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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

Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis.

Bivariate calibration algorithm is compared with the results obtained by the usage of high-dimensional calibration methods such as partial least squares (PLS) and multi-way partial least-squares (N-PLS) by using UV-Vis spectrophotometric data of first and second-order. The algorithms were applied to the determination of a mixture of an analgesic and a stimulant compound and their actual concentrations of them were calculated by using spectroscopic data. The direct reading of absorbance values at 227 nm and 271 nm were employed for quantification of the compounds in the case of the bivariate method. The approaches of first-order and multi-way methods were applied with a previous optimization of the calibration matrix by constructing sets of calibration and validation with 20 and 10 samples (mixtures) respectively according to a central composite design and their UV absorption spectra were recorded at 200-350 nm. All algorithms were satisfactorily applied to the simultaneous determination of these compounds in pharmaceutical formulations with mean percentage recovery of 100.5 ± 3.67, 98.7 ± 3.42, and 100.5 ± 3.74 for bivariate, PLS-1, and N-PLS, respectively. The statistical evaluation of the bivariate method showed that this procedure is comparable with those algorithms that employ high-dimensional structured information. The aim of the work is to compare the methods under study and it can be seen that there are no significant differences, so a simple spectrophotometer can be used up to a very specialized one. However, the advantage of bivariate calibration is its simplicity, due to the minimal experimental manipulation.

Gold salts have been used to treat rheumatoid arthritis (RA) since the 1940s, and, with advances in nanotechnology, the use of nanogold provides multiple options for anti-inflammatory therapies. This paper presents the synthesis and characterization of silica-gold nanostructures (SGNs) and their therapeutic effect in collagen-induced arthritis (CIA) in DBA/1 mice. At the end of the treatment, the synovial membranes, kidneys, livers, and spleens were dissected and analyzed by inductively coupled plasma mass spectroscopy (ICP) showing less than 0.0001 and 0.1% of the administered doses of Au and Si, respectively. Remains of the SGNs were visually identified in the synovial membrane by scanning electron microscopy (SEM), and the bone density of the hind paws was observed by computerized tomography (CT) indicating a reduction of porosity in the CIA-experimental group. The DNA microarray analysis carried out with RNA obtained from the hind paws showed 2628 differentially expressed genes (DEGs) by SGNs. The bioinformatic analysis showed that DEGs were significantly associated with several inflammatory signalling pathways including chemokines, cytokine-cytokine receptor interaction, PI3K-Akt, TNF, IL-17, NFκβ, MAPK, and RA. SGNs downregulated relevant inflammatory genes in the arthritic joints, including Tnf, Ifng, Il6, and Cxcl5; immunohistochemistry (IHC) confirmed the reduction of TNFα, IL-6, NFκβ, and VEGF in the joints due to the effect of SGNs. TNFα and IL-6 were also reduced in the serum of DBA/1 mice treated with SGNs.

Most studies on the effects of physical exercise have focused on its influence on muscle tissue, forgetting its interference in liver function. Ageing leads to the progressive impairment of hepatic functions. Several biochemical and bioenergetics parameters were determined to test the impact of a lifelong aerobic training program in the hepatic age-related and the development of an adaptative response. Liver samples were collected from 28 male Wistar rats (4-week-old, 159.4 ± 11.9 g at the beginning of the protocol), randomly distributed into two groups: non-exercised or exercised and submitted to a treadmill exercise program (60 min/day, 5 days/week, at 70% of maximal running speed), for 24 (n = 9) or 54 weeks (n = 10). A maximal running speed test was performed to determine the training speed. Antioxidant enzyme activity, cellular redox status, oxidative stress, mitochondrial respiratory chain enzymes and respiratory activity were performed in liver samples. Lifelong exercise decreased the age-associated decline in mitochondrial dysfunction, increasing the respiratory rate in state 2 (mitochondrial respiration stimulated by the substrate in the absence of added ADP) (p = 0.03) and citrate synthase enzymatic activity (p = 0.007). Complex II (p < 0.0001) and IV (p < 0.001) showed a decrease in enzymatic activity. Ageing-related oxidative stress was also attenuated by physical exercise, as showed by the increase in first-line defense antioxidant enzymes (superoxide dismutase (p = 0.07) and catalase (p = 0.03)), decreased lipid peroxidation levels (p = 0.864 for total fraction, p = 0,27 for mitochondrial fraction) and higher glutathione reduced/oxidized ratio (p = 0.02). According to our results, the regular practice of exercise can prevent the liver’s mitochondrial dysfunction and loss of antioxidant system efficacy that may arise from ageing, highlighting the benefit of lifelong aerobic exercise in preventing age-related hepatic impairment and associated diseases.

The present review was conducted to determine the efficacy of high-voltage monophasic pulsed current (HVMPC) in treating diabetic ulcers, assess its effect on skin lesions with each of the pathophysiologic factors potentially contributing to diabetic ulcers, evaluate its safety, and identify treatment parameters. Electronic search of PubMed, Scopus, PEDro, and Google Scholar databases was conducted. The revised tool for assessing risk of bias in randomized trials (RoB 2), the risk of bias in non-randomized studies-of interventions (ROBINS-I), and the Joanna Briggs Institute (JBI) critical appraisal tool were used to assess risk of bias and methodological quality. Overall quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principles. Thirty-two studies matched the eligibility criteria, and included 1061 patients with 1103 skin lesions of selected etiologies; twelve randomized controlled trials were included in quantitative synthesis. HVMPC plus standard wound care (SWC) likely increased the probability of complete wound healing of pressure ulcers compared with sham/no stimulation plus SWC; relative risk (RR) 2.08; 95% CI: [1.42, 3.04], P=0.0002; I

A wealth of evidence supports an association between physical exercise, decreased tumor growth rate, and reduced risk of cancer mortality. In this context, the tumor vascular microenvironment may play a key role in modulating tumor biologic behavior. The present systematic review and meta-analysis aimed to summarize the evidence regarding the effects of physical exercise on tumor vasculature in pre-clinical studies. We performed a computerized research on the PubMed, Scopus, and EBSCO databases to identify pre-clinical studies that evaluated the effect of physical exercise on tumor vascular outcomes. Mean differences were calculated through a random effects model. The present systematic review included 13 studies involving 373 animals. From these, 11 studies evaluated chronic intratumoral vascular adaptations and 2 studies assessed the acute intratumoral vascular adaptations to physical exercise. The chronic intratumoral vascular adaptations resulted in higher tumor microvessel density in 4 studies, increased tumor perfusion in 2 studies, and reduced intratumoral hypoxia in 3 studies. Quantitatively, regular physical exercise induced an increased tumor vascularization of 2.13 [1.07, 3.20] (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.

Objective To summarize evidence in the last decade regarding the efficacy of physical therapy interventions to treat tendinopathy, as a single disease entity, as determined in systematic reviews (SRs) and/or meta-analyses (MAs). Methods Electronic search of PubMed, PEDro, and Scopus database was performed from year 2010 to January 2020. The methodological quality of the identified studies was assessed using the AMSTAR 2 tool. Studies scoring 9 points or higher were further analyzed using GRADE principles. Results 40 SRs and/or MAs were included in qualitative synthesis, whereas only 5 MAs were included in quantitative synthesis. Low-level laser therapy (LLLT) intervention showed a pooled improvement in pain reduction of 1.53 cm; 95% CI, [1.14, 1.91] (I2 = 1.9%, p = 0.361) on visual analogue scale, and grip strength of 9.59 kg; 95% CI, [5.90, 13.27]. Conclusions Moderate-quality evidence may support these following interventions: LLLT revealed a statistically and potentially clinically significant improvement in pain and function on the short-term. Extracorporeal shockwave therapy showed a statistically significant enhancement in pain and function at all follow-up durations; however, its clinical significance was undetermined. Eccentric exercise was supported by qualitative evidence only. Caution is advised when interpreting results due to possible pathological differences in tendinopathy at each region.

