Dietary lipids are pivotal in modulating metabolic inflammation. Among the inflammatory mediators characterizing metabolic inflammation, interleukin 18 (IL-18) has been consistently associated with ...obesity and insulin resistance. This study aims to evaluate whether the quality of lipid intake impacts upon IL-18 plasma levels and the implications on insulin resistance computed by the homeostatic model assessment for insulin resistance (HOMA-IR). Using a cross-sectional design, this study confirmed that IL-18 correlated positively with insulin resistance and individuals with a HOMA-IR ≥ 2.5 displayed higher circulating IL-18 levels compared with their insulin-sensitive counterparts. In terms of the effect of the quality of dietary lipids on IL-18 circulating levels, the ratio between monounsaturated, omega-3, polyunsaturated and saturated fatty acids as well as the intake of eicosapentaenoic and docosahexaenoic acids correlated negatively with IL-18. Despite this, IL-18 circulating levels, but not dietary fatty acid quality, predicted insulin resistance. Nevertheless, the ratio between omega 3 and saturated fatty acids was a predictor of IL-18 plasma levels. Thus, the downregulation of IL-18 may underpin, at least partially, the beneficial metabolic effects of substituting omega 3 for saturated fatty acids with this cytokine potentially representing a biomarker linking dietary lipids and metabolic outcomes.
While the relationship between total cholesterol (TC) and cardiovascular disease (CVD) progressively weakens with aging, several studies have shown that low TC is associated with increased mortality ...in older individuals. However, the possible additive/synergic contribution of the two most important cholesterol rich fractions (LDL-C and HDL-C) to mortality risk has not been previously investigated. Our study aimed to investigate the relationship between baseline LDL-C and HDL-C, both separately and combined, and 9-years mortality in a sample of community dwelling older individuals from the InCHIANTI study.
1044 individuals over 64 years were included. CVD and cancer mortality were defined by ICD-9 codes 390-459 and 140-239, respectively. LDL-C <130 mg/dL (3.36 mmol/L) was defined as "optimal/near optimal". Low HDL-C was defined as <40/50 mg/dL (1.03/1.29 mmol/L) in males/females, respectively. Nine-years mortality risk was calculated by multivariate Cox proportional hazards model. We found that, compared to subjects with high LDL-C and normal HDL-C (reference group), total mortality was significantly increased in subjects with optimal/near optimal LDL-C and low HDL-C (H.R.:1.58; 95%CI:1.11-2.25). As regards the specific cause of death, CVD mortality was not affected by LDL-C/HDL-C levels, while cancer mortality was significantly increased in all subjects with optimal/near optimal LDL-C (with normal HDL-C: H.R.: 2.49; with low HDL-C: H.R.: 4.52). Results were unchanged after exclusion of the first three years of follow-up, and of subjects with low TC (<160 g/dL-4.13 mmol/L).
Our findings suggest that, in community dwelling older individuals, the combined presence of optimal/near optimal LDL-C and low HDL-C represents a marker of increased future mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A large body of evidences obtained in human and animal brain tissue suggest a role of oxidative stress (OxS) in the pathogenesis of late onset Alzheimer's disease (LOAD); on the contrary, data on ...peripheral markers of OxS in LOAD are still controversial. We evaluated the serum levels of products of lipid peroxidation, hydroperoxides, advanced oxidation protein products, total and residual antioxidant power, thiols, and uric acid in a sample of 334 older individuals: 101 LOAD patients, 134 patients with mild cognitive impairment (MCI), and 99 controls. At univariate analysis, serum hydroperoxides were higher while residual antioxidant power was lower in MCI and LOAD compared with in controls. By multivariate logistic regression analysis we found that, compared with controls, high levels (over median value) of serum hydroperoxides were independently associated with an increase in the likehood of having MCI (Odd Ratio: 2.59, 95% Confidence Interval: 1.08-6.21) or LOAD (OR: 4.09, 95%CI: 1.36-11.81). Furthermore, low levels of residual antioxidant power (below the median value) were associated with increased risk of having MCI (OR: 3.97, 95% CI: 1.62-9.72), but not dementia (OR: 2.31, 95%CI: 0.83-6.63). Our study suggests that a systemic redox-imbalance leading to OxS might be associated not only with LOAD but also with MCI.
In earlier studies, it has been observed that 8-week treatment with a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids, and ...hydroxytyrosol improves lipid profile and endothelial function and reduces the level of oxidized low-density lipoprotein (oxLDL). We hypothesize that this effect might be, at least in part, explained by positive modulation exerted by the NC on the atheroprotective function of high-density lipoprotein (HDL).
This study aimed to evaluate whether the NC could influence determinants of HDL function.
