Epigenetic age across development in children and adolescents with ADHD.

Unlabelled: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition, though symptoms vary both within and between people in the population. We aimed to investigate trajectories of individual biological aging through the change in residuals of DNA methylation age estimates (EpiAge) regressed on chronological age (EpiAge Gap) in children and adolescents with and without ADHD.

Methods: Three well-established epigenetic clocks (PedBE, Horvath, and Skin & blood) were used to estimate EpiAge in 293 saliva samples from 169 participants (91 with ADHD symptoms) from the Neuroimaging of the Children's Attention Project (NICAP).

Epigenetic age acceleration and cognitive performance over time in older adults.

Introduction: This study investigated whether epigenetic age acceleration (AA) is associated with the change in cognitive function and the risk of incident dementia over 9 years, separately in males and females.

Methods: Six epigenetic AA measures, including GrimAge, were estimated in baseline blood samples from 560 Australians aged ≥70 years (50.7% female).

Epigenetic age acceleration and the risk of frailty, and persistent activities of daily living (ADL) disability.

Background: Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) is associated with the change in frailty scores over 7 years and the 7-year risk of incident frailty and persistent Activities of Daily Living (ADL) disability among 560 Australians (50.7% females) aged ≥70 years.

Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries.

Importance: Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited.

Objective: To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs.

Sex differences in biological aging and the association with clinical measures in older adults.

Females live longer than males, and there are sex disparities in physical health and disease incidence. However, sex differences in biological aging have not been consistently reported and may differ depending on the measure used. This study aimed to determine the correlations between epigenetic age acceleration (AA), and other markers of biological aging, separately in males and females.

Lifestyle Enrichment in Later Life and Its Association With Dementia Risk.

Importance: Lifestyles enriched with socially and mentally stimulating activities in older age may help build cognitive reserve and reduce dementia risk.

Objective: To investigate the association of leisure activities and social networks with dementia risk among older individuals.

Design, Setting, And Participants: This longitudinal prospective cohort study used population-based data from the ASPREE Longitudinal Study of Older Persons (ALSOP) for March 1, 2010, to November 30, 2020.

Lifetime posttraumatic stress disorder as a predictor of mortality: a systematic review and meta-analysis.

Background: Posttraumatic Stress Disorder (PTSD) could potentially increase the risk of mortality, and there is a need for a meta-analysis to quantify this association. This study aims to determine the extent to which PTSD is a predictor of mortality.

Methods: EMBASE, MEDLINE, and PsycINFO were searched systematically on 12th February 2020, with updated searches conducted in July 2021, and December 2022 (PROSPERO CRD42019142971).

The association between sex hormones and the change in brain-predicted age difference in older women.

Objective: The role of circulating sex hormones on structural brain ageing is yet to be established. This study explored whether concentrations of circulating sex hormones in older women are associated with the baseline and longitudinal changes in structural brain ageing, defined by the brain-predicted age difference (brain-PAD).

Design: Prospective cohort study using data from NEURO and Sex Hormones in Older Women; substudies of the ASPirin in Reducing Events in the Elderly clinical trial.

Health-related heterogeneity in brain aging and associations with longitudinal change in cognitive function.

Introduction: Neuroimaging-based 'brain age' can identify individuals with 'advanced' or 'resilient' brain aging. Brain-predicted age difference (brain-PAD) is predictive of cognitive and physical health outcomes. However, it is unknown how individual health and lifestyle factors may modify the relationship between brain-PAD and future cognitive or functional performance.

Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation.

Herein, we report the discovery of a first-in-class chemotype 2-(alkylsulfonamido)thiazol-4-yl)acetamides that act as pan-selective inhibitors of cytidine 5'-triphosphate synthetase (CTPS1/2), critical enzymes in the pyrimidine synthesis pathway. Weak inhibitors identified from a high-throughput screening of 240K compounds have been optimized to a potent, orally active agent, compound , which has shown significant pharmacological responses at 10 mg/kg dose BID in a well-established animal model of inflammation.

Factors Influencing Change in Brain-Predicted Age Difference in a Cohort of Healthy Older Individuals.

Background: There is considerable variability in the rate at which we age biologically, and the brain is particularly susceptible to the effects of aging.

Objective: We examined the test-retest reliability of brain age at one- and three-year intervals and identified characteristics that predict the longitudinal change in brain-predicted age difference (brain-PAD, defined by deviations of brain age from chronological age).

Methods: T1-weighted magnetic resonance images were acquired at three timepoints from 497 community-dwelling adults (73.

Brain-predicted age difference is associated with cognitive processing in later-life.

