitch, postural or locomotor), gender, age, muscle performance, duration and intensity of stimulus exposure, among others. All these issues together with the crosstalk between cell signaling pathways make difficult to correlate a unique signaling pathway or molecular player to a specific effect on muscle remodeling. This chapter overviews the mechanical and chemical transduction pathways, and the molecular players involved in the regulation of skeletal muscle mass, contractile activity and metabolism.

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.

This review was conducted to determine and quantify the efficacy of high-voltage monophasic pulsed current (HVMPC) in the treatment of stage II-IV pressure ulcers (PrUs), identify the details of HVMPC intervention parameters and the superior protocol, and ascertain other potential benefits and the safety of HVMPC intervention. Eleven studies, nine randomized controlled trials (RCTs) and two case series studies, matched the criteria and were included in the systematic review, whereas, only level 1 evidence RCTs were included in the meta-analysis. The percentage of wound surface area reduction per week was 12.39%; 95% CI, [10.43-14.37] for HVMPC plus standard wound care (SWC) and 6.96%; 95% CI, [5.56-8.38] for SWC alone or SWC plus sham HVMPC. The net effect of HVMPC was 5.4% per week (an increase of 78% greater than SWC alone or SWC plus sham HVMPC). Level 1, 2 and 4 evidence studies have consistently indicated that HVMPC plus SWC were more effective than SWC alone or SWC plus sham HVMPC in treating stage II-IV PrUs. Level 1 evidence studies showed that HVMPC intervention improved the healing of PrUs (reduced wound surface area), and combined with SWC, increased the probability of complete healing and almost eliminated the probability of worsening of healing. HVMPC intervention was shown to be relatively safe, with rare adverse reactions.

Despite the importance attributed to exercise training in the breast cancer (BC) continuum, the underlying mechanisms modulating tumor behavior are unknown. We evaluated the effects of long-term moderate-exercise in the development of mammary tumors, and studied the microenvironment of infiltrative lesions, the amount of connective tissue, and balance between cellular proliferation/death.Fifty Sprague-Dawley rats, randomly assigned into four groups: two control groups (sedentary and exercised) and two models of BC groups (sedentary and exercised) induced by N-methyl-N-nitrosoureia (MNU), were sacrificed after 35 weeks of moderate-exercise, and all perceptible tumors were removed for histological and immunohistochemistry analysis.The median number of infiltrative-lesions per animal was lower in the MNU exercised animals (p=0.02). More than one histological pattern was identified, and papillary carcinoma was the most frequent in both groups. Within infiltrative-lesions, the number of immunopositive cells per μm2 of Ki67 was lower in exercised animals (p=0.002). This presents increased cell death per μm2 (p=0.019). Tumors from sedentary animals had a higher expression of collagen deposition (p=0.027).Long-term moderate-exercise has beneficial effects in tumor development with a diminished prevalence of malignancy. Within infiltrative-lesions, moderate-exercise improves the balance between cell-proliferation and cell-death with decreased connective tissue that suggests lower tumor aggressiveness.

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.

Resume Introduction Les troubles temporomandibulaires ou les desordres de l’appareil manducateur (DAM) comportent plusieurs risques et differents facteurs associes avec, par consequent, des approches therapeutiques variees. Il est important d’identifier les troubles caracteristiques du patient qui relevent d’orthodontie, de kinesitherapie, ou d’autres modalites therapeutiques plus ou moins combinees. Presentation des cas cliniques Nous presentons trois cas de patients presentant des signes et/ou symptomes communs de troubles temporomandibulaires avec des approches therapeutiques et des resultats differents ; et notre but est de comprendre ce qui pourrait expliquer les differences de resultats observees et reconnaitre les elements particuliers squelettiques, musculaires, faciaux et occlusaux qui pourraient justifier le benefice d’une intervention particuliere. Conclusion Il a ete demontre que l’orthodontie joue un role important pour resoudre des problemes occlusaux et modifier la dimension verticale. D’un autre cote, la kinesitherapie s’est averee efficace dans la gestion et l’amelioration de l’intensite de la douleur, lorsque les changements musculosquelettiques sont clairement constates. Enfin, il a egalement ete demontre qu’une approche pluridisciplinaire peut s’averer essentielle : le clinicien doit etre conscient de l’interet d’une evaluation globale, prenant en compte tous les facteurs associes, en particulier les facteurs psychologiques.

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

We report on near band edge and local defects emissions in Cd0·025Mg0·10Zn0·875O (CdMgZnO) nanoparticles (NPs) as a function of temperature, where a strong temperature-dependent near-infrared emission around 1.7 eV (~730 nm) has been observed. The NPs were synthesized by a modified sol-gel method and were annealed at 750 °C after growing. The crystallographic parameters have been determined by 2-dimensional synchrotron x-ray diffraction (XRD) and conventional XRD analysis, confirming their growth within the wurtzite phase with a preferred orientation along the (101) plane and an apparent crystallite size of 52.72 ± 0.18 nm. This apparent crystallite size is consistent with the nearly hexagonal particle shape (50.15 ± 0.38 nm) obtained from high resolution transmission electron microscopy. Valence Electron Energy Loss Spectroscopy (VEELS) has been conducted to gain information on the band structure and interband transitions. From the VEELS spectrum, an onset bandgap of 3.2 ± 0.3 eV was attributed to Cd/Mg co-doped ZnO. The temperature-dependent photoluminescence properties and enhancement of the optically active local defects emission have been analyzed.

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

Background Deep friction massage is one of several physiotherapy interventions suggested for the management of tendinopathy. Objectives To determine the prevalence of deep friction massage use in clinical practice, to characterize the application parameters used by physiotherapists, and to identify empirical model-based patterns of deep friction massage application in degenerative tendinopathy. Design observational, analytical, cross-sectional and national web-based survey. Methods 478 physiotherapists were selected through snow-ball sampling method. The participants completed an online questionnaire about personal and professional characteristics as well as specific questions regarding the use of deep friction massage. Characterization of deep friction massage parameters used by physiotherapists were presented as counts and proportions. Latent class analysis was used to identify the empirical model-based patterns. Crude and adjusted odds ratios and 95% confidence intervals were computed. Results The use of deep friction massage was reported by 88.1% of the participants; tendinopathy was the clinical condition where it was most frequently used (84.9%) and, from these, 55.9% reported its use in degenerative tendinopathy. The "duration of application" parameters in chronic phase and "frequency of application" in acute and chronic phases are those that diverge most from those recommended by the author of deep friction massage. Conclusion We found a high prevalence of deep friction massage use, namely in degenerative tendinopathy. Our results have shown that the application parameters are heterogeneous and diverse. This is reflected by the identification of two application patterns, although none is in complete agreement with Cyriax's description.

Recently it has been shown that folic acid can have an important role in bone regeneration. For this reason, combining a classic bone regeneration system as, hydroxyapatite, loaded with folic acid, may be an important issue to be developed. To address this issue, hydroxyapatite nanoparticles loaded with folic acid were designed as an effective bone regenerative system, to induce osteoblast differentiation and improve the bone regeneration. HapNP were prepared by a hydrothermal method that used citric acid as a tailoring agent of particles morphology and, simultaneously, had the particularly to let carboxylic pendant groups in the particle surface, which provided a platform for the immobilization of folic acid (FA), producing HapNP-FA. A comparative study among hydroxyapatite nanoparticles loaded and unloaded with folic acid in presence of human mesenchymal stem cells was performed. The results demonstrate, that nanoparticles were able to be internalized by human mesenchymal stem cells. In addition, cell proliferation and viability were not affected in a wide concentration range. Both particles induced the expression of Runx2 and the expression and activity of alkaline phosphatase. However, HapNP-FA caused a significantly higher overexpression of Runx2. The osteoblastic differentiation confirms the potential applicability of HapNP-FA in the local bone regeneration.

