Kinetic Modeling of Brain [18-F]FDG Positron Emission Tomography Time Activity Curves with Input Function Recovery (IR) Method.

Accurate positron emission tomography (PET) data quantification relies on high-quality input plasma curves, but venous blood sampling may yield poor-quality data, jeopardizing modeling outcomes. In this study, we aimed to recover sub-optimal input functions by using information from the tail (5th-100th min) of curves obtained through the frequent sampling protocol and an input recovery (IR) model trained with reference curves of optimal shape. Initially, we included 170 plasma input curves from eight published studies with clamp [18F]-fluorodeoxyglucose PET exams. Model validation involved 78 brain PET studies for which compartmental model (CM) analysis was feasible (reference (ref) + training sets). Recovered curves were compared with original curves using area under curve (AUC), max peak standardized uptake value (maxSUV). CM parameters (ref + training sets) and fractional uptake rate (FUR) (all sets) were computed. Original and recovered curves from the ref set had comparable AUC (d = 0.02, not significant (NS)), maxSUV (d = 0.05, NS) and comparable brain CM results (NS). Recovered curves from the training set were different from the original according to maxSUV (d = 3) and biologically plausible according to the max theoretical K1 (53//56). Brain CM results were different in the training set (p < 0.05 for all CM parameters and brain regions) but not in the ref set. FUR showed reductions similarly in the recovered curves of the training and test sets compared to the original curves (p < 0.05 for all regions for both sets). The IR method successfully recovered the plasma inputs of poor quality, rescuing cases otherwise excluded from the kinetic modeling results. The validation approach proved useful and can be applied to different tracers and metabolic conditions.

Insulin-stimulated brain glucose uptake correlates with brain metabolites in severe obesity: A combined neuroimaging study.

The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (1H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)) was also performed in a subset of subjects during clamp. In dataset A, 48 participants were studied during fasting with brain 1H-MRS, while in dataset B 21 participants underwent paired brain 1H-MRS acquisitions under fasting and clamp conditions. In dataset C 16 subjects underwent brain 18F-FDG-PET and 1H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity.

Toward a more precise prognostic stratification in acute decompensation of cirrhosis: The Padua model 2.0.

BACKGROUND: The clinical course of acutely decompensated cirrhosis (AD) is heterogeneous. Presepsin (PSP) is a plasmatic biomarker that reflects Toll-like receptor activity and systemic inflammation. We conducted a prospective study to: (1) measure PSP in AD and (2) assess whether PSP in AD can predict the development of acute-on-chronic liver failure (ACLF). METHODS: Patients with AD were prospectively recruited at admission and underwent determination of PSP. In study part 1, we compared PSP in AD versus controls (stable decompensated and compensated cirrhosis). In study part 2, we prospectively followed patients with AD for 1 year and evaluated predictors of ACLF. RESULTS: One hundred and seventy three patients with AD were included (median MELD: 18; CLIF-C AD score: 54). Compared with controls, patients with AD had higher levels of PSP (674 ng/L vs. 310 ng/L vs. 157 ng/L; p < 0.001). In patients with AD, Child-Pugh C and acute kidney injury were associated with higher levels of PSP. During the follow-up, 52 patients developed ACLF (median time from recruitment: 66 days). PSP, CLIF-C AD score, and Child-Pugh stage were independently associated with ACLF. A predictive model combining these variables (Padua model 2.0) accurately identified patients at higher risk of ACLF (AUROC 0.864; 95% CI 0.780-0.947; sensitivity 82.9%, specificity 76.7%). In patients at lower risk of ACLF based on a CLIF-C AD <50, a PSP >674 ng/L could discriminate between two groups at significantly different risk of ACLF. Finally, in patients who did not develop ACLF, baseline PSP was significantly higher in those who progressed toward unstable versus stable decompensated cirrhosis. CONCLUSION: The Padua model 2.0 can be used to identify patients with AD at high risk of ACLF. If these results are validated by external cohorts, PSP could become a new biomarker to improve risk stratification in AD.

Mapping Lesion-Related Epilepsy to a Human Brain Network.

