Epigenetic Age Acceleration and Change in Frailty in MOBILIZE Boston

Age-associated changes in DNA methylation have been implicated as one mechanism to explain the development of frailty, however previous cross-sectional studies of epigenetic age acceleration (eAA) and frailty have had inconsistent findings. Few longitudinal studies have considered the association of eAA with change in frailty. We sought to determine the association between eAA and change in frailty in the MOBILIZE Boston cohort. Participants were assessed at two visits 12-18 months apart. Intrinsic, extrinsic, GrimAge, and PhenoAge eAA were assessed from whole blood DNA methylation at baseline using the Infinium 450k array. Frailty was assessed by a continuous frailty score based on the frailty phenotype and by frailty index (FI). Analysis was by correlation and linear regression with adjustment for age, sex, smoking status, and BMI. 395 participants with a frailty score and 431 with a FI had epigenetic and follow-up frailty measures. For the frailty score and FI cohorts, respectively, mean (SD) ages were 77.8 (5.49) and 77.9 (5.47), 232 (58.7%) and 257 (59.6%) were female. All participants with epigenetic data identified as white. Baseline frailty score was not correlated with intrinsic or extrinsic eAA, but was correlated with PhenoAge and, even after adjustment for covariates, GrimAge. Baseline FI was correlated with extrinsic, GrimAge, and PhenoAge eAA with and without adjustment. No eAA measure was associated with change in frailty, with or without adjustment. Our results suggest that no eAA measure was associated with change in frailty. Further studies should consider longer periods of follow-up and repeated eAA measurement.

Association of Dietary Patterns with MRI Markers of Hepatic Inflammation and Fibrosis in the MAST4HEALTH Study

Whereas the etiology of non-alcoholic fatty liver disease (NAFLD) is complex, the role of nutrition as a causing and preventive factor is not fully explored. The aim of this study is to associate dietary patterns with magnetic resonance imaging (MRI) parameters in a European population (Greece, Italy, and Serbia) affected by NAFLD. For the first time, iron-corrected T1 (cT1), proton density fat fraction (PDFF), and the liver inflammation fibrosis score (LIF) were examined in relation to diet. A total of 97 obese patients with NAFLD from the MAST4HEALTH study were included in the analysis. A validated semi-quantitative food frequency questionnaire (FFQ) was used to assess the quality of diet and food combinations. Other variables investigated include anthropometric measurements, total type 2 diabetes risk, physical activity level (PAL), and smoking status. Principal component analysis (PCA) was performed to identify dietary patterns. Six dietary patterns were identified, namely “High-Sugar”, “Prudent”, “Western”, “High-Fat and Salt”, “Plant-Based”, and “Low-Fat Dairy and Poultry”. The “Western” pattern was positively associated with cT1 in the unadjusted model (beta: 0.020, p-value: 0.025) and even after adjusting for age, sex, body mass index (BMI), PAL, smoking, the center of the study, and the other five dietary patterns (beta: 0.024, p-value: 0.020). On the contrary, compared with low-intake patients, those with medium intake of the “Low-Fat Dairy and Poultry” pattern were associated with lower values of cT1, PDFF, and LIF. However, patients with a “Low-Fat Dairy and Poultry” dietary pattern were negatively associated with MRI parameters (cT1: beta: −0.052, p-value: 0.046, PDFF: beta: −0.448, p-value: 0.030, LIF: beta: −0.408, p-value: 0.025). Our findings indicate several associations between MRI parameters and dietary patterns in NAFLD patients, highlighting the importance of diet in NAFLD.

