Search results for "OLD"
showing 10 items of 6469 documents
Feasibility of sample size calculation for RNA-seq studies
2017
Sample size calculation is a crucial step in study design but is not yet fully established for RNA sequencing (RNA-seq) analyses. To evaluate feasibility and provide guidance, we evaluated RNA-seq sample size tools identified from a systematic search. The focus was on whether real pilot data would be needed for reliable results and on identifying tools that would perform well in scenarios with different levels of biological heterogeneity and fold changes (FCs) between conditions. We used simulations based on real data for tool evaluation. In all settings, the six evaluated tools provided widely different answers, which were strongly affected by FC. Although all tools failed for small FCs, s…
Use of deep learning methods to translate drug-induced gene expression changes from rat to human primary hepatocytes
2020
In clinical trials, animal and cell line models are often used to evaluate the potential toxic effects of a novel compound or candidate drug before progressing to human trials. However, relating the results of animal and in vitro model exposures to relevant clinical outcomes in the human in vivo system still proves challenging, relying on often putative orthologs. In recent years, multiple studies have demonstrated that the repeated dose rodent bioassay, the current gold standard in the field, lacks sufficient sensitivity and specificity in predicting toxic effects of pharmaceuticals in humans. In this study, we evaluate the potential of deep learning techniques to translate the pattern of …
L1 syndrome diagnosis complemented with functional analysis of L1CAM variants located to the two N-terminal Ig-like domains
2016
L1CAM gene mutations cause neurodevelopmental disorders collectively termed L1 syndrome. Insufficient information about L1CAM variants complicates clinical prognosis, genetic diagnosis and genetic counseling. We combined clinical data, in silico effect predictions and functional analysis of four L1CAM variants, p.I37N, p.T38M, p.M172I and p.D202Y, located to the two N-terminal Ig-like domains present in five families with symptoms of L1 syndrome. Software tools predicted destabilizing effects of p.I37N and p.D202Y but results for p.T38M and p.M172I were inconsistent. Cell surface expression of mutant proteins L1-T38M, L1-M172I and L1-D202Y was normal. Conversely, L1-I37N accumulated in the …
FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability
2021
Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and pr…
A comparison of the performance of natural hybrids Saccharomyces cerevisiae × Saccharomyces kudriavzevii at low temperatures reveals the crucial role…
2018
Fermentation performance at low temperature is a common approach to obtain wines with better aroma, and is critical in industrial applications. Natural hybrids S. cerevisiae × S. kudriavzevii, isolated from fermentations in cold-climate European countries, have provided an understanding of the mechanisms of adaptation to grow at low temperature. In this work, we studied the performance of 23 S. cerevisiae × S. kudriavzevii hybrids at low temperature (8, 12 and 24 °C) to characterize their phenotypes. Kinetic parameters and spot tests revealed a different ability to grow at low temperature. Interestingly, the genome content of the S. kudriavzevii in hybrids was moderately correlated with a s…
The free radical theory of frailty: Mechanisms and opportunities for interventions to promote successful aging
2019
The free radical theory of ageing has provided a framework of research into ageing based on Harman's idea that ageing was caused by damage produced by free radicals. However, several experiments have cast doubts on the general validity of the theory. The postulation of the free radical theory of frailty came from two basic facts: first that radicals not only act as damaging molecules, but also as signals to control cell function and second that on many occasions oxidative damage does not correlate with chronological but rather with unsuccessful ageing. Frailty is a geriatric concept by which an older person shows a lack of the feeling of wellbeing, unintentional weight loss, a relatively lo…
A multidimensional approach to frailty in older people
2020
Frailty is an important factor determining a higher risk of adverse health outcomes in older adults. Although scientific community in the last two decades put a lot of effort for its definition, to date no consensus was reached on its assessment. The mainstream thinking describes frailty as a loss of physical functions or as accumulation of multiple deficits. Recently, a novel conceptual model of frailty has emerged based on the loss of harmonic interaction between multiple domains (also referred as dimensions) including genetic, biological, functional, cognitive, psychological and socio-economic domain that ultimately lead to homeostatic instability. Therefore, the multidimensional aspects…
Multidimensional frailty increases cardiovascular risk in older people: An 8-year longitudinal cohort study in the Osteoarthritis Initiative.
2021
Background:\ud \ud Cardiovascular diseases (CVDs) are the most important cause of mortality and an important cause of disability. Frailty seems to be associated with higher cardiovascular risk, but limited research has been done using a multidimensional approach to frailty. Thus, the present study aimed to investigate whether the multidimensional prognostic index (MPI), based on comprehensive geriatric assessment (CGA), is associated with CVD risk in the Osteoarthritis Initiative (OAI) study.\ud \ud Methods:\ud \ud Community-dwellers affected by knee OA or at high risk for this condition were followed for 8 years. A standardized CGA including information on functional, nutritional, mood, co…
Predictive ability of the Mini Nutritional Assessment Short Form (MNA-SF) in a free-living elderly population: a cross-sectional study
2017
Background Various scales have been used to perform a quick and first level nutritional assessment, and the MNA is one of the most used and recommended by experts in the elderly in all areas. This scale has a short form, the MNA-SF, revised and validated in 2009, which has two versions: the BMI-MNA-SF contains the first six items of the full scale including Body Mass Index while the CC-MNA-SF includes Calf Circumference instead of BMI. Objective To evaluate the predictive ability for nutritional status of the two versions of the MNA-SF against the MNA in free-living elderly in the province of Valencia. Methods Cross-sectional study of 660 free-living elderly in the province of Valencia sel…
Specific approaches to patients affected by dementia and covid-19 in nursing homes: the role of the geriatrician
2021
The coronavirus disease 19 (COVID-19) is relevant in older people. Attention was given to the nursing homes in which frailer people are usually admitted. In this review, we discuss the approaches for daily problems found in nursing home as geriatricians and potentially new research directions. We start with the problem of the older people affected by dementia and Behavioral and Psychological Symptoms of Dementia for which also the execution of a simple diagnostic test (such as nasopharyngeal swab) could be problematic. Another important problem is the management of wandering patients for which the re-organization of the spaces and vaccination could be the solutions. The relationship with fa…