Background: Immune-related adverse events (IRAE) represent a challenge, potentially limiting the clinical benefits of immune check point inhibitors therapy (ICI). Aim: To evaluate the prevalence and identified potential predictive factors (PF) of IRAE in clinical practice. Methods: We retrospectively identified thoracic tumors patients (pts) treated with ICI between 2016-2018. The type and severity of IRAE, as well as potential PF were collected. Biserial’s correlation coefficient was applied. Results: 44 pts were included (41 (93%) men, mean age at diagnosis of 65±10 years) who received at least one cycle of ICI. 26 pts (59%) were treated with Nivolumab, 16 pts (36%) with Pembrolizumab and 3 pts with Atezolizumab (1 switched from Nivolumab). 19 pts (43%) had IRAE, 3 pts had multiple IRAE. In most pts (74%), the IRAE were of severity grade 1 or 2. In 47% of pts the toxicity was controlled with supportive care and in 26% pts it was administered corticosteroid. In five (26%) of the pts experiencing IRAE, the ICI agent was permanently discontinue due to toxicity. The IRAE most commonly involved the skin (5pts), thyroid (5 pts) and gastrointestinal system (5 pts). Two pts had infusion reactions to nivolumab. The pts that had IRAE had Body Mass Index (BMI) higher than pts without IRAE (27±6 kg/m² vs 23±4 kg/m², p=0.037). No statistically significant association was observed between history of autoimmune disease or chronic infection, kidney function, specific medications and prevalence of IRAE. Conclusion: The prevalence of IRAE in our sample is similar to the reported in literature. Pts with higher BMI are more likely to experience IRAE. One potential explanation is pharmacokinetic changes induced by overweight.

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

Objectives Physical inactivity (PIn) and a fatty diet (FD) are closely linked to development of metabolic syndrome (MetS), overloading the endocrine pancreas seeking energy homeostasis. However, the relative contribution of FD and PIn to the pancreatic overload is unknown. The aim of this study was to verify the isolated and conjugated influence of FD and PIn in the islets of Langer hans (islets) structure and function related to overload in Wistar rats. Methods Male Wistar rats were divided into four groups (n = 10/group): active groups, fed with fat (AFD) or standard (ASD) diet; and physically inactive groups, fed with fat (SFD) or standard (SSD) diet for 21 wk. Glucose tolerance (GT) and insulin sensitivity (IS) were assessed before sacrifice. Retroperitoneal adipose tissue and pancreas were weighted (PW), and pancreas samples processed for histologic analyses. Results Only the FD-fed animals presented MS. Compared with standard diet, FD impaired GT and IS, decreased PW, and enlarged islets dimensions, with islets cellular death, inflammatory response, and enhanced collagen content, which were attenuated in AFD. Independent of the diet, PIn groups presented higher amounts of islets connective tissue, but without influence on inflammatory reaction and cellular death. The GT impairment was higher in the FD-fed groups, whereas the decreased IS was more pronounced in the PIn groups. Conclusion FD induced MS with detrimental effects on pancreas overload, inducing islets morphologic and functional maladaptation, which were attenuated in active animals. Physical activity was not able to prevent FD-induced MS. FD showed a negative influence on GT, whereas PIn mainly affected IS.