Association of Angio-LncRNAs MIAT rs1061540/MALAT1 rs3200401 Molecular Variants with Gensini Score in Coronary Artery Disease Patients Undergoing Angiography

Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic and/or prognostic utility in several diseases, including coronary artery disease (CAD). We aimed for the first time to investigate the potential association of five angiogenesis-related lncRNAs (PUNISHER, SENCR, MIAT, MALAT1, and GATA6-AS) variants with CAD susceptibility and/or severity. TaqMan Real-Time genotyping for PUNISHER rs12318065A/C, SENCR rs12420823C/T, MIAT rs1061540C/T, MALAT1 rs3200401T/C, and GATA6-AS1 rs73390820A/G were run on the extracted genomic DNA from 100 unrelated patients with stable CAD undergoing diagnostic coronary angiography and from 100 controls. After adjusting covariates, the studied variants showed no association with disease susceptibility; however, MIAT*T/T genotype was associated with a more severe Gensini score. In contrast, MALAT1*T/C heterozygosity was associated with a lower score. The lipid profile, and to a lesser extent smoking status, male sex, weight, hypertension, and MALAT1 (T > C) (negative correlation), explained the variance between patients/control groups via a principal component analysis. Incorporating the principal components into a logistic regression model to predict CAD yielded a 0.92 AUC. In conclusion: MIAT rs1061540 and MALAT1 rs3200401 variants were associated with CAD severity and Gensini score in the present sample of the Egyptian population. Further large multi-center and functional analyses are needed to confirm the results and identify the underlying molecular mechanisms.

Mortality from various diseases of the circulatory system in the Russian Mayak nuclear worker cohort: 1948–2018

The paper reports on findings of the study of mortality from diseases of circulatory system (DCS) in Russian nuclear workers of the Mayak Production Association (22,377 individuals with 25.4% of females) who were hired at the facility in 1948–1982 and followed up until end-2018. Using the AMFIT module of EPICURE software, relative risks and excess relative risks per unit absorbed dose (ERR/Gy) for the entire Mayak cohort, the subcohort of workers who were residents of the dormitory town of Ozyorsk and the subcohort of migrants from Ozyorsk were calculated based on maximum likelihood. The mean cumulative liver absorbed gamma-ray dose from external exposure was 0.45 (0.65) Gy (mean (standard deviation) gray) for males and 0.37 (0.56) Gy for females. The mean cumulative liver absorbed alpha dose from internal exposure to incorporated plutonium was 0.18 (0.65) Gy for males and 0.40 (1.92) Gy for females. By the end of the follow-up, 6019 deaths from DCS as the main cause of death were registered among Mayak PA workers (including 3828 deaths in the subcohort of residents and 2191 deaths in the subcohort of migrants) over 890,132 (622,199/267,933) person-years of follow-up. The linear model that took into account non-radiation factors (sex, attained age, calendar period, smoking status and alcohol drinking status) and alpha radiation dose (via adjusting) did not demonstrate significant associations of mortality from DCS, ischemic heart disease (IHD) and cerebrovascular disease (CeVD) with gamma-ray exposure dose in the entire cohort, the resident subcohort and the migrant subcohort (either in males or females). For the subcohort of residents, a significant association with gamma dose was observed for mortality from ischemic stroke in males with ERR/Gy=0.43 (95% CI 0.08; 0.99); there were no significant associations with liver absorbed gamma dose for any other considered outcomes. As for internal exposure, for males no significant associations of mortality from any of the DCS with liver absorbed alpha dose were observed, but for females positive associations were found for DCS (the entire cohort and the resident subcohort) and IHD (the entire cohort) mortality. No significant associations of mortality from various types of DCS with neutron dose were observed either in males or females, although neutron absorbed doses were recorded only in 18% of the workers.

