Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need to find a broadly acceptable and useful definition of health, based on a list of (molecular) features; to operationalize features of health so that it can be measured; to identify predictive biomarkers and (molecular) pathways of health; and to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of physiological, cognitive, physical and reproductive function, and a lack of disease. We further define aging as the aggregate of all processes in an individual that reduce its wellbeing , that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts.
Blood-borne small non-coding (sncRNAs) are among the prominent candidates for blood-based diagnostic tests. Often, high-throughput approaches are applied to discover biomarker signatures. These have to be validated in larger cohorts and evaluated by adequate statistical learning approaches. Previously, we published high-throughput sequencing based microRNA (miRNA) signatures in Alzheimer’s disease (AD) patients in the United States (US) and Germany. Here, we determined abundance levels of 21 known circulating miRNAs in 465 individuals encompassing AD patients and controls by RT-qPCR. We computed models to assess the relation between miRNA expression and phenotypes, gender, age, or disease severity (Mini-Mental State Examination; MMSE). Of the 21 miRNAs, expression levels of 20 miRNAs were consistently de-regulated in the US and German cohorts. 18 miRNAs were significantly correlated with neurodegeneration (Benjamini-Hochberg adjusted P < 0.05) with highest significance for miR-532-5p (Benjamini-Hochberg adjusted P = 4.8 × 10−30). Machine learning models reached an area under the curve (AUC) value of 87.6% in differentiating AD patients from controls. Further, ten miRNAs were significantly correlated with MMSE, in particular miR-26a/26b-5p (adjusted P = 0.0002). Interestingly, the miRNAs with lower abundance in AD were enriched in monocytes and T-helper cells, while those up-regulated in AD were enriched in serum, exosomes, cytotoxic t-cells, and B-cells. Our study represents the next important step in translational research for a miRNA-based AD test.
MiRNAs have the potential to support AD diagnosis and patient care.
Purpose Hip fractures are of growing interest due to their increasing number, subsequent functional decline and high institutionalization rate of patients, mortality, and costs. Several process measurements are essential for hip fracture care. To compare and improve these, hip fracture registries in Europe became popular. This systematic review aims to describe the differences between hip fracture registries in Europe as well as the differences in hip fracture treatment between countries. Methods A systematic search using the keywords “hip fracture” AND “national” AND “database OR audit OR registry OR register” was performed in PubMed, Embase and Cochrane Library according to PRISMA guidelines till 3rd December 2020. Recent annual reports of identified hip fracture registries in Europe were additionally identified in June 2021. Comparisons of most common case-mix, process and outcome measurements were performed. Results 11 registries in Europe were identified. Differences were observed regarding inclusion criteria of the different registries. Comparison of the different registries was difficult due to differences in the way to report measurements. While mortality rates differed substantially between countries, most of the process measurements met recommendations according to recent guidelines. Conclusion Hip fracture registries were a valid tool to compare hospitals within one country. However, a comparison between registries of different countries should have also been easily possible. For this, the registries need to make their data easily accessible and further unify their way of measuring and reporting.
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