9,764 research outputs found
HIV clinical indicator diseases prior to HIV diagnosis are correlated to clinical progression in Late Presenters
No full textGWAS, prevenzione cardiovascolare e medicina di precisione (GWAS, cardiovascular prevention and precision medicine)
No full textGenome-wide association studies provide a great opportunity for medical research and for clinical
practice that goes from discovery of new possible therapeutic targets to the identification of subjects
with beneficial (or detrimental) response to drugs. In this review, we highlight some examples that
path the way to a precision medicine approach in cardiovascular prevention: e.g. the use of genetic information
to identify subjects with better response to statin therapy, and a genome-wide analysis identifying
carriers of variants responsible for higher cardiovascular mortality rate during intensive glycemic
control in type 2 diabetes. While further studies are warranted before the clinical translation of
these findings, it is conceivable that similar precision medicine approaches will not be long in coming
Sindrome delle apnee ostruttive nei pazienti obesi: effetti sul profilo metabolico e cardiovascolare e risposta a 6 mesi alla terapia comportamentale.
No full textSindrome delle apnee ostruttive nei pazienti obesi: effetti sul profilo metabolico e cardiovascolare e risposta a 6 mesi alla terapia comportamentale. 30° Congresso Nazionale Società Italiana Studio Aterosclerosi, Roma, 20-22 novembre 2016
Association of 1513CC P2X7 receptor genotype with age
No full textAging is a progressive degenerative process associated with chronic low-level inflammation. P2X7R is a receptor for extracellular ATP that plays an important role in inflammation and has been associated with different age-related pathologies. The 1513A>C P2RX7 polymorphism causes an impairment in receptor responses with complete loss-of-function in 1513CC P2RX7 homozygous.
We carried out a literature analysis to verify an association between the 1513CC genotype frequency and age. Our analysis shows no association between these parameters in the overall population or extra- European subjects. However, frequency of 1513CC P2RX7 homozygous increased with age in Caucasian European subjects. This result was confirmed when we examined genetic data from two genome-wide association studies including USA Caucasian cohorts.
In conclusion, this study suggest that Caucasian individuals with an anti-inflammatory P2X7 receptor phenotype could have a longer life expectancy in high-income countries where the main causes of death are chronic inflammatory diseases
I fibrati: dal loro impiego in terapia agli studi di farmacogenetica (Fibrates: from clinical practice to pharmacogenetic studies)
No full textOver the last decades, the use of fibrates has been pursued as a strategy to reduce cardiovascular risk.
These drugs are agonists of peroxisome proliferator-activated receptor-alpha (PPAR-a) - a transcription
factor that regulates lipid metabolism via several routes, but mostly via direct up-regulation of specific
PPAR-a target genes. The main effects of fibrates on lipid metabolism are a decrease in serum
triglycerides (TG), an increase in HDL cholesterol, and an increase in the size of LDL particles,
making them less atherogenic. Additionally, fibrates reduce systemic inflammation independently
from their effect on lipid metabolism. Despite such beneficial effects, results from clinical trial have
been overall disappointing, for this reason, their use in clinical practice for cardiovascular prevention is
not generally recommended. At the same time, meta-analysis of post-hoc studies in specific subgroups
of patients, i.e. subjects with atherogenic dyslipidemia (= high TG combined with low HDL cholesterol
levels) have consistently showed a cardiovascular benefit of fibrates. For this reason, fenofibrate might
be considered to reduce residual cardiovascular risk (aiming to reduce levels of non-HDL cholesterol)
as second or third line treatments among patients with atherogenic dyslipidemia. Interest in these
drugs have been increased also by recent genetic and epidemiological studies reinvigorating the
possible beneficial effect of improving lipid profile beyond LDL-cholesterol reduction. Furthermore,
pharmacogenetic studies suggest the possibilities of further optimizing fibrate therapy with a
“precision medicine” approach based also on genetic markers. This approach looks promising but will
need further confirmation before its translation in clinical practice
Sindrome metabolica e infiammazione sistemica
No full textSommARIo
La sindrome metabolica (SM), intesa come l’associazione di condizioni cliniche specifiche (obesità androide,
iperglicemia, ipertensione arteriosa, dislipidemia e iperuricemia) è nota fin dal 18° secolo. Tuttavia
il riconoscimento e il passaggio da sindrome a malattia, per cui è necessario riconoscere un fattore
eziopatogenico comune, è ancora in corso. Reaven ipotizzò che l’insulino-resistenza (IR) fosse il “primum
movens” della SM e tale linea di pensiero si è mantenuta fino al riscontro di altri due possibili fattore
determinanti: l’obesità centrale e l’infiammazione sistemica. Numerosi studi hanno dimostrato il ruolo
pro-infiammatorio dell’eccesso di tessuto adiposo e il ruolo dell’infiammazione sistemica cronica di basso
grado come nuovo fattore di rischio cardio-vascolare. Recentemente abbiamo confermato come, in una
