Search

L'articolo affronta il tema dei contratti di fiume in Sicilia. A partire dalla costruzione dello stato dell'arte e delle esperienze attualmente in corso, si pone in evidenza il vuoto normativo in materia e contestualmente la vivacità dei territori nella capacità aggregativa e di costruzioni di politiche. Viene assunto come caso di studio l'esperienza pilota del Patto di Fiume Simeto.

Objective: Whether intracerebral hemorrhage (ICH) associated with non–vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. Methods: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. Results: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67–1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = −2.83, 95% CI = −5.28 to −0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30–0.84), and smaller baseline hematoma volume (linear regