Approach for Phased Sequence-Based Genotyping of the Critical Pharmacogene Dihydropyrimidine Dehydrogenase ().

Pre-treatment genotyping of four well-characterized toxicity risk-variants in the dihydropyrimidine dehydrogenase gene () has been widely implemented in Europe to prevent serious adverse effects in cancer patients treated with fluoropyrimidines. Current genotyping practices are largely limited to selected commonly studied variants and are unable to determine phasing when more than one variant allele is detected. Recent evidence indicates that common variants modulate the functional impact of deleterious variants in a phase-dependent manner, where a - or a -configuration translates into different toxicity risks and dosing recommendations.

In Silico Models to Validate Novel Blood-Based Biomarkers.

Biological validation of preliminary findings is a key prerequisite in biomarker discovery. In recent years, the development of advanced large-scale sequencing technologies combined with high-throughput computational analysis methods led to the extraction of considerable amount of data from healthy and diseased tissues. Stored in large open-access repositories, these data can be accessed and interrogated by researchers aiming at understanding the biological rationale behind their results.

Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults.

Background: Identifying individuals before the onset of overt symptoms is key in the prevention of Alzheimer's disease (AD).

Objectives: Investigate the use of miRNA as early blood-biomarker of cognitive decline in older adults.

Design: Cross-sectional.

Effects of vitamin D, omega-3 and a simple strength exercise programme in cardiovascular disease prevention: The DO-HEALTH randomized controlled trial.

Background: The effects of non-pharmaceutical interventions in the prevention of cardiovascular diseases (CVD) in older adults remains unclear. Therefore, the aim was to investigate the effect of 2000 IU/day of vitamin D, omega-3 fatty acids (1 g/day), and a simple home strength exercise program (SHEP) (3×/week) on lipid and CVD biomarkers plasma changes over 3 years, incident hypertension and major cardiovascular events (MACE).

Methods: The risk of MACE (coronary heart event or intervention, heart failure, stroke) was an exploratory endpoint of DO-HEALTH, incident hypertension and change in biomarkers were secondary endpoints.

Association of Chronic Pain with Biomarkers of Neurodegeneration, Microglial Activation, and Inflammation in Cerebrospinal Fluid and Impaired Cognitive Function.

Objective: Debate surrounds the role of chronic pain as a risk factor for cognitive decline and dementia. This study aimed at examining the association of chronic pain with biomarkers of neurodegeneration using data from the Alzheimer's Disease Neuroimaging Initiative.

Methods: Participants were classified using the ATN (amyloid, tau, neurodegeneration) classification.

Bat activity is related to habitat structure and time since prescribed fire in managed pine barrens in New England.

Background: Several insectivorous bat species are found in New England, yet research on them is still scarce. Current research shows the ecological importance of bats due to their control of insect populations, but they are endangered by habitat loss and White Nose Syndrome, among other threats. Pine barrens are an uncommon ecosystem found in New England that supports other rare taxa and could be important for these bat species.

Implementation of dihydropyrimidine dehydrogenase deficiency testing in Europe.

Background: The main cause for fluoropyrimidine-related toxicity is deficiency of the metabolizing enzyme dihydropyrimidine dehydrogenase (DPD). In 2020, the European Medicines Agency (EMA) recommended two methods for pre-treatment DPD deficiency testing in clinical practice: phenotyping using endogenous uracil concentration or genotyping for DPYD risk variant alleles. This study assessed the DPD testing implementation status in Europe before (2019) and after (2021) the release of the EMA recommendations.

Iron Deficiency and Incident Infections among Community-Dwelling Adults Age 70 Years and Older: Results from the DO-HEALTH Study.

Objectives: To assess if baseline iron deficiency, with or without anemia, is associated with incident infections over 3 years among community-dwelling older adults.

Design: Prospective secondary analysis of DO-HEALTH, a 3-year randomized, double-blind controlled trial.

Setting And Participants: 2157 community-dwelling adults age 70+ from 5 European countries with good cognitive function and mobility and no major health events in the 5 years prior to enrollment Measurements: Incident infections, their severity and type were recorded every 3 months throughout the 3-year follow-up.

Prevalence of polypharmacy in community-dwelling older adults from seven centres in five European countries: a cross-sectional study of DO-HEALTH.

Objective: To investigate the prevalence of polypharmacy and characteristics associated with polypharmacy in older adults from seven European cities.

Design: Cross-sectional study of baseline data from DO-HEALTH.

Setting And Participants: DO-HEALTH enrolled 2157 community-dwelling adults age 70 and older from seven centres in Europe.

Prospective Study of Ageing Trajectories in the European DO-HEALTH Study.

Introduction: Ageing trajectories range from delayed ageing with extended health to accelerated ageing, with an increased risk of frailty. We evaluated the prevalence and prospective change between health states among community-dwelling European older adults.

Methods: This prospective study is a secondary analysis of DO-HEALTH, a randomized trial that included adults aged 70 years and older across 5 European countries.

Prevalence of healthy aging among community dwelling adults age 70 and older from five European countries.

Background: To compare the prevalence of healthy aging among adults age 70 and older from 5 European countries recruited for the DO-HEALTH clinical trial. Participants were selected for absence of prior major health events.

Methods: Cross-sectional analysis of DO-HEALTH baseline data.

