Segmental analysis of human hair reveals intra-annual variation in 25(OH)D concentrations in modern and archaeological individuals.

Vitamin D is essential for healthy skeletal growth and is increasingly recognised for its role in chronic disease development, inflammation and immunity. 25-hydroxyvitamin D (25(OH)D) concentrations are an indicator of vitamin D status and are normally analysed in plasma or serum samples in clinical settings, while archaeological studies rely on the identification of skeletal markers of vitamin D deficiency, such as rickets. Here, we determined 25(OH)D concentrations in hair specimens ('locks') that had been sampled close to the root, aligned by cut end, and sliced into sequential segments from participants (n = 16), from Aberdeen, Scotland, using a modified protocol designed to minimise sample size.

Audiology Through a Psychologically Informed Practice Lens.

Psychologically informed practice is a structural framework originating in physiotherapy, that aids clinicians to identify, consider, and address the psychological factors related to chronic conditions and their management. Hearing loss is a chronic condition associated with a variety of psychosocial impacts, and psychological factors are known to heavily influence the engagement, adherence, and success of hearing rehabilitation. This framework could provide a structured method to manage these factors by using evidence-based psychological theory and applications.

The determination of endogenous steroids in hair and fur: A systematic review of methodologies.

Background: Endogenous steroid hormone assessment is essential for clinical practice. These hormones are typically measured in blood. More recently, measurement of steroids in hair samples has been gaining in popularity, so we have reviewed the methodologies used for this to-date.

SmartCADD: AI-QM Empowered Drug Discovery Platform with Explainability.

Artificial intelligence (AI) has emerged as a pivotal force in enhancing productivity across various sectors, with its impact being profoundly felt within the pharmaceutical and biotechnology domains. Despite AI's rapid adoption, its integration into scientific research faces resistance due to myriad challenges: the opaqueness of AI models, the intricate nature of their implementation, and the issue of data scarcity. In response to these impediments, we introduce SmartCADD, an innovative, open-source virtual screening platform that combines deep learning, computer-aided drug design (CADD), and quantum mechanics methodologies within a user-friendly Python framework.

Identification of the Clinical Candidate (), a Highly Potent and Brain Penetrant BRAF Inhibitor for the Treatment of Cancer.

Mutant BRAF is one of the most common oncogenic drivers in metastatic melanoma. While first generation BRAF inhibitors are capable of controlling tumors systemically, they are unable to adequately treat tumors that have metastasized to the brain due to insufficient penetration across the blood-brain barrier (BBB). Through a combination of structure-based drug design (SBDD) and the optimization of physiochemical properties to enhance BBB penetration, we herein report the discovery of the brain-penetrant BRAF inhibitor () In mice studies, proved to be highly brain-penetrant and was able to drive regressions of A375 BRAF tumors implanted both subcutaneously and intracranially.

Identification of nutrition factors in the metabolic syndrome and its progression over time in older adults: analysis of the TUDA cohort.

Background: Nutrition is recognized as playing an important role in the metabolic syndrome (MetS), but the dietary components involved are unclear. We aimed to investigate nutrition factors in relation to MetS and its progression in older adults over a follow-up period of 5.4 years.

Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

Introduction: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults.

Method: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years.

Physical activity dose for generalized anxiety disorder & worry: Results from the Irish longitudinal study on ageing.

The lowest moderate-to-vigorous physical activity (MVPA) dose that conveys protection for Generalized Anxiety Disorder (GAD) and worry is unknown. This study quantified associations of weekly accumulated MVPA doses with GAD and worry across 10 years using data from The Irish Longitudinal Study on Ageing (TILDA). Continuous MVPA (metabolic equivalent of task [MET] minutes per week [MET.

Low-Grade systemic inflammation is associated with domain-specific cognitive performance and cognitive decline in older adults: Data from the TUDA study.

Studies examining the relationships between chronic inflammation, cognitive function and cognitive decline in older adults have yielded conflicting results. In a large cohort of older adults free from established dementia (n = 3270; 73.1 ± 7.

Vitamin D: determinants of status, indications for testing and knowledge in a convenience sample of Irish adults.

Vitamin D deficiency is common in Irish adults, though there is limited research on its determinants, knowledge of vitamin D or indications for testing. We aimed to explore the determinants of vitamin D status in adults and examine knowledge and reasons for testing. The study population comprised adults who had serum 25-hydroxyvitamin D tested by general practitioners request at a Dublin Hospital in 2020.

Azimuthal Correlations within Exclusive Dijets with Large Momentum Transfer in Photon-Lead Collisions.

The structure of nucleons is multidimensional and depends on the transverse momenta, spatial geometry, and polarization of the constituent partons. Such a structure can be studied using high-energy photons produced in ultraperipheral heavy-ion collisions. The first measurement of the azimuthal angular correlations of exclusively produced events with two jets in photon-lead interactions at large momentum transfer is presented, a process that is considered to be sensitive to the underlying nuclear gluon polarization.

The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture-results of a large observational cohort study.

Unlabelled: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.

