Mesoporous carbide-derived carbon with porosity tuned for efficient adsorption of cytokines

Biomaterials, 27(34): pp. 5755-5762.Porous carbons can be used for the purification of various bio-fluids, including the cleansing blood of inflammatory mediators in conditions such as sepsis or auto-immune diseases. Here we show that the control of pore size in carbons is a key factor to achieving efficient removal of cytokines. In particular, the surface area accessible by the protein governs the rate and effectiveness of the adsorption process. We demonstrate that novel mesoporous carbon materials synthesized from ternary MAX-phase carbides can be optimized for efficient adsorption of large inflammatory proteins. The synthesized carbons, having tunable pore size with a large volume of slit-shaped mesopores, outperformed all other materials or methods in terms of efficiency of TNF-α removal and the results are comparable only with highly specific antibody-antigen interactions

Resveralogues protect HepG2 cells against cellular senescence induced by hepatotoxic metabolites

Progressive liver disease and dysfunction cause toxic metabolites including ammonia andunconjugated bilirubin to accumulate in plasma. As the population ages alternatives to livertransplantation become increasingly important. One approach for use as a bridge to transplant or recovery is the use of bioartificial liver systems (BALS) containing primary or immortalised hepatocytes as ex-vivo replacements or supports for endogenous liver function.However, exposure to the hepatotoxic metabolites present in plasma causes the rapid failure of these cells to carry out their primary metabolic functions despite remaining viable.Hypothesising that this loss of core hepatocyte phenotypes was caused by cell senescence weexposed HepG2 cell populations, grown in both standard two-dimensional tissue culture systems and in three dimensional cultures on novel alginate modified HEMA-MBA cryogels, to physiologically reflective concentrations of hepatotoxic metabolites and cytokines. HepG2 cells are forced into senescence by the toxic metabolites in under six hours (as measured by loss of thymidine analogue incorporation or detectable Ki67 staining) which is associated with a ten to twenty-fold reduction in the capacity of the cultures to synthesis albumin or urea. This state of senescence induced by liver toxins (SILT) can be prevented by preincubation with either 2-5μM resveratrol, its major in vivo metabolite dihydroresveratrol or a series of novel resveralogues with differential capacities to scavenge radicals and activate SIRT1 (including V29 which does not interact with the protein). SILT appears to be a previously unrecognised barrier to the development of BALS which can now be overcome using small molecules that are safe for human use at concentrations readily achievable in vivo

Brain Ageing, Cognition in Youth and Old Age and Vascular Disease in the Lothian Birth Cohort 1936: Rationale, Design and Methodology of the Imaging Protocol

Rationale As the population of the world ages, age-related cognitive decline is becoming an ever-increasing problem. However, the changes in brain structure that accompany normal aging, and the role they play in cognitive decline, remain to be fully elucidated. Aims This study aims to characterize changes in brain structure in old age, and to investigate relationships between brain aging and cognitive decline using the Lothian Birth Cohort 1936. Here, we report the rationale, design and methodology of the brain and neurovascular imaging protocol developed to study this cohort. Design An observational, longitudinal study of the Lothian Birth Cohort 1936, which comprises 1091 relatively healthy individuals now in their 70s and living in the Edinburgh area. They are surviving participants of the Scottish Mental Survey 1947, which involved a test of general intelligence taken at age 11 years. At age 70 years, the Lothian Birth Cohort 1936 undertook detailed cognitive, medical and genetic testing, and provided social, family, nutritional, quality of life and physical activity information. At mean age 73 years they underwent detailed brain MRI and neurovascular ultrasound imaging, repeat cognitive and other testing. The MRI protocol is designed to provide qualitative and quantitative measures of gray and white matter atrophy, severity and location of white matter lesions, enlarged perivascular spaces, brain mineral deposits, microbleeds and integrity of major white matter tracts. The neurovascular ultrasound imaging provides velocity, stenosis and intima–media thickness measurements of the carotid and vertebral arteries. Study This valuable imaging dataset will be used to determine which changes in brain structural parameters have the largest effects on cognitive aging. Analysis will include multimodal image analysis and multivariate techniques, such as factor analysis and structural equation modelling. Especially valuable is the ability within this sample to examine the influence that early life intelligence has on brain structural parameters in old age, and the role of genetic, vascular, educational and lifestyle factors. Outcomes Final outcomes include associations between early and late life cognition and integrity of key white matter tracts, volume of gray and white matter, myelination, brain water content, and visible abnormalities such as white matter lesions and mineral deposits; and influences of vascular risk factors, diet, environment, social metrics, education and genetics on healthy brain aging. It is intended that this information will help to inform and develop strategies for successful cognitive aging

Survivorship care for postmenopausal breast cancer patients in Ireland: what do women want?

Purpose: The aim of this study was to identify the concerns of postmenopausal breast cancer patients in Ireland and inform the development of a survivorship care plan.Method: A qualitative participatory approach was used. Focus group interviews (n = 6) with 51 women were undertaken. Following analysis of the focus group discussions, two nominal group technique (NGT) (consensus workshops) involving representatives (n = 17) from each of the six focus groups were held.Results: Ten key issues were highlighted by women in the focus groups and these were prioritised at the consensus workshops. The most important issues in survivorship care planning prioritised by the women were as follows: meet the same healthcare professional at each review visit; contact number of a named person that you can contact if you have any concerns between review visits; at each review visit, have a physical examination and blood tests and explanation from health care professional outlining if follow up scans needed and if not, why not; information on signs and symptoms of recurrence; advice on diet, exercise, healthy lifestyle and advice on coping and pacing yourself; information and management of side effects of therapy-long and short term.Conclusion: Survivorship care planning for breast cancer is underdeveloped in Ireland. There is a lack of consensus regarding its provision and a lack of structured approach to its implementation. This study demonstrates the role of postmenopausal breast cancer patients' involvement in identifying their needs and reports that continuity of care was their top priority and the need for an adoption of a survivorship care plan was emphasised by participants. (C) 2017 The Authors. Published by Elsevier Ltd.peer-reviewe