Spouse's subjective social status predicts older adults’ prospective cognitive functioning

Objectives: The current study aims to investigate the association between subjective social status (SSS) and prospective cognitive functioning of older adults and their spouses, and to explore the potential mediating roles of health habits and physical activities in this association.

Method: Using the longitudinal data of 512 pairs of community-dwelling older couples aged 65–91 years (M = 72.2 ± 4.6), we tested the effects of SSS in cognitive functioning using an Actor-Partner Interdependence Model. SSS was measured by a self-anchoring social ladder, and cognitive functioning was measured by the Mini-Mental State Examination at baseline and 4-year follow-up. Socioeconomic status (i.e. education) was tested as a moderator, and physical activity (measured by the Physical Activity Scale for the Elderly) as well as health habits (i.e. tobacco and alcohol consumption) were included as potential mediators.

Results: A partner effect of SSS was found only in the low-education group, in which the wife's higher level of SSS in the community was associated with the husband's better cognitive functioning in the follow-up. A small proportion of this effect was found to be partially mediated by participation in housework, such that the wife's higher SSS was associated with the husband's increased housework activity, which was related to higher prospective cognitive functioning.

Conclusion: By examining the dyadic effects of SSS with a longitudinal design, our findings extended the understanding on how subjective social status influenced older couples’ cognitive health, and provided evidence-based insights for future studies on cognitive health in later life.     

Profiles of sleep changes during the COVID‐19 pandemic: Demographic,behavioural and psychological factors

This study aimed to evaluate changes in sleep during the COVID‐19 outbreak, and used data‐driven approaches to identify distinct profiles of changes in sleep‐related behaviours. Demographic, behavioural and psychological factors associated with sleep changes were also investigated. An online population survey assessing sleep and mental health was distributed between 3 April and 24 June 2020. Retrospective questions were used to estimate temporal changes from before to during the outbreak. In 5,525 Canadian respondents (67.1% females, 16–95 years old: Mean ± SD = 55.6 ± 16.3 years), wake‐up times were significantly delayed relative to pre‐outbreak estimates (p < .001,  = 0.04). Occurrences of clinically meaningful sleep difficulties significantly increased from 36.0% before the outbreak to 50.5% during the outbreak (all p < .001, g ≥ 0.27). Three subgroups with distinct profiles of changes in sleep behaviours were identified: “Reduced Time in Bed”, “Delayed Sleep” and “Extended Time in Bed”. The “Reduced Time in Bed” and “Delayed Sleep” subgroups had more adverse sleep outcomes and psychological changes during the outbreak. The emergence of new sleep difficulties was independently associated with female sex, chronic illnesses, being employed, family responsibilities, earlier wake‐up times, higher stress levels, as well as heavier alcohol use and television exposure. The heterogeneity of sleep changes in response to the pandemic highlights the need for tailored interventions to address sleep problems.     

GLI1-induced mammary gland tumours are transplantable and maintain major molecular features

Increased expression of GLI1, the main Hedgehog signalling pathway effector, is related to unfavourable prognosis and progressive disease of certain breast cancer subtypes. We used conditional transgenic mice induced to overexpress GLI1 in the mammary epithelium either alone or in combination with deletion of one Trp53 allele to address the role of elevated GLI1 expression in breast tumour initiation and progression. Induced GLI1 expression facilitates mammary gland tumour formation and this was further increased upon heterozygous deletion of Trp53. The GLI1-induced primary tumours were of different murine molecular subtypes, including Normal-like^Ex, Class8^Ex, Claudin-Low^Ex and Erbb2-like^Ex. The gene expression profiles of some of the tumours correlated well with the PAM50 subtypes for human breast cancer. Whole-exome sequencing revealed somatic mutation profiles with only little overlap between the primary tumours. Orthotopically serially transplanted GLI1-induced tumours maintained the main morphological characteristics of the primary tumours for ≥10 generations. Independent of Trp53 status and molecular subtype, the serially transplanted GLI1-induced tumours were able to grow both in the absence of transgenic GLI1 expression and in the presence of the GLI1 inhibitor GANT61. These data suggest that elevated GLI1 expression has a determinant role in tumour initiation; however, additional genetic events are required for tumour progression.     

Photoperiod-induced neurotransmitter plasticity declines with aging: An epigenetic regulation?

Neuroplasticity has classically been understood to arise through changes in synaptic strength or synaptic connectivity. A newly discovered form of neuroplasticity, neurotransmitter switching, involves changes in neurotransmitter identity. Chronic exposure to different photoperiods alters the number of dopamine (tyrosine hydroxylase, TH+) and somatostatin (SST+) neurons in the paraventricular nucleus (PaVN) of the hypothalamus of adult rats and results in discrete behavioral changes. Here, we investigate whether photoperiod-induced neurotransmitter switching persists during aging and whether epigenetic mechanisms of histone acetylation and DNA methylation may contribute to this neurotransmitter plasticity. We show that this plasticity in rats is robust at 1 and at 3 months but reduced in TH+ neurons at 12 months and completely abolished in both TH+ and SST+ neurons by 18 months. De novo expression of DNMT3a catalyzing DNA methylation and anti-AcetylH3 assessing histone 3 acetylation were observed following short-day photoperiod exposure in both TH+ and SST+ neurons at 1 and 3 months while an overall increase in DNMT3a in SST+ neurons paralleled neuroplasticity reduction at 12 and 18 months. Histone acetylation increased in TH+ neurons and decreased in SST+ neurons following short-day exposure at 3 months while the total number of anti-AcetylH3+ PaVN neurons remained constant. Reciprocal histone acetylation in TH+ and SST+ neurons indicates the importance of studying epigenetic regulation at the circuit level for identified cell phenotypes. The findings may be useful for developing approaches for noninvasive treatment of disorders characterized by neurotransmitter dysfunction.     

The impact of cytogenetic risk on the outcomes of allogeneic hematopoietic cell transplantation in patients with relapsed/refractory acute myeloid leukemia: On behalf of the acute leukemia working party (ALWP) of the European group for blood and marrow transplantation (EBMT)

Karyotypic analysis at time of diagnosis has an important value in determining initial response to treatment, remission duration and overall survival (OS) in acute myeloid leukemia (AML). Less is known about its value before allogeneic hematopoietic cell transplantation (allo‐HCT) in patients transplanted with active disease, either relapsed or primary refractory (Rel‐Ref) AML. We explored the impact of cytogenetic risk (stratification according to MRC‐UK) in 2089 patients with either Ref (n = 972) or Rel AML (n = 1117) transplanted during the period 2000‐2017. Overall, 154 patients had a favorable risk, 1283 had an intermediate risk and 652 had an adverse cytogenetic risk. Median follow‐up was 49 months. Compared to the favorable risk group, intermediate and adverse risk patients were associated with worse leukemia‐free survival and OS and also with a higher incidence of relapse. In a subgroup analysis of patients in the intermediate risk group harboring Fms‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD), this remained an important prognostic factor, being associated with worse outcomes. When analyzing patients according to the intensity of the conditioning regimen, no differences were observed for the main transplant outcomes. In conclusion, in patients diagnosed with AML and transplanted with active disease, karyotype remains an important prognostic factor, allowing splitting patients into different risk groups according to their cytogenetics. Similarly, FLT3‐ITD mutation also remains a negative prognostic factor in this population.