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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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

Background Vascular homeostasis is ensured by a dynamic interplay involving the endothelium, the platelets and the coagulation system. Thus, the vascular safety of particulate materials must address this integrated system, an approach that has been largely neglected. This work analysed the effects of commercial hydroxyapatite (HA) particles in blood compatibility and in endothelial cell behavior, due to their clinical relevance and scarcity of data on their vascular biosafety. Results Particles with similar chemical composition and distinct size and morphology were tested, i.e. rod-like, nano dimensions and low aspect ratio (HAp1) and needle-shape with wider size and aspect ratio (HAp2). HAp1 and HAp2, at 1 to 10 mg/mL, did not affect haemolysis, platelet adhesion, aggregation and activation, or the coagulation system (intrinsic and extrinsic pathways), although HAp2 exhibited a slight thrombogenic potential at 10 mg/mL. Notwithstanding, significantly lower levels presented dose-dependent toxicity on endothelial cells’ behavior. HAp1 and HAp2 decreased cell viability at levels ≥ 250 and ≥ 50 μg/mL, respectively. At 10 and 50 μg/mL, HAp1 did not interfere with the F-actin cytoskeleton, apoptotic index, cell cycle progression, expression of vWF, VECad and CD31, and the ability to form a network of tubular-like structures. Comparatively, HAp2 caused dose-dependent toxic effects in these parameters in the same concentration range. Conclusion The most relevant observation is the great discrepancy of HA particles’ levels that interfere with the routine blood compatibility assays and the endothelial cell behavior. Further, this difference was also found to be dependent on the particles’ size, morphology and aspect ratio, emphasizing the need of a complementary biological characterization, taking into consideration the endothelial cells’ functionality, to establish the vascular safety of particulate HA.

Summary Introduction Temporomandibular disorders (TMDs) present several risks and different contributing factors with consequently diverse treatment approaches. It is important to recognize what patients’ characteristics may benefit from orthodontics, from physiotherapy, from other treatment modalities or even from a combined approach. Cases presentation We present three cases of patients with common TMDs signs and/or symptoms and different treatment approaches and outcomes, and our aim is to understand what might explain the different outcomes observed and also provide a rationale about the skeletal, muscular, facial and occlusal characteristics that may be indicative of a particular intervention benefit. Conclusion It has been shown that orthodontics plays an important role solving occlusal problems as well as changes in the vertical dimension. On the other hand, physiotherapy was effective in pain management and range improvement, when musculoskeletal changes were clearly found. Finally, it has also been shown that a multidisciplinary approach may be crucial, and the clinician should be aware of a comprehensive assessment, valuing all the contributing factors, namely the psychological ones.

Iron oxide nanoparticles (ION) have great potential for an increasing number of medical and biological applications, particularly those focused on nervous system. Although ION seem to be biocompatible and present low toxicity, it is imperative to unveil the potential risk for the nervous system associated to their exposure, especially because current data on ION effects on human nervous cells are scarce. Thus, in the present study potential toxicity associated with silica-coated ION (S-ION) exposure was evaluated on human A172 glioblastoma cells. To this aim, a complete toxicological screening testing several exposure times (3 and 24 h), nanoparticle concentrations (5-100 μg/ml), and culture media (complete and serum-free) was performed to firstly assess S-ION effects at different levels, including cytotoxicity - lactate dehydrogenase assay, analysis of cell cycle and cell death production - and genotoxicity - H2AX phosphorylation assessment, comet assay, micronucleus test and DNA repair competence assay. Results obtained showed that S-ION exhibit certain cytotoxicity, especially in serum-free medium, related to cell cycle disruption and cell death induction. However, scarce genotoxic effects and no alteration of the DNA repair process were observed. Results obtained in this work contribute to increase the knowledge on the impact of ION on the human nervous system cells. This work was funded by Xunta de Galicia (ED431B 2016/013). V. Valdiglesias was supported by a Xunta de Galicia postdoctoral fellowship (reference ED481B 2016/190-0). N. Fernández-Bertólez was supported by an INDITEX-UDC fellowship. F. Brandão is supported by the grant SFRH/BD/101060/2014, funded by FCT (financing subsided by national fund of MCTES). Authors would also like to acknowledge COST Action CA15132 “The comet assay as a human biomonitoring tool (hCOMET)” info:eu-repo/semantics/publishedVersion

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans., Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013.