Context: Deep friction massage (DFM) is often used in the treatment of tendinopathies; however, the pressure applied may vary and interfere with the obtained results. Objective: To assess whether the immediate effects of DFM on pain (pain intensity and time to onset of analgesia) and muscle strength are dependent on the pressure applied during the DFM application in athletes with patellar tendinopathy. Design: Randomized, controlled, cross-over trial. Setting: University research laboratory (institutional). Participants: Ten athletes with diagnosis of unilateral patellar tendinopathy (age 27.90 [5.24] y). Interventions: All participants attended 4 sessions, 3 treatment sessions with DFM applied with different pressures (the mean pressure—previously determined for each participant—and the mean pressure ± 25%) and a control session, each of which was separated by 48 hours. Main Outcome Measures: Pain (intensity upon palpation and time to onset of analgesia), and muscle strength of knee extensors were assessed before and immediately after each session. Results: Pain intensity changed significantly over time (F1,9 = 52.364; P ) and among sessions (F3,27 = 82.588; P ), with a significant interaction for group × time (F3,27 = 19.841; P ). The knee extensors strength did not change significantly over time (F1,9 = 2.240; P = .17; ), nor a significant interaction for session × time was observed (F3,27 = 3.276; P = .07; ). Regardless of the pressure applied, the time to onset of analgesia was not significantly different (F2,18 = 1.026; P > .05; ). Conclusion: It was shown that DFM induces an immediate reduction in pain intensity upon palpation, regardless of the pressure performed. Notwithstanding, the reader should take into account the small sample size and the caution needed in the results’ interpretation.

Amanita phalloides is one of the most toxic mushrooms worldwide, and it is involved in the majority of human fatal cases of mushroom poisoning. α-Amanitin, the most deleterious toxin of A. phalloides to humans, inhibits RNA polymerase II (RNAPII), causing hepatic and renal failure. Previously, we have shown that polymyxin B (polB) reverts α-amanitin inhibition of RNAPII, although it was not able to guarantee the full survival of α-amanitin-intoxicated mice or prevent α-amanitin pro-inflammatory effects. α-Amanitin is also a substrate of the organic-anion-transporting polypeptide 1B3 (OATP1B3) and Na(+)-taurocholate cotransporter polypeptide (NTCP) transporters. Therefore, in the present work, we used a combination of polB [(2.5 mg/kg intraperitoneal (i.p.)] with the anti-inflammatory and NTCP inhibitor drug, methylprednisolone (MP) (10 mg/kg i.p.), as an attempt to fully revert α-amanitin-induced toxicity (0.33 mg/kg i.p.) in CD-1 mice. Results showed that the administration of the polB + MP combination, 4 h after α-amanitin, led to the full survival of the intoxicated animals, with a significant attenuation of α-amanitin-induced renal and hepatic necrosis. Also, the combination polB + MP led to a decrease of aminotransferase plasma levels, of the renal myeloperoxidase activity and of renal inflammatory cell infiltrate promoted by α-amanitin, although not preventing any of the hepatic pro-inflammatory effect of the toxin. The obtained results indicate that this combination may represent an important and valuable therapeutic approach to be used against α-amanitin intoxication.

Kitchen workers are more prone to be injured due to slips and falls, being the floor surface contamination often the cause of slip accidents. The aim of the present study is the identification of the most efficient solutions to prevent the risk of slipping in kitchens. According to PRISMA statement guidelines, a short review was performed on 15 databases with 28 combinations of keywords. A total of 10 studies were considered eligible and were included in this study. The use of objective and subjective measures to assess floor slipperiness can help to identify and to evaluate workplace slip and fall hazards. Slipperiness causes and workers’ perception should be taken into consideration to identify slipping hazards and develop different solutions based on the various functional areas. The establishment of measures to better control floor surface contamination, the reduction in transient exposures such as rushing, distraction and walking on a contaminated floor, the use of slip-resistant shoes and the identification of floor cleaning procedure may reduce the incidence of slipping and the risk of slipping in kitchens.

