Utilización de microhilos magnéticos para promover la muerte de células de osteosarcoma mediante hipertermia magnética in vitro

Los tratamientos para el cáncer que se llevan a cabo actualmente tienen una serie de limitaciones que, unido a que se trata de técnicas invasivas, hace que se tienda a buscar nuevas alternativas. Una de ellas es la hipertermia dirigida, cuyo objetivo son las células cancerígenas. Se trata de una técnica relativamente nueva, por lo que aún no se ha estudiado en profundidad. En este trabajo, se han utilizado microhilos magnéticos amorfos recubiertos de vidrio para calentar células de osteosarcoma aplicando un campo magnético alterno. De acuerdo con los resultados obtenidos de los ensayos realizados “in vitro”, se puede confirmar que la utilización de estos microhilos magnéticos reduce la proliferación de células cancerígenas dando lugar finalmente a la muerte celular. Además, esta técnica es un proceso mucho menos invasivo que los utilizados actualmente y que requiere exposiciones breves a campos magnéticos débiles. Por todo esto, la hipertermia dirigida se presenta como una alternativa efectiva para el tratamiento de osteosarcoma.Por último, agradecer a Tamag Ibérica S.L. por proporcionarnos los microhilos magnéticos para poder llevar a cabo este estudio y a Fomento de San Sebastián por financiar el proyecto de investigació

Haemoglobin mass and running time trial performance after recombinant human erythropoietin administration in trained men

<p>Recombinant human erythropoietin (rHuEpo) increases haemoglobin mass (Hbmass) and maximal oxygen uptake (v˙ O2 max).</p> <p>Purpose: This study defined the time course of changes in Hbmass, v˙ O2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field.</p> <p>Methods: 19 trained men received rHuEpo injections of 50 IUNkg21 body mass every two days for 4 weeks. Hbmass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. v˙ O2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study.</p> <p>Results: Relative to baseline, running performance significantly improved by ,6% after administration (10:3061:07 min:sec vs. 11:0861:15 min:sec, p,0.001) and remained significantly enhanced by ,3% 4 weeks after administration (10:4661:13 min:sec, p,0.001), while v˙ O2 max was also significantly increased post administration (60.765.8 mLNmin21Nkg21 vs. 56.066.2 mLNmin21Nkg21, p,0.001) and remained significantly increased 4 weeks after rHuEpo (58.065.6 mLNmin21Nkg21, p = 0.021). Hbmass was significantly increased at the end of administration compared to baseline (15.261.5 gNkg21 vs. 12.761.2 gNkg21, p,0.001). The rate of decrease in Hbmass toward baseline values post rHuEpo was similar to that of the increase during administration (20.53 gNkg21Nwk21, 95% confidence interval (CI) (20.68, 20.38) vs. 0.54 gNkg21Nwk21, CI (0.46, 0.63)) but Hbmass was still significantly elevated 4 weeks after administration compared to baseline (13.761.1 gNkg21, p<0.001).</p> <p>Conclusion: Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with rHuEpo-induced elevated v˙ O2 max and Hbmass.</p&gt

The interaction of aluminum with catecholamine-based neurotransmitters: Can the formation of these species be considered a potential risk factor for neurodegenerative diseases?

The potential neurotoxic role of Al(iii) and its proposed link with the insurgence of Alzheimer's Disease (AD) have attracted increasing interest towards the determination of the nature of bioligands that are propitious to interact with aluminum. Among them, catecholamine-based neurotransmitters have been proposed to be sensitive to the presence of this non-essential metal ion in the brain. In the present work, we characterize several aluminum-catecholamine complexes in various stoichiometries, determining their structure and thermodynamics of formation. For this purpose, we apply a recently validated computational protocol with results that show a remarkably good agreement with the available experimental data. In particular, we employ Density Functional Theory (DFT) in conjunction with continuum solvation models to calculate complexation energies of aluminum for a set of four important catecholamines: l-DOPA, dopamine, noradrenaline and adrenaline. In addition, by means of the Quantum Theory of Atoms in Molecules (QTAIM) and Energy Decomposition Analysis (EDA) we assessed the nature of the Al-ligand interactions, finding mainly ionic bonds with an important degree of covalent character. Our results point at the possibility of the formation of aluminum-catecholamine complexes with favorable formation energies, even when proton/aluminum competition is taken into account. Indeed, we found that these catecholamines are better aluminum binders than catechol at physiological pH, because of the electron withdrawing effect of the positively-charged amine that decreases their deprotonation penalty with respect to catechol. However, overall, our results show that, in an open biological environment, the formation of Al-catecholamine complexes is not thermodynamically competitive when compared with the formation of other aluminum species in solution such as Al-hydroxide, or when considering other endogenous/exogenous Al(iii) ligands such as citrate, deferiprone and EDTA. In summary, we rule out the possibility, suggested by some authors, that the formation of Al-catecholamine complexes in solution might be behind some of the toxic roles attributed to aluminum in the brain. An up-to-date view of the catecholamine biosynthesis pathway with sites of aluminum interference (according to the current literature) is presented. Alternative mechanisms that might explain the deleterious effects of this metal on the catecholamine route are thoroughly discussed, and new hypotheses that should be investigated in future are proposed

Impact of prior accumulated work and intensity on power output in elite/international level road cyclists—a pilot study

Background. This study aimed to investigate the impact of the intensity of prior accumulated work on the decline in power output in elite/international level road cyclists, comparing the effects of prior continuous moderate intensity versus intermittent high intensity cycling.Methods. Nine elite/international level road cyclists (age 26.2 +/- 4.0 years; body mass: 66.6 +/- 5.5 kg; height: 176 +/- 0.4 cm) conducted a 12-min field test (12 min(fresh)) during two consecutive training camps. Participants then performed both a 150-min moderate intensity continuous (MIC) work bout or a 150-min high intensity intermittent (HII) race simulation in randomized order, cross-over design. After each condition a 12-min field test (12 min(fatigue)) was completed.Results. Absolute and relative 12min(fresh) power output were not significantly different between training camps (p>0.05). The 12 min(fatigue) power after HII was significantly lower than 12min(fatigue) after MIC (Delta=14W; p=0.014). Participants recorded more percentage time (%Time) in heart rate (HR) zone 3 (Delta=9.2%; p=0.003) and power output band between 5.0-7.9W.kg(-1) (Delta=8.9%; p=0.002) as well as higher total work (Delta=237 kJ; p <= 0.001) during HII.Conclusion. These findings reveal that the decline in power output is higher after HII compared to MIC cycling work bouts. This suggests that the quantification of total work and intensity should be used in conjunction to predict a distinctive decline in power output. Future research is required to better understand the mechanisms of endurance "durability" in elite/international level road cyclists

Nutrition Strategies for Triathlon

Contemporary sports nutrition guidelines recommend that each athlete develop a personalised, periodised and practical approach to eating that allows him or her to train hard, recover and adapt optimally, stay free of illness and injury and compete at their best at peak races. Competitive triathletes undertake a heavy training programme to prepare for three different sports while undertaking races varying in duration from 20 min to 10 h. The everyday diet should be adequate in energy availability, provide CHO in varying amounts and timing around workouts according to the benefits of training with low or high CHO availability and spread high-quality protein over the day to maximise the adaptive response to each session. Race nutrition requires a targeted and well-practised plan that maintains fuel and hydration goals over the duration of the specific event, according to the opportunities provided by the race and other challenges, such as a hot environment. Supplements and sports foods can make a small contribution to a sports nutrition plan, when medical supplements are used under supervision to prevent/treat nutrient deficiencies (e.g. iron or vitamin D) or when sports foods provide a convenient source of nutrients when it is impractical to eat whole foods. Finally, a few evidence-based performance supplements may contribute to optimal race performance when used according to best practice protocols to suit the triathlete’s goals and individual responsiveness

Effects of Bed Rest on Physical Performance in Athletes: A Systematic and Narrative Review.

BACKGROUND: Athletes can face scenarios in which they are confined to bed rest (e.g., due to injury or illness). Existing research in otherwise healthy individuals indicates that those entering bed rest with the greatest physical performance level might experience the greatest performance decrements, which indirectly suggests that athletes might be more susceptible to the detrimental consequences of bed rest than general populations. Therefore, a comprehensive understanding of the effects of bed rest might help guide the medical care of athletes during and following bed rest. OBJECTIVE: This systematic and narrative review aimed to (1) establish the evidence for the effects of bed rest on physical performance in athletes; (2) discuss potential countermeasures to offset these negative consequences; and (3) identify the time-course of recovery following bed rest to guide return-to-sport rehabilitation. METHODS: This review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four databases were searched (SPORTDiscus, Web of Science, Scopus, and MEDLINE/PubMed) in October of 2022, and studies were included if they were peer-reviewed investigations, written in English, and investigated the effects of horizontal bed rest on changes in physical capacities and qualities in athletes (defined as Tier 3-5 participants). The reporting quality of the research was assessed using a modified version of the Downs & Black checklist. Furthermore, findings from studies that involved participants in Tiers 1-2 were presented and synthesized using a narrative approach. RESULTS: Our systematic review of the literature using a rigorous criterion of 'athletes' revealed zero scientific publications. Nevertheless, as a by-product of our search, seven studies were identified that involved apparently healthy individuals who performed specific exercise training prior to bed rest. CONCLUSIONS: Based on the limited evidence from studies involving non-athletes who were otherwise healthy prior to bed rest, we generally conclude that (1) bed rest rapidly (within 3 days) decreases upright endurance exercise performance, likely due to a rapid loss in plasma volume; whereas strength is reduced within 5 days, likely due to neural factors as well as muscle atrophy; (2) fluid/salt supplementation may be an effective countermeasure to protect against decrements in endurance performance during bed rest; while a broader array of potentially effective countermeasures exists, the efficacy of these countermeasures for previously exercise-trained individuals requires further study; and (3) athletes likely require at least 2-4 weeks of progressive rehabilitation following bed rest of ≤ 28 days, although the timeline of recovery might need to be extended depending on the underlying reason for bed rest (e.g., injury or illness). Despite these general conclusions from studies involving non-athletes, our primary conclusion is that substantial effort and research is still required to quantify the effects of bed rest on physical performance, identify effective countermeasures, and provide return-to-sport timelines in bona fide athletes. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Registration ID: osf.io/d3aew; Date: October 24, 2022

SEOM clinical guideline for the management of cutaneous melanoma (2020)

Tractament adjuvant; Melanoma; EscenificacióAdjuvant treatment; Melanoma; StagingTratamiento adyuvante; Melanoma; EscenificaciónMelanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I–III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available

The reliability, validity and sensitivity of a novel soccer-specific reactive repeated-sprint test (RRST).

PURPOSE: The aim of this study was to determine the reliability, validity and sensitivity of a reactive repeated-sprint test (RRST). METHODS: Elite (n = 72) and sub-elite male (n = 87) and elite female soccer players (n = 12) completed the RRST at set times during a season. Total distance timed was 30 m and the RRST performance measure was the total time (s) across eight repetitions. Competitive match running performance was measured using GPS and high-intensity running quantified (≥ 19.8 km h(-1)). RESULTS: Test-retest coefficient of variation in elite U16 and sub-elite U19 players was 0.71 and 0.84 %, respectively. Elite U18 players' RRST performances were better (P < 0.01) than elite U16, sub-elite U16, U18, U19 and elite senior female players (58.25 ± 1.34 vs 59.97 ± 1.64, 61.42 ± 2.25, 61.66 ± 1.70, 61.02 ± 2.31 and 63.88 ± 1.46 s; ES 0.6-1.9). For elite U18 players, RRST performances for central defenders (59.84 ± 1.35 s) were lower (P < 0.05) than full backs (57.85 ± 0.77 s), but not attackers (58.17 ± 1.73 s) or central and wide midfielders (58.55 ± 1.08 and 58.58 ± 1.89 s; ES 0.7-1.4). Elite U16 players demonstrated lower (P < 0.01) RRST performances during the preparation period versus the start, middle and end of season periods (61.13 ± 1.53 vs 59.51 ± 1.39, 59.25 ± 1.42 and 59.20 ± 1.57 s; ES 1.0-1.1). Very large magnitude correlations (P < 0.01) were observed between RRST performance and high-intensity running in the most intense 5-min period of a match for both elite and sub-elite U18 players (r = -0.71 and -0.74), with the best time of the RRST also correlating with the arrowhead agility test for elite U16 and U18 players (r = 0.84 and 0.75). CONCLUSION: The data demonstrate that the RRST is a reliable and valid test that distinguishes between performance across standard, position and seasonal period