This manuscript highlights and critically analyses clinical and forensic signs related to chemical burns. Signs that may lead to suspicion of a particular chemical are thoroughly discussed regarding its underlying mechanisms. Burns due to sulfuric, hydrofluoric, nitric, hydrochloric (muriatic) and acetic (including derivatives) acids, hydrogen sulphide, sodium (caustic soda) and calcium (cement) hydroxides, paraquat, burns after inflation and rupture of airbags, povidone-iodine, chlorhexidine/alcohol (in preterm infants), laxatives, and vesicants (warfare agents), will be reviewed since these are the most common agents found in daily practice, for which relevant and timed information may be helpful in formulating an emergency treatment protocols and toxicological analysis. Language: en

Current evidence points to a high prevalence of urinary incontinence among female athletes. In this context, this study aims to assess if structural and biomechanical characteristics of the pubovisceral muscles may lead to urine leakage. Clinical and demographic data were collected, as well as pelvic Magnetic Resonance Imaging. Furthermore, computational models were built to verify if they were able to reproduce similar biomechanical muscle response as the one measured by dynamic imaging during active contraction by means of the percent error. Compared to the continent ones (n=7), incontinent athletes (n=5) evidenced thicker pubovisceral muscles at the level of the midvagina (p=0.019 and p=0.028 for the right and left sides, respectively). However, there were no differences neither in the strength of contraction in the Oxford Scale or in the displacement of the pelvic floor muscles during simulation of voluntary contraction, which suggests that urine leakage may be related with alterations in the intrafusal fibers than just the result of thicker muscles. Additionally, we found similar values of displacement retrieved from dynamic images and numerical models (6.42 ± 0.36 mm vs. 6.10 ± 0.47 mm; p=0.130), with a percent error ranging from 1.47% to 17.20%. However, further refinements in the mechanical properties of the striated skeletal fibers of the pelvic floor muscles and the inclusion of pelvic organs, fascia and ligaments would reproduce more realistically the pelvic cavity.

The aim of this study was to investigate in young nulliparous female trampolinists the hypothetical associations between the level of athletic performance and the volume of training with urine leakage.Cross-sectional cohort study.Professional trampolinists.Twenty-two female athletes participating in a trampoline national championship were included in this study.The associations for player-related performance variables were evaluated using Spearman rank correlation and Kruskal-Wallis H test verified the differences between the tertiles.Rate of urinary incontinence (UI) among young athletes and the relationship with the athletic performance. Screening was performed through a questionnaire. This included the demographic sample characterization, the assessment of training volume, and the athletes' ranking in the championship. Additionally, it included the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-UI-SF) to assess the leakage.About 72.7% of the participants reported that they experienced urine leakage during trampoline practice and described that the episodes of leakage started after the beginning of the trampoline. Significant associations between the athletic performance and the training volume were observed with the severity of incontinence. Dividing the sample in tertiles of training volume, it was observed that the third tertile was the one with greatest impact of incontinence on their quality of life (ICIQ score).The results confirm a high frequency of UI in young trampolinists and reveal a clear identification of the athletes' ranking and the training volume as risk factors to develop and worsen urine loss.Special attention from team physicians and trainers is required for this athletes' problem that is often hidden by shame. In addition, female athletes practicing high-impact sports should be informed about the risk to develop pelvic floor muscles dysfunction and should be encouraged to seek help from health professionals to minimize or even eliminate the urine incontinence.

A 69-year-old caucasian male with a history of hypertension, dyslipidemia, obesity and tobacco use was admitted due to an inferior ST-segment elevation myocardial infarction with two hours evolution. He was treated with aspirin, clopidogrel and unfractioned heparin, and an emergent transradial coronary angiography was performed. Ectasic dilatation of left main, left anterior descending and circumflex arteries were documented, with distal TIMI 2 flow (Figure 1A). The dominant right coronary artery (RCA) was massively dilated proximally and occluded in the mid segment (Figure 1B). Figure 1 Percutaneous coronary intervention of RCA was attempted, using an AL 1 6 Fr catheter. Thrombus aspiration and balloon dilation of the mid/distal segments were performed, with distal flow recovery (TIMI 2) (Figure 1C). Given the massive ectasy, no stent was implanted. After five days of triple therapy (aspirin, clopidogrel and warfarin) a new coronariography was performed: intracoronary echocardiography revealed an ectasic RCA, with recanalyzed thrombus. The maximum diameter was 14 mm proximally and 8 mm in the middle segment, at the previous occlusion site (Figure 1D). The patient was managed conservatively with long-term anticoagulation. Giant coronary artery aneurysms (CAA) are rare and convey a risk of acute coronary syndromes, usually due to local thrombosis. In addition to antiplatelet therapy, anticoagulation is recommended, with surgical or percutaneous excision of CAA in patients with ischemia or a significant change in dimension over time. In this case, given the diffuse character of these lesions, this approach was unsuitable. In recurrent cases, the use of peripheral, self-expanding stents, may be considered. Video Watch the videos here: http://www.arquivosonline.com.br/2016/english/10703/video_ing.asp

