Identifying People at High Risk for Severe Aortic Stenosis: Aortic Valve Calcium Versus Lipoprotein(a) and Low-Density Lipoprotein Cholesterol.

BACKGROUND: Aortic valve calcification (AVC), Lp(a) [lipoprotein(a)], and low-density lipoprotein cholesterol (LDL-C) are associated with severe aortic stenosis (AS). We aimed to determine which of these risk factors were most strongly associated with the risk of incident severe AS. METHODS: A total of 6792 participants from the MESA study (Multi-Ethnic Study of Atherosclerosis) had computed tomography-quantified AVC, Lp(a), and LDL-C values at MESA visit 1 (2000-2002). We calculated the absolute event rate of incident adjudicated severe AS per 1000 person-years and performed multivariable adjusted Cox proportional hazards regression. RESULTS: The mean age was 62 years old, and 47% were women. Over a median 16.7-year follow-up, the rate of incident severe AS increased exponentially with higher AVC, regardless of Lp(a) or LDL-C values. Participants with AVC=0 had a very low rate of severe AS even with elevated Lp(a) ≥50 mg/dL (<0.1/1000 person-years) or LDL-C ≥130 mg/dL (0.1/1000 person-years). AVC >0 was strongly associated with severe AS when Lp(a) <50 mg/dL hazard ratio (HR) of 33.8 (95% CI, 16.4-70.0) or ≥50 mg/dL HR of 61.5 (95% CI, 7.7-494.2) and when LDL-C <130 mg/dL HR of 31.1 (95% CI, 14.4-67.1) or ≥130 mg/dL HR of 50.2 (95% CI, 13.2-191.9). CONCLUSIONS: AVC better identifies people at high risk for severe AS compared with Lp(a) or LDL-C, and people with AVC=0 have a very low long-term rate of severe AS regardless of Lp(a) or LDL-C level. These results suggest AVC should be the preferred prognostic risk marker to identify patients at high risk for severe AS, which may help inform participant selection for future trials testing novel strategies to prevent severe AS.

Association of aortic valve calcium with dementia and stroke: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional hazards ratios (HR). RESULTS: Overall, 6812 participants had AVC quantified with a mean age of 62.1 years old, 52.9 % were women, and the median 10-year estimated atherosclerotic cardiovascular disease (ASCVD) risk was 13.5 %. Participants with AVC >0 were older and less likely to be women compared to those with AVC=0. Over a median 16-year follow-up, there were 535 cases of dementia and 376 cases of stroke. The absolute risk of newly diagnosed dementia increased in a stepwise pattern with higher AVC scores, and stroke increased in a logarithmic pattern. In multivariable analyses, AVC was significantly associated with newly diagnosed dementia as a log-transformed continuous variable (HR 1.09; 95 % CI 1.04-1.14) and persons with AVC ≥300 had nearly a two-fold higher risk (HR 1.77; 95 % CI 1.14-2.76) compared to those with AVC=0. AVC was associated with an increased risk of stroke after adjustment for age, sex, and race/ethnicity, but not after adjustment for ASCVD risk factors. CONCLUSIONS: After multivariable adjustment, AVC >0 was significantly associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional ASCVD risk factors.

Parents' Perceptions of Schools' COVID-19 Mitigation Strategies: A Phenomenological Study.

BACKGROUND: At the onset of the COVID-19 pandemic, schools closed across the United States. Given the impact of virtual learning and lost access to school resources, schools eventually reopened with COVID-19 mitigation protocols in place. This qualitative study sought to understand parental perceptions of school-based COVID-19 mitigation strategies. METHODS: Using a phenomenology approach, nine focus groups were completed with 40 parents of children in grades K-8 representing eight Maryland counties. Based on acceptance of masking policies (as indicated on a survey), parents were sorted into 2 groups-lower and higher masking acceptance. A thematic analysis was conducted for each group and themes were compared between the 2 groups. RESULTS: The main themes were related to parents' general sentiments regarding COVID-19, compliance, pandemic-related changes over time, changes in personal opinions, and in-person learning. Both groups described challenges related to inconsistent COVID-19 mitigation policies and practices, the challenges of rapid and frequent changes in guidelines during the pandemic, and the benefits of in-person learning. CONCLUSIONS: Parents of elementary and middle school children, regardless of general acceptance of masking policies, shared concerns about implementation and guidance regarding school-based mitigation strategies.

The DEAD-box helicase Mss116 plays distinct roles in mitochondrial ribogenesis and mRNA-specific translation.

Members of the DEAD-box family are often multifunctional proteins involved in several RNA transactions. Among them, yeast Saccharomyces cerevisiae Mss116 participates in mitochondrial intron splicing and, under cold stress, also in mitochondrial transcription elongation. Here, we show that Mss116 interacts with the mitoribosome assembly factor Mrh4, is required for efficient mitoribosome biogenesis, and consequently, maintenance of the overall mitochondrial protein synthesis rate. Additionally, Mss116 is required for efficient COX1 mRNA translation initiation and elongation. Mss116 interacts with a COX1 mRNA-specific translational activator, the pentatricopeptide repeat protein Pet309. In the absence of Mss116, Pet309 is virtually absent, and although mitoribosome loading onto COX1 mRNA can occur, activation of COX1 mRNA translation is impaired. Mutations abolishing the helicase activity of Mss116 do not prevent the interaction of Mss116 with Pet309 but also do not allow COX1 mRNA translation. We propose that Pet309 acts as an adaptor protein for Mss116 action on the COX1 mRNA 5΄-UTR to promote efficient Cox1 synthesis. Overall, we conclude that the different functions of Mss116 in the biogenesis and functioning of the mitochondrial translation machinery depend on Mss116 interplay with its protein cofactors.