RESUMO
BACKGROUND: Alcohol exposure has adverse effects on stress physiology and behavioral reactivity. This is suggested to be due, in part, to the effect of alcohol on ß-endorphin (ß-EP)-producing neurons in the hypothalamus. In response to stress, ß-EP normally provides negative feedback to the hypothalamic-pituitary-adrenal axis and interacts with other neurotransmitter systems in the amygdala to regulate behavior. We examined whether ß-EP neuronal function in the hypothalamus reduces the corticosterone response to acute stress, attenuates anxiety-like behaviors, and modulates alcohol drinking in rats. METHODS: To determine whether ß-EP neuronal transplants modulate the stress response, anxiety behavior, and alcohol drinking, we implanted differentiated ß-EP neurons into the paraventricular nucleus (PVN) of the hypothalamus of normal, prenatal alcohol-exposed, and alcohol-preferring (P) and alcohol-non-preferring (NP) rats. We then assessed corticosterone levels in response to acute restraint stress and other markers of stress response in the brain and anxiety-like behaviors in the elevated plus maze and open-field assays. RESULTS: We showed that ß-EP neuronal transplants into the PVN reduced the peripheral corticosterone response to acute stress and attenuated anxiety-like behaviors. Similar transplants completely reduced the hypercorticosterone response and elevated anxiety behaviors in prenatal alcohol-exposed adult rats. Moreover, we showed that ß-EP reduced anxiety behavior in P rats with minimal effects on alcohol drinking during and following restraint stress. CONCLUSIONS: These data further establish a role of ß-EP neurons in the hypothalamus for regulating physiological stress response and anxiety behavior and resemble a potential novel therapy for treating stress-related psychiatric disorders in prenatal alcohol-exposed children and those genetically predisposed to increased alcohol consumption.
Assuntos
Consumo de Bebidas Alcoólicas/terapia , Ansiedade/terapia , Neurônios/transplante , Núcleo Hipotalâmico Paraventricular/cirurgia , Efeitos Tardios da Exposição Pré-Natal/terapia , beta-Endorfina/uso terapêutico , Tonsila do Cerebelo/metabolismo , Animais , Corticosterona/sangue , Hormônio Liberador da Corticotropina/biossíntese , Feminino , Masculino , Aprendizagem em Labirinto , Camundongos Endogâmicos , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Receptores de Hormônio Liberador da Corticotropina/biossíntese , Restrição Física , beta-Endorfina/metabolismoRESUMO
Prolonged subjection to unstable work or lighting schedules, particularly in rotating shift-workers, is associated with an increased risk of immune-related diseases, including several cancers. Consequences of chronic circadian disruption may also extend to the innate immune system to promote cancer growth, as NK cell function is modulated by circadian mechanisms and plays a key role in lysis of tumor cells. To determine if NK cell function is disrupted by a model of human shift-work and jet-lag, Fischer (344) rats were exposed to either a standard 12:12 light-dark cycle or a chronic shift-lag paradigm consisting of 10 repeated 6-h photic advances occurring every 2 d, followed by 5-7 d of constant darkness. This model resulted in considerable circadian disruption, as assessed by circadian running-wheel activity. NK cells were enriched from control and shifted animals, and gene, protein, and cytolytic activity assays were performed. Chronic shift-lag altered the circadian expression of clock genes, Per2 and Bmal1, and cytolytic factors, perforin and granzyme B, as well as the cytokine, IFN-γ. These alterations were correlated with suppressed circadian expression of NK cytolytic activity. Further, chronic shift-lag attenuated NK cell cytolytic activity under stimulated in vivo conditions, and promoted lung tumor growth following i.v. injection of MADB106 tumor cells. Together, these findings suggest chronic circadian disruption promotes tumor growth by altering the circadian rhythms of NK cell function.
Assuntos
Transtornos Cronobiológicos/complicações , Relógios Circadianos/fisiologia , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/etiologia , Animais , Western Blotting , Proteínas CLOCK/imunologia , Proteínas CLOCK/metabolismo , Transtornos Cronobiológicos/imunologia , Neoplasias Pulmonares/imunologia , Masculino , Fotoperíodo , Ratos , Ratos Endogâmicos F344 , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Background: Although fastpitch softball participation continues to rise, there is a lack of established pitch count guidelines, potentially putting young female athletes at risk of overuse injuries. In addition to coaches, caregivers' ability to recognize and employ safe pitching guidelines plays an important role in athlete safety. Purpose/Hypothesis: The purpose of this study was to assess caregivers' knowledge of their child's pitching practices and their familiarity with softball pitching recommendations. We hypothesized that caregivers would be unaware of safe pitching recommendations in youth fastpitch softball. Study Design: Cross-sectional study. Methods: A 30-question survey was distributed to caregivers of youth fastpitch softball pitchers in age groups 10U (ie, ≤10 years), 12U, 14U, 16U, and 18U. The survey included questions on the demographic characteristics of caregivers and athletes, caregivers' knowledge of safe pitching recommendations, and athletes' pitching background and throwing habits. Comparisons of responses between the age groups were conducted using the chi-square test, Fisher exact test, or 1-way analysis of variance, as appropriate. Results: A total of 115 caregivers completed the survey. Of the respondents, 84% were between 31 and 50 years, and 81.7% had a degree beyond high school. Only 28.1% of caregivers reported participating in youth sports. When asked to estimate the number of pitches they considered a safe amount during a single outing, 28.7% of caregivers (n = 33) did not provide a limit, 4.3% (n = 5) stated no limit was needed, 32.2% (n = 37) suggested 25 to 80 pitches, 21.7% (n = 25) suggested 81 to 100 pitches, 12.2% (n = 14) suggested 100 to 150 pitches, and 0.9% (n = 1) suggested that >150 pitches were acceptable. These data emphasized that only 14.8% of the caregivers were aware of any pitching guidelines. However, 93% of caregivers acknowledged that they would adhere to recommendations if guidelines were made available. Conclusion: The study findings demonstrated that a majority of caregivers are unaware of current youth fastpitch softball pitching recommendations.
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Before Perseverance, Jezero crater's floor was variably hypothesized to have a lacustrine, lava, volcanic airfall, or aeolian origin. SuperCam observations in the first 286 Mars days on Mars revealed a volcanic and intrusive terrain with compositional and density stratification. The dominant lithology along the traverse is basaltic, with plagioclase enrichment in stratigraphically higher locations. Stratigraphically lower, layered rocks are richer in normative pyroxene. The lowest observed unit has the highest inferred density and is olivine-rich with coarse (1.5 millimeters) euhedral, relatively unweathered grains, suggesting a cumulate origin. This is the first martian cumulate and shows similarities to martian meteorites, which also express olivine disequilibrium. Alteration materials including carbonates, sulfates, perchlorates, hydrated silicates, and iron oxides are pervasive but low in abundance, suggesting relatively brief lacustrine conditions. Orbital observations link the Jezero floor lithology to the broader Nili-Syrtis region, suggesting that density-driven compositional stratification is a regional characteristic.
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Imagery research has identified two main visual perspectives, external visual imagery (EVI, third person) and internal visual imagery (IVI, first person). Based upon findings from brain imaging literature showing that different neural substrates are recruited for IVI and EVI perspectives, and that IVI activates motor system brain areas, we hypothesised that a concurrent action dual task would cause greater interference in performance for IVI than EVI. In a first experiment, participants were allocated to either an IVI or an EVI group, and were tasked with moving an onscreen marker towards a target in three blocked conditions: imagery, imagery with a concurrent motor dual-task of sequencing, and a math control. An interaction between imagery group and condition was driven by greater root mean square error for participants in the dual-task condition in the IVI group compared with the EVI group. We replicated the experiment with an eye-tracking objective measure of IVI; the results again showed that participants in the IVI group made more errors in motor movements, and an interference effect in eye movements, during the dual-task sequencing condition compared with the EVI group. The results of the two experiments reveal that a secondary motor task does interfere with IVI, providing behavioural evidence that IVI appears to rely on motor system processes more than EVI. These results have important implications for the use of visual imagery perspectives across a number of domains, with this paper being an essential reference for those conducting visual imagery perspectives research.