Brain age is a neuroimaging-based biomarker of aging. This study examined whether the difference between brain age and chronological age (brain-PAD) is associated with cognitive function at baseline and longitudinally. Participants were relatively healthy, predominantly white community-dwelling older adults (n = 531, aged ≥70 years), with high educational attainment (61% ≥12 years) and socioeconomic status (59% ≥75th percentile).

Factors associated with brain ageing - a systematic review.

Background: Brain age is a biomarker that predicts chronological age using neuroimaging features. Deviations of this predicted age from chronological age is considered a sign of age-related brain changes, or commonly referred to as brain ageing. The aim of this systematic review is to identify and synthesize the evidence for an association between lifestyle, health factors and diseases in adult populations, with brain ageing.

Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults.

Background: The neurocognitive effect of statins in older adults remain uncertain.

Objectives: The aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults.

Methods: This analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.

A Systematic Review and Meta-analysis of Environmental, Lifestyle, and Health Factors Associated With DNA Methylation Age.

DNA methylation (DNAm) algorithms of biological age provide a robust estimate of an individual's chronological age and can predict their risk of age-related disease and mortality. This study reviewed the evidence that environmental, lifestyle and health factors are associated with the Horvath and Hannum epigenetic clocks. A systematic search identified 61 studies.

The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis.

Background: Ageing is one of the principal risk factors for many chronic diseases. However, there is considerable between-person variation in the rate of ageing and individual differences in their susceptibility to disease and death. Epigenetic mechanisms may play a role in human ageing, and DNA methylation age biomarkers may be good predictors of age-related diseases and mortality risk.

Brain-derived neurotrophic factor DNA methylation mediates the association between neighborhood disadvantage and adolescent brain structure.

Prior research indicates that socioeconomic disadvantage is associated with prefrontal cortical (PFC) development in childhood and adolescence, however the mechanisms of this link are unclear. This study investigated whether DNA methylation of the brain-derived neurotrophic factor (BDNF, which plays a key role in synaptic plasticity), mediated the association between neighborhood disadvantage and thickness of the PFC in adolescents. Neighborhood disadvantage was measured in 33 adolescents aged 12-13 years using the Socio-Economic Indexes for Areas.

Association between DNA methylation of the KITLG gene and cortisol levels under stress: a replication study.

A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age ≥ 65), randomly selected from the electoral rolls of the Montpellier district, in France.

Phenotypic Heterogeneity in Dementia: A Challenge for Epidemiology and Biomarker Studies.

Dementia can result from a number of distinct diseases with differing etiology and pathophysiology. Even within the same disease, there is considerable phenotypic heterogeneity with varying symptoms and disease trajectories. Dementia diagnosis is thus very complex, time-consuming, and expensive and can only be made definitively post-mortem with histopathological confirmation.

New heteroannulation reactions of N-alkoxybenzamides by Pd(II) catalyzed C-H activation.

A new palladium(II) catalyzed methodology for the direct synthesis of alkylidene isoindolinones from N-alkoxybenzamides is presented. Isoindolinone formation proceeds through a highly efficient and E-selective C-H activation/Heck/Aza-Wacker sequence. Substoichiometric amounts of benzoquinone can be employed in a cooperative oxidation system with O(2), leading to facile purification of products.

2,2-Difunctionalization of alkenes via Pd(II)-catalyzed aza-Wacker reactions.

N-Ts and N-Boc derivatives of 1,2-diamines and 1,2-amino alcohols are shown to undergo efficient Pd(II)-catalyzed aza-Wacker reactions with a large range of electron-deficient alkenes. The resulting enamine intermediate generally undergoes cyclization with the second heteroatom to form 1,3-heterocycles. The sequence facilitates the rapid synthesis of saturated oxazolidines, imidazolidines, and their derivatives.

Molecular evidence for the role of a ferric reductase in iron transport.

Duodenal cytochrome b (Dcytb) is a haem protein similar to the cytochrome b561 protein family. Dcytb is highly expressed in duodenal brush-border membrane and is implicated in dietary iron absorption by reducing dietary ferric iron to the ferrous form for transport via Nramp2/DCT1 (divalent-cation transporter 1)/DMT1 (divalent metal-transporter 1). The protein is expressed in other tissues and may account for ferric reductase activity at other sites in the body.

2, 4-diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum.

Background: It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy.

Results: Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species.

A study of the effects of indometacin on liver mitochondria from rats, mice and humans.

Background: A part of the mechanism of the gastrointestinal toxicity exhibited by non-steroidal anti-inflammatory drugs is believed to involve the uncoupling of mitochondrial oxidative phosphorylation. Most previous uncoupling studies have used rat liver mitochondria. There is little information on the effects of the drugs on mitochondria from other species.

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat.

Background: The pathogenesis of NSAID-induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation.

Aims: To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat.