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Cancer cells are embedded within the tissue and interact dynamically with its components during cancer progression. Understanding the contribution of cellular components within the tumor microenvironment is crucial for the success of therapeutic applications. Here, we reveal the presence of perivascular GFAP+/Plp1+ cells within the tumor microenvironment. Using in vivo inducible Cre/loxP mediated systems, we demonstrated that these cells derive from tissue-resident Schwann cells. Genetic ablation of endogenous Schwann cells slowed down tumor growth and angiogenesis. Schwann cell-specific depletion also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of tumor biopsies revealed that increased expression of Schwann cell-related genes within melanoma was associated with improved survival. Collectively, our study suggests that Schwann cells regulate tumor progression, indicating that manipulation of Schwann cells may provide a valuable tool to improve cancer patients' outcomes.
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Neoplasias , Neuroglia , Humanos , Estudos Retrospectivos , Neuroglia/metabolismo , Células de Schwann/metabolismo , Células de Schwann/patologia , Pericitos , Microambiente Tumoral/fisiologia , Neoplasias/patologiaRESUMO
We summarize and elaborate on the challenges of researching in the field of human health in Antarctica based on the conceptual and methodological specificities of a line of investigation that aims to study the human presence in Antarctica in all of its dimensions (biological, psychological, and socio-anthropological). Herein, we discuss the principal results and limitations of the research carried out by researchers of MEDIANTAR (Antarctic medicine, physiology, and anthropology) group of Programa Antártico Brasileiro in isolated, confined, and extreme environments over the last six years. Fieldwork has been carried out in remote research camps, Brazilian navy ships (Almirante Maximiano/H-41 and Ary Rongel/H-44), and Comandante Ferraz Antarctic Station. Adaptative responses to isolated, confined, and extreme environments were studied based on questionnaires, interviews, participative observation, biological samples, anthropometric, and physiological parameters. Our researchers face the unique situation of concomitantly working under the stressful living conditions that are the object of their investigation. A critical examination of the socio-methodological characteristics and challenges of this research niche indicates the need for exchanging the lessons learned and limitations of these practices with researchers in the humanities field, with attention to the human resources needs in multidisciplinary human-related studies.
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Adaptação Fisiológica , Ambientes Extremos , Regiões Antárticas , Brasil , Humanos , PesquisadoresRESUMO
Open-water diving in a polar environment is a psychophysiological challenge to the human organism. We evaluated the effect of short-term diving (i.e., 10 min) in Antarctic waters on autonomic cardiac control, thyroid hormone concentration, body temperatures, mood, and neuropsychological responses (working memory and sleepiness). Data collection was carried out at baseline, before, and after diving in four individuals divided into the supporting (n=2) and diving (n=2) groups. In the latter group, autonomic cardiac control (by measuring heart rate variability) was also assessed during diving. Diving decreased thyroid-stimulating hormone (effect size = 1.6) and thyroxine (effect size = 2.1) concentrations; these responses were not observed for the supporting group. Diving also reduced both the parasympathetic (effect size = 2.6) and sympathetic activities to the heart (ES > 3.0). Besides, diving reduced auricular (effect size > 3.0), skin [i.e., hand (effect size = 1.2) and face (effect size = 1.5)] temperatures compared to pre-dive and reduced sleepiness state (effect size = 1.3) compared to basal, without changing performance in the working memory test. In conclusion, short-term diving in icy waters affects the hypothalamic-pituitary-thyroid axis, modulates autonomic cardiac control, and reduces body temperature, which seems to decrease sleepiness.