Exercise training (ExT) is widely used for the prevention and treatment of several chronic cardiovascular diseases. However, only recently it started to be recognized as safe and beneficial in pulmonary arterial hypertension. Despite the consistency of its favorable effects on exercise tolerance and quality of life, the mechanisms underlying these meaningful clinical improvements remain unclear. Current studies emphasize the exercise-induced changes on skeletal muscle but the impact of ExT at the level of the pulmonary circulation and right ventricle should not be overlooked. In this chapter, we summarize the main findings from pre-clinical studies analyzing the impact of exercise in pulmonary hypertension and right heart failure.

Autophagy has an essential role in neuronal homeostasis and its dysregulation has been recently linked to neurotoxic effects of a growing list of psychoactive drugs, including amphetamines. However, the role of autophagy in β-keto amphetamine (β-KA) designer drugs-induced neurotoxicity has hitherto not been investigated. In the present study, we show that two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), elicit morphological changes consistent with autophagy and neurodegeneration, including formation of autophagic vacuoles and neurite retraction in dopaminergic SH-SY5Y cells. Methylone and MDPV prompted the formation of acidic vesicular organelles (AVOs) and lead to increased expression of the autophagy-associated protein LC3-II in a concentration- and time-dependent manner. Electron microscopy confirmed the presence of autophagosomes with typical double membranes and autolysosomes in cells exposed to both β-KA. The autophagic flux was further confirmed using bafilomycin A1, a known inhibitor of the late phase of autophagy. Moreover, we showed that autophagy markers were activated before the triggering of cell death and caspase 3 activation, suggesting that β-KA-induced autophagy precedes apoptotic cell death. To address the role of oxidative stress in autophagy induction, we also investigated the effects of antioxidant treatment with N-acetyl-l-cysteine (NAC) on autophagy and apoptotic markers altered by these drugs. NAC significantly attenuated methylone- and MDPV-induced cell death by completely inhibiting the generation of reactive oxygen and nitrogen species, and hampering both apoptotic and autophagic activity, suggesting that oxidative stress plays an important role in mediating autophagy and apoptosis elicited by these drugs.

Alterations in muscle mitochondrial bioenergetics during cancer cachexia were previously suggested; however, the underlying mechanisms are not known. So, the goal of this study was to evaluate mitochondrial phospholipid remodeling in cancer-related muscle wasting and its repercussions to respiratory chain activity and fiber susceptibility to apoptosis. An animal model of urothelial carcinoma induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and characterized by significant body weight loss due to skeletal muscle mass decrease was used. Morphological evidences of muscle atrophy were associated to decreased respiratory chain activity and increased expression of mitochondrial UCP3, which altogether highlight the lower ability of wasted muscle to produce ATP. Lipidomic analysis of isolated mitochondria revealed a significant decrease of phosphatidic acid, phosphatidylglycerol and cardiolipin in BBN mitochondria, counteracted by increased phosphatidylcholine levels. Besides the impact on membrane fluidity, this phospholipid remodeling seems to justify, at least in part, the lower oxidative phosphorylation activity observed in mitochondria from wasted muscle and their increased susceptibility to apoptosis. Curiously, no evidences of lipid peroxidation were observed but proteins from BBN mitochondria, particularly the metabolic ones, seem more prone to carbonylation with the consequent implications in mitochondria functionality. Overall, data suggest that bladder cancer negatively impacts skeletal muscle activity specifically by affecting mitochondrial phospholipid dynamics and its interaction with proteins, ultimately leading to the dysfunction of this organelle. The regulation of phospholipid biosynthetic pathways might be seen as potential therapeutic targets for the management of cancer-related muscle wasting.

