Bmc Med
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Chronic musculoskeletal pain has been linked to dementia; however, chronic pain typically occurs in multiple sites; therefore, this study was to investigate whether greater number of chronic pain sites is associated with a higher risk of dementia and its subtypes. ⋯ Greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia and AD, suggesting that chronic pain in multiple sites may contribute to individuals' dementia risk and is an underestimated risk factor for dementia.
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Alzheimer's disease (AD) pathology impairs cognitive function. Yet some individuals with high amounts of AD pathology suffer marked memory impairment, while others with the same degree of pathology burden show little impairment. Why is this? One proposed explanation is cognitive reserve i.e., factors that confer resilience against, or compensation for the effects of AD pathology. Deep NREM slow wave sleep (SWS) is recognized to enhance functions of learning and memory in healthy older adults. However, that the quality of NREM SWS (NREM slow wave activity, SWA) represents a novel cognitive reserve factor in older adults with AD pathology, thereby providing compensation against memory dysfunction otherwise caused by high AD pathology burden, remains unknown. ⋯ These findings indicate that NREM SWA is a novel cognitive reserve factor providing resilience against the memory impairment otherwise caused by high AD pathology burden. Furthermore, this cognitive reserve function of NREM SWA remained significant when accounting both for covariates, and factors previously linked to resilience, suggesting that sleep might be an independent cognitive reserve resource. Beyond such mechanistic insights are potential therapeutic implications. Unlike many other cognitive reserve factors (e.g., years of education, prior job complexity), sleep is a modifiable factor. As such, it represents an intervention possibility that may aid the preservation of cognitive function in the face of AD pathology, both present moment and longitudinally.
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Long-term intake of a Western diet (WD), characterized by a high-fat content and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms by which dietary changes contribute to IBD development remain unknown. Therefore, we examined the influence of long-term intake of a WD on intestinal inflammation and the mechanisms by which WD intake affects IBD development. ⋯ Our findings suggest that the TAS1R3-mTOR-PPARγ axis in the gut links Western diet consumption with intestinal inflammation and is a potential therapeutic target for IBD.
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Furmonertinib (AST2818) is a brain penetrant pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR sensitizing mutations and T790M mutation. We report the pooled central nervous system (CNS) efficacy data of furmonertinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC) from two phase 2 studies. ⋯ Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutated NSCLC.
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Considerable evidence has been reported that tobacco use could cause alterations in gut microbiota composition. The microbiota-gut-brain axis also in turn hinted at a possible contribution of the gut microbiota to smoking. However, population-level studies with a higher evidence level for causality are lacking. ⋯ In summary, the current study suggested the role of the specific gut microbes on the risk for cigarette smoking (likely involving alterations in metabolites) and in turn smoking on specific gut microbes. Our findings highlighted the hazards of tobacco use for gut flora dysbiosis and shed light on the potential role of specific gut microbiota for smoking behaviors.