Background Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol ...intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. Methods We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). Results Baseline chronological age (51.3 + or - 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02). Conclusions This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging. Trial registration ClinicalTrials.gov, NCT03020186. Keywords: Epigenetics, Weight loss, Green-MED diet, Urolithins, Tyrosol, Methylation age, Urine metabolomics
Objective
To examine the association between exposure to radiation from computed tomography (CT) studies and the incidence of cataract.
Methods
In a nested case–control study, all cataract cases and ...their matched controls were sampled from a retrospective cohort of Israeli residents who underwent CT scans or ultrasonic tests in Soroka Medical Center, Beer-Sheva, Israel, between the years 1996 and 2014. The risk of cataract associated with head, neck or the rest of the body CT was assessed using Poisson survival analysis.
Results
The nested matched sample included 3841 cataract cases and their age- and sex-matched controls (
n
= 228,743). CT radiation exposure was more frequent in the cataract group, with 9.7% head CT, 1.2% neck CT and 6.6% other CT, compared to 5%, 0.7% and 3.7% among person-years without cataract (
p
< 0.001). In a multivariate analysis, a similar increased risk of cataract associated with head (hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.11; 1.38) and other CT (HR: 1.25, 95% CI: 1.10; 1.43) was found. No association with neck CT (HR: 1.07, 95% CI: 0.80; 1.43) was observed.
Conclusion
In our study population, a similar risk of cataract with head, neck or the rest of the body CT was detected.
Benign external hydrocephalus (BEH) is defined by rapid increase in head circumference in infancy, with neuroimaging evidence of enlarged cerebrospinal fluid (CSF) spaces. BEH was postulated to ...predispose to subdural hematoma, neurocognitive impairments, and autism. There is currently no consensus on BEH diagnostic criteria and no biomarkers to predict neurological sequalae.
MRI-based quantitative approach was used for measurement of potential imaging markers related to external hydrocephalus and their association with neurological outcomes. We scanned 23 infants diagnosed with BEH and 11 age-similar controls. Using anatomical measurements from a large sample of healthy infants (
= 150), Z-scores were calculated to classify subject's CSF spaces as enlarged (≥1.96SD of mean values) or normal.
Subjects with abnormally enlarged CSF spaces had a significantly wider and longer ON (
= 0.017 and
= 0.020, respectively), and a significantly less tortuous ON (
= 0.006). ON deformity demonstrated a high diagnostic accuracy for abnormally enlarged frontal subarachnoid space (AUC = 0.826) and interhemispheric fissure (AUC = 0.833). No significant association found between enlarged CSF spaces and neurological complications (OR = 0.330, 95%CI 0.070-1.553,
= 0.161). However, cluster analysis identified a distinct subgroup of children (23/34, 67.6%) with enlarged CSF spaces and a wider, longer and less tortuous ON, to have an increased risk for neurological complications (RR = 7.28, 95%CI 1.07-49.40).
This is the first report on the association between external hydrocephalus, ON deformity and neurological complications. Our findings challenge the current view of external hydrocephalus as a benign condition. ON deformity is a potential auxiliary marker for risk stratification in patients with enlarged CSF spaces.
Cerebral hyperperfusion syndrome (CHS) may occur as a severe complication following surgical treatment of carotid stenosis. However, the mechanism inducing neurological symptoms in CHS remains ...unknown. We describe a patient with CHS presenting with seizures 24 h following carotid endarterectomy. Imaging demonstrated early ipsilateral blood–brain barrier (BBB) breakdown with electroencephalographic evidence of cortical dysfunction preceding brain edema. Using in vitro experiments on rat cortical tissue, we show that direct exposure of isolated brain slices to a serum-like medium induces spontaneous epileptiform activity, and that neuronal dysfunction is triggered by albumin. We propose BBB breakdown and subsequent albumin extravasation as a novel pathogenic mechanism underlying CHS and a potential target for therapy.