Cardiac cachexia (CC) affects a large proportion of patients with chronic heart failure, a major public health issue in western countries. The pathophysiology of CC is complex and multifactorial, resulting from several factors interacting in a complex system with metabolic, immune and neurohormonal consequences, triggered to protect the heart and the circulation from damage. Despite the adverse clinical effects, CC diagnosis is not straightforward and has not specifically been targeted, with therapeutic strategies only comprising interventions with appetite stimulants, and anti-inflammatory substances. Here we review the molecular pathways underlying CC-related muscle wasting aiming to provide clues for the definition of CC-specific biomarkers and for the development of drugs that prevent and/or counteract muscle impairment, which will certainly impact the management of cardiovascular disorders.

The heart is a target organ for oxidative stress-related injuries. Because of its very high energetic metabolic demand, the heart has the highest rate of production of reactive oxygen species, namely, hydrogen peroxide (H2O2), per gram of tissue. Additionally, the heart has lower levels of antioxidants and total activity of antioxidant enzymes when compared to other organs. Furthermore, drugs that have relevant antioxidant activity and that are used in the treatment of oxidative stress related cardiac diseases demonstrate better clinical cardiac outcomes than other drugs with similar receptor affinity but with no antioxidant activity. Several xenobiotics particularly target the heart and promote toxicity. Anticancer drugs, like anthracyclines, cyclophosphamide, mitoxantrone, and more recently tyrosine kinase targeting drugs, are well-known cardiac toxicants whose therapeutic application has been associated to a high prevalence of heart failure. High levels of catecholamines or drugs of abuse, namely, amphetamines, cocaine, and even the consumption of alcohol for long periods of time, are linked to cardiovascular abnormalities. Oxidative stress may be one common link for the cardiac toxicity elicited by these compounds. We aim to revise the mechanisms involved in cardiac lesions caused by the above-mentioned substances specially focusing in oxidative stress related pathways. Oxidative stress biomarkers can be useful in the early recognition of cardiotoxicity in patients treated with these drugs and aid to minimize the setting of cardiac irreversible events.

Cardiovascular diseases (CVD) are a global epidemic in developed countries. Cumulative evidence suggests that myocyte formation is preserved during postnatal life, in adulthood or senescence, suggesting the existence of a growth reserve of the heart throughout lifespan. Several medical therapeutic approaches to CVD have considerably improved the clinical outcome for patients. Intense interest has been focused on regenerative medicine as an emerging strategy for CVD. Cellular therapeutic approaches have been proposed for enhancing survival and propagation of stem cells in myocardium, leading to cardiac cellular repair. Strong epidemiological and clinical data exists concerning the impact of regular physical exercise on cardiovascular health. Several mechanisms of acute and chronic exercise-induced cardiovascular adaptations to exercise have been presented, considering primary and secondary prevention of CVD. In this context, exercise-related improvements in the function and regeneration of the cardiovascular system may be associated with the exercise-induced activation, mobilization, differentiation, and homing of stem and progenitor cells. In this review several topics will be addressed concerning the relation between exercise, recruitment and biological activity of blood-circulating progenitor cells and resident cardiac stem cells. We hypothesize that exercise-induced stem cell activation may enhance overall heart function and improve the efficacy of cardiac cellular therapeutic protocols.

Objective “Krokodil” is the street name for an impure homemade drug mixture used as a cheap substitute for heroin, containing desomorphine as the main opioid. Abscesses, gangrene, thrombophlebitis, limb ulceration and amputations, jaw osteonecrosis, skin discoloration, ulcers, skin infections, and bleeding are some of the typical reported signs in humans. This study aimed to understand the toxicity of krokodil using Wistar male rats as experimental model. Methods Animals were divided into seven groups and exposed subcutaneously to NaCl 0.9% (control), krokodil mixture free of psychotropic substances (blank krokodil), pharmaceutical grade desomorphine 1 mg/kg, and four different concentrations of krokodil (containing 0.125, 0.25, 0.5, and 1 mg/kg of desomorphine) synthesized accordingly to a “domestic” protocol followed by people who inject krokodil (PWIK). Daily injections for five consecutive days were performed, and animals were sacrificed 24 hr after the last administration. Biochemical and histological analysis were carried out. Results It was shown that the continuous use of krokodil may cause injury at the injection area, with formation of necrotic zones. The biochemical results evidenced alterations on cardiac and renal biomarkers of toxicity, namely, creatine kinase, creatine kinase-MB, and uric acid. Significant alteration in levels of reduced and oxidized glutathione on kidney and heart suggested that oxidative stress may be involved in krokodil-mediated toxicity. Cardiac congestion was the most relevant finding of continuous krokodil administration. Conclusions These findings contribute notably to comprehension of the local and systemic toxicological impact of this complex drug mixture on major organs and will hopefully be useful for the development of appropriate treatment strategies towards the human toxicological effects of krokodil.

