RESUMEN
OBJECTIVES: Loss of weight is associated with cognitive decline as well as several adverse outcomes in dementia. The aim of this study was to assess whether weight loss is associated with mortality and hospitalization in dementia subtypes. METHODS: A cohort of 11,607 patients with dementia in Alzheimer's disease (AD), vascular dementia (VD), or dementia with Lewy bodies (DLB) was assembled from a large dementia care health records database in Southeast London. A natural language processing algorithm was developed to established whether loss of weight was recorded around the time of dementia diagnosis. Cox proportional hazard models were applied to examine the associations of reported weight loss with mortality and emergency hospitalization. RESULTS: Weight loss around the time of dementia was recorded in 25.5% of the whole sample and was most common in patients with DLB. A weight loss-related increased risk for mortality was detected after adjustment for confounders (Hazard ratio (HR):1.07; 95% confidence interval (CI):1.02-1.15) and in patients with AD (HR: 1.11; 95% CI: 1.04-1.20), but not in DLB and VD. Weight loss was associated with a significantly increased emergency hospitalization risk (HR: 1.14; 95% CI: 1.08-1.20) and in all three subtypes. CONCLUSIONS: While there were associations with increased hospitalization risk for all three subtype diagnoses, weight loss was only associated with increased mortality in AD. Weight loss should be considered as an accompanying symptom in dementia and interventions should be considered to ameliorate risk of adverse outcomes.
RESUMEN
Background: Anticipatory stress (AS) is denoted by concern about future events for which there is little control. Most AS research has been physiological studies such as measuring salivary cortisol levels. Medical learners may experience AS regarding employment after residency, however AS a psychological construct across career stages has not previously been studied. The objective of this study is to explore the psychological construct of employment AS in medical students, residents, and former Program Directors (PDs). Methods: Participants were recruited from a large Canadian medical school via purposive sampling. Semi-structured interviews with n=21 participants (six medical students, nine residents, and six PDs) were transcribed verbatim, and coded by two independent reviewers using thematic analysis. Results: Participants agreed that financial, family, and geographical factors exacerbate AS, and it is mitigated by flexibility, social support, and being proactive. External support, job market saturation, and differences between medical specialities also influence AS. Perspectives unique to participant groups included: medical students reflecting on a hidden curriculum and preoccupation with proximal issues over distal concerns of employment; residents experiencing competing residency program demands; former PDs finding that resident competency, yearly hiring fluctuations, and existing stress impact AS. Consequences of AS include physical and psychological manifestations, performance anxiety, and pursuing additional training. Conclusions: Perceptions of AS vary by medical career stage. Individual, program and systems-level changes can help manage and address the underlying cause of AS: an unreliable job market for physicians. Correcting the mismatch between residency positions and job openings may be a proactive, preventative approach.
RESUMEN
The regenerative capacity of injured peripheral nerves is diminished with aging. To identify factors that contribute to this impairment, we compared the immune cell response in young vs. aged animals following nerve injury. First, we confirmed that macrophage accumulation is delayed in aged injured nerves which is due to defects in monocyte migration as a result of defects in site-specific recruitment signals in the aged nerve. Interestingly, impairment in both macrophage accumulation and functional recovery could be overcome by transplanting bone marrow from aged animals into young mice. That is, upon exposure to a youthful environment, monocytes/macrophages originating from the aged bone marrow behaved similarly to young cells. Transcriptional profiling of aged macrophages following nerve injury revealed that both pro- and anti-inflammatory genes were largely downregulated in aged compared to young macrophages. One ligand of particular interest was macrophage-associated secreted protein (MCP1), which exhibited a potent role in regulating aged axonal regrowth in vitro. Given that macrophage-derived MCP1 is significantly diminished in the aged injured nerve, our data suggest that age-associated defects in MCP1 signaling could contribute to the regenerative deficits that occur in the aged nervous system.
RESUMEN
Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its "immune privileged" status.