Importance: It remains unclear why lesions in some locations cause epilepsy while others do not. Identifying the brain regions or networks associated with epilepsy by mapping these lesions could inform prognosis and guide interventions. Objective: To assess whether lesion locations associated with epilepsy map to specific brain regions and networks. Design, Setting, and Participants: This case-control study used lesion location and lesion network mapping to identify the brain regions and networks associated with epilepsy in a discovery data set of patients with poststroke epilepsy and control patients with stroke. Patients with stroke lesions and epilepsy (n = 76) or no epilepsy (n = 625) were included. Generalizability to other lesion types was assessed using 4 independent cohorts as validation data sets. The total numbers of patients across all datasets (both discovery and validation datasets) were 347 with epilepsy and 1126 without. Therapeutic relevance was assessed using deep brain stimulation sites that improve seizure control. Data were analyzed from September 2018 through December 2022. All shared patient data were analyzed and included; no patients were excluded. Main Outcomes and Measures: Epilepsy or no epilepsy. Results: Lesion locations from 76 patients with poststroke epilepsy (39 [51%] male; mean [SD] age, 61.0 [14.6] years; mean [SD] follow-up, 6.7 [2.0] years) and 625 control patients with stroke (366 [59%] male; mean [SD] age, 62.0 [14.1] years; follow-up range, 3-12 months) were included in the discovery data set. Lesions associated with epilepsy occurred in multiple heterogenous locations spanning different lobes and vascular territories. However, these same lesion locations were part of a specific brain network defined by functional connectivity to the basal ganglia and cerebellum. Findings were validated in 4 independent cohorts including 772 patients with brain lesions (271 [35%] with epilepsy; 515 [67%] male; median [IQR] age, 60 [50-70] years; follow-up range, 3-35 years). Lesion connectivity to this brain network was associated with increased risk of epilepsy after stroke (odds ratio [OR], 2.82; 95% CI, 2.02-4.10; P < .001) and across different lesion types (OR, 2.85; 95% CI, 2.23-3.69; P < .001). Deep brain stimulation site connectivity to this same network was associated with improved seizure control (r, 0.63; P < .001) in 30 patients with drug-resistant epilepsy (21 [70%] male; median [IQR] age, 39 [32-46] years; median [IQR] follow-up, 24 [16-30] months). Conclusions and Relevance: The findings in this study indicate that lesion-related epilepsy mapped to a human brain network, which could help identify patients at risk of epilepsy after a brain lesion and guide brain stimulation therapies.

Profiling of plasma biomarkers in the context of memory assessment in a tertiary memory clinic.

Plasma biomarkers have shown promising performance in research cohorts in discriminating between different stages of Alzheimer's disease (AD). Studies in clinical populations are necessary to provide insights on the clinical utility of plasma biomarkers before their implementation in real-world settings. Here we investigated plasma biomarkers (glial fibrillary acidic protein (GFAP), tau phosphorylated at 181 and 231 (pTau181, pTau231), amyloid ß (Aß) 42/40 ratio, neurofilament light) in 126 patients (age = 65 ± 8) who were admitted to the Clinic for Cognitive Disorders, at Karolinska University Hospital. After extensive clinical assessment (including CSF analysis), patients were classified as: mild cognitive impairment (MCI) (n = 75), AD (n = 25), non-AD dementia (n = 16), no dementia (n = 9). To refine the diagnosis, patients were examined with [18F]flutemetamol PET (Aß-PET). Aß-PET images were visually rated for positivity/negativity and quantified in Centiloid. Accordingly, 68 Aß+ and 54 Aß- patients were identified. Plasma biomarkers were measured using single molecule arrays (SIMOA). Receiver-operated curve (ROC) analyses were performed to detect Aß-PET+ using the different biomarkers. In the whole cohort, the Aß-PET centiloid values correlated positively with plasma GFAP, pTau231, pTau181, and negatively with Aß42/40 ratio. While in the whole MCI group, only GFAP was associated with Aß PET centiloid. In ROC analyses, among the standalone biomarkers, GFAP showed the highest area under the curve discriminating Aß+ and Aß- compared to other plasma biomarkers. The combination of plasma biomarkers via regression was the most predictive of Aß-PET, especially in the MCI group (prior to PET, n = 75) (sensitivity = 100%, specificity = 82%, negative predictive value = 100%). In our cohort of memory clinic patients (mainly MCI), the combination of plasma biomarkers was sensitive in ruling out Aß-PET negative individuals, thus suggesting a potential role as rule-out tool in clinical practice.

