Oxidative stress in relation to diet and physical activity among premenopausal women

Abstract Higher levels of oxidative stress, as measured by F 2 -isoprostanes, have been associated with chronic diseases such as CVD and some cancers. Improvements in diet and physical activity may help reduce oxidative stress; however, previous studies regarding associations between lifestyle factors and F 2 -isoprostane concentrations have been inconsistent. The aim of this cross-sectional study was to investigate whether physical activity and intakes of fruits/vegetables, antioxidant nutrients, dietary fat subgroups and alcohol are associated with concentrations of F 2 -isoprostane and the major F 2 -isoprostane metabolite. Urinary F 2 -isoprostane and its metabolite were measured in urine samples collected at enrolment from 912 premenopausal women (aged 35–54 years) participating in the Sister Study. Physical activity, alcohol consumption and dietary intakes were self-reported via questionnaires. With adjustment for potential confounders, the geometric means of F 2 -isoprostane and its metabolite were calculated according to quartiles of dietary intakes, alcohol consumption and physical activity, and linear regression models were used to evaluate trends. Significant inverse associations were found between F 2 -isoprostane and/or its metabolite and physical activity, vegetables, fruits, vitamin C, α -carotene, vitamin E, β -carotene, vitamin A, Se, lutein+zeaxanthin and long-chain n -3 fatty acids. Although trans fats were positively associated with both F 2 -isoprostane and its metabolite, other dietary fat subgroups including SFA, n -6 fatty acids, n -3 fatty acids, MUFA, PUFA, short-chain n -3 fatty acids, long-chain n -3 fatty acids and total fat were not associated with either F 2 -isoprostane or its metabolite. Our findings suggest that lower intake of antioxidant nutrients and higher intake of trans fats may be associated with greater oxidative stress among premenopausal women

The role of phosphodiesterase 12 (PDE12) as a negative regulator of the innate immune response and the discovery of antiviral inhibitors

2',5'-Oligoadenylate synthetase (OAS) enzymes and RNase-L constitute a major effector arm of interferon (IFN)-mediated antiviral defense. OAS produces a unique oligonucleotide second messenger, 2',5'-oligoadenylate (2-5A), that binds and activates RNase-L. This pathway is down-regulated by virus- and host-encoded enzymes that degrade 2-5A. Phosphodiesterase 12 (PDE12) was the first cellular 2-5A- degrading enzyme to be purified and described at a molecular level. Inhibition of PDE12 may up-regulate the OAS/RNase-L pathway in response to viral infection resulting in increased resistance to a variety of viral pathogens. We generated a PDE12-null cell line, HeLaΔPDE12, using transcription activator-like effector nuclease-mediated gene inactivation. This cell line has increased 2-5A levels in response to IFN and poly(I-C), a double-stranded RNA mimic compared with the parental cell line. Moreover, HeLaΔPDE12 cells were resistant to viral pathogens, including encephalomyocarditis virus, human rhinovirus, and respiratory syncytial virus. Based on these results, we used DNA-encoded chemical library screening to identify starting points for inhibitor lead optimization. Compounds derived from this effort raise 2-5A levels and exhibit antiviral activity comparable with the effects observed with PDE12 gene inactivation. The crystal structure of PDE12 complexed with an inhibitor was solved providing insights into the structure-activity relationships of inhibitor potency and selectivity

Advancing Newborn Screening Long-Term Follow-Up: Integration of <i>Epic</i>-Based Registries, Dashboards, and Efficient Workflows

The Connecticut Newborn Screening (NBS) Network, in partnership with the Connecticut Department of Public Health, strategically utilized the Epic electronic health record (EHR) system to establish registries for tracking long-term follow-up (LTFU) of NBS patients. After launching the LTFU registry in 2019, the Network obtained funding from the Health Resources and Services Administration to address the slow adoption by specialty care teams. An LTFU model was implemented in the three highest-volume specialty care teams at Connecticut Children’s, involving an early childhood cohort diagnosed with an NBS-identified disorder since the formation of the Network in March 2019. This cohort grew from 87 to 115 over the two-year project. Methods included optimizing registries, capturing external data from Health Information Exchanges, incorporating evidence-based guidelines, and conducting qualitative and quantitative evaluations. The early childhood cohort demonstrated significant and sustainable improvements in the percentage of visits up-to-date (%UTD) compared to the non-intervention legacy cohort of patients diagnosed with an NBS disorder before the formation of the Network. Positive trends in the early childhood cohort, including %UTD for visits and condition-specific performance metrics, were observed. The qualitative evaluation highlighted the achievability of practice behavior changes for specialty care teams through responsive support from the nurse analyst. The Network’s model serves as a use case for applying and achieving the adoption of population health tools within an EHR system to track care delivery and quickly fill identified care gaps, with the aim of improving long-term health for NBS patients