Ultra-processed food and incident type 2 diabetes: studying the underlying consumption patterns to unravel the health effects of this heterogeneous food category in the prospective Lifelines cohort

Background The overall consumption of ultra-processed food (UPF) has previously been associated with type 2 diabetes. However, due to the substantial heterogeneity of this food category, in terms of their nutritional composition and product type, it remains unclear whether previous results apply to all underlying consumption patterns of UPF. Methods Of 70,421 participants (35–70 years, 58.6% women) from the Lifelines cohort study, dietary intake was assessed with a food frequency questionnaire. UPF was identified according to the NOVA classification. Principal component analysis (PCA) was performed to derive UPF consumption patterns. The associations of UPF and adherence to UPF consumption patterns with incidence of type 2 diabetes were studied with logistic regression analyses adjusted for age, sex, diet quality, energy intake, alcohol intake, physical activity, TV watching time, smoking status, and educational level. Results During a median follow-up of 41 months, a 10% increment in UPF consumption was associated with a 25% higher risk of developing type 2 diabetes (1128 cases; OR 1.25 [95% CI 1.16, 1.34]). PCA revealed four habitual UPF consumption patterns. A pattern high in cold savory snacks (OR 1.16 [95% CI 1.09, 1.22]) and a pattern high in warm savory snacks (OR 1.15 [95% CI 1.08, 1.21]) were associated with an increased risk of incident type 2 diabetes; a pattern high in traditional Dutch cuisine was not associated with type 2 diabetes incidence (OR 1.05 [95% CI 0.97, 1.14]), while a pattern high in sweet snacks and pastries was inversely associated with type 2 diabetes incidence (OR 0.82 [95% CI 0.76, 0.89]). Conclusions The heterogeneity of UPF as a general food category is reflected by the discrepancy in associations between four distinct UPF consumption patterns and incident type 2 diabetes. For better public health prevention, research is encouraged to further clarify how different UPF consumption patterns are related to type 2 diabetes.

Functional status, mood state, and physical activity among women with post-acute COVID-19 syndrome

Objectives: While organ-specific pathophysiology has been well-described in SARS-CoV-2 infection, less is known about the attendant effects on functional status, mood state and leisure-time physical activity (PA) in post-acute COVID-19 syndrome. Methods: A case-control design was employed to recruit 32 women (n = 17 SARS-CoV-2; n = 15 controls) matched on age (54 +/- 12 years), body mass index (27 +/- 6 kg/m2), smoking status, and history of cardiopulmonary disease. Participants completed a series of assessments including the Modified Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ-M), Profile of Mood States (POMS), and Godin-Shephard Leisure-Time PA. Results: SARS-CoV-2 participants exhibited poorer functional status (p = 0.008) and reduced leisure-time PA (p = 0.004) compared to controls. Significant between-group differences were also detected for the POMS total mood disturbance with sub-scale analyses revealing elevated tension, confusion, and lower vigor among SARS-CoV-2 participants (all p-values < 0.05). The number of SARS-CoV-2 symptoms (e.g.,loss of taste / smell, muscle aches etc.) were associated (r = 0.620, p = 0.008) with confusion. Conclusion: The sequela of persistent SARS-CoV-2 symptoms elicit clear disturbances in functional status, mood state, and leisure-time PA among women with post-acute COVID-19 syndrome.

Neuroimmunological investigations of cerebrospinal fluid in patients with recent onset depression – a study protocol

Background A proinflammatory response has been suggested to be involved in the pathophysiology of depression in a subgroup of patients. However, comprehensive largescale studies on neuroimmunological investigations of the cerebrospinal fluid (CSF) are lacking and no largescale longitudinal CSF studies comparing patients with depression to healthy controls currently exist. Methods A longitudinal case-control study including at least 100 patients with first time depression (ICD-10: F32) within the past year with ongoing symptoms and at least 100 sex and age matched healthy controls with collection of CSF, blood, and fecal samples. All individuals will be evaluated by neurological examination including neurological soft signs, interviewed for psychopathology assessment and have symptomatology evaluated by relevant rating scales. Level of functioning and quality of life will be evaluated by a panel of interview questions and rating scales, and cognitive function assessed by a relevant test battery. In addition, a large number of potential confounders will be registered (BMI, smoking status, current medication etc.). Primary outcomes: CSF white cell count, CSF/serum albumin ratio, CSF total protein levels, IgG index, CSF levels of IL-6 and IL-8, and the prevalence of any CNS-reactive autoantibody in CSF and/or blood. Secondary outcomes: exploratory analyses of a wide range of neuroimmunological markers and specific autoantibodies. Power calculations are computed for all primary outcomes based on previous CSF studies including patients with depression and healthy controls. Discussion This study will represent the hitherto largest investigation of CSF in patients with recent onset depression compared to healthy controls. We expect to elucidate neuroimmunological alterations in individuals with depression and characterize an immunological profile paving the way for the development of effective treatments based on biomarkers. Trial registration The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945).

Identifying best modelling practices for tobacco control policy simulations: a systematic review and a novel quality assessment framework

BackgroundPolicy simulation models (PSMs) have been used extensively to shape health policies before real-world implementation and evaluate post-implementation impact. This systematic review aimed to examine best practices, identify common pitfalls in tobacco control PSMs and propose a modelling quality assessment framework.MethodsWe searched five databases to identify eligible publications from July 2013 to August 2019. We additionally included papers from Feirman et al for studies before July 2013. Tobacco control PSMs that project tobacco use and tobacco-related outcomes from smoking policies were included. We extracted model inputs, structure and outputs data for models used in two or more included papers. Using our proposed quality assessment framework, we scored these models on population representativeness, policy effectiveness evidence, simulated smoking histories, included smoking-related diseases, exposure-outcome lag time, transparency, sensitivity analysis, validation and equity.FindingsWe found 146 eligible papers and 25 distinct models. Most models used population data from public or administrative registries, and all performed sensitivity analysis. However, smoking behaviour was commonly modelled into crude categories of smoking status. Eight models only presented overall changes in mortality rather than explicitly considering smoking-related diseases. Only four models reported impacts on health inequalities, and none offered the source code. Overall, the higher scored models achieved higher citation rates.ConclusionsWhile fragments of good practices were widespread across the reviewed PSMs, only a few included a ‘critical mass’ of the good practices specified in our quality assessment framework. This framework might, therefore, potentially serve as a benchmark and support sharing of good modelling practices.

Smoking in social housing among adults in England, 2015-2020

Objectives: To analyse associations between living in social housing and smoking in England and evaluate progress toward reducing disparities in smoking prevalence among residents of social housing compared with other housing types. Design: Nationally-representative, cross-sectional survey between January 2015 and February 2020. Setting: England. Participants: 105,562 adults (≥16y). Primary and secondary outcome measures: Linear and logistic regression were used to analyse associations between living in social housing (vs. other housing types) and smoking status, cigarettes per day, time to first cigarette, exposure to smoking by others, motivation to stop smoking, quit attempts, and use of cessation support. Analyses adjusted for sex, age, social grade, region, and survey year. Results: Adults living in social housing had twice the odds of being a smoker (ORadj=2.17, 95%CI 2.08-2.27), and the decline in smoking prevalence between 2015 and 2020 was less pronounced in this high-risk group (-7%; ORadj=0.98, 95%CI 0.96-1.01) than among adults living in other housing types (-24%; ORadj=0.95, 95%CI 0.94-0.96; housing tenure*survey year interaction p=0.020). Smokers living in social housing were more addicted than those in other housing (smoking within 30 minutes of waking: ORadj=1.50, 95%CI 1.39-1.61), but were no less motivated to stop smoking (ORadj=1.06, 95%CI 0.96-1.17) and had higher odds of having made a serious attempt to quit in the past year (ORadj=1.16, 95%CI 1.07-1.25). Among smokers who had tried to quit, those living in social housing had higher odds of using evidence-based cessation support (ORadj=1.22, 95%CI 1.07-1.39) but lower odds of remaining abstinent (ORadj=0.63, 95%CI 0.52-0.76). Conclusions: There remain stark inequalities in smoking and quitting behaviour by housing tenure in England, with declines in prevalence stalling between 2015 and 2020 despite progress in the rest of the population. In the absence of targeted interventions to boost quitting among social housing residents, inequalities in health are likely to worsen.