Different Psychophysiological Responses to a High-intensity Repetition Session Performed Alone or in a Group by Elite Middle-distance Runners

Internal training load refers to the degree of disturbance in psychophysiological homeostasis provoked by a training session and has been traditionally measured through session-RPE, which is the product of the session Rate of Perceived Exertion (RPE) and the duration. External training load refers to the actual physical work completed, and depends on session volume, intensity, frequency and density. Drafting, which is achieved by running closely behind another runner has been demonstrated to reduce the energy cost of running at a fixed speed and to improve performance. Therefore, it is hypothesized that psychophysiological responses might reflect different levels of internal load if training is performed individually or collectively. 16 elite middle-distance runners performed two high-intensity training sessions consisting of 4 repetitions of 500 m separated by 3 minutes of active recovery. Sessions were performed individually and collectively. Times for each repetition, RPE, core affect (valence and felt arousal) and blood lactate concentrations [BLa] were measured after each repetition. Main time effect was significant and increased across repetitions for [BLa] and RPE (p <0.001), and decreased for valence (p =0.001). Main group effect was significant and values were higher when training individually for [BLa] (p =0.003) and RPE (p =0.001), and lower for valence (p =0.001). No differential responses were found between conditions in terms of repeat time or felt arousal. Findings demonstrate that elite middle-distance athletes running collectively display lower levels of internal training load compared to running alone, despite external training load being similar

Aluminum's preferential binding site in proteins: sidechain of amino acids versus backbone interactions

The interaction of aluminum ion Al(III) with polypeptides is a subject of paramount importance, since it is a central feature to understand its deleterious effects in biological systems. Various drastic effects have been attributed to aluminum in its interaction with polypeptides and proteins. These interactions are thought to be established mainly through the binding of aluminum to phosphorylated and non-phosphorylated amino acid sidechains. However, a new structural paradigm has recently been proposed, in which aluminum interacts directly with the backbone of the proteins, provoking drastic changes in their secondary structure and leading ultimately to their denaturation. In the present paper, we use computational methods to discuss the possibility of aluminum to interact with the backbone of peptides and compare it with the known ability of aluminum to interact with amino acid sidechains. To do so, we compare the thermodynamics of formation of prototype aluminum-backbone structures with prototype aluminum-sidechain structures, and compare these results with previous data generated in our group in which aluminum interacts with various types of polypeptides and known aluminum biochelators. Our results clearly points to a preference of aluminum towards amino acid sidechains, rather than towards the peptide backbone. Thus, structures in which aluminum is interacting with the carbonyl group are only slightly exothermic, and they become even less favorable if the interaction implies additionally the peptide nitrogen. However, structures in which aluminum is interacting with negatively-charged sidechains like aspartic acid, or phosphorylated serines are highly favored thermodynamically.Technical and human support was provided by SGI/IZO (SGIker) of UPV/EHU and European funding (ERDF and ESF). Financial support comes from UPV/EHU (PES14/35), Eusko Jaurlaritza (IT588-13) and the Spanish Ministerio de Ciencia e Innovación (MINECO/FEDER) (CTQ2015-67608-P). GdT thanks the European Union for a Ph.D. grant inside the ITN-TCCM-642294 program