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors with high prevalence among adult populations and elevated costs for public health systems worldwide. Despite the lack of consensus regarding the syndrome definition and diagnosis criteria, it is characterized by the coexistence of risk factors such as abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, a prothrombotic and pro-inflammatory state, insulin resistance (IR), and higher glucose levels, factors indubitably linked to an increased risk of developing chronic conditions, such as type 2 diabetes (T2D) and cardiovascular disease (CVD). The syndrome has a complex and multifaceted origin not fully understood; however, it has been strongly suggested that sedentarism and unbalanced dietary patterns might play a fundamental role in its development. The purpose of this review is to provide an overview from the syndrome epidemiology, costs, and main etiological traits from its relationship with unhealthy diet patterns and sedentary lifestyles.

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.

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

Dear EditorsThe authors would like to thank Dr. Seet-Lee and colleagues for their comments on our recently-published manuscript in the International Journal of Sports Medicine 1. Dr. Seet-Lee and colleagues highlighted some inadequacies, specifically when using mean difference or raw mean difference as effect measure. However, when evaluating blood vessel density by different reliable and validated histological procedures, would it be wrong to assume, as we did, that all the obtained measurements from different staining always vary equally, directly and linearly, with the actual parameter under study? Are Dr. Seet-Lee and colleagues assuming that the results of histological observations of blood vessels, marked with different techniques and stains, are neither compatible nor governed by the same measurement scales? We regret, but we are firmly convinced that we proceeded properly. Moreover, we should not assume that standardized effect sizes will make comparisons meaningful 2. Particularly, as the standardized mean difference indicates the difference before and after the intervention in terms of standard deviations instead of actual scores, it assumes that different outcome scales are linear transformation of each other and the standard deviation (SD) is equal across all studies 3.

PurposeAlthough the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice.MethodsMale Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting.ResultsResistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia.ConclusionOur results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.

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.

Joint laxity should be distinguished from instability and its objective assessment is a determinant of safety and effectiveness clinical management of anterior cruciate ligament (ACL) tear and other often injured structures through injury mechanisms as knee sprains. Clinical evaluation is mandatory for all clinicians but requires the addition of medical devices for diagnosis or follow-up workflow objective assessment. Magnetic resonance imaging (MRI) instrumented-assessment of knee joint laxity combines the visual inspection of structural injury and multiplanar joint laxity quantification. The Porto knee Testing Device (PKTD) is an MRI-safe knee arthrometer that provides for accurate measurement of multiplanar joint laxity. Restoration of passive knee sagittal and transversal knee stability is the main objective of surgical interventions addressing ligaments reconstruction as ACL and pre- and post-operative measurements should be systematically performed and support precision orthopedic medicine.

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.

Study Design: Systematic review.Background: Existing systematic reviews and meta-analyses do not support a specific physical therapy treatment for lateral elbow tendinopathy (LET). The results of t...

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.

Nanoparticles of Cd x Mg 0.12 − x Zn 0.88 O ( 0 ≤ x ≤ 0.02 ) were synthesized by a simple sol gel route with the combination of chelating agents. Effect of cadmium on the phase, structural, morphological and optical properties of the synthesized nanoparticles has been studied and reported by using X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), Fourier transform infrared spectroscopy (FTIR) and UV–Vis diffuse reflectance spectroscopy (UV–vis DRS). The crystal size, lattice parameters, unit cell volume, X-ray density, inter-planar distances and bond length were obtained and analyzed from the XRD data. The X-ray analysis reveals the formation of a single phase with a hexagonal wurtzite structure, where an increase of the cell volume was achieved as the Cd content was increased as well. Synthesized nanoparticle were nearly spherical at nano-size regime and are loosely agglomerated as observed from the SEM analysis. EDX spectra of the composition confirmed the appropriate stoichiometric ratio. A fundamental absorption peak centered at 375 nm was observed from the UV–visible absorption spectra which shifted towards a higher wavelength correlating the narrowing of the energy band gap due to increase in Cd content. The structural adjustment from the IR spectra confirmed the stretching vibration of Zn–O in the Cd x Mg 0.12 − x Zn 0.88 O lattice with Cd content.