Mitoxantrone (MTX) is a pharmaceutical drug used in the treatment of several cancers and refractory multiple sclerosis (MS). Despite its therapeutic value, adverse effects may be severe, namely the frequently reported cardiotoxicity, whose mechanisms need further research. This work aimed to assess if inflammation or oxidative stress-related pathways participate in the cardiotoxicity of MTX, using the mouse as an animal model, at two different age periods (infant or adult mice) using two therapeutic relevant cumulative doses. Histopathology findings showed that MTX caused higher cardiac toxicity in adults. In MTX-treated adults, at the highest dose, noradrenaline cardiac levels decreased, whereas at the lowest cumulative dose, protein carbonylation increased and the expression of nuclear factor kappa B (NF-κB) p65 subunit and of M1 macrophage marker increased. Moreover, MTX-treated adult mice had enhanced expression of NF-κB p52 and tumour necrosis factor (TNF-α), while decreasing interleukin-6 (IL-6). Moreover, while catalase expression significantly increased in both adult and infant mice treated with the lowest MTX cumulative dose, the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glutathione peroxidase only significantly increased in infant animals. Nevertheless, the ratio of GAPDH to ATP synthase subunit beta decreased in adult animals. In conclusion, clinically relevant doses of MTX caused dissimilar responses in adult and infant mice, being that inflammation may be an important trigger to MTX-induced cardiotoxicity.

Aims Well-characterized animal tumor models of cancer cachexia are warranted to elucidate underlying mechanisms and provide a better approach to the human scenario. We aimed to investigate whether solid Ehrlich carcinoma reproduces clinical, functional and biological conditions of tumor-induced cachexia in mice. Methods Eight-week old female Swiss mice were subcutaneously inoculated with Ehrlich tumor cells (tumor-bearing, TB group) or vehicle (sham) into the right flank and monitored for 28 days. Tumor histopathological features and tumor–host interaction, including tissue weight, muscle structure, strength and biochemical parameters were carried out. Key findings Tumor growth curve demonstrated a linear pattern with no difference in final carcass weight between groups. A well-defined capsule composed by connective tissue infiltrated by inflammatory and neoplastic cells surrounded the tumors. The TB group had reduced handgrip strength, aside from lower cross sectional area (CSA) and critically reduced parametrial fat pads. Plasma parameters of lactate dehydrogenase (LDH), creatine kinase (CK) and tumor necrosis factor-α (TNF-α) were higher in the TB group, suggesting predominance of catabolic and pro-inflammatory activities. Conversely, food intake and tissue weight did not differ between groups. Significance Our data elucidated that the solid Ehrlich tumor model is feasible and effective in reproducing some of the relevant issues experienced by cancer patients with cachexia. The solid Ehrlich carcinoma emerges as an alternative tool against more aggressive cancer cachexia models during preclinical research.

Doxorubicin (DOX) is used in pediatric cancer treatment. This study assessed the effects of 7 weeks of DOX and 10-week recovery on bone quality and biomechanical properties in sedentary and exercised Wistar rats. DOX decreases femur diaphysis radial growth and biomechanical properties. Some of these DOX effects were aggravated by exercise.Bone growth in pre-pubertal years critically influences adult fracture risk. DOX is widely used in the treatment of pediatric cancers, but there is limited evidence on its potential negative effects on bone growth. Exercise improves bone growth in children, but there is no evidence if it protects against DOX-induced bone toxicity. This study investigates the early and intermediate effects of a 7-week course of DOX on bone histomorphometry and strength in sedentary and exercised growing animal models.Sixty-eight male Wistar rats (8 weeks) were treated with DOX (2 mg kgDOX treatment reduced the femur diaphysis radial growth, with DOX-treated animals having a lower tissue area, cortical area, cortical thickness, and moment of inertia. DOX also decreased distal femur trabecular bone volume and trabecular number and increased trabecular separation. Femur diaphysis stiffness and maximum load were also reduced in past DOX-treated animals. Exercise was shown to worsen the effects of past DOX treatment on the femur diaphysis mechanical properties.DOX negatively affects bone geometry, trabecular microarchitecture, and femur mechanical properties in growing Wistar rats. Exercise further aggravates the detrimental effects of past DOX treatment on bone mechanical properties.

Knowledge is an important factor in patients with ankylosing spondylitis regarding the adoption of appropriate behaviours and education. The aim of this study was to culturally adapt and validate "The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire" for the Portuguese population with ankylosing spondylitis. The Portuguese version of "The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire" was administered to a sample of 180 subjects, from which 63 individuals responded. The adaptation process involved translation, back-translation and submission to a committee of experts in the area, culminating with a Portuguese version of the instrument. Next, the scale reliability and validity were assessed. There was a statistically significant decrease from test to retest, although the intra-class correlation coefficient between test and retest was 0.76 (95 % CI 0.61-0.86), which was considered good. From 180 individuals, 63 (35.0 %) subjects were available for the present study. The proportion of individuals that correctly answered each item ranged from 19 to 92 %, corresponding to items 8 and 13, respectively. The mean number of correct answers was 8.5 [mean (SD) = 2.4] in 12 questions. The proposed Portuguese version of the ankylosing spondylitis knowledge scale showed good reliability, reproducibility and construct validity.

Background Exercise training has been recognized as a non-pharmacological therapeutic approach in several chronic diseases; however it remains to be tested if exercise preconditioning can positively interfere with the natural history of pulmonary arterial hypertension (PAH). This is important since the majority of these patients are diagnosed at advanced stages of the disease, when right ventricle (RV) impairment is already present. Objectives In the current study, we evaluated the preventive effect of exercise preconditioning on RV failure secondary to PAH, with a focus on the signaling pathways modulated by pro-inflammatory cytokines from TNF superfamily. Methods We analyzed the RV muscle from adult male Wistar rats exposed to a 4-week treadmill exercise training or sedentary regime, prior to the administration of monocrotaline (MCT) to induce PAH or with saline solution (controls). Results Data indicate that exercise preconditioning prevented cardiac hypertrophy and RV diastolic dysfunction. At a molecular level, exercise modulated the TWEAK/NF-κB signaling axis and prevented the shift in MHC isoforms towards an increased expression of beta-MHC. Exercise preconditioning also prevented the increase of atrogin-1 expression, and induced a shift of MMP activity from MMP-9 to MMP-2 activity. Conclusions Altogether, data support exercise as a preventive strategy for the management of PAH, which is of particular relevance for the familial form of PAH that is manifested by greater severity or earlier onset.

The growth of CdxMg0.125-xZn0.875O nanoparticles with yellow-orange luminescence is achieved up to 2.5 at. % Cd via a modified sol–gel process. X-ray diffraction analysis confirmed that all the nanoparticles have the hexagonal wurtzite structure. It is found that Cd doping has a considerable effect on the crystal size, microstrain, band gap, and photoluminescence of the Mg0·125Zn0·875O structure, originating from a preferred crystallographic orientation along the (101) plane of the wurtzite structure. The shift and broadening of the E2(high) mode observed in the Raman spectra due to growth-induced strain corroborates the small distortion observed in the X-ray diffraction data. The optical band gap varies from 3.21 eV to 2.74 eV, being redshifted with increasing Cd concentration (from 0 at. % to 2.5 at. %). The photoluminescence obtained with an excitation wavelength of 325 nm has a broad yellow-orange emission peak at around 640 nm due to transitions related to oxygen vacancies and interstitial oxygen atoms. We located the yellow-orange emission in the chromaticity coordinate diagram in the 2683–2777 K colour temperature region, demonstrating that CdxMg0.125-xZnO0.875 nanoparticles have potential applications in white light-emitting diodes.