Conclusions The results provide preliminary evidence that corticosteroids were not effective in all grades of dysfunction and for achieving a rapid remission in the early phase of BP, highlighting the need to define standard and rigorous criteria to prescribe corticosteroids in these patients. Objectives The main aim of this study was to investigate whether the use of corticosteroids better associated than paralleled with neuromuscular training (C + FNT) is more effective than facial neuromuscular training (FNT) applied alone, in terms of recovery degree and facial symmetry during the early phase of Bell's palsy (BP). Patients and methods A prospective single-blinded study involved 73 patients: the C + FNT group (n = 42; median age = 37.5 years) and FNT group (n = 31; median age = 49.0 years). Patients were assessed before and 6 weeks after treatment by House-Brackmann (HB-FGS) and Sunnybrook Facial Grading System (SB-FGS). Results Recovery degree and facial symmetry improved significantly in both groups (p 0.001), without differences between groups (p 0.05). However, the C + FNT group displayed better outcomes for cheek (p = 0.004) and mouth (p = 0.022) resting symmetry at SB-FGS, instead of compared to the FNT group. The corticosteroids had no significant effect on all recovery degrees (p = 0.992) and rapid remission (p = 0.952). Multiple linear regression analysis showed that the type of intervention was not a significant predictor for recovery degree (p = 0.917).

Introduction: Heart rate recovery, defined as the fall in heart rate during the first minute after exercise, is an indicator of autonomic function, and has been found to be an independent predictor of mortality after acute myocardial infarction. Exercise training has several well-known benefits in terms of cardiorespiratory fitness, modifiable cardiovascular risk factors and prognosis after acute coronary events. However, there are no randomized controlled studies in the literature evaluating the effects of exercise training per se, controlling for changes in medication and diet, on heart rate recovery. Thus, this study aims to assess the effects of exercise training on autonomic function in coronary artery disease patients recovering from acute myocardial infarction. Methods: Thirty-eight patients following a first acute myocardial infarction participated in this prospective randomized clinical trial. Patients were randomized into two groups: exercise training or control. The exercise group participated in an 8-week aerobic exercise program, while the control received standard medical care and follow-up. Changes in hemodynamics at rest and at peak exercise (heart rate, systolic and diastolic blood pressure, and rate pressure product), dietary intake, cardiorespiratory fitness, and heart rate recovery were assessed. Results: Medication and diet remained unchanged in both groups during the study period. The exercise-training group improved resting hemodynamics, particularly resting heart rate (from 68.0 ± 9.2 to 62.6 ± 8.7 bpm, p = 0.030) and systolic blood pressure (from 135 ± 7.1 to 125.6 ± 11.3 mmHg, p = 0.012), cardiorespiratory fitness (from 30.8 ± 7.8 to 33.9 ± 8.3 ml/min/kg, p = 0.016), and heart rate recovery (from 20 ± 6 to 24 ±5 bpm, p = 0.007). No significant changes were observed in the control group. Conclusions: Exercise training improved autonomic function, assessed by heart rate recovery, resting heart rate and systolic blood pressure, in the absence of changes in diet or medication. Resumo: Introdução: A frequência cardíaca de recuperação, definida como a diminuição na frequência cardíaca durante o primeiro minuto após a cessação do exercício, é indicador da função autonómica e tem sido descrito como preditor independente de mortalidade após enfarte agudo do miocárdio. Os benefícios do exercício regular na capacidade cardiorrespiratória, nos factores de risco tradicionais modificáveis e no prognóstico após evento coronário agudo são bem conhecidos. Contudo, continua a faltar na literatura um estudo randomizado, controlado, avaliando os efeitos do exercício regular per se, controlando para alterações na medicação e dieta, na frequência cardíaca de recuperação. Desta forma, este estudo tem por objectivo avaliar o efeito de um programa de exercício físico na função autonómica em doentes com doença coronária após enfarte agudo do miocárdio. Métodos: Participaram neste estudo prospectivo, randomizado, controlado 38 doentes após o primeiro enfarte agudo do miocárdio. Os doentes foram divididos em 2 grupos: grupo de exercício e grupo controlo. O grupo de exercício participou num programa de exercício aeróbio com 8 semanas de duração, enquanto o grupo controlo recebeu os cuidados e o seguimento médico habitual. Foram avaliadas as alterações nos parâmetros hemodinâmicos em repouso e no pico de exercício (frequência cardíaca, pressão arterial sistólica e diastólica e duplo produto), dieta, capacidade cardiorespiratória e frequência cardíaca de recuperação. Resultados: Durante o estudo a medicação e a dieta não sofreram alterações em ambos os grupos. O grupo de exercício melhorou os parâmetros hemodinâmicos em repouso, nomeadamente a frequência cardíaca (68.0 ± 9.2 para 62,6 ± 8,7 bpm, P = 0,030) e a pressão arterial sistólica (135 ± 7.1 para 125,6 ± 11.3 mmHg, P = 0,012), a capacidade cardiorespiratória (30,8 ± 7,8 para 33,9 ± 8,3 ml/min/kg, P = 0,016) e frequência cardíaca de recuperação (20 ± 6 para 24 ± 5 bpm, P = 0,007). Não se observaram diferenças significativas no grupo controlo. Conclusões: O programa de exercício físico melhorou a função autonómica, avaliada através da frequência cardíaca de recuperação, a frequência cardíaca e a pressão arterial de repouso mesmo na ausência de alterações na dieta e na medicação. Keywords: Heart rate recovery, Coronary artery disease, Cardiac rehabilitation, Diet, Exercise training, Palavras-chave: Frequência cardíaca de recuperação, Doença das artérias coronárias, Reabilitação cardíaca, Dieta, Exercício

