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81 result(s) for "Shelef, Ilan"
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Bone mineral density alteration in obstructive sleep apnea by derived computed tomography screening
The association between obstructive sleep apnea (OSA) and bone mineral density (BMD) is poorly elucidated and has contradictory findings. Abdominal computed tomography (CT) for other indications can provide a valuable opportunity for osteoporosis screening. Thus, we retrospectively explored the association between OSA and BMD by examining abdominal CT vertebrae images for a multitude of conditions and indications. We included 315 subjects (174 with OSA and 141 without OSA) who performed at least two CT scans (under similar settings). Both groups had a similar duration between the first and second CT scans of 3.6 years. BMD decreased in those with OSA and increased age. A multivariate linear regression indicated that OSA is associated with BMD alterations after controlling for age, gender, and cardiovascular diseases. Here, we report that OSA is associated with BMD alterations. Further studies are required to untangle the complex affect of OSA on BMD and the possible clinical implications of vertebra-depressed or femoral neck fractures.
Detection of breast cancer in digital breast tomosynthesis with vision transformers
Digital Breast Tomosynthesis (DBT) has revolutionized more traditional breast imaging through its three-dimensional (3D) visualization capability that significantly enhances lesion discernibility, reduces tissue overlap, and improves diagnostic precision as compared to conventional two-dimensional (2D) mammography. In this study, we propose an advanced Computer-Aided Detection (CAD) system that harnesses the power of vision transformers to augment DBT’s diagnostic efficiency. This scheme uses a neural network to glean attributes from the 2D slices of DBT followed by post-processing that considers features from neighboring slices to categorize the entire 3D scan. By leveraging a transfer learning technique, we trained and validated our CAD framework on a unique dataset consisting of 3,831 DBT scans and subsequently tested it on 685 scans. Of the architectures tested, the Swin Transformer outperformed the ResNet101 and vanilla Vision Transformer. It achieved an impressive AUC score of 0.934 ± 0.026 at a resolution of 384 × 384. Increasing the image resolution from 224 to 384 not only maintained vital image attributes but also led to a marked improvement in performance (p-value = 0.0003). The Mean Teacher algorithm, a semi-supervised method using both labeled and unlabeled DBT slices, showed no significant improvement over the supervised approach. Comprehensive analyses across different lesion types, sizes, and patient ages revealed consistent performance. The integration of attention mechanisms yielded a visual narrative of the model’s decision-making process that highlighted the prioritized regions during assessments. These findings should significantly propel the methodologies employed in DBT image analysis by setting a new benchmark for breast cancer diagnostic precision.
The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity
Obesity is linked with the brain aging faster than would normally be expected. Researchers are able to capture this process by calculating a person’s ‘brain age’ – how old their brain appears on detailed scans, regardless of chronological age. This approach also helps to monitor how certain factors, such as lifestyle, can influence brain aging over relatively short time scales. It is not clear whether lifestyle interventions that promote weight loss can help to slow obesity-driven brain aging. To answer this question, Levakov et al. studied 102 individuals who met the criteria for obesity and took part in a lifestyle intervention aimed to improve diet and physical activity levels over 18 months. The participants received a brain scan at the beginning and the end of the program; additional tests and measurements were also conducted at these times to capture other biological processes impacted by obesity, such as liver health. Levakov et al. used the brain scans taken at the start and end of the study to examine the impact of the lifestyle intervention on the aging trajectory. The results revealed that a reduction in body weight of 1% led to the participants’ brain age being nearly 9 months younger than the expected brain age after 18 months. This attenuated aging was associated with changes in other biological measures, such as decreased liver fat and liver enzymes. Increases in liver fat and production of specific liver enzymes were previously shown to negatively impact brain health in Alzheimer’s disease. Finally, examining more closely the food consumption reports completed by participants showed that reduced consumption of processed food, sweets and beverages were linked to attenuated brain aging. The findings show that lifestyle interventions which promote weight loss can have a beneficial impact on the aging trajectory of the brain observed with obesity. The next steps will include determining whether slowing down obesity-driven brain aging results in better clinical outcomes for patients. In addition, the work by Levakov et al. demonstrates a potential strategy to evaluate the success of lifestyle changes on brain health. With global rates of obesity rising, identifying interventions that have a positive impact on brain health could have important clinical, educational and social impacts.