Gender, Obesity, Fat Distribution and 25-Hydroxyvitamin D.

Background and Objectives: Obesity is a worldwide disease associated with systemic complications. In recent years, there has been growing interest in studying vitamin D but data related to obese subjects are still poor. AIM: The aim of this study was to evaluate the relationship between obesity degree and 25-hydroxyvitamin D [25(OH)D] levels. Materials and Methods: We recruited 147 Caucasian adult obese patients (BMI > 30 Kg/m2; 49 male; median age 53 years), and 20 overweight subjects as control group (median age 57 years), who had been referred to our Obesity Center of Chieti (Italy) between May 2020 and September 2021. Results: The median BMI was 38 (33-42) kg/m2 for obese patients and 27 (26-28) kg/m2 for overweight patients. 25(OH)D concentrations were lower in the obese population compared to the overweight population (19 ng/mL vs. 36 ng/mL; p < 0.001). Considering all obese subjects, a negative correlation was observed between 25(OH)D concentrations and obesity-related parameters (weight, BMI, waist circumference, fat mass, visceral fat, total cholesterol, LDL cholesterol) and glucose metabolism-related parameters. 25(OH)D was also negatively correlated with blood pressure. Conclusions: Our data confirmed the inverse relationship between obesity and blood concentration of 25(OH)D and highlighted how 25(OH)D levels decrease in the presence of glucose and lipid metabolism alterations.

Risk Factors and Immunoinflammatory Mechanisms Leading to Atherosclerosis: Focus on the Role of Oral Microbiota Dysbiosis.

Cardiovascular diseases (CVD), including myocardial infarction and stroke, are currently the leading cause of morbidity, disability and mortality worldwide. Recently, researchers have focused their attention on the alterations of the gut and oral microbiota, investigating the possible role of their dysbiosis in the pathogenesis and/or progression of CVD. In this regard, it has been shown that endothelial dysfunction, a major feature of CVD, can also be induced by chronic periodontal infection, due to a systemic pro-inflammatory condition, as suggested by increased plasma levels of acute phase proteins, IL-6 and fibrinogen. Moreover, proatherogenic dysfunctions can also be promoted by direct bacterial invasion of the endothelium. This review reports the current evidence about the possible role of oral microbiota dysbiosis and the related immunoinflammatory components in the pathophysiology of atherosclerosis and associated CVD. It is concluded that integration of oral microbiota sampling into clinical practice may result in a more accurate assessment of CV risk in patients and even modify their prognosis.

Astrocyte Signature in Alzheimer's Disease Continuum through a Multi-PET Tracer Imaging Perspective.

Reactive astrogliosis is an early event in the continuum of Alzheimer's disease (AD). Current advances in positron emission tomography (PET) imaging provide ways of assessing reactive astrogliosis in the living brain. In this review, we revisit clinical PET imaging and in vitro findings using the multi-tracer approach, and point out that reactive astrogliosis precedes the deposition of Aß plaques, tau pathology, and neurodegeneration in AD. Furthermore, considering the current view of reactive astrogliosis heterogeneity-more than one subtype of astrocyte involved-in AD, we discuss how astrocytic body fluid biomarkers might fit into trajectories different from that of astrocytic PET imaging. Future research focusing on the development of innovative astrocytic PET radiotracers and fluid biomarkers may provide further insights into the heterogeneity of reactive astrogliosis and improve the detection of AD in its early stages.

The "Dedicated" C.B.C.T. in Dentistry.