The pharmacological action of salicylates has been historically related to their ability to inhibit cyclooxygenases, thereby blocking the synthesis of prostaglandins and thromboxane A2. On the other hand, several studies have suggested that salicylates have a multitude of cyclooxygenase-independent actions specially related with their antioxidant properties, which might contribute to the overall salutary effects of these compounds. Although salicylates are well-known antioxidants through their ability to scavenge hydroxyl radical, their antioxidant mechanisms of action have not been fully compiled and characterized. In this context, several mechanisms of action have been suggested, namely i) scavenging of hydroxyl radical and chelation of transition metals; ii) upregulation of nitric oxide; iii) increased synthesis of lipoxins; iv) inhibition of neutrophil oxidative burst; v) inhibition of NF-κB and AP-1 protein kinases; and vii) inhibiton of lectin-like oxidized LDL receptor-1. The newly discovered acetyl salicylic acid-triggered lipoxins probably play a key role in the maintenance of the oxidative stress balance. Furthermore, salicylates have shown to protect low-density lipoprotein from oxidation and elicit an inhibitory effect on the expression of lectin-like receptors on endothelial cells. This review aims to provide an overview of the various proposed antioxidant mechanisms of salicylates.

In recent years, there has been an increased interest in the study of saliva. This bodily fluid contains a vast number of protein species, the salivary peptidome, of low molecular weight, comprising approximately 40-50% of the total secreted proteins, in addition to peptides generated by proteolysis of proteins of different sources. Owing to the presence of other components, in particular mucins and enzymes, some distinctive requirements and precautions related to sample collection, time of analysis, sample preservation and treatment are necessary for the successful analysis of salivary peptides. More than 2000 peptides compose the salivary peptidome, from which only 400-600 are directly derived from salivary glands, suggesting an important qualitative peptide contribution of other sources, namely of epithelial cells. Proteolysis events are the main supply for the peptidome and considerable efforts have been made to identify the resulting fragments, the cleavage sites and the involved proteases. The salivary proteins more prone to proteolysis are proline-rich proteins (PRPs; acidic PRPs and basic PRPs), statherin, histatins and P-B peptide. Gln-Gly cleavages are largely associated with PRP classes, while Tyr-Gly cleavages are related to histatin 1 and to the P-B peptide. The interest in saliva has been growing for clinical purposes, as it is an alternative sample to other traditional bodily fluids, such as blood or urine, since it involves an easy and noninvasive collection. In fact, apart from its usefulness as a source of information for the prognosis, diagnosis and treatment of oral diseases, such as Sjögren's syndrome, gum disease, tooth decay or oral cancer, saliva might also be seen as a potential tool to the diagnosis of systemic diseases. Owing to the enormous amount of previously discovered salivary peptide species, in this article, we attempt to harmonize the nomenclature, following International Union of Pure and Applied Chemistry recommendations.