Sensitivity of Diffusion Tensor Imaging for Assessing Injury Severity in a Rat Model of Isolated Diffuse Axonal Injury: Comparison with Histology and Neurological Assessment
Diffuse axonal brain injury (DAI) is a common, debilitating consequence of traumatic brain injury, yet its detection and severity grading remain challenging in clinical and experimental settings. This study evaluated the sensitivity of diffusion tensor imaging (DTI), histology, and neurological severity scoring (NSS) in assessing injury severity in a rat model of isolated DAI. A rotational injury model induced mild, moderate, or severe DAI in male and female rats. Neurological deficits were assessed 48 h after injury via NSS. Magnetic resonance imaging, including DTI metrics, such as fractional anisotropy (FA), relative anisotropy (RA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD), was performed prior to tissue collection. Histological analysis used beta amyloid precursor protein immunohistochemistry. Sensitivity and variability of each method were compared across brain regions and the whole brain. Histology was the most sensitive method, requiring very small groups to detect differences. Anisotropy-based MRI metrics, especially whole-brain FA and RA, showed strong correlations with histology and NSS and demonstrated high sensitivity with low variability. NSS identified injury but required larger group sizes. Diffusivity-based MRI metrics, particularly RD, were less sensitive and more variable. Whole-brain FA and RA were the most sensitive MRI measures of DAI severity and were comparable to histology in moderate and severe groups. These findings support combining NSS and anisotropy-based DTI for non-terminal DAI assessment in preclinical studies.
The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial
Background Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). Methods In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3–4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. Results Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m 2 ; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: − 2.7%, green-MED: − 3.9%) and waist circumference (MED: − 4.7%, green-MED: − 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: − 4.2%, MED: − 6.0%, green-MED: − 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa ; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid ), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss ( p < 0.05, multivariate models). Conclusions A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression. Trial registration ClinicalTrials.gov , NCT03020186
The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial
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 ± 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.
Neural correlates of future weight loss reveal a possible role for brain-gastric interactions
•We examined neural correlates of weight loss following a lifestyle intervention.•Weight loss correlated with baseline connectivity within a functional subnetwork.•The weight loss subnetwork is comprised of senso-motor cortical regions.•We tested a novel hypothesis regarding the role of brain-gastric interaction. Lifestyle dietary interventions are an essential practice in treating obesity, hence neural factors that may assist in predicting individual treatment success are of great significance. Here, in a prospective, open-label, three arms study, we examined the correlation between brain resting-state functional connectivity measured at baseline and weight loss following 6 months of lifestyle intervention in 92 overweight participants. We report a robust subnetwork composed mainly of sensory and motor cortical regions, whose edges correlated with future weight loss. This effect was found regardless of intervention group. Importantly, this main finding was further corroborated using a stringent connectivity-based prediction model assessed with cross-validation thus attesting to its robustness. The engagement of senso-motor regions in this subnetwork is consistent with the over-sensitivity to food cues theory of weight regulation. Finally, we tested an additional hypothesis regarding the role of brain-gastric interaction in this subnetwork, considering recent findings of a cortical network synchronized with gastric activity. Accordingly, we found a significant spatial overlap with the subnetwork reported in the present study. Moreover, power in the gastric basal electric frequency within our reported subnetwork negatively correlated with future weight loss. This finding was specific to the weight loss related subnetwork and to the gastric basal frequency. These findings should be further corroborated by combining direct recordings of gastric activity in future studies. Taken together, these intriguing results may have important implications for our understanding of the etiology of obesity and the mechanism of response to dietary intervention.
Balance recovery stepping responses during walking were not affected by a concurrent cognitive task among older adults
Background Most of older adults’ falls are related to inefficient balance recovery after an unexpected loss of balance, i.e., postural perturbation. Effective balance recovery responses are crucial to prevent falls. Due to the considerable consequences of lateral falls and the high incidence of falls when walking, this study aimed to examine the effect of a concurrent cognitive task on older adults’ balance recovery stepping abilities from unannounced lateral perturbations while walking. We also aimed to explore whether cognitive performance accuracy is affected by perturbed walking and between task trade-offs. Methods In a laboratory-based study, 20 older adults (> 70 years old) performed the following test conditions: (1) cognitive task while sitting; (2) perturbed walking; and (3) perturbed walking with a concurrent cognitive task. The cognitive task was serial numbers subtraction by seven. Single-step and multiple-step thresholds, highest perturbation achieved, 3D kinematic analysis of the first recovery step, and cognitive task performance accuracy were compared between single-task and dual-task conditions. Between task trade-offs were examined using dual-task cost (DTC). Results Single-step and multiple-step thresholds, number of recovery step trials, number of foot collision, multiple-step events and kinematic recovery step parameters were all similar in single-task and dual-task conditions. Cognitive performance was not significantly affected by dual-task conditions, however, different possible trade-offs between cognitive and postural performances were identified using DTC. Conclusions In situations where postural threat is substantial, such as unexpected balance loss during walking, balance recovery reactions were unaffected by concurrent cognitive load in older adults (i.e., posture first strategy). The study was approved by the Helsinki Ethics Committee of Soroka University Medical Center in Beer-Sheva, Israel (ClinicalTrials.gov Registration number NCT04455607 , ID Numbers: Sor 396–16 CTIL; 02/07/2020).