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Mergulho , Regiões Antárticas , Brasil , Mergulho/fisiologia , Congelamento , Frequência Cardíaca/fisiologia , Humanos , Sonolência , Hormônios TireóideosRESUMO
We evaluated the influence of a 32-day camping in Antarctica on physical performance and exercise-induced thermoregulatory responses. In Brazil, before and after the Antarctic camping, the volunteers performed an incremental exercise at temperate conditions and, two days later, an exercise heat stress protocol (45-min running at 60% of maximum aerobic speed, at 31°C and 60% of relative humidity). In Antarctica, core temperature was assessed on a day of fieldwork, and average values higher than 38.5°C were reported. At pre- and post-Antarctica, physiological (whole-body and local sweat rate, number of active sweat glands, sweat gland output, core and skin temperatures) and perceptual (thermal comfort and sensation) variables were measured. The Antarctic camping improved the participants' performance and induced heat-related adaptations, as evidenced by sweat redistribution (lower in the chest but higher in grouped data from the forehead, forearm, and thigh) and reduced skin temperatures in the forehead and chest during the exercise heat stress protocol. Notwithstanding the acclimatization, the participants did not report differences of the thermal sensation and comfort. In conclusion, staying in an Antarctic camp for 32 days improved physical performance and elicited physiological adaptations to heat due to the physical exertion-induced hyperthermia in the field.
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Termotolerância , Aclimatação/fisiologia , Regiões Antárticas , Temperatura Corporal/fisiologia , Exercício Físico/fisiologia , Temperatura Alta , HumanosRESUMO
Thermoregulatory changes may influence the rats' prolonged physical performance and are commonly evaluated during treadmill running. Therefore, we determined the reliability of performance and thermoregulatory parameters in rats subjected to incremental-speed exercises (i.e., we assessed whether the testing protocol provides measurements that are consistent and free from error). Twenty rats were subjected to two sessions of incremental exercises at 24 °C, separated by 48 h, until they were fatigued. The rats' performance and thermoregulatory responses were determined, and values concerning the reliability of these parameters [e.g., intraclass correlation coefficient (ICC) and minimal detectable change (MDC)] were calculated. Our data revealed that the core temperature (TCORE) at fatigue and heat loss threshold were the most reproducible parameters, showing good reliability (ICC between 0.75 and 0.90). Moreover, all performance parameters assessed, the change in TCORE, the rate of TCORE increase, and the TCORE increase-to-distance traveled ratio presented moderate reliability. We then investigated whether changes in performance and thermoregulation induced by a warm environment were greater than the MDC95% values determined in the first experiment. Eight rats were subjected to incremental exercises at two environmental conditions: 24 °C and 31 °C. Individual analyses showed that most rats presented thermoregulatory differences between exercises at 31 °C and 24 °C greater than the calculated MDC95% values; this was not the case for their performance. In conclusion, we provide data on the reliability of rats' performance and thermoregulatory parameters during incremental-speed running. Also, the exercise in a warm environment produced detectable thermoregulatory changes relative to the exercise under temperate conditions.
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Regulação da Temperatura Corporal , Corrida , Animais , Fadiga , Desempenho Físico Funcional , Ratos , Ratos Wistar , Reprodutibilidade dos TestesRESUMO
Antarctica is a space-analog ICE (isolated, cold, and extreme) environment. Cardiovascular and heart autonomic adjustments are key-adaptive physiological responses to Antarctica, both in summer camps and in research stations winter-over. Research fieldwork in ICE environments imposes limitations such as energy restriction, the need for portable and easy-to-handle resources, and resistance of materials to cold and snow/water. Herein, we present the methods we use for cardiac monitoring in the Antarctic field, the limitations of the equipment currently available, and the specific demands for smart wearables to physiological and health tracking in ICE environments, including the increased remote monitoring demand due to COVID-19 restrictions.
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Ambientes Extremos , Dispositivos Eletrônicos Vestíveis , Regiões Antárticas , HumanosRESUMO
Physical activity can prevent many organic and mental pathologies. For people living in extreme southern high-latitude environments, weather conditions can affect these activities, altering their psychological well-being and favoring the prevalence of seasonal sensitivity (SS). This study aims to determine the relationships between the practice of physical activity, seasonal sensitivity and well-being in people living in high southern latitudes. A cross-sectional study was conducted, using the Seasonal Pattern Assessment Questionnaire (SPAQ), applying a psychological well-being scale, and determining sports practice according to the recommendations of the World Health Organization (WHO) for the 370 male (n = 209; 55%) and female (n = 173; 45%) participants. The main results indicated that 194 people (52 ± 7.7 years) reported physical activity. High-intensity physical activity practitioners recorded a significantly lower proportion of SS. In terms of psychological well-being, an adverse effect was found between the Seasonal Score Index (SSI) and five subcategories of the Ryff well-being scale. In conclusion, those who perform high-intensity physical activity have a lower SS, and those who have a higher SS have a lower psychological well-being.
