Systemic Treatment with Fas-Blocking Peptide Attenuates Apoptosis in Brain Ischemia.

Apoptosis plays a crucial role in neuronal injury, with substantial evidence implicating Fas-mediated cell death as a key factor in ischemic strokes. To address this, inhibition of Fas-signaling has emerged as a promising strategy in preventing neuronal cell death and alleviating brain ischemia. However, the challenge of overcoming the blood-brain barrier (BBB) hampers the effective delivery of therapeutic drugs to the central nervous system (CNS). In this study, we employed a 30 amino acid-long leptin peptide to facilitate BBB penetration. By conjugating the leptin peptide with a Fas-blocking peptide (FBP) using polyethylene glycol (PEG), we achieved specific accumulation in the Fas-expressing infarction region of the brain following systemic administration. Notably, administration in leptin receptor-deficient db/db mice demonstrated that leptin facilitated the delivery of FBP peptide. We found that the systemic administration of leptin-PEG-FBP effectively inhibited Fas-mediated apoptosis in the ischemic region, resulting in a significant reduction of neuronal cell death, decreased infarct volumes, and accelerated recovery. Importantly, neither leptin nor PEG-FBP influenced apoptotic signaling in brain ischemia. Here, we demonstrate that the systemic delivery of leptin-PEG-FBP presents a promising and viable strategy for treating cerebral ischemic stroke. Our approach not only highlights the therapeutic potential but also emphasizes the importance of overcoming BBB challenges to advance treatments for neurological disorders.

Risk-Likelihood Perceptions and Preventive Behaviors Against Infectious Diseases: Testing Different Types of Risk-Likelihood Perceptions in the Context of MERS and COVID-19.

Effective public health communication should take into the consideration how communicated risk perceptions might influence the public. Although many health behavior theories claim that high perceived risk likelihood motivates preventive health behaviors, this general prediction is complicated by different ways of estimating risk likelihood. Our review of 14 previous studies on perceived risk of infectious diseases revealed different measures of risk likelihood and inconsistent findings regarding the relationship between perceived risk likelihood and behavioral intention. Drawn from the review, we examined the predictive power of different types of risk likelihood on intention to prevent infectious diseases. Using two separate data sets, collected during the 2015 outbreak of the Middle East respiratory syndrome (N = 557) and the COVID-19 pandemic of 2021 (N = 1,001), we demonstrated that perceived risk likelihood that specifies future inaction on health behaviors (i.e., conditional absolute risk perception) better predicted behavioral intention than did other types of risk perceptions. When the effect of conditional absolute risk perception was controlled, the behavioral intention and unconditional absolute risk perception showed a negative relationship. The findings have theoretical and practical implications that can inform strategic communication during future outbreaks.

Patterns of Focal Amyloid Deposition Using 18F-Florbetaben PET in Patients with Cognitive Impairment.

Accumulation of aggregated amyloid-ß (Aß) in the brain is considered the first pathological event within the pathogenesis of Alzheimer's disease (AD). It is difficult to accurately identify the initial brain regions of Aß accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aß deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aß accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aß accumulation in the brain of people with AD continuum.

Conditional risk perception and protection behavior: Testing the behavior motivation hypothesis and the risk reappraisal hypothesis.

There exist two distinctive hypotheses on the relationship between perceived risk and protection behavior: the behavioral motivation hypothesis (i.e., a higher risk perception motivates protection behaviors) and the risk reappraisal hypothesis (i.e., protection behaviors reduce perceived risk). To test these competing hypotheses, we examined how risk perception, behavioral intention, and behavior are affected by conditional risk information. In a two-wave panel experiment conducted online in South Korea (Time 1 N = 450; Time 2 N = 276), we manipulated the risk level (high vs. low) of gum disease in a health message both for the inaction of the recommended preventive behavior (flossing) and for the action of the behavior. The results showed that information about high (vs. low) inaction conditional risk indirectly led to greater flossing intention via changing inaction risk perception. In contrast, information about high (vs. low) action conditional risk increased action risk perception, which was negatively linked to flossing intention. Greater inaction risk perception at Time 1 significantly increased actual flossing behavior at Time 2. The decrease in risk perception between Time 1 (inaction conditional) and Time 2 (unconditional) was greater with increasing intentions at Time 1 and with actual behavioral engagement between Time 1 and Time 2. The findings of this study supported both the behavioral motivation hypothesis and the risk reappraisal hypothesis.

Elucidating the Risk Factors for Progression from Amyloid-Negative Amnestic Mild Cognitive Impairment to Dementia.

BACKGROUND: Amyloid PET allows for the assessment of amyloid ß status in the brain, distinguishing true Alzheimer's disease from Alzheimer's disease-mimicking conditions. Around 15-20% of patients with clinically probable Alzheimer's disease have been found to have no significant Alzheimer's pathology on amyloid PET. However, a limited number of studies had been conducted on this subpopulation in terms of clinical progression. OBJECTIVE: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). METHODS: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. RESULTS: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer's diseaselike pattern despite the lack of evidence for significant Alzheimer's disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. CONCLUSION: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer's disease-mimicking dementia are warranted.

Success Expectancy: A Mediator of the Effects of Source Similarity and Self-Efficacy on Health Behavior Intention.

Although many health communication studies have substantiated the role of self-efficacy as one of the most proximal determinants of behavioral intention, a recent body of research has also shown that high self-efficacy does not always translate into intention to perform a recommended health behavior. Recognizing the common ground among three independent lines of research on outcome expectancy, goal attainability, and expectation of success, the present study proposed success expectancy, or perceived likelihood of goal achievement, as a mediator between self-efficacy and health behavior intention, which may explain the inconsistent findings on self-efficacy. An online experiment (N = 336), in which similarity of the source in health messages was manipulated, demonstrated that success expectancy indeed mediated the relationship between self-efficacy and behavioral intention. Success expectancy also mediated the effects of source similarity on behavioral intention, while neither task nor coping self-efficacy showed such effects. These results suggest that health promotion messages focusing specifically on increasing perceptions of success expectancy may be more effective in inducing health behaviors than messages that promote self-efficacy, particularly in health contexts, in which people with high self-efficacy do not tend to successfully enact recommended health behaviors.