Radiological signs supporting idiopathic intracranial hypertension in symptomatic patients with lumbar puncture opening pressure < 250 mm
Lumbar puncture opening pressure (LPOP) exceeding 250mmH 2 O is key in diagnosing idiopathic intracranial hypertension (IIH), per revised Friedman’s criteria. Some patients do not meet LPOP criteria (with or without papilledema), despite having IIH-related symptoms and neuroimaging findings. This study aimed to investigate the radiological findings and clinical symptoms in patients suspected of having IIH without meeting the LPOP criteria. We retrospectively evaluated cerebral venous sinus stenosis using the conduit Farb score (CFS) and other radiological findings suggestive of IIH by computed tomography venography and magnetic resonance venography in females ≥ 18 years-old with chronic headaches, suspected IIH, and LPOP < 250 mm. Eighty-eight women (56 with LPOP < 200 mm H 2 O and 32 with LPOP ranging between 200 and 250mmH 2 O) were included. Among patients with LPOP 200–250mmH 2 O, 40% (12) exhibited three or more radiological findings supporting IIH, compared to 17% (8) in the LPOP < 200 mmH 2 O group ( p  = 0.048). Cerebral venous stenosis (CFS ≤ 5) was observed in 80% (24) of those with LPOP 200–250 mmH 2 O, contrasting with 40% (19) of those with LPOP < 200 mmH 2 O (p < 0.001). Cerebral venous stenosis was significantly more common in patients with LPOP 200–250 mmH 2 O than < 200 mmH 2 O, suggesting that they may benefit from IIH treatment.
Interleukin-1β Regulates Fat-Liver Crosstalk in Obesity by Auto-Paracrine Modulation of Adipose Tissue Inflammation and Expandability
The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role of IL-1β was clinically demonstrated to mediate only the pancreatic beta-cell demise, and in mice mainly the intra-hepatic manifestations of obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed to mainly function locally, could regulate dysfunctional inter-organ crosstalk in obesity. Here we show that High-fat-fed (HFF) mice exhibited a preferential increase of IL-1β in portal compared to systemic blood. Moreover, portally-drained mesenteric fat transplantation from IL-1βKO donors resulted in lower pyruvate-glucose flux compared to mice receiving wild-type (WT) transplant. These results raised a putative endocrine function for visceral fat-derived IL-1β in regulating hepatic gluconeogenic flux. IL-1βKO mice on HFF exhibited only a minor or no increase in adipose expression of pro-inflammatory genes (including macrophage M1 markers), Mac2-positive crown-like structures and CD11b-F4/80-double-positive macrophages, all of which were markedly increased in WT-HFF mice. Further consistent with autocrine/paracrine functions of IL-1β within adipose tissue, adipose tissue macrophage lipid content was increased in WT-HFF mice, but significantly less in IL-1βKO mice. Ex-vivo, adipose explants co-cultured with primary hepatocytes from WT or IL-1-receptor (IL-1RI)-KO mice suggested only a minor direct effect of adipose-derived IL-1β on hepatocyte insulin resistance. Importantly, although IL-1βKOs gained weight similarly to WT-HFF, they had larger fat depots with similar degree of adipocyte hypertrophy. Furthermore, adipogenesis genes and markers (pparg, cepba, fabp4, glut4) that were decreased by HFF in WT, were paradoxically elevated in IL-1βKO-HFF mice. These local alterations in adipose tissue inflammation and expansion correlated with a lower liver size, less hepatic steatosis, and preserved insulin sensitivity. Collectively, we demonstrate that by promoting adipose inflammation and limiting fat tissue expandability, IL-1β supports ectopic fat accumulation in hepatocytes and adipose-tissue macrophages, contributing to impaired fat-liver crosstalk in nutritional obesity.