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Transtorno Afetivo Sazonal , Humanos , Masculino , Feminino , Transtorno Afetivo Sazonal/epidemiologia , Transtorno Afetivo Sazonal/prevenção & controle , Transtorno Afetivo Sazonal/psicologia , Estações do Ano , Estudos Transversais , Bem-Estar Psicológico , Exercício FísicoRESUMO
Antarctic camps pose psychophysiological challenges related to isolated, confined, and extreme (ICE) conditions, including meals composed of sealed food. ICE conditions can influence the microbiome and inflammatory responses. Seven expeditioners took part in a 7-week Antarctic summer camp (Nelson Island) and were evaluated at Pre-Camp (i.e., at the beginning of the ship travel), Camp-Initial (i.e., 4th and 5th day in camp), Camp-Middle (i.e., 19th-20th, and 33rd-34th days), Camp-Final (i.e., 45th-46th day), and at the Post-Camp (on the ship). At the Pre-Camp, Camp-Initial, and Camp-Final, we assessed microbiome and inflammatory markers. Catecholamines were accessed Pre- and Post-Camp. Heart rate variability (HRV), leptin, thyroid stimulating hormone (TSH), and thyroxine (T4) were accessed at all time points. Students' t-tests or repeated-measures analysis of variance (one or two-way ANOVA) followed by Student-Newman-Keuls (post hoc) were used for parametric analysis. Kruskal-Wallis test was applied for non-parametric analysis. Microbiome analysis showed a predominance of Pseudomonadota (34.01%), Bacillota (29.82%), and Bacteroidota (18.54%), followed by Actinomycetota (5.85%), and Fusobacteria (5.74%). Staying in a long-term Antarctic camp resulted in microbiome fluctuations with a reduction in Pseudomonadota-a "microbial signature" of disease. However, the pro-inflammatory marker leptin and IL-8 tended to increase, and the angiogenic factor VEGF was reduced during camp. These results suggest that distinct Antarctic natural environments and behavioral factors modulate oral microbiome and inflammation.
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Background/Aims: Chagasic megacolon is caused by Trypanosoma cruzi, which promotes in several cases, irreversible segmental colonic dilation. This alteration is the major anatomic-clinical disorder, characterized by the enteric nervous system and muscle wall structural damage. Herein, we investigate how T. cruzi -induced progressive colonic structural changes modulate the colonic contractile pattern activity. Methods: We developed a murine model of T. cruzi-infection that reproduced long-term modifications of the enlarged colon. We evaluated colonic and total intestinal transit time in animals. The patterns of motor response at several time intervals between the acute and chronic phases were evaluated using the organ bath assays. Enteric motor neurons were stimulated by electric field stimulation. The responses were analyzed in the presence of the nicotinic and muscarinic acetylcholine receptor antagonists. Western blot was performed to evaluate the expression of nicotinic and muscarinic receptors. The neurotransmitter expression was analyzed by real-time polymerase chain reaction. Results: In the chronic phase of infection, there was decreased intestinal motility associated with decreased amplitude and rhythmicity of intestinal contractility. Pharmacological tests suggested a defective response mediated by acetylcholine receptors. The contractile response induced by acetylcholine was decreased by atropine in the acute phase while the lack of its action in the chronic phase was associated with tissue damage, and decreased expression of choline acetyltransferase, nicotinic subunits of acetylcholine receptors, and neurotransmitters. Conclusions: T. cruzi -induced damage of smooth muscles was accompanied by motility disorders such as decreased intestinal peristalsis and cholinergic system response impairment. This study allows integration of the natural history of Chagasic megacolon motility disorders and opens new perspectives for the design of effective therapeutic.