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.

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.

This study aims to determine if a dose&ndash, response relationship exists between the pressure applied during deep friction massage (DFM) and the time to the onset of analgesia in an asymptomatic patellar tendon. For this purpose, pressures applied by physiotherapists during DFM (study 1) were characterized and then, based on these pressures, the effects of different DFM pressures on the time to the onset of analgesia were assessed (study 2). First, the mean pressure applied by 40 physiotherapists during a DFM session was assessed with a pressure sensor through an observational, cross-sectional and analytical study. Next, the effects of different pressure intensities (the median, the percentile 25 (P25), and the percentile 75 (P75) of the mean pressure obtained in study 1) were studied in a crossover trial enrolling 30 participants with an asymptomatic patellar tendon. A pressure sensor was used to register the pressures applied during DFM. Our main results indicated that the physiotherapists applied pressures with a wide variation ((mean pressure: 2.317 kg/cm2 (P25: 1.022 kg/cm2, P75: 4.161 kg/cm2)). It was also shown that higher pressures had shorter times to the onset of analgesia (pressure: 1 kg/m2, time to the onset of analgesia: 67.0 s (P25: 84.5 s, P75: 113.5 s), pressure: 2.3 kg/m2, time to the onset of analgesia: 59.0 s (P25: 73.5 s, P75: 87.3 s), pressure: 4.2 kg/m2, time to the onset of analgesia: 37.8 s (P25: 54.0 s, P75: 62.0 s)) (p &le, 0.001). In conclusion, the mean DFM pressure obtained by the physiotherapists was 2.3 kg/cm2 (P25: 1.02 kg/cm2, P75: 4.16 kg/cm2). Higher pressures of DFM resulted in shorter times to the onset of analgesia.

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.

Background Intensive Care Unit (ICU) patients are known to lose muscle mass and function during ICU stay. Ultrasonography (US) application for the assessment of the skeletal muscle is a promising tool and might help detecting muscle changes and thus several dysfunctions during early stages of ICU stay. MUSiShock is a research project aiming to investigate structure and function of diaphragm and peripheral muscles using ultrasound techniques in septic shock patients, and to assess their relevance in several clinical outcomes such as the weaning process. Methods and design This is a research protocol from an observational prospective cohort study. We plan to assess eighty-four septic shock patients during their ICU stay at the following time-points: at 24 hours of ICU admission, then daily until day 5, then weekly, at extubation time and at ICU discharge. At each time-point, we will measure the quadriceps rectus femoris and diaphragm muscles, using innovative US muscle markers such as Shear-Wave Elastography (SWE). In parallel, the Medical Research Council (MRC) sum score for muscle testing and the Airway occlusion pressure (P0.1) will also be collected. We will describe the association between SWE assessment and other US markers for each muscle. The association between the changes in both diaphragm and rectus femoris US markers over time will be explored as well; finally, the analysis of a combined model of one diaphragm US marker and one limb muscle US marker to predict weaning success/failure will be tested. Discussion By using muscle ultrasound at both diaphragm and limb levels, MUSiShock aims to improve knowledge in the early detection of muscle dysfunction and weakness, and their relationship with muscle strength and MV weaning, in critically ill patients. A better anticipation of these short-term muscle structure and function outcomes may allow clinicians to rapidly implement measures to counteract it. Trial registration ClinicalTrials.gov, NCT04550143. Registered on 16 September 2020.

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.