Proline-rich proteins (PRPs) are the most complex family of salivary peptides with distinct isoforms and PTMs. Up to date, only the serine phosphorylation at positions 8, 17, and 22 have been experimentally observed on acidic PRP (aPRPs), and at position 8 on basic PRP1 and 2. The presence of a glucoronyl group at Ser17 was also noticed on aPRP. The main goal of this study was to identify new PTMs and distinct isoforms of salivary PRPs using LC-MALDI-TOF/TOF. Through the salivary peptidome characterization of 20 different subjects from Control, Diabetic, and Head and Neck Cancer groups, it was possible to identify the following species: (i) N-glycosylation sites: two in basic proline-rich protein 2 (bPRP2), one in bPRP3 and one in bPRP4; (ii) O-glycosylation sites: two in bPRP2 and one in aPRP; (iii) other terminal monosaccharide sites: six in bPRP1, two in bPRP2 and two in bPRP3; (iv) other modifications such as N-terminal pyro-Glu (two in bPRP1, six in bPRP2, eight in bPRP3 and nine in bPRP4); (v) phosphorylation in serine, three in bPRP1, one in bPRP2, one in bPRP3 and one in aPRP1; (vi) bPRP1 (allele S, allele M and variant CP5) and bPRP4 (allele M). In summary, salivary peptidome data analysis allowed the identification of 45 new PRP-modified residues, mainly due to glycosylation, phosphorylation and conversion of Gln to pyro-Glu. Moreover, comparing all subject groups, it was noticed a predominance of N-acetyl hexosamine modification on bPRPs in the Head and Neck Cancer patients.

The use of targeted nanoparticles for magnetic hyperthermia (MHT) increases MHT selectivity, but often at the expense of its effectiveness. Consequently, targeted MHT is typically used in combination with other treatment modalities. This work describes an implementation of a highly effective monotherapeutic in vitro MHT treatment based on two populations of magnetic particles. Cells were sequentially incubated with two populations of magnetic particles: nonfunctionalized superparamagnetic nanoparticles and anti-CXCR4-functionalized particles. After removing the excess of free particles, an alternating magnetic field (AMF) was applied to produce MHT. The induced cytotoxicity was assessed at different time-points after AMF application. Complete loss of cell viability was observed 72 h after MHT when the iron loading of the anti-CXCR4-functionalized particles was boosted by that of a nontargeted population. Additionally, induction of necrosis resulted in more efficient cell death than did induction of apoptosis. Achieving a uniquely high effectiveness in monotherapeutic MHT demonstrates the potential of this approach to achieve complete loss of viability of cancer cells while avoiding the side effects of dual-treatment strategies that use MHT only as a sensitizing therapy.

Gene variants, such as creatine kinase (CK) polymorphisms, have been suggested to explain the inter-individual blood CK response to eccentric exercise. However, since this association is still doubtful, the purpose of this study was to analyse the relationship between the magnitudes of the CK response to exercise with the occurrence of muscle CK-MM NcoI polymorphism in young healthy subjects. Blood CK activity was assessed in 70 subjects immediately before and 3, 24, 48, 72, 96, 120, 168 h after strenuous eccentric exercise. Based on the amount of CK release by each subject, the sample was distributed in quartiles and the genotype and allele frequency distribution was compared among quartiles. Despite the inter-individual variability of CK response observed between subjects, there were no differences in genotype and allele frequencies among quartiles. The results allowed us to conclude that CK response after exhaustive eccentric exercise is not associated with CK-MM Ncol polymorphism.