Oxidative stress in relation to diet and physical activity among premenopausal women

Higher levels of oxidative stress, as measured by F(2)-isoprostanes, have been associated with chronic diseases such as CVD and some cancers. Improvements in diet and physical activity may help reduce oxidative stress; however, previous studies regarding associations between lifestyle factors and F(2)-isoprostane concentrations have been inconsistent. The aim of this cross-sectional study was to investigate whether physical activity and intakes of fruits/vegetables, antioxidant nutrients, dietary fat subgroups and alcohol are associated with concentrations of F(2)-isoprostane and the major F(2)-isoprostane metabolite. Urinary F(2)-isoprostane and its metabolite were measured in urine samples collected at enrolment from 912 premenopausal women (aged 35–54 years) participating in the Sister Study. Physical activity, alcohol consumption and dietary intakes were self-reported via questionnaires. With adjustment for potential confounders, the geometric means of F(2)-isoprostane and its metabolite were calculated according to quartiles of dietary intakes, alcohol consumption and physical activity, and linear regression models were used to evaluate trends. Significant inverse associations were found between F(2)-isoprostane and/or its metabolite and physical activity, vegetables, fruits, vitamin C, α-carotene, vitamin E, β-carotene, vitamin A, Se, lutein + zeaxanthin and long-chain n-3 fatty acids. Although trans fats were positively associated with both F(2)-isoprostane and its metabolite, other dietary fat subgroups including SFA, n-6 fatty acids, n-3 fatty acids, MUFA, PUFA, short-chain n-3 fatty acids, long-chain n-3 fatty acids and total fat were not associated with either F(2)-isoprostane or its metabolite. Our findings suggest that lower intake of antioxidant nutrients and higher intake of trans fats may be associated with greater oxidative stress among premenopausal women

Fatness, fitness and the aging brain: A cross sectional study of the associations between a physiological estimate of brain age and physical fitness, activity, sleep, and body composition.

IntroductionChanges in brain structure and function occur with aging. However, there is substantial heterogeneity both in terms of when these changes begin, and the rate at which they progress. Understanding the mechanisms and/or behaviors underlying this heterogeneity may allow us to act to target and slow negative changes associated with aging.MethodsUsing T1 weighted MRI images, we applied a novel algorithm to determine the physiological age of the brain (brain-predicted age) and the predicted age difference between this physiologically based estimate and chronological age (BrainPAD) to 551 sedentary adults aged 65 to 84 with self-reported cognitive complaint measured at baseline as part of a larger study. We also assessed maximal aerobic capacity with a graded exercise test, physical activity and sleep with accelerometers, and body composition with dual energy x-ray absorptiometry. Associations were explored both linearly and logistically using categorical groupings.ResultsVisceral Adipose Tissue (VAT), Total Sleep Time (TST) and maximal aerobic capacity all showed significant associations with BrainPAD. Greater VAT was associated with higher (i.e,. older than chronological) BrainPAD (r = 0.149 p = 0.001)Greater TST was associated with higher BrainPAD (r = 0.087 p = 0.042) and greater aerobic capacity was associated with lower BrainPAD (r = - 0.088 p = 0.040). With linear regression, both VAT and TST remained significant (p = 0.036 and 0.008 respectively). Each kg of VAT predicted a 0.741 year increase in BrainPAD, and each hour of increased TST predicted a 0.735 year increase in BrainPAD. Maximal aerobic capacity did not retain statistical significance in fully adjusted linear models.DiscussionAccumulation of visceral adipose tissue and greater total sleep time, but not aerobic capacity, total daily physical activity, or sleep quantity and/or quality are associated with brains that are physiologically older than would be expected based upon chronological age alone (BrainPAD)

Defining the Minimal Long-Term Follow-Up Data Elements for Newborn Screening

Newborn screening (NBS) is hailed as a public health success, but little is known about the long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on the minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions