ABSTRACT
The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.
Subject(s)
Disease Susceptibility , Genetic Variation , Immunity/genetics , Leukemia, Myeloid, Acute/etiology , Adult , Aged , Alleles , Biomarkers, Tumor , Disease Susceptibility/immunology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Immunomodulation/genetics , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk Assessment , Risk Factors , Steroids/metabolismABSTRACT
A hallmark of obesity is chronic low-grade inflammation, which plays a major role in the process of atherosclerotic cardiovascular disease (ACVD). Gut microbiota is one of the factors influencing systemic immune responses, and profound changes have been found in its composition and metabolic function in individuals with obesity. This systematic review assesses the association between the gut microbiota and markers of low-grade inflammation in humans. We identified 14 studies which were mostly observational and relatively small (n = 10 to 471). The way in which the microbiome is analysed differed extensively between these studies. Lower gut microbial diversity was associated with higher white blood cell counts and high sensitivity C-reactive protein (hsCRP) levels. The abundance of Bifidobacterium, Faecalibacterium, Ruminococcus and Prevotella were inversely related to different markers of low-grade inflammation such as hsCRP and interleukin (IL)-6. In addition, this review speculates on possible mechanisms through which the gut microbiota can affect low-grade inflammation and thereby ACVD. We discuss the associations between the microbiome and the inflammasome, the innate immune system, bile acids, gut permeability, the endocannabinoid system and TMAO. These data reinforce the importance of human research into the gut microbiota as potential diagnostic and therapeutic strategy to prevent ACVD.
Subject(s)
Atherosclerosis/microbiology , Gastrointestinal Microbiome , Inflammation/microbiology , Obesity/microbiology , HumansABSTRACT
The CAMCOG, the cognitive section of the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), was administered twice to 53 patients with a clinical diagnosis ranging from no dementia to severe dementia. The stability of the total CAMCOG score was high (0.97). Patients with less than moderate dementia were differentiated well by the total score and by subscales with a range of more than 8 points, except when education was low or age was higher than 78. Because performance on most (sub)scales is modified by age and education level, stratified norms are desirable. Only the Praxis subscale, and specifically performance on drawing tasks, appeared to be influenced by depression.
Subject(s)
Dementia/diagnosis , Aged , Cognition Disorders/etiology , Dementia/complications , Female , Humans , Language Disorders/diagnosis , Language Disorders/etiology , Language Tests , Male , Middle Aged , Psychiatric Status Rating Scales , Psychometrics , Severity of Illness IndexABSTRACT
Patients with multiple sclerosis reported less left ear numbers but more right ear numbers than controls in a dichotic listening test. The multiple sclerosis patients were also relatively impaired on three learning tasks; one of these, a test for paired-associate learning of names and faces, correlated with left ear findings; the results are interpreted as supporting a hypothesised disconnection mechanism.