Background: Despite pulmonary arterial hypertension (PAH) directly affects the right ventricle (RV), important structural, functional, and molecular changes also occur in left ventricle (LV). The objective of our study was to analyze the hypothetical cardioprotective effects of exercise preconditioning on LV in rats with monocrotaline (MCT)-induced PAH. Methods: Forty male Wistar rats were randomly separated in sedentary (SED) and trained group (EX; running sessions of 60 min/day, 5 days/wk, at 25 m/min, for 4 weeks). After 4 weeks, animals were injected with MCT (60 mg/kg; SED + MCT; EX + MCT) or vehicle (SED + V). Following an additional period of 4 weeks where all animals remained sedentary, we completed LV hemodynamic evaluation in baseline and isovolumic conditions and collected LV samples for histological and molecular analysis. Results: Preconditioning with exercise was capable to restore LV systolic and diastolic dysfunction in both baseline and isovolumic conditions (P < .05). This improved was paralleled with prevention of LV cardiomyocytes atrophy, fibrosis, and endothelin 1 mRNA levels (P < .05). Conclusions: Our findings suggest that exercise preconditioning can prevent LV dysfunction secondary to MCT-induced PAH, which is of particular interest for the familial form of the disease that is manifested by greater severity or earlier onset. info:eu-repo/semantics/publishedVersion

Repeated bouts of endurance exercise promotes numerous biochemical adaptations in skeletal muscle fibers resulting in a muscle phenotype that is protected against a variety of homeostatic challenges; these exercise-induced changes in muscle phenotype are often referred to as "exercise preconditioning." Importantly, exercise preconditioning provides protection against several threats to skeletal muscle health including cancer chemotherapy (e.g., doxorubicin) and prolonged muscle inactivity. This review summarizes our current understanding of the mechanisms responsible for exercise-induced protection of skeletal muscle fibers against both doxorubicin-induced muscle wasting and a unique form of inactivity-induced muscle atrophy (i.e., ventilator-induced diaphragm atrophy). Specifically, the first section of this article will highlight the potential mechanisms responsible for exercise-induced protection of skeletal muscle fibers against doxorubicin-induced fiber atrophy. The second segment will discuss the biochemical changes that are responsible for endurance exercise-mediated protection of diaphragm muscle against ventilator-induced diaphragm wasting. In each section, we highlight gaps in our knowledge in hopes of stimulating future research in this evolving field of investigation.

Objective – Update the last known umbrella review and summarize the available high-quality evidence from systematic reviews on the effectiveness of non-pharmacological and non-surgical interventions for patients with knee OA. Methods – The systematic reviews were identified thought electronic databases such as, MEDLINE, Embase, Physiotherapy Evidence Database (PEDro), The Cochrane Library, SciELo, Science Direct, Google Scholar, Research Gate and B-ON. The studies selection respected the following terms to guide the search strategy using the P (humans with knee osteoarthritis) I (non-pharmacological and non-surgical treatments) C (pharmacological, surgical, placebo, no intervention, or other non-pharmacological/ non-surgical conservative treatments) O (pain, functional status, stiffness, inflammation, quality of life and patient global assessment) model. Results – Following the PRISMA statement, 41 systematic reviews were found on the electronic databases that could be included in the umbrella review. After methodical analysis (R-AMSTAR), only 35 had sufficient quality to be included. There is gold evidence that Standard Exercise programs can reduce pain and improve physical function in patients with knee OA. Additionally, there is silver evidence for Acupuncture, Aquatic Exercise, Electroacupuncture, Interferential Current, Kinesio Taping, Manual Therapy, Moxibustion, Pulsed Electromagnetic Fields, Tai Chi, Ultrasound, Yoga, and Whole-Body Vibration. For other interventions, the quality of evidence is low or did not show sufficient efficacy from the systematic reviews to support their use. Conclusion – Comparing to last known umbrella review, similar results were achieved on Acupuncture and Exercise interventions to improve the patients’ pain, stiffness, function and quality of life, but it was found different results regarding the utilization of Transcutaneous Electrical Nerve Stimulation and Low-Level Laser Therapy as they do not improved the patients’ pain and physical function.

The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats. Wistar rats were randomly assigned into three groups (n = 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals’ weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin–proteasome pathways were also evaluated using real-time PCR and immunoblotting. The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy. Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis.