Plos One
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β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) initiates the production of β-amyloid (Aβ), the major constituent of amyloid plaques in Alzheimer's disease (AD). BACE1 is elevated ∼2-3 fold in AD brain and is concentrated in dystrophic neurites near plaques, suggesting BACE1 elevation is Aβ-dependent. Previously, we showed that phosphorylation of the translation initiation factor eIF2α de-represses translation of BACE1 mRNA following stress such as energy deprivation. ⋯ We conclude that amyloid-associated BACE1 elevation is not caused by translational de-repression via eIF2α phosphorylation, but instead appears to involve a post-translational mechanism. These definitive genetic results exclude a role for eIF2α phosphorylation in Aβ-dependent BACE1 and APP elevation. We suggest a vicious pathogenic cycle wherein Aβ42 toxicity induces peri-plaque BACE1 and APP accumulation in dystrophic neurites leading to exacerbated Aβ production and plaque progression.
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Impaired healing and non-union of skeletal fractures is a major public health problem, with morbidity exacerbated in patients with diabetes mellitus (DM). DM is prevalent worldwide and affects approximately 25.8 million US adults, with >90% having obesity-related type 2 DM (T2DM). While fracture healing in type 1 DM (T1DM) has been studied using animal models, an investigation into delayed healing in an animal model of T2DM has not yet been performed. ⋯ Our murine model of T2DM demonstrated delayed fracture healing and weakened biomechanical properties, and was distinctly characterized by increased callus adiposity. This suggests altered mesenchymal stem cell fate determination with a shift to the adipocyte lineage at the expense of the osteoblast lineage. The up-regulation of PPARγ in fracture calluses of HFD-fed mice is likely involved in the proposed fate switching.
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The risk of incidents involving mass decontamination in response to a chemical, biological, radiological, or nuclear release has increased in recent years, due to technological advances, and the willingness of terrorists to use unconventional weapons. Planning for such incidents has focused on the technical issues involved, rather than on psychosocial concerns. This paper presents a novel experimental study, examining the effect of three different responder communication strategies on public experiences and behaviour during a mass decontamination field experiment. ⋯ The communication strategy which resulted in the most efficient progression of participants through the decontamination process, as well as the fewest observations of non-compliance and confusion, was that which included both health-focused explanations about decontamination and sufficient practical information. Further, this strategy resulted in increased perceptions of responder legitimacy and increased identification with responders, which in turn resulted in higher levels of expected compliance during a real incident, and increased willingness to help other members of the public. This study shows that an understanding of the social identity approach facilitates the development of effective responder communication strategies for incidents involving mass decontamination.
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Observational Study
Organizational factors and long-term mortality after hip fracture surgery. A cohort study of 6143 consecutive patients undergoing hip fracture surgery.
In hospital and health care organizational factors may be changed to reduce postoperative mortality. The aim of this study is to evaluate a possible association between mortality and 'length of hospital stay', 'priority of surgery', 'time of surgery', or 'surgical delay' in hip fracture surgery. ⋯ Non-scheduled surgery and length of hospital stay were associated with increased mortality. Confounding by indication may bias observational studies evaluating early and late discharge as well as priority; therefore cluster randomized clinical trials comparing different clinical set ups may be warranted evaluating health care organizational factors.
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Adaptive anxiety relies on a balance between the generalization of fear acquisition and fear extinction. Research on fear (extinction) generalization has focused mostly on perceptual similarity, thereby ignoring the importance of conceptual stimulus relations in humans. The present study used a laboratory procedure to create de novo conceptual categories of arbitrary stimuli and investigated fear and extinction generalization among these stimuli. ⋯ Subsequent extinction of the conditioned member also generalized to the other members. However, extinguishing a non-conditioned member failed to reduce fear of the conditioned member itself. We conclude that fears generalize readily across conceptually related stimuli, but that the degree of extinction generalization depends on the stimulus subjected to extinction.