This position statement represents a consensus of an expert committee composed by the Italian Academy of General Dentistry (Accademia Italiana Odontoiatria Generale COI-AIOG) and Italian Academy of Legal and Forensic Dentistry (Accademia Italiana di Odontoiatria Legale e Forense OL-F) on the appropriate use of cone beam computed tomography (C.B.C.T.) in dentistry. This paper analyzes the use of C.B.C.T. in light of the rapid evolution of volumetric technologies, with the new low- and ultra-low-dose exposure programs. These upgrades are determining an improvement in the precision and safety of this methodology; therefore, the need of a guideline revision of the use of C.B.C.T. for treatment planning is mandatory. It appears necessary to develop a new model of use, which, in compliance with the principle of justification and as low as reasonably achievable (ALARA) and as low as diagnostically acceptable (ALADA), can allow a functional "Dedicated C.B.C.T." exam optimized for the individuality of the patient.

APOE ε4 gene dose effect on imaging and blood biomarkers of neuroinflammation and beta-amyloid in cognitively unimpaired elderly.

BACKGROUND: Neuroinflammation, characterized by increased reactivity of microglia and astrocytes in the brain, is known to be present at various stages of the Alzheimer's disease (AD) continuum. However, its presence and relationship with amyloid pathology in cognitively normal at-risk individuals is less clear. Here, we used positron emission tomography (PET) and blood biomarker measurements to examine differences in neuroinflammation and beta-amyloid (Aß) and their association in cognitively unimpaired homozygotes, heterozygotes, or non-carriers of the APOE ε4 allele, the strongest genetic risk for sporadic AD. METHODS: Sixty 60-75-year-old APOE ε4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) were recruited in collaboration with the local Auria biobank. The participants underwent 11C-PK11195 PET (targeting 18-kDa translocator protein, TSPO), 11C-PiB PET (targeting Aß), brain MRI, and neuropsychological testing including a preclinical cognitive composite (APCC). 11C-PK11195 distribution volume ratios and 11C-PiB standardized uptake value ratios (SUVRs) were calculated for regions typical for early Aß accumulation in AD. Blood samples were drawn for measuring plasma glial fibrillary acidic protein (GFAP) and plasma Aß1-42/1.40. RESULTS: In our cognitively unimpaired sample, cortical 11C-PiB-binding increased according to APOE ε4 gene dose (median composite SUVR 1.47 (range 1.38-1.66) in non-carriers, 1.55 (1.43-2.02) in heterozygotes, and 2.13 (1.61-2.83) in homozygotes, P = 0.002). In contrast, cortical composite 11C-PK11195-binding did not differ between the APOE ε4 gene doses (P = 0.27) or between Aß-positive and Aß-negative individuals (P = 0.81) and associated with higher Aß burden only in APOE ε4 homozygotes (Rho = 0.47, P = 0.043). Plasma GFAP concentration correlated with cortical 11C-PiB (Rho = 0.35, P = 0.040), but not 11C-PK11195-binding (Rho = 0.13, P = 0.47) in Aß-positive individuals. In the total cognitively unimpaired population, both higher composite 11C-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, whereas elevated 11C-PiB-binding was associated with lower APCC scores. CONCLUSIONS: Only Aß burden measured by PET, but not markers of neuroinflammation, differed among cognitively unimpaired elderly with different APOE ε4 gene dose. However, APOE ε4 gene dose seemed to modulate the association between neuroinflammation and Aß.

Blood ß-synuclein is related to amyloid PET positivity in memory clinic patients.

INTRODUCTION: ß-synuclein is an emerging blood biomarker to study synaptic degeneration in Alzheimer´s disease (AD), but its relation to amyloid-ß (Αß) pathology is unclear. METHODS: We investigated the association of plasma ß-synuclein levels with [18F] flutemetamol positron emission tomography (PET) in patients with AD dementia (n = 51), mild cognitive impairment (MCI-Aß+ n = 18, MCI- Aß- n = 30), non-AD dementias (n = 22), and non-demented controls (n = 5). RESULTS: Plasma ß-synuclein levels were higher in Aß+ (AD dementia, MCI-Aß+) than in Aß- subjects (non-AD dementias, MCI-Aß-) with good discrimination of Aß+ from Aß- subjects and prediction of Aß status in MCI individuals. A positive correlation between plasma ß-synuclein and Aß PET was observed in multiple cortical regions across all lobes. DISCUSSION: Plasma ß-synuclein demonstrated discriminative properties for Aß PET positive and negative subjects. Our data underline that ß-synuclein is not a direct marker of Aß pathology and suggest different longitudinal dynamics of synaptic degeneration versus amyloid deposition across the AD continuum. HIGHLIGHTS: Blood and CSF ß-synuclein levels are higher in Aß+ than in Aß- subjects. Blood ß-synuclein level correlates with amyloid PET positivity in multiple regions. Blood ß-synuclein predicts Aß status in MCI individuals.

Resistance Training Increases White Matter Density in Frail Elderly Women.

We aimed to investigate the effects of maternal obesity on brain structure and metabolism in frail women, and their reversibility in response to exercise. We recruited 37 frail elderly women (20 offspring of lean/normal-weight mothers (OLM) and 17 offspring of obese/overweight mothers (OOM)) and nine non-frail controls to undergo magnetic resonance and diffusion tensor imaging (DTI), positron emission tomography with Fluorine-18-fluorodeoxyglucose (PET), and cognitive function tests (CERAD). Frail women were studied before and after a 4-month resistance training, and controls were studied once. White matter (WM) density (voxel-based morphometry) was higher in OLM than in OOM subjects. Exercise increased WM density in both OLM and OOM in the cerebellum in superior parietal regions in OLM and in cuneal and precuneal regions in OOM. OLM gained more WM density than OOM in response to intervention. No significant results were found from the Freesurfer analysis, nor from PET or DTI images. Exercise has an impact on brain morphology and cognition in elderly frail women.

Brain lesion locations associated with secondary seizure generalization in tumors and strokes.

Structural brain lesions are the most common cause of adult-onset epilepsy. The lesion location may contribute to the risk for epileptogenesis, but whether specific lesion locations are associated with a risk for secondary seizure generalization from focal to bilateral tonic-clonic seizures, is unknown. We identified patients with a diagnosis of adult-onset epilepsy caused by an ischemic stroke or a tumor diagnosed at the Turku University Hospital in 2004-2017. Lesion locations were segmented on patient-specific MR imaging and transformed to a common brain atlas (MNI space). Both region-of-interest analyses (intersection with the cortex, hemisphere, and lobes) and voxel-wise analyses were conducted to identify the lesion locations associated with focal to bilateral tonic-clonic compared to focal seizures. We included 170 patients with lesion-induced epilepsy (94 tumors, 76 strokes). Lesions predominantly localized in the cerebral cortex (OR 2.50, 95% C.I. 1.21-5.15, p = .01) and right hemisphere (OR 2.22, 95% C.I. 1.17-4.20, p = .01) were independently associated with focal to bilateral tonic-clonic seizures. At the lobar-level, focal to bilateral tonic-clonic seizures were associated with lesions in the right frontal cortex (OR 4.41, 95% C.I. 1.44-13.5, p = .009). No single voxels were significantly associated with seizure type. These effects were independent of lesion etiology. Our results demonstrate that lesion location is associated with the risk for secondary generalization of epileptic seizures. These findings may contribute to identifying patients at risk for focal to bilateral tonic-clonic seizures.

[11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue.

PURPOSE: Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally. Therefore, it is important to know whether MOR expression in BAT shows seasonal variation. METHODS: We determined the effect of photoperiod on BAT MOR availability using [11C]carfentanil positron emission tomography (PET). Adult rats (n = 9) were repeatedly imaged under various photoperiods in order to simulate seasonal changes. RESULTS: Long photoperiod was associated with low MOR expression in BAT (ß = - 0.04, 95% confidence interval: - 0.07, - 0.01), but not in muscles. We confirmed the expression of MOR in BAT and muscle using immunofluorescence staining. CONCLUSION: Photoperiod affects MOR availability in BAT. Sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. The present study supports the utility of [11C]carfentanil PET to study the peripheral MOR system.

Obesity risk is associated with brain glucose uptake and insulin resistance.

Objective: To investigate whether alterations in brain glucose uptake (BGU), insulin action in the brain-liver axis and whole-body insulin sensitivity occur in young adults in pre-obese state. Methods: Healthy males with either high risk (HR; n = 19) or low risk (LR; n = 22) for developing obesity were studied with [18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography during hyperinsulinemic-euglycemic clamp. Obesity risk was assessed according to BMI, physical activity and parental overweight/obesity and type 2 diabetes. Brain, skeletal muscle, brown adipose tissue (BAT), visceral adipose tissue (VAT) and abdominal and femoral s.c. adipose tissue (SAT) glucose uptake (GU) rates were measured. Endogenous glucose production (EGP) was calculated by subtracting the exogenous glucose infusion rate from the rate of disappearance of [18F]FDG. BGU was analyzed using statistical parametric mapping, and peripheral tissue activity was determined using Carimas Software imaging processing platform. Results: BGU was higher in the HR vs LR group and correlated inversely with whole-body insulin sensitivity (M value) in the HR group but not in the LR group. Insulin-suppressed EGP did not differ between the groups but correlated positively with BGU in the whole population, and the correlation was driven by the HR group. Skeletal muscle, BAT, VAT, abdominal and femoral SAT GU were lower in the HR group as compared to the LR group. Muscle GU correlated negatively with BGU in the HR group but not in the LR group. Conclusion: Increased BGU, alterations in insulin action in the brain-liver axis and decreased whole-body insulin sensitivity occur early in pre-obese state.

Oral Porphyromonas gingivalis and Fusobacterium nucleatum Abundance in Subjects in Primary and Secondary Cardiovascular Prevention, with or without Heterozygous Familial Hypercholesterolemia.

BACKGROUND: Low-grade chronic inflammation, promoted by dysbiosis of the gut and oral microbiota, has been shown to contribute to individual susceptibility to atherosclerotic cardiovascular disease (ASCVD). High oral Porphyromonas gingivalis (Pg) and lower Fusobacterium nucleatum (Fn) concentrations have been associated with clinical and experimental atherosclerosis. We assessed oral Pg and Fn abundance in very high-risk patients with previously diagnosed ASCVD, with or without heterozygous familial hypercholesterolemia (HeFH), in subjects with HeFH in primary prevention and in healthy subjects. METHODS: In this cross-sectional study, 40 patients with previously diagnosed ASCVD (10 with genetically proven HeFH, and 30 without FH), 26 subjects with HeFH in primary prevention, and 31 healthy subjects were selected to quantify oral Pg and Fn abundance by qPCR and assess oral health status. RESULTS: Compared to healthy subjects, patients with previously diagnosed ASCVD showed greater Pg abundance (1101.3 vs. 192.4, p = 0.03), but similar Fn abundance. HeFH patients with ASCVD had an even greater Pg abundance than did non-HeFH patients and healthy subjects (1770.6 vs. 758.4 vs. 192.4, respectively; p = 0.048). No differences were found in the levels of Pg and Fn abundance in HeFH subjects in primary prevention, as compared to healthy subjects. CONCLUSIONS: Greater oral Pg abundance is present in very high-risk patients with previously diagnosed ASCVD, with or without FH, suggesting a potential relationship with CV events. Future studies will assess the predictive value of Pg abundance measurement in ASCVD risk stratification.

Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia.

Background: Primary aldosteronism (PA) is characterized by several metabolic changes such as insulin resistance, metabolic syndrome, and adipose tissue (AT) inflammation. Mi(cro)RNAs (miRNAs) are a class of non-coding small RNA molecules known to be critical regulators in several cellular processes associated with AT dysfunction. The aim of this study was to evaluate the expression of some miRNAs in visceral and subcutaneous AT in patients undergoing adrenalectomy for aldosterone-secreting adrenal adenoma (APA) compared to the samples of AT obtained in patients undergoing adrenalectomy for non-functioning adrenal mass (NFA). Methods: The quantitative expression of selected miRNA using real-time PCR was analyzed in surrounding adrenal neoplasia, peri-renal, and subcutaneous AT samples of 16 patients with adrenalectomy (11 patients with APA and 5 patients with NFA). Results: Real-time PCR cycles for miRNA-132, miRNA-143, and miRNA-221 in fat surrounding adrenal neoplasia and in peri-adrenal AT were significantly higher in APA than in patients with NFA. Unlike patients with NFA, miRNA-132, miRNA-143, miRNA-221, and miRNA-26b were less expressed in surrounding adrenal neoplasia AT compared to subcutaneous AT in patients with APA. Conclusion: This study, conducted on tissue expression of miRNAs, highlights the possible pathophysiological role of some miRNAs in determining the metabolic alterations in patients with PA.

