11 research outputs found
Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene
To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (FundaciĂł ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P=0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio=1.31; confidence interval 95% (1.19-1.44); P=9.74 Ă 10 - 9)
AnĂĄlise da variabilidade da frequĂȘncia cardĂaca em cordeiros da raça BergamĂĄcia, do nascimento aos 35 dias de idade
New insights into the genetic etiology of Alzheimer's disease and related dementias.
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele
Electrocardiographic evaluation of two anesthetic combinations in dogs
This study aimed to investigate electrocardiographic changes in dogs aged 5 years or more submitted to two anesthetic combinations: atropine, levomeprazine, thiopental and halothane (ALTH), and atropine, tiletamine and zolazepam (ATZ). Forty dogs (24 males/16 females) weighing 5-24kg, were used. Dogs had no cardiac problems and were submitted to tartarectomy. All animals were submitted to two electrocardiograms (ECG), one before anesthesia and other immediately before surgery. The dogs were divided into two groups: group 1 received ALTH and group 2 received ATZ. Alterations in the ST segment, T wave, cardiac rhythm and a significant reduction of vagal tonus index were observed in both groups, but in group 2 a significant reduction of the PR and QT intervals and an increase in heart rate were also observed. These data suggest that the ALTH combination caused fewer changes in the ECG than the ATZ combination
Variabilidade da freqĂŒĂȘncia cardĂaca em cĂŁes anestesiados com infusĂŁo contĂnua de propofol e sufentanil Heart rate variability in dogs anesthetized with propofol and sufentanil
Foram avaliados os efeitos do propofol associado ao sufentanil sobre o balanço das atividades simpĂĄtica e parassimpĂĄtica do coração, investigando-se um possĂvel efeito dose dependente do opiĂłide. Analisou-se a variabilidade da freqĂŒĂȘncia cardĂaca (VFC) de 12 cĂŁes adultos prĂ©-medicados com maleato de acepromazina e anestesiados com propofol e trĂȘs doses diferentes de sufentanil, que variou de 0,025 a 0,1”g/kg/min. Registrou-se o eletrocardiograma 15 minutos apĂłs a medicação prĂ©-anestĂ©sica e 15, 30, 60, 90 e 120 minutos apĂłs a indução anestĂ©sica. A VFC foi calculada no domĂnio da freqĂŒĂȘncia, mediante anĂĄlise de 10 intervalos RR consecutivos. Houve redução acentuada da freqĂŒĂȘncia cardĂaca, mas a VFC permaneceu relativamente inalterada.<br>The effects of propofol and sufentanil on cardiac sympathetic and parasympathetic balance were studied, in order to evaluate if sufentanil plays a role in this balance. The heart rate variability of 12 adult dogs was assessed, after premedication with acepromazine and anesthetized with propofol and three different doses of sufentanil, ranging from 0.025 to 0.1”g/kg/min. Electrocardiograms were recorded 15 minutes after premedication and 15, 30, 60, 90, and 120 minutes after anesthetic induction. Heart rate variability was calculated in frequency domain through the analysis of 10 consecutive RR intervals. Results showed an absence of important changes in heart rate variability, although a significant decrease in heart rate was observed
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele. © 2022. The Author(s)