popolazione anziana, la relazione tra elevati valori di PCR e SM sia fortemente condizionata dalla presenza
di obesità androide, e indipendentemente dalla presenza di IR. Successivamente abbiamo dimostrato
che il trans-signalling dell’IL-6 (cioè la diffusione del segnale dell’IL-6 a tutti i tessuti dell’organismo con
un effetto sistemico e cronicizzato) è correlato esclusivamente alla presenza di IR. Questi risultati suggeriscono
due diversi aspetti nel rapporto tra SM e infiammazione sistemica. Da un lato viene confermato
come l’infiammazione, legata all’aumento di citochine quali IL-6 e IL-18, sia sostanzialmente dipendente
dall’adiposità viscerale. Dall’altro, la diffusione del segnale infiammatorio a livello sistemico (trans-signalling
della IL-6) sembra correlato alla presenza di IR. Appare quindi evidente come, oltre alla IR, anche
infiammazione sistemica e obesità addominale siano ormai da considerare due fattori determinanti nella
patogenesi della SM
Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care
No full textAim Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI. Methods We collected data from 46 diabetes clinics (n = 281,381 T2D patients), extracted data to calculate HSI and validated it against ultrasound-detected hepatic steatosis. We then examined changes in HSI among patients with a follow-up visit within 1 year after initiating newer GLMs. Results MAFLD (defined by HSI > 36, i.e., a high probability of steatosis) was present in 76.3% of the 78,895 included patients, while only 2.7% had HSI < 30 (low probability of steatosis). After age- and sex-adjusting, higher HSI was associated with higher prevalence of chronic kidney disease (odds ratio 1.35; 95%CI 1.22-1.51) and macroangiopathy (odds ratio 1.18; 95%CI 1.07-1.30). Among 2,179 subjects in the validation cohort, the prevalence of MAFLD was 67.8% and was greater in those with high HSI. Performance of HSI for ultrasound-detected MAFLD was moderate (AUROC 0.70), yet steatosis prevalence was > threefold higher among subjects with HSI > 36 than among those with HSI < 30. Notably, HSI declined significantly similar to 6 months after initiation of dapagliflozin or incretin-based therapies, but not gliclazide. Conclusion About three quarters of patients with T2D have HSI values suggestive of MAFLD, a condition associated with macroangiopathy and nephropathy. Treatment with dapagliflozin or incretin therapies might improve MAFLD in T2D
Brain-derived neurotrophic factor plasma levels: Relationship with dementia and diabetes in the elderly population
No full textThe mechanisms linking diabetes and cognitive impairment/dementia, two common conditions of elderly people, are not completely known. Brain-derived neurotrophic factor (BDNF) has antidiabetic properties, and reduced circulating BDNF was associated with dementia. We investigated the relationship between plasma BDNF levels, dementia, and diabetes in a sample of 164 community-dwelling elderly individuals, including 50 participants with vascular dementia, 44 with late onset Alzheimer's disease, 23 with cerebrovascular disease not dementia, and 47 controls (C). Presence/absence of diabetes was registered; new diagnoses of diabetes were made by the American Diabetes Association criteria. BDNF plasma levels were measured by ELISA. Both diagnosis of dementia and diabetes were associated with lower BDNF plasma values compared with the respective controls; moreover, dementia and diabetes correlated with BDNF plasma levels, independent of possible confounders. A progressive reductions of BDNF plasma levels from C (383.9 ± 204.6 pg/mL), to cerebrovascular disease not dementia (377.1 ± 130.2), to vascular dementia (313.3 ± 114.8), to late onset Alzheimer's disease (264.7 ± 147.7) was observed, (late onset Alzheimer's disease vs C, p:.03; late onset Alzheimer's disease vs cerebrovascular disease not dementia, p:.002). Demented patients affected by diabetes had the lowest BDNF mean levels (264.9 pg/mL) among individuals enrolled in this sample, suggesting the existence of a "synergistic" effect of dementia and diabetes on BDNF levels
Metadata Representations for Queryable ML Model Zoos
No full textMachine learning (ML) practitioners and organizations are building model zoos of pre-trained models, containing metadata describing properties of the ML models and datasets that are useful for reporting, auditing, reproducibility, and interpretability purposes. The metatada is currently not standardised; its expressivity is limited; and there is no interoperable way to store and query it. Consequently, model search, reuse, comparison, and composition are hindered. In this paper, we advocate for standardized ML model metadata representation and management, proposing a toolkit supported to help practitioners manage and query that metadata.Web Information SystemsHuman-Centred Artificial Intelligenc
A Manifesto of Nodalism
Get PDFThis paper proposes the notion of Nodalism as a means describing contemporary culture and of understanding my own creative practice in electronic music composition. It draws on theories and ideas from Kirby, Bauman, Bourriaud, Deleuze, Guatarri, and Gochenour, to demonstrate how networks of ideas or connectionist neural models of cognitive behaviour can be used to contextualize, understand and become a creative tool for the creation of contemporary electronic music
- …