Circulating neurofilament is linked with morbid obesity, renal function, and brain density.

Neurofilament light chain (NfL) is a novel biomarker reflecting neuroaxonal damage and associates with brain atrophy, and glial fibrillary acidic protein (GFAP) is a marker of astrocytic activation, associated with several neurodegenerative diseases. Since obesity is associated with increased risk for several neurodegenerative disorders, we hypothesized that circulating NfL and GFAP levels could reflect neuronal damage in obese patients. 28 morbidly obese and 18 lean subjects were studied with voxel based morphometry (VBM) MRI to assess gray and white matter densities. Serum NfL and GFAP levels were determined with single-molecule array. Obese subjects were re-studied 6 months after bariatric surgery. Morbidly obese subjects had lower absolute concentrations of circulating NfL and GFAP compared to lean individuals. Following bariatric surgery-induced weight loss, both these levels increased. Both at baseline and after weight loss, circulating NfL and GFAP values correlated inversely with eGFR. Cross-sectionally, circulating NfL levels correlated inversely with gray matter (GM) density, and this association remained significant also when accounting for age and total eGFR. GFAP values did not correlate with GM density. Our data suggest that when determining circulating NfL and GFAP levels, eGFR should also be measured since renal function can affect these measurements. Despite the potential confounding effect of renal function on NfL measurement, NfL correlated inversely with gray matter density in this group of subjects with no identified neurological disorders, suggesting that circulating NfL level may be a feasible biomarker of cerebral function even in apparently neurologically healthy subjects.

Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome in Women: Effects of Lifestyle Modifications.

Non-alcoholic fatty liver disease (NAFLD) is the most widespread liver disease, characterized by fatty acids liver accumulation and subsequent fibrosis. NAFLD prevalence ranges from 80% to 90% in obese subjects and is estimated to be around 50% in patients with metabolic syndrome. In this clinical scenario, diet and lifestyle modifications can play an important role. There are several imaging techniques that can accurately diagnose fatty liver. Recently, ultrasound has acquired a leading role in the diagnosis and follow-up of fatty liver disease. Furthermore, elastosonography represents a valid alternative to liver biopsy. Shear wave elastosonography evaluates the elastic and mechanical properties of liver tissue. The aim is to evaluate the effects of lifestyle and nutritional interventions and a loss of body weight during hepatic steatosis through ultrasonographic and elastosonographic techniques. Thirty-two female subjects with metabolic syndrome were subjected to clinical, anthropometric, and laboratory assessments, as well as abdominal ultrasonographic/elastosonographic measurements taken from enrollment time (T0) and after 3 months (T1) of lifestyle modifications. After 3 months of lifestyle changes, significant weight loss was observed, with a marked improvement in all adiposity indices. The laboratory parameters at T1 showed significant decreases in total and LDL cholesterol, triglycerides, basal blood glucose, 120 min glycaemia, basal insulin and HOMA Index (p < 0.001). A similar improvement was observed at T1 for steatosis degree (p < 0.01) and elastosonographic measurements (Kpa p < 0.001). The linear regression analysis of the baseline conditions documented that the size of the liver positively correlated with body weight, BMI, neck and waist circumferences, waist to height ratio (WhtR), insulin and HOMA Index, fat mass and visceral fat, and steatosis grade. After 3 months, the liver size showed improvement with positive correlations to all previous variables. Hepatic stiffness (Kpa) positively correlated with neck circumference, visceral fat, and ALT, with basal insulin, gamma-GT, and AST, and with waist circumference, WhtR, and fat mass. The degree of steatosis was positively correlated with more variables and with greater statistical significance at T1 with respect to T0. Particularly, the positive correlations between the degree of steatosis and neck circumference (p < 0.001), HOMA Index, and triglycerides (p < 0.001) appeared to be very significant. NAFLD management in women with metabolic syndrome should be focused on lifestyle modifications. Moreover, liver involvement and improvement at follow-up could be evaluated in a non-invasive manner through ultrasonographic and elastosonographic techniques.