Missing the target: including perspectives of women with overweight and obesity to inform stigma-reduction strategies

OBJECTIVE: Pervasive weight stigma and discrimination have led to ongoing calls for efforts to reduce this bias. Despite increasing research on stigma-reduction strategies, perspectives of individuals who have experienced weight stigma have rarely been included to inform this research. The present study conducted a systematic examination of women with high body weight to assess their perspectives about a broad range of strategies to reduce weight-based stigma. METHODS: Women with overweight or obesity (N = 461) completed an online survey in which they evaluated the importance, feasibility and potential impact of 35 stigma-reduction strategies in diverse settings. Participants (91.5% who reported experiencing weight stigma) also completed self-report measures assessing experienced and internalized weight stigma. RESULTS: Most participants assigned high importance to all stigma-reduction strategies, with school-based and healthcare approaches accruing the highest ratings. Adding weight stigma to existing anti-harassment workplace training was rated as the most impactful and feasible strategy. The family environment was viewed as an important intervention target, regardless of participants\u27 experienced or internalized stigma. CONCLUSION: These findings underscore the importance of including people with stigmatized identities in stigma-reduction research; their insights provide a necessary and valuable contribution that can inform ways to reduce weight-based inequities and prioritize such efforts

S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model

Inflammation, insoluble protein deposition and neuronal cell loss are important features in the Alzheimer's disease (AD) brain. To investigate the regulatory genes responsible for the neuropathology in AD, we performed microarray analysis with APPV717I-CT100 transgenic mice, an animal model of AD, and isolated the S100a9 gene, which encodes an inflammation-associated calcium binding protein. In another AD animal model, Tg2576 mouse brain, and in human AD brain, induction of S100a9 was confirmed. The endogenous expression of S100a9 was induced by treatment with Aβ or CT peptides in a microglia cell line, BV2 cells. In these cells, silencing study of S100a9 showed that the induction of S100a9 increased the intracellular calcium level and up-regulated the inflammatory cytokines (IL-1β and TNFα) and iNOS. S100a9 lentiviral short hairpin RNA (sh-S100a9) was injected into the hippocampus region of the brains of 13-month-old Tg2576 mice. At two months after injection, we found that knockdown of S100a9 expression had improved the cognition decline of Tg2576 mice in the water maze task, and had reduced amyloid plaque burden. These results suggest that S100a9 induced by Aβ or CT contributes to cause inflammation, which then affects the neuropathology including amyloid plaques burden and impairs cognitive function. Thus, the inhibition of S100a9 is a possible target for AD therapy

Risk and sensitivity quantification of fracture failure employing cohesive zone elements

Many structures are subjected to the risk of fatigue failure. For their reliability-based design, it is thus important to calculate the probability of fatigue failure and assess the relative importance of the involved parameters. Although various studies have analyzed the fatigue failure, the stage of fracture failure has been less focused. In particular, the risk analysis of fracture failure needs to be conducted considering its importance in actual structures. This article proposes a new probabilistic framework for the risk and sensitivity analysis of structural fatigue failure employing cohesive zone elements. The proposed framework comprises three steps, namely finite element analysis using cohesive zone elements, response surface construction, and risk and sensitivity analysis of fatigue failure, which require several mathematical techniques and algorithms. The proposed framework is tested by applying it to an illustrative example, and the corresponding analysis results of fracture failure probability with different threshold values of a limit-state function are presented. In addition, the sensitivities of failure risk with respect to the statistical parameters of random variables are presented and their relative importance is discussed

Orthogonal-view Microscope for the Biomechanics Investigations of Aquatic Organisms

Microscopes are essential for biomechanics and hydrodynamical investigation of small aquatic organisms. We report a DIY microscope (GLUBscope) that enables the visualization of organisms from two orthogonal imaging planes (top and side views). Compared to conventional imaging systems, this approach provides a comprehensive visualization strategy of organisms, which could have complex shapes and morphologies. The microscope was constructed by combining custom 3D-printed parts and off-the-shelf components. The system is designed for modularity and reconfigurability. Open-source design files and build instructions are provided in this report. Additionally, proof of use experiments, particularly with Hydra and other organisms that combine the GLUBscope with an analysis pipeline, were demonstrated. Beyond the applications demonstrated, the system can be used or modified for various imaging applications

Amyloid Precursor Protein Binding Protein-1 Modulates Cell Cycle Progression in Fetal Neural Stem Cells

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of the amyloid precursor protein (APP) and serves as the bipartite activation enzyme for the ubiquitin-like protein, NEDD8. In the present study, we explored the physiological role of APP-BP1 in the cell cycle progression of fetal neural stem cells. Our results show that cell cycle progression of the cells is arrested at the G1 phase by depletion of APP-BP1, which results in a marked decrease in the proliferation of the cells. This action of APP-BP1 is antagonistically regulated by the interaction with APP. Consistent with the evidence that APP-BP1 function is critical for cell cycle progression, the amount of APP-BP1 varies depending upon cell cycle phase, with culminating expression at S-phase. Furthermore, our FRET experiment revealed that phosphorylation of APP at threonine 668, known to occur during the G2/M phase, is required for the interaction between APP and APP-BP1. We also found a moderate ubiquitous level of APP-BP1 mRNA in developing embryonic and early postnatal brains; however, APP-BP1 expression is reduced by P12, and only low levels of APP-BP1 were found in the adult brain. In the cerebral cortex of E16 rats, substantial expression of both APP-BP1 and APP mRNAs was observed in the ventricular zone. Collectively, these results indicate that APP-BP1 plays an important role in the cell cycle progression of fetal neural stem cells, through the interaction with APP, which is fostered by phopshorylation of threonine 668