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Objective: To study the differences in cardiac autonomic modulation in response to muscle fatigue caused by high-intensity exercise during two consecutive competition periods in young swimmers. Methods: Twenty-six competitive swimmers, selected by their training volume, were separated in two groups, females (n = 12 [46%], age: 13.5 ± 1.4 years) and males (n = 14 [54%], age: 13.9 ± 1.7 years), aged between 10 and 16 years, were evaluated five times as follow: (i) 21 days before the first competition (t-0); (ii) two days before (t-1; t-3); and (iii) two days after (t-2; t-4) of the first and second competitions. Morphological measurements (body mass, percentage of total body fat and height), blood pressure, power, and resting heart rate variability (RR with Polar band) were recorded before and after Wingate test at each time. Results: Body fat was higher in females compared to males. However, no differences were found in other morphological parameters. An intra-subject analysis grouped by sex in cardiovascular parameters shows longitudinal variations in systolic pressure and mean pressure among females. Additionally, females depicted higher, very low frequency (VLF, which is intrinsically generated by the heart and strongly associated with emotional stress) after physical fatigue compared to males at t-1. Further, before the competition, the high frequency (HF) component of HRV (parasympathetic drive) was higher in males than females at t-0 and t-4. Conclusion: Our data revealed that males displayed greater parasympathetic reactivity after an anaerobic muscle fatigue test during their competition periods. Contrarily, females had a less cardiac autonomic modulation when comparing the pre-post Wingate test after two consecutive competition periods.
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We evaluated the influence of an Antarctic expedition, consisting of 26-day ship travel followed by 24-day camping in the Antarctic field during the summer season, on hormonal responses, autonomic cardiac control, and mood states in individuals that live in tropical regions. Data collection was carried out in 10 individuals on the 2nd, 16th, and 26th days aboard the ship (characterized by exposure to low-luminosity and temperature-controlled environments) and on the 4th, 11th, and 23rd days of camping in the Antarctic field (prolonged exposure to natural luminosity and cold environments). Morning samples of saliva (to determine testosterone and cortisol concentrations) and blood [to determine thyroid-stimulating hormone (TSH) and thyroxine (T4) concentrations] were obtained. Next, resting heart rate variability (HRV) was recorded, and the volunteers answered a mood questionnaire. Samples of saliva for measurement of melatonin concentration were obtained at night. At the end of ship travel, blood TSH and salivary melatonin increased by 15.6% and 72.3%, respectively, whereas salivary cortisol reduced by 37.1% compared to initial values and T4 reduced by 12.2% compared to 16th day. These hormonal changes occurred alongside increased depression score and biphasic changes in HRV parameters; for example, the RMSSD, a parasympathetic-related parameter, initially decreased by 47.8% and then returned towards baseline values by the end of the ship travel. In contrast, during the camp period, blood TSH and T4 reduced by 26.5% and 34.1%, respectively, and salivary cortisol increased by 72.1%, without concomitant changes in melatonin and HRV. Also, tension score transiently reduced and then increased towards the pre-camp score by the end of the field period. Testosterone remained unaltered throughout the expedition. In conclusion, ship travel and camping in Antarctica induced distinct neuroendocrine changes, cardiac autonomic regulation, and mood states. These specific changes most likely resulted from exposure to different natural luminosity, degrees of confinement, and ambient temperature in these environments.