Physical Activity Dose and Depression in a Cohort of Older Adults in The Irish Longitudinal Study on Ageing.

Importance: Among older adults (aged ≥50 years), depression is associated with an increased risk of physical, social, and cognitive dysfunction. Regular moderate to vigorous physical activity (MVPA) has been associated with lower odds of depression. However, the lowest dose for protection against depression and the extent to which exceeding this level conveys additional protection are unknown.

Vitamin D status & associations with inflammation in older adults.

Research studies have observed associations of vitamin D with inflammation but data in representative older adult studies is lacking. We aimed to investigate the association of C-reactive protein (CRP) with vitamin D status in a representative sample of the older Irish population. The concentrations of 25-hydroxyvitamin D (25(OH)D) and CRP was measured in 5,381 community dwelling Irish adults aged ≥50 years from the Irish Longitudinal Study on Ageing (TILDA).

Association of dietary flavan-3-ol intakes with plasma phenyl-γ-valerolactones: analysis from the TUDA cohort of healthy older adults.

Background: Dietary polyphenols, including flavan-3-ols (F3O), are associated with better health outcomes. The relationship of plasma phenyl-γ-valerolactones (PVLs), the products of colonic bacterial metabolism of F3O, with dietary intakes is unclear.

Objectives: To investigate whether plasma PVLs are associated with self-reported intakes of total F3O and procyanidins+(epi)catechins.

Physical activity for depression among the chronically Ill: Results from older diabetics in the Irish longitudinal study on ageing.

Among chronically-ill older adults, the benefits of moderate-to-vigorous physical activity (MVPA) are established. Comorbid depressive symptoms and Major Depression are prevalent among the chronically-ill, but how different doses of MVPA may protect against depression remains understudied. Thus, using 10 years of data from The Irish Longitudinal Study on Ageing, we quantified longitudinal associations between MVPA doses and depressive symptoms and Major Depression among chronically-ill older adults living with type 2 diabetes (T2DM).

SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy.

Unlabelled: Rationally targeted therapies have transformed cancer treatment, but many patients develop resistance through bypass signaling pathway activation. PF-07284892 (ARRY-558) is an allosteric SHP2 inhibitor designed to overcome bypass-signaling-mediated resistance when combined with inhibitors of various oncogenic drivers. Activity in this setting was confirmed in diverse tumor models.

Vitamin D intake and status in Ireland: a narrative review.

Vitamin D is crucial for musculoskeletal health, with evidence suggesting non-skeletal benefits. Cutaneous vitamin D synthesis is limited in Ireland due to its northern latitude (52-55°N) and the population is dependent on dietary sources, yet intakes are inadequate. No study to-date has comprehensively examined vitamin D intakes and status in Ireland (Northern Ireland and the Republic).

Sustaining an ageing population: the role of micronutrients in frailty and cognitive impairment.

Age-related frailty and cognitive decline are complex multidimensional conditions that significantly impact the ability of older adults to sustain functional capacity and independence. While underlying causes remain poorly understood, nutrition continually emerges as one associated risk element. Many studies have addressed the importance of adequate nutrition in delaying the onset of these conditions, but the specific role of micronutrients is not well established.

Association between metabolic syndrome and risk of both prevalent and incident frailty in older adults: Findings from The Irish Longitudinal Study on Ageing (TILDA).

Objectives: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease, diabetes, and all-cause mortality. Frailty is a condition of decreased multi-system physiological reserve where one has increased vulnerability to stressors. This study aimed to examine if MetS is associated with prevalent and incident frailty over a 4-year follow-up period in an aged population.

Measurements of the associated production of a W boson and a charm quark in proton-proton collisions at .

Measurements of the associated production of a W boson and a charm ( ) quark in proton-proton collisions at a centre-of-mass energy of 8 are reported. The analysis uses a data sample corresponding to a total integrated luminosity of 19.7 collected by the CMS detector at the LHC.

Association between vitamin D deficiency and the risk of prevalent type 2 diabetes and incident prediabetes: A prospective cohort study using data from The Irish Longitudinal Study on Ageing (TILDA).

Background: It is hypothesized that vitamin D contributes to the aetiology of type 2 diabetes mellitus (diabetes). This study's objective was to examine the relationships between baseline vitamin D status (as measured by plasma 25-hydroxyvitamin D concentration) and both prevalent diabetes and prospective risk of developing diabetes, including prediabetes, in a population with historically low levels of vitamin D.

Methods: In this prospective cohort study, data from The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort of adults aged ≥50 years residing in Ireland were analysed, including wave 1 (October 2009-June 2011) ( = 5272) and wave 3 (March 2014-October 2015) ( = 3828).

An examination of the prevalence of metabolic syndrome in older adults in Ireland: Findings from The Irish Longitudinal Study on Ageing (TILDA).

Metabolic syndrome (MetS) consists of the cluster of central obesity, insulin resistance, hypertension and atherogenic dyslipidaemia. It is a risk factor for cardiovascular disease, diabetes, and mortality. The prevalence of MetS has not been described in older adults from a population-representative sample in a European country before.