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PCSK9 is secreted into the circulation, mainly by the liver, and interacts with low-density lipoprotein receptor (LDLR) homologous and non-homologous receptors, including CD36, thus favouring their intracellular degradation. As PCSK9 deficiency increases the expression of lipids and lipoprotein receptors, thus contributing to cellular lipid accumulation, we investigated whether this could affect heart metabolism and function.
Wild-type (WT), Pcsk9 KO, Liver conditional Pcsk9 KO and Pcsk9/Ldlr double KO male mice were fed for 20 weeks with a standard fat diet and then exercise resistance, muscle strength, and heart characteristics were evaluated. Pcsk9 KO presented reduced running resistance coupled to echocardiographic abnormalities suggestive of heart failure with preserved ejection fraction (HFpEF). Heart mitochondrial activity, following maximal coupled and uncoupled respiration, was reduced in Pcsk9 KO mice compared to WT mice and was coupled to major changes in cardiac metabolism together with increased expression of LDLR and CD36 and with lipid accumulation. A similar phenotype was observed in Pcsk9/Ldlr DKO, thus excluding a contribution for LDLR to cardiac impairment observed in Pcsk9 KO mice. Heart function profiling of the liver selective Pcsk9 KO model further excluded the involvement of circulating PCSK9 in the development of HFpEF, pointing to a possible role locally produced PCSK9. Concordantly, carriers of the R46L loss-of-function variant for PCSK9 presented increased left ventricular mass but similar ejection fraction compared to matched control subjects.
PCSK9 deficiency impacts cardiac lipid metabolism in an LDLR independent manner and contributes to the development of HFpEF.
PCSK9 deficiency impacts cardiac lipid metabolism in an LDLR independent manner and contributes to the development of HFpEF.Understanding how older people respond to SARS-CoV-2 is critical if we are to confront the COVID-19 pandemic and establish effective vaccination strategies. Immunosenescence reduces the ability to respond to neoantigens and may compromise the life of infected individuals. Here, we analysed the immunological memory to SARS-CoV-2 in 102 recovered patients aged over 60 years several months after the infection had been resolved. Specific memory T lymphocytes against the virus were measured by IFN-γ and granzyme B release by ELISpot; memory B lymphocyte responses were quantified by detection of anti-S IgG1 producer cells by ELISpot and anti-S and anti-N antibodies were determined by ELISA. Memory T lymphocytes were found in peripheral blood of most of the studied donors, more than seven months after the infection in some of them. Fewer patients maintained memory B lymphocytes, but antibodies, mainly anti-S, were highly durable and positively correlated with T responses. More robust humoral responses were found in patients who had more severe symptoms and had been admitted to hospital. We concluded that specific immunity against SARS-CoV-2 is effectively preserved regardless of age, despite the great heterogeneity of their immune responses, and that memory T lymphocytes and anti-S IgG might be more durable than memory B cells and anti-N IgG.
The COVID-19 pandemic has left older adults around the world bereaved by the sudden death of relatives and friends. We examine if COVID-19 bereavement corresponds with older adults' reporting depression in 27 countries, and test for variation by gender and country context.
We analyze SHARE COVID-19 data collected between June-August 2020 from N=51,383 older adults (age 50-104) living in 27 countries, of whom 1,363 reported the death of a relative or friend from COVID-19. We estimate pooled-multilevel logit regression models to examine if COVID-19 bereavement was associated with self-reported depression and worsening depression, and we test whether national COVID-19 mortality rates moderate these assocations.
COVID-19 bereavement is associated with significantly higher probabilities of both reporting depression and reporting worsened depression among older adults. Net of one's own personal loss, living in a country with the highest COVID-19 mortality rate is associated with women's reports of worsened depression but not men's. However, the country's COVID-19 mortality rate does not moderate associations between COVID-19 bereavement and depression.
COVID-19 deaths have lingering mental health implications for surviving older adults. Even as the collective toll of the crisis is apparent, bereaved older adults are in particular need of mental health support.
COVID-19 deaths have lingering mental health implications for surviving older adults. Even as the collective toll of the crisis is apparent, bereaved older adults are in particular need of mental health support.
5A's counselling is recommended for screening and treating patients with smoking addiction. The emergency department (ED) setting might be a suitable environment for conducting interventions for smoking cessation. The present study aims to determine the feasibility and effectiveness on smoking cessation of 5A's counselling administered to ED patients by nurses.
Parallel group randomized trial assessing 5A's counselling for smoking cessation vs. usual care at a University Hospital in the North of Italy. The primary end-point was prevalence of tobacco-free patients. The secondary outcomes at 6- and 12-month follow-up were (i) consecutive past 30-day smoking abstinence; (ii) past 7-day 50%, or more, decrease in daily tobacco consumption over baseline; and (iii) number of attempts to quit smoking.
A total of 480 patients were randomized to intervention (n = 262) or usual care (n = 218). see more Intention to treat analysis displayed no differences in primary and secondary outcomes between groups. A slight but not statistically significant enhancement in cessation was recorded in the intervention group [relative risk (RR) = 1.04, 95% confidence interval (CI) = 0.58-1.87] at 6 months, whereas a reversed observation at 12 months (RR = 0.86, 95% CI = 0.50-1.47). Similar results were obtained for the secondary outcomes. Per protocol analysis increased the size of the results. Of the 126 smokers receiving counselling, 18 were visited and treated at the local smoking cessation centre, with 12 of them successfully completing the treatment.
The results of this study indicate that the ED is not a suited environment for 5A's counselling.
The results of this study indicate that the ED is not a suited environment for 5A's counselling.
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