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Acampamento , Expedições , Regiões Antárticas , Humanos , Hidrocortisona , Navios , NeveRESUMO
Different methodological approaches have been used to conduct experiments with rats subjected to treadmill running. Some experimenters have exposed rats to the treadmill setup before initiating exercise to minimize the influences of handling and being placed in an anxiety-inducing environment on the physiological responses to subsequent running. Other experimenters have subjected rats to exercise immediately after placing them on the treadmill. Thus, the present study aimed to evaluate the effects of pre-exercise exposure to the treadmill on physical performance and cardiovascular and thermoregulatory responses during subsequent exercise. Male Wistar rats were subjected to fatiguing incremental-speed exercise at 24°C immediately after being placed on the treadmill or after being exposed to the treadmill for 70 min following removal from their home cages. Core body temperature (TCORE), tail-skin temperature (TSKIN), heart rate (HR) and mean arterial pressure (MAP) were recorded throughout the experiments. Rats exposed to the treadmill started exercise with higher TCORE, lower HR and MAP, and unaltered TSKIN. This exposure did not influence performance, but it markedly affected the exercise-induced increases in the four physiological parameters evaluated; for example, the TSKIN increased earlier and at a higher TCORE. Moreover, previous treadmill exposure notably allowed expected exercise-induced changes in cardiovascular parameters to be observed. Collectively, these data indicate that pre-exercise exposure to the treadmill induces important effects on physiological responses during subsequent treadmill running. The present data are particularly relevant for researchers planning experiments involving physical exercise and the recording of physiological parameters in rats.
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Antarctic climate is challenging, since the cold, wind and sensory monotony are stressful stimuli to individuals. Moreover, camp activities and heavy clothes may contribute to increase physiological strain. Thus, we aimed to characterise the physiological demand of a 24-day period in the Antarctic field and then to evaluate the effect of this expedition on the aerobic fitness in individuals with heterogeneous initial aerobic fitness (as determined by estimating maximum oxygen consumption - VÌO2MAX). Before and after the 24-day period in Antarctica, 7 researchers and 2 mountaineers were subjected to incremental tests to estimate their VÌO2MAX. Field effort was characterised by measuring heart rate (HR). During the field trips, their HR remained 33.4% of the recording time between 50-60% HRMAX, 22.3% between 60-70% HRMAX, and only 1.4% between 80 and 90% HRMAX. The changes in estimated VÌO2MAX during the expedition depended on the pre-expedition aerobic fitness. The post-expedition VÌO2MAX increased by 5.9% and decreased by 14.3%in individuals with lower (researchers) and higher (mountaineers) initial VÌO2MAX, respectively. We concluded that physical effort in the Antarctic field is characterised as predominantly of low- to moderate-intensity. This effort represented an effective training load for individuals with lower initial VÌO2MAX, but not for those with higher VÌO2MAX.
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Expedições , Consumo de Oxigênio/fisiologia , Esforço Físico/fisiologia , Adulto , Idoso , Regiões Antárticas , Pesos e Medidas Corporais , Feminino , Frequência Cardíaca , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Aptidão FísicaRESUMO
Listening to melodic music is regarded as a non-pharmacological intervention that ameliorates various disease symptoms, likely by changing the activity of brain monoaminergic systems. Here, we investigated the effects of exposure to melodic music on the concentrations of dopamine (DA), serotonin (5-HT) and their respective metabolites in the caudate-putamen (CPu) and nucleus accumbens (NAcc), areas linked to reward and motor control. Male adult Wistar rats were randomly assigned to a control group or a group exposed to music. The music group was submitted to 8 music sessions [Mozart's sonata for two pianos (K. 488) at an average sound pressure of 65â¯dB]. The control rats were handled in the same way but were not exposed to music. Immediately after the last exposure or control session, the rats were euthanized, and their brains were quickly removed to analyze the concentrations of 5-HT, DA, 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the CPu and NAcc. Auditory stimuli affected the monoaminergic system in these two brain structures. In the CPu, auditory stimuli increased the concentrations of DA and 5-HIAA but did not change the DOPAC or 5-HT levels. In the NAcc, music markedly increased the DOPAC/DA ratio, suggesting an increase in DA turnover. Our data indicate that auditory stimuli, such as exposure to melodic music, increase DA levels and the release of 5-HT in the CPu as well as DA turnover in the NAcc, suggesting that the music had a direct impact on monoamine activity in these brain areas.