Muscle contraction acutely increases glucose transport in both healthy and type 2 diabetic individuals. Since glucose uptake during muscle contraction has been observed in the absence of insulin, the existence of an insulin-independent pathway has been suggested to explain this phenomenon. However, the exact mechanism behind the translocation of GLUT4 vesicles through the sarcolemma during muscle contraction is still unknown. Some substances, such as AMPK and calcium activated proteins, have been suggested as potential mediators but the exact mechanisms of their involvement remain to be elucidated. A hypothetical convergence point between the insulin cascade and the potential pathways triggered by muscle contraction has been suggested. Therefore, the earliest concept that two different routes exist in skeletal muscle has been progressively modified to the notion that glucose uptake is induced by muscle contraction via components of the insulin pathway. With further consideration, increased glucose uptake and enhanced insulin sensitivity observed during/after exercise might be explained by a metabolic- and calcium-dependent activation of several intermediate molecules of the insulin cascade. This paper aimed to review the literature in order to examine in detail these concepts behind muscle contraction-induced glucose uptake.

In order to understand the role of thegluteus mediusmuscle (GM) in hip joint osteoarthritis, the objective of this study was to analyze the cor- relation between morphometric data of GM sam- ples with osteoarthritis scores of ipsilateral and contralateral hips in 41 patients. GM samples ob- tained during unilateral hip replacement surgery were used to evaluate muscle fibers in the cross- sectional area (CSA) and other features indicative for muscle aging. Clinical symptoms were as- sessed by the Lequesne pain score. Hip osteo- arthritis was graded by the Kellgren score and by measuring the sum joint space width (sumJSW) at three different articular locations and minimal JSW in a.p. radiographs. Varying degrees of GM muscle atrophy correlated with the pain score; pain score also correlated with radiographic signs of osteoarthritis. GM CSA was significantly correlated with all radiographic signs of the con- tralateral hip, but only with the sumJSW in the ipsilateral hip. It can be concluded that a weak GM may be the result of ipsilateral osteoarthitis, but may especially predispose the contralateral hip to develop osteoarthritis. This can be associ- ated with an impaired GM capacity to avoid the shock impact in the load transfer during gait. Muscle strengthening is therefore recommended. " hip osteoarthritis l " muscle histology l " muscle fiber area l " Kellgren index l " joint space width

It is known that coagulation and fibrinolysis are activated after exercise, and that the response is related to exercise intensity. The contribution, however, of eccentric exercise has not yet been investigated. Twenty boys (age 13 years) were randomly assigned to two experimental groups, which had to perform a monopedal stepping exercise until exhaustion. One group had to step up and down (U/D) in the same rhythm of one second each, while the other group (U/DD) had to step up during one second and to step down during two seconds, thereby experiencing a higher eccentric load. Blood samples were collected before and at 0, 1, and 24 hrs after exercise, and F VIII, t-PA, PAI-1, and D-dimer were determined as markers for coagulation or fibrinolysis, respectively. While the tendency for hypercoagulability was counterbalanced by fibrinolysis in the U/D group, the U/DD group showed a prothrombotic and hypofibrinolytic hemostatic response. It is assumed that eccentric exercise, beyond the well-known muscle fiber damage, also leads to some damage of the endothelial cells, affecting their capacity to liberate sufficient amounts of fibrinolytic agents.

Human acquired enamel pellicle is the result of a selective interaction of salivary proteins and peptides with the tooth surface. In the present work, the characterization of the peptides as well as the type of interactions established with the enamel surface was performed. Peptides from in vivo bovine enamel implants in the human oral cavity were sequentially extracted using guanidine and trifluoroacetic acid solutions and the fractions obtained were analysed by LC-MS and LC-MS/MS. Based on the LC-MS data, six phosphorylated peptides were identified in an intact form, strongly adsorbed to the enamel surface. Data from the LC-MS/MS analyses allowed us to identified 30 fragment peptides non-covalently bonded to enamel [basic proline-rich proteins, histatins (I and 3) and acidic proline-rich protein classes]. The tandem mass spectrometry experiments showed the existence of a pattern of amide bond cleavage for the different identified peptide classes suggesting a selective proteolytic activity. For histatins, a predominance of cleavage at Arg, Lys and His residues was observed, while for basic proline-rich proteins, cleavage at Arg and Pro residues prevailed. In the case of acidic proline-rich proteins, a clearly predominance of cleavage of the Gln-Gly amide bond was evident. Copyright (c) 2007 John Wiley & Sons, Ltd.