The relation between changes in respiratory quotient (RQ) following dietary interventions and clinical parameters and body fat pools remains unknown. In this randomized controlled trial, participants ...with moderate abdominal obesity or/and dyslipidemia (n = 159) were randomly assigned to a Mediterranean/low carbohydrate (MED/LC, n = 80) or a low fat (LF, n = 79) isocaloric weight loss diet and completed a metabolic assessment. Changes in RQ (measured by indirect calorimeter), adipose-tissue pools (MRI), and clinical measurements were assessed at baseline and after 6 months of intervention. An elevated RQ at baseline was significantly associated with increased visceral adipose tissue, hepatic fat, higher levels of insulin and homeostatic insulin resistance. After 6 months, body weight had decreased similarly between the diet groups (−6 ± 6 kg). However, the MED/LC diet, which greatly improved metabolic health, decreased RQ significantly more than the LF diet (−0.022 ± 0.007 vs. −0.002 ± 0.008, p = 0.005). Total cholesterol and diastolic blood pressure were independently associated with RQ changes (p = 0.045). RQ was positively associated with increased superficial subcutaneous-adipose-tissue but decreased renal sinus, pancreatic, and intramuscular fats after adjusting for confounders. Fasting RQ may reflect differences in metabolic characteristics between subjects affecting their potential individual response to the diet.
We aimed to assess the clinical significance of M1-MCA occlusion with visualization of both MCA-M2 segments "Tilted-V sign" (TVS) on initial CT angiography (CTA) in patients with acute ischemic ...stroke (AIS) undergoing endovascular thrombectomy (EVT).
Data for patients with consecutive AIS undergoing EVT for large vessel occlusion (LVO) in two academic centers are recorded in ongoing databases. Patients who underwent EVT for M1-MCA occlusions ≤ 6 h from symptom onset were included in this retrospective analysis.
A total of 346 patients met the inclusion criteria; 189 (55%) had positive TVS. Patients with positive TVS were younger (68 ± 14 vs. 71 ± 14 years,
= 0.028), with similar rates of vascular risk factors and baseline modified Rankin scores (mRS) 0-2. The rates of achieving thrombolysis in cerebral ischemia (TICI) 2b-3 were similar to the two groups (79%), although successful first-pass recanalization was more common with TVS (64 vs. 36%,
= 0.01). On multivariate analysis, higher collateral score odds ratio (OR) 1.38 per unit increase,
= 0.008 and lower age (OR 0.98 per year increase,
= 0.046) were significant predictors of TVS. Patients with positive TVS had higher post-procedural Alberta Stroke Program Early CT Score (ASPECTS; 6.9 ± 2.2 vs. 5.2 ± 2.3,
= 0.001), were discharged with lower National Institutes of Health Stroke Score (NIHSS; 6±6 vs. 9±7,
= 0.003) and higher rates of mRS 0-2 (29.5 vs. 12%,
= 0.001), and had lower rates of 90-day mortality (13.2 vs. 21.6%,
= 0.038). However, TVS was not an independent predictor of functional independence (OR 2.51; 95% CI 0.7-8.3).
Tilted-V Sign, an easily identifiable radiological marker, is associated with fewer recanalization attempts, better functional outcomes, and reduced mortality.
