Differential Methylation of Telomere-Related Genes Is Associated with Kidney Disease in Individuals with Type 1 Diabetes.

Diabetic kidney disease (DKD) represents a major global health problem. Accelerated ageing is a key feature of DKD and, therefore, characteristics of accelerated ageing may provide useful biomarkers or therapeutic targets. Harnessing multi-omics, features affecting telomere biology and any associated methylome dysregulation in DKD were explored.

Neurofunctional characteristics of executive control in older people with HIV infection: a comparison with Parkinson's disease.

Expression of executive dysfunctions is marked by substantial heterogeneity in people living with HIV infection (PLWH) and attributed to neuropathological degradation of frontostriatal circuitry with age and disease. We compared the neurophysiology of executive function in older PLWH and Parkinson's disease (PD), both affecting frontostriatal systems. Thirty-one older PLWH, 35 individuals with PD, and 28 older healthy controls underwent executive task-activated fMRI, neuropsychological testing, and a clinical motor exam.

Association between exposure to second-hand smoke and telomere length: cross-sectional study of 1303 non-smokers.

Background: Both active smoking and second-hand smoke (SHS) are important risk factors for many age-related diseases. Active smoking is associated with shortened telomere length. However, whether SHS accelerates telomere attrition with age is uncertain.

Is a Chest Radiograph Required After Removal of Chest Tubes in Children?

Our objective was to determine the clinical value of obtaining a chest radiograph after removal of a chest tube. We conducted a retrospective chart review of pediatric general surgical patients with a chest tube in place after a thoracic procedure over a 3-year time period. Postremoval films were considered to be of value if they led to a change in clinical management.

Optimising the use of observational electronic health record data: Current issues, evolving opportunities, strategies and scope for collaboration.

Background: With increasing computerisation in general practice, national primary care networks are mooted as sources of data for health services and population health research and planning. Existing data collection programs - MedicinesInsight, Improvement Foundation, Bettering the Evaluation and Care of Health (BEACH) - vary in purpose, governance, methodologies and tools. General practitioners (GPs) have significant roles as collectors, managers and users of electronic health record (EHR) data.

SIRT3 & SIRT7: Potential Novel Biomarkers for Determining Outcome in Pancreatic Cancer Patients.

Purpose: The sirtuin gene family has been linked with tumourigenesis, in both a tumour promoter and suppressor capacity. Information regarding the function of sirtuins in pancreatic cancer is sparse and equivocal. We undertook a novel study investigating SIRT1-7 protein expression in a cohort of pancreatic tumours.

Reproducibility of telomere length assessment: an international collaborative study.

Background: Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of measurement reproducibility within and between laboratories.

Methods: We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques [Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR)] performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques.

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of Bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1.

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim.

Treating psychological trauma among Rwandan orphans is associated with a reduction in HIV risk-taking behaviors: A pilot study.

The nongovernmental organization, Uyisenga N'Manzi (UNM), provides Rwandan orphans of genocide and HIV/AIDS with education, social, and mental health services. Many orphans in UNM report symptoms of psychological trauma. The primary study objective was to evaluate a multidisciplinary program integrating HIV prevention with an existing package of mental health services.

SIRT2: tumour suppressor or tumour promoter in operable breast cancer?

Purpose: Sirtuins comprise a family of genes involved in cellular stress, survival and damage responses. They have been implicated in a range of diseases including cancer, with most information pertaining to their function in tumourigenesis being derived from in vitro studies, or model organisms. Their putative roles as tumour suppressors or tumour promoters remain to be validated in vivo.

The in situ local immune response, tumour senescence and proliferation in colorectal cancer.

Background: Immune cell infiltrates are important determinants of colorectal cancer (CRC) outcome. Their presence may be driven by tumour or host-specific factors. From previous studies in mice, senescence, a state of cell cycle arrest, may moderate tumour progression through upregulation of antitumour immune responses.

Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria.

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post-transplant serum creatinine when compared to "Gold Standard" clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function.

Accelerated biological ageing in HIV-infected individuals in South Africa: a case-control study.

Objectives: Little is known about the impact of HIV infection on biological ageing in sub-Saharan Africa. The study aimed to assess biological ageing in South African HIV-infected adults and HIV-seronegative individuals using two validated biomarkers, telomere length and CDKN2A expression (a mediator of cellular senescence).

Design: A case-control study.

Do symptoms of depression predict telomere length? Evidence from the west of Scotland twenty-07 study.

Objective: Psychological factors such as the stress of caregiving are emerging as predictors of telomere length, an index of biological aging. However, although lifetime major depressive disorder is associated with shorter telomeres, less is known about depressive symptoms. Depression and depressive symptoms are associated with a range of morbidities and mortality, but the extent to which they predict biological aging is unclear.

Pathfinder cells provide a novel therapeutic intervention for acute kidney injury.

Pathfinder cells (PCs) are a novel class of adult-derived cells that facilitate functional repair of host tissue. We used rat PCs to demonstrate that they enable the functional mitigation of ischemia reperfusion (I/R) injury in a mouse model of renal damage. Female C57BL/6 mice were subjected to 30 min of renal ischemia and treated with intravenous (i.

Interactions between MAP kinase and oestrogen receptor in human breast cancer.

Purpose: The oestrogen receptor (ERα) may be activated in a ligand-dependent manner, via oestrogen, or in a ligand-independent manner, via signal transduction pathways. Mitogen Activated Protein Kinase (MAPK) is known to directly phosphorylate ERα at serine 118 in a ligand-independent manner. This study investigated the interaction between MAPK and ERα in breast cancer.

The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism.

Reprogramming of cellular metabolism is a key event during tumorigenesis. Despite being known for decades (Warburg effect), the molecular mechanisms regulating this switch remained unexplored. Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells.

Is telomere length a biomarker for aging: cross-sectional evidence from the west of Scotland?

Background: The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA.

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 Study.

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years.

Socio-economic status is associated with epigenetic differences in the pSoBid cohort.

Background: Epigenetic programming and epigenetic mechanisms driven by environmental factors are thought to play an important role in human health and ageing. Global DNA methylation has been postulated as an epigenetic marker for epidemiological studies as it is reflective of changes in gene expression linked to disease. How epigenetic mechanisms are affected by psychological, sociological and biological determinants of health still remains unclear.

Accelerated telomere attrition is associated with relative household income, diet and inflammation in the pSoBid cohort.

Background: It has previously been hypothesized that lower socio-economic status can accelerate biological ageing, and predispose to early onset of disease. This study investigated the association of socio-economic and lifestyle factors, as well as traditional and novel risk factors, with biological-ageing, as measured by telomere length, in a Glasgow based cohort that included individuals with extreme socio-economic differences.

Methods: A total of 382 blood samples from the pSoBid study were available for telomere analysis.