Prevalence of Physical Frailty: Results from the DO-HEALTH Study.

Background: Frailty is a geriatric syndrome associated with multiple negative health outcomes. However, its prevalence varies by population and instrument used. We investigated frailty and pre-frailty prevalence by 5 instruments in community-dwelling older adults enrolled to a randomized-controlled trial in 5 European countries.

Iron deficiency and biomarkers of inflammation: a 3-year prospective analysis of the DO-HEALTH trial.

Background: The longitudinal association between iron deficiency and inflammatory biomarkers levels has not been fully explored among relatively healthy older adults.

Aims: To assess whether iron deficiency at baseline and at any yearly follow-up time point, with or without anemia, was associated with changes from baseline in high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels over 3 years.

Methods: This is a post-hoc observational analysis of DO-HEALTH, a double-blind, randomized controlled trial including 2157 European community-dwelling adults age 70+.

Are patients with cognitive impairment fit to fly? Current evidence and practical recommendations.

Background: The worldwide prevalence of dementia is increasing and represents a major public health concern. In the last decades, air travel services have undergone an impressive expansion and one of ten passengers is aged 65 years and older. While air travel can be stressful at all ages and health conditions, older individuals with cognitive impairment carry a greater risk for air-travel-related complications.

Soluble TREM2 and Inflammatory Proteins in Alzheimer's Disease Cerebrospinal Fluid.

The present study explores the associations of soluble TREM2, an important regulator of microglial activity linked to Alzheimer's disease (AD), with other known inflammatory proteins in cerebrospinal fluid (CSF). We studied 303 participants, including 89 controls, 135 mild cognitive impairment, and 79 AD dementia patients. Using established CSF biomarkers, subjects were classified according to the National Institute on Aging-Alzheimer's Association research framework, which groups markers into those of amyloid-β deposition (A), tau pathology (T), and neurodegeneration (N).

Differential expression of microRNAs in Alzheimer's disease brain, blood, and cerebrospinal fluid.

Introduction: Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive.

Methods: A systematic literature review was performed, followed by standardized multistage data extraction, quality control, and meta-analyses on eligible data for brain, blood, and cerebrospinal fluid specimens. Results were compared with miRNAs reported in the abstracts of eligible studies or recent qualitative reviews to assess novelty.

miRNAs Identify Shared Pathways in Alzheimer's and Parkinson's Diseases.

Despite the identification of several dozens of common genetic variants associated with Alzheimer's disease (AD) and Parkinson's disease (PD), most of the genetic risk remains uncharacterised. Therefore, it is important to understand the role of regulatory elements, such as miRNAs. Dysregulated miRNAs are implicated in AD and PD, with potential value in dissecting the shared pathophysiology between the two disorders.

Increased brain age in adults with Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is the most common genetic obesity syndrome, with associated learning difficulties, neuroendocrine deficits, and behavioural and psychiatric problems. As the life expectancy of individuals with PWS increases, there is concern that alterations in brain structure associated with the syndrome, as a direct result of absent expression of PWS genes, and its metabolic complications and hormonal deficits, might cause early onset of physiological and brain aging. In this study, a machine learning approach was used to predict brain age based on grey matter (GM) and white matter (WM) maps derived from structural neuroimaging data using T1-weighted magnetic resonance imaging (MRI) scans.

Direct oral anticoagulants in the elderly: systematic review and meta-analysis of evidence, current and future directions.

Background: Concerns regarding the use of direct oral anticoagulants (DOACs: apixaban, dabigatran, edoxaban, rivaroxaban) in the elderly persist owing to the lack of randomised controlled trials targeting this age group.

Objectives: The aim of this study was to assess the efficacy and safety of DOACs in elderly patients (aged 75 years or more) with atrial fibrillation or venous thromboembolism (VTE), based on already published large randomised trials.

Methods: EMBASE, MEDLINE and the Cochrane Library were searched from inception to June 2015 for phase III trials.

The vitamin C:vitamin K3 system - enhancers and inhibitors of the anticancer effect.

The oxidizing anticancer system of vitamin C and vitamin K₃ (VC:VK₃, producing hydrogen peroxide via superoxide) was combined individually with melatonin, curcumin, quercetin, or cholecalciferol (VD₃) to determine interactions. Substrates were LNCaP and PC-3 prostate cancer cell lines. Three of the tested antioxidants displayed differences in cell line cytotoxicity.

A case of MRSA controlled: predisposing factors and immune stimulation.

Most treatments for methicillin-resistant Staphylococcus aureus (MRSA) focus on agents to eliminate the bacterium. Since MRSA infection is not universal, susceptibility factors are possible. Immune resistance could be lowered in such individuals; therefore, locating immune-inhibiting or immune-enhancing factors might decrease susceptibility.

Immune-modifying and antimicrobial effects of Eucalyptus oil and simple inhalation devices.

Eucalyptus oil (EO) and its major component, 1,8-cineole, have antimicrobial effects against many bacteria, including Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus (MRSA), viruses, and fungi (including Candida). Surprisingly for an antimicrobial substance, there are also immune-stimulatory, anti-inflammatory, antioxidant, analgesic, and spasmolytic effects. Of the white blood cells, monocytes and macrophages are most affected, especially with increased phagocytic activity.