While the typical patient with idiopathic intracranial hypertension (IIH) is an obese female of childbearing age, there are unique patient populations, such as non-obese females, that have not been ...well studied. Characterizing this subpopulation may increase awareness our of it, which may prevent underdiagnosis and improve our understanding of IIH's underlying pathophysiology. We retrospectively reviewed electronic medical records and compared the clinical and radiological characteristics of non-obese (BMI < 30) and obese (BMI > 30) female patients with IIH. Two hundred and forty-six patients (age 32.3 ± 10) met our inclusion criteria. The non-obese patients (
= 59, 24%) were significantly younger than the obese patients (29.4 ± 9.9 vs. 33.2 ± 10.2,
= 0.004) and had higher rates of severe papilledema (Friesen 4-5; 25.4% vs. 11.8%,
= 0.019), scleral flattening (62.7% vs. 36.9%,
= 0.008), and optic nerve dural ectasia (78.0% vs. 55.6%,
= 0.044). Non-obese patients also had a tendency to have a higher lumbar puncture opening pressure (368 ± 92.7 vs. 344 ± 76.4,
= 0.062). Non-obese patients were three times more likely to present with a combination of scleral flattening and optic nerve dural ectasia (OR = 3.00, CI: 1.57-5.72, χ
= 11.63, α < 0.001). Overall, non-obese females with IIH were found to have a more fulminant presentation, typified by higher rates of severe papilledema and radiological findings typical for IIH.
Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss ...directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/- physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m
) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (-13.1% and -5.3%, respectively,
< 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (-5%,
< 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10;
= 0.05), HbA1c (β = 0.12;
= 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12;
= 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16;
= 0.02) and leptin (β = 0.19;
= 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724).
Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among ...participants with abdominal fat, remain unclear.
In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28g·day-1 of walnuts). After 6-months, the participants were re-randomized to moderate intense physical activity (PA+) or non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats.
Across the 277 participants 86% men, age = 48 years, body-mass-index (BMI) = 31kg/m2, visceral fat = 33% 86% completed the 18-m trial. At baseline, women had higher IMTG than men (3.4% vs. 2.3%, p<0.001) and increased IMTG was associated with aging and higher BMI, visceral and intermuscular fats, HbA1c%, HDL-c and leptin(p<0.05), but not with intra-hepatic fat. After 18 month of intervention and a -3 kg mean weight loss, participants significantly increased IMTG by 25%, with a distinct effect in the MED/LCPA+ group as compared to the other intervention groups (57% vs. 9.5-18.5%, p<0.05). Changes in IMTG were associated with visceral and intermuscular fat, metabolic syndrome, insulin and leptin (p<0.05 for all), however, these associations did not remain after adjustment for visceral fat changes.
Lifestyle strategies differentially affect IMTG accumulation; combination of exercise with decreased carbohydrate/increased unsaturated fat proportion intake greatly increase IMTG. Our findings suggest that increased IMTG during diet-induced moderate weight loss may not be directly related to cardiometabolic risk.
ClinicalTrials.gov NCT01530724.
The blood-brain barrier (BBB) is a functional and structural barrier separating the intravascular and neuropil compartments of the brain. It characterizes the vascular bed and is essential for normal ...brain functions. Dysfunction in the BBB properties have been described in most common neurological disorders, such as stroke, traumatic injuries, intracerebral hemorrhage, tumors, epilepsy and neurodegenerative disorders. It is now obvious that the BBB plays an important role in normal brain activity, stressing the need for applicable imaging and assessment methods. Recent advancements in imaging techniques now make it possible to establish sensitive and quantitative methods for the assessment of BBB permeability. However, most of the existing techniques require complicated and demanding dynamic scanning protocols that are impractical and cannot be fulfilled in some cases. We review existing methods for the evaluation of BBB permeability, focusing on quantitative magnetic resonance-based approaches and discuss their drawbacks and limitations. In light of those limitations we propose two new approaches for BBB assessment with less demanding imaging sequences: the "post-pre" and the "linear dynamic" methods, both allow semi-quantitative permeability assessment and localization of dysfunctional BBB with simple/partial dynamic imaging protocols and easy-to-apply analysis algorithms. We present preliminary results and show an example which compares these new methods with the existing standard assessment method. We strongly believe that the establishment of such "easy to use" and reliable imaging methods is essential before BBB assessment can become a routine clinical tool. Large clinical trials are awaited to fully understand the significance of BBB permeability as a biomarker and target for treatment in neurological disorders.
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