Forty-five subjects with low-moderate dyslipidaemia were enrolled and treated for 8 weeks with the NC, followed by 4 weeks of washout. Blood samples were collected at every time point to evaluate changes in lipid profile, endothelial function, oxLDL, and markers of HDL function, such as the anti-oxidant activities of paraoxonase-1, glutathione peroxidase-3 (Gpx3), lipoprotein-phospholipase A2 (Lp-PLA2), and pro-oxidant activity of myeloperoxidase (MPO).
Although the concentration of HDL-C did not change, the activity of Lp-PLA2 significantly decreased upon treatment (-11.6%, p<0.001) and returned to baseline level 4 weeks after the end of treatment. In contrast, Gpx3 increased after treatment (+5%, p<0.01) and remained unvaried after 4 weeks. Both MPO activity and concentration significantly decreased after the washout period (-33 and 32%, p<0.001).
For the first time, it was found that the administration of an NC with beneficial effects on lipid homeostasis also positively impacts HDL function by improving the balance between protective and damaging determinants. Further investigation is required to corroborate our findings.
•Diabetes mellitus is a frequent comorbidity in patients with COVID-19 infection•Diabetic patients with COVID-19 infection are at higher risk to be admitted to intensive care unit•Diabetic patients ...with COVID-19 infection have an higher mortality risk
The prognostic significance of diabetes mellitus (DM) in patients with coronavirus 2019 disease (COVID-19) remains unknown.
To assess the risk of ICU admission and morality risk in diabetic COVID-19 patients.
A database search was conducted to identify studies comparing diabetic COVID-19 patients hospitalized in intensive care unit (ICU) and those reporting the overall mortality of these patients published up to March 25, 2020 within MEDLINE, Scopus and Web of Science.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. The main outcome was the risk of ICU admission in diabetic patients with COVID-19 infection while the second was the mortality risk in overall diabetic COVID-19 patients. Data were pooled using the Mantel-Haenszel random effects models with odds ratio (OR) as the effect measure with the related 95 % confidence interval (CI). Statistical heterogeneity between groups was measured using the Higgins I2 statistic.
Among 1382 patients (mean age 51.5 years, 798 males), DM resulted to be the second more frequent comorbidities. Diabetic patients resulted to have a significant increased risk of ICU admission (OR: 2.79, 95 % CI 1.85–4.22, p < 0.0001, I2 = 46 %). In 471 patients (mean age 56.6 years, 294 males) analysed for the secondary outcome diabetic subjects resulted to be at higher mortality risk (OR 3.21, 95 % CI 1.82–5.64, p < 0.0001, I2 = 16 %).
Diabetic patients with COVID-19 patients are at higher risk of ICU admission and show an higher mortality risk.
Cerebrovascular hemodynamic impairment has been reported in Alzheimer's disease (AD). We performed a systematic review and meta-analysis to investigate changes in cerebral blood flow (CBF) in AD ...patients.
Data were obtained by searching MEDLINE and Scopus for all investigations published between 1 January 2011 and 1 November 2021, comparing the cerebrovascular hemodynamic between AD patients and cognately healthy age-matched controls, using transcranial Doppler (TCD) ultrasound.
Twelve studies, based on 685 patients 395 with AD and 290 age-matched cognitively healthy controls, with a mean age of 71.5 and 72.1 years, respectively were included in the analysis. A random effect model revealed that AD patients, in the proximal segments of the middle cerebral artery (MCA), have a significantly lower CBF velocity, compared to controls (MD: -7.80 cm/s, 95%CI: -10.78 to -5.13,
< 0.0001, I
= 71.0%). Due to a significant Egger's test (t = 3.12,
= 0.008), a trim-and-fill analysis was performed, confirming the difference (MD: -11.05 cm/s, 95%CI: -12.28 to -9.82,
< 0.0001). Meta-regression analysis demonstrated that the mean CBF at the proximal MCA was directly correlated with arterial hypertension (
= 0.03) and MMSE score (
< 0.001), but inversely correlated with age (
= 0.01). In AD patients, the pulsatility index was significantly higher compared to controls (MD: 0.16, 95%CI: 0.07 to 0.25,
< 0.0001, I
: 84.5%), while the breath-holding index test results were significant lower (MD: -1.72, 95%CI: -2.53 to -0.91,
< 0.001, I
: 85.4%).
AD patients have a significant impairment in relation to their cerebrovascular perfusion, suggesting that cerebrovascular hemodynamic deterioration, evaluated using TCD, may be a useful diagnostic tool.
Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL), in addition to having a prognostic value in patients with cardiovascular disease, seems to interact with adiposity, insulin resistance ...and other cardiovascular risk factors. However, the results of previous clinical studies, focused on the association of TRAIL with selected metabolic or anthropometric indices were inconclusive. The aim of this study was to further investigate how soluble TRAIL concentrations independently correlate with major cardiovascular risk factors, including lipid, glycemic and anthropometric features.
We examined the associations between serum soluble TRAIL concentrations, measured by ELISA, and lipid, glycemic and anthropometric features in 199 subjects recruited at our Metabolic Outpatient Clinic.
Soluble TRAIL concentrations had a significant and direct correlation with total cholesterol (p = 0.046), LDL-cholesterol (p = 0.032), triglycerides (p = 0.01), body mass index (p = 0.046), waist circumference (p = 0.008), fat mass (p = 0.056) and insulin (p = 0.046) and an inverse correlation with HDL-cholesterol (p = 0.02). In multivariable regression analyses adjusted for potential confounders (age, gender, C-reactive protein, HDL-cholesterol, triglycerides, waist circumference, and insulin), TRAIL levels continued to have an independent correlation with LDL-cholesterol and waist circumference (r(2) = 0.04).
Serum TRAIL levels were weakly but significantly and independently associated with waist circumference, a marker of visceral adiposity, and with LDL-cholesterol. Further studies are needed to clarify the biological basis of these relationships.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Brain-derived neurotrophic factor (BDNF) is a member of the family of neurotrophins and has been implicated in brain resistance to insults. Murine studies have demonstrated increased hippocampal ...concentration after acute immobilization and decreased concentration after chronic immobilization. In humans, chronic stress and sedentary lifestyle result in decreased plasma BDNF levels, but there no data exist regarding acute immobilization. The aim of our study was to evaluate age-related responses comparing 7 younger subjects (age 23 ± 3 yr) and 8 older subjects (age 60 ± 4 yr) of plasma BDNF before (baseline data collection, BDC) and after 14 days (BR14) of horizontal bed rest (BR). At BDC, BDNF levels were not different between the two groups (P = 0.101), although at BR14, BDNF levels were higher in older subjects (62.02 ± 18.31) than in younger subjects (34.36 ± 15.24 pg/ml) (P = 0.002). A general linear model for repeated measures showed a significant effect of BR on BDNF (P = 0.002). The BDC BDNF levels correlated with fat-free mass in both populations (ALL) (R = 0.628, P = 0.012), (older, R = 0.753, P = 0.031; younger, R = 0.772, P = 0.042), and with total cholesterol in ALL (R = 0.647, P = 0.009) and older study subjects (R = 0.805, P = 0.016). At BR14, BDNF correlated with total cholesterol (R = 0.579, P = 0.024) and age (R = 0.647, P = 0.009) in ALL. With an increase in age, the brain could become naturally less resistant to acute stressors, including the detrimental effects of prolonged bed rest, and thus the increase in BDNF in the older study group might reflect a protective overshooting of the brain to counteract the negative effects in such conditions.
The ability to remain mobile is an essential aspect of quality of life and is critical for the preservation of independence in old age. One of the cornerstones of comprehensive geriatric assessment ...is the evaluation of functional and mobility status, because it provides clinicians pivotal information on overall health status, quality of life, needs for formal and informal care, and short and long term prognosis. As a consequence, many assessment tools have been developed and proposed for clinical use, including simple self-report measures assessing basic abilities and more complex and challenging performance-based objective tools. Both self-report and objective measures might be used to investigate specific steps of the age-related disablement process. In general, self-report and performance based instruments should not be used interchangeably, since they provide different and complementary information. Selection of the more appropriate tool strongly depends on clinical setting, patient characteristics, and clinical or research objective.
One of the main risk factors for brain diseases is aging. Recent studies have shown that aging is a progressive degenerative process associated with chronic low-level inflammation. The ATP-gated P2X7 ...receptor (P2X7R) plays an important role in inflammation and has been associated with different brain (e.g., Alzheimer's and Parkinson's) or other age-related (osteoporosis, arthritis, cancer) diseases. Several single nucleotide polymorphisms (SNPs) in the
gene have been identified, including the loss-of-function 1513A>C and 1405A>G SNPs, and the gain-of-function 489C>T and 1068G>A SNPs. We carried out a literature analysis to verify an association between
SNPs' frequency and age. In 34 worldwide eligible studies (11.858 subjects) no correlation between 1513CC genotype frequency and age emerged. On the contrary, analysis of European Caucasian cohorts (7.241 subjects) showed a significant increase in 1513CC frequency with age (
= 0.027). In agreement with these findings, analysis of two publicly available datasets, including USA Caucasian cohorts, unveiled an increased frequency of 1513CC and 489CC genotypes with age (
= 0.0055 and
= 0.0019, respectively). Thus, hypomorphic
genotypes may be positively selected with age in European and North American Caucasian populations. We hypothesize that Caucasian individuals bearing an anti-inflammatory P2X7R phenotype and living in high-income countries may have a longer life expectancy.
PDF
