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Cramer Chase posted an update 6 months, 2 weeks ago
We observed that free simvastatin (CS3) was able to reduce the enzymatic activity of pyruvate kinase, an important enzyme for brain energy homeostasis, without affecting the memory of the animals that received a standard diet. However, it failed to improve the cognitive damage caused by a diet high in cholesterol and saturated fats. On the other hand, when simvastatin is “camouflaged” in the lipid-core nanocapsules (HNS3), this cognitive impairment improves. Thus, SV-LNC is a promising alternative therapy for the treatment of cognitive impairment.UV-A and visible light are thought to excite endogenous photosensitizers in microbes, thereby initiating complex chemical interactions that ultimately kill cells. Natural solar-based disinfection methods have been adapted into commercial lighting technologies with varying degrees of reported efficacy and associated safety hazards for human exposure. Here we utilize a narrow-spectrum UV-A LED prototype (currently in development for health care applications) to investigate the mechanism of bacterial photoinactivation using 365 nm light. Using a combination of reverse genetics and biochemical investigation, we report mechanistic evidence that 365nm light initiates a chain-reaction of superoxide-mediated damage via auto-excitation of vitamin-based electron carriers, specifically vitamin K2 menaquinones and the FAD flavoprotein in Complex II in the electron transport chain. We observe that photoinactivation is modifiable through supplementation of the environment to bypass cell damage. Lastly, we observe that bacteria forced into metabolic dormancy by desiccation become hypersensitized to the effects of UV-A light, thereby permitting photoinactivation at fluences that are significantly lower than the industry threshold for safe human exposure. In total, these results substantiate the mechanism and potential application of narrow- spectrum UV-A light for bacterial disinfection purposes.Research suggests that the electrophysiological correlates of consciousness are similar in hearing as in vision the auditory awareness negativity (AAN) and the late positivity (LP). However, from a recently proposed signal-detection perspective, these correlates may be confounded by performance, as the strength of the internal responses differs between aware and unaware trials. Here, we tried to apply this signal-detection approach to correct for performance in an auditory discrimination and detection task (N = 28). A large proportion of subjects had to be excluded because even a small response bias distorted the correction. For the remaining subjects, the correction mainly increased noise in the measurement. Furthermore, the signal-detection approach is theoretically problematic because it may isolate post-perceptual processes and eliminate awareness-related activity. Therefore, we conclude that AAN and LP are not confounded by performance and that the contrastive analysis identifies both as correlates of awareness.Losing a spouse can increase the risk for premature mortality, and declines in immune health are thought to play a role. Most of the supporting data have come from cross-sectional studies comparing already-bereaved individuals to matched controls, which provides valuable information about health disparities between groups but does not reveal health changes over time. Moreover, the health consequences of bereavement may be unique for dementia family caregivers, a large and growing segment of the population. The current study sought to evaluate the course of health around 52 dementia spousal caregivers’ bereavement by capturing lymphocyte proliferation to Con A and PHA and self-rated health before and after spousal loss. Lenumlostat To investigate the moderating role of the social environment, we examined associations between social ties and health trajectories before and after spousal loss. Using piecewise linear mixed models to allow for turning points in caregivers’ trajectories, we found that, for the average caregiver, lymphocyte proliferation to both mitogens weakened as bereavement neared and continued to decline after the loss, but at a slower pace. In tandem, perceived health degraded as bereavement approached but rebounded thereafter. Further, we found that socially isolated caregivers showed marked declines in immune responses to Con A and PHA over time both before and after bereavement, whereas their socially connected counterparts had shallower declines to PHA and maintained a level immune response to Con A. In addition, socially isolated caregivers reported poorer health before and after bereavement compared to their counterparts, whose self-rated health declined as the loss neared but later recovered to exceed prior levels. These findings shed new light on the dynamics of immune function in response to spousal bereavement after dementia caregiving longitudinal data reveal a pattern of health recovery following caregivers’ loss, particularly among those with more robust social networks prior to bereavement.Identifying individual differences in stress reactivity is of particular interest in the context of stress-related disorders and resilience. Previous studies already identified several factors mediating the individual stress response of the hypothalamus-pituitary-adrenal axis (HPA). However, the impact of long-term HPA axis activity on acute stress reactivity remains inconclusive. To investigate associations between long-term HPA axis variation and individual acute stress reactivity, we tested 40 healthy volunteers for affective, endocrine, physiological, and neural reactions to a modified, compact version of the established in-MR stress paradigm ScanSTRESS (ScanSTRESS-C). Hair cortisol concentrations (HCC) served as an integrative marker of long-term HPA axis activity. First, the ScanSTRESS-C version proved to be valid in evoking a subjective, endocrine, physiological, and neural stress response with enhanced self-reported negative affect and cortisol levels, increased heart rate as well as increased activation in the anterior insula and the dorso-anterior cingulate cortex (dACC). Second and interestingly, results indicated a lower neuroendocrine stress response in individuals with higher HCC HCC was negatively correlated with the area under the curve (respect to increase; AUCi) of saliva cortisol and with a stress-related increase in dACC activity. The present study explicitly targeted the relationship between HCC and acute stress reactivity on multiple response levels, i.e. subjective, endocrine and neural stress responses. The lower stress reactivity in individuals with higher HCC levels indicates the need for further research evaluating the role of long-term HPA axis alterations in the context of vulnerability or immunization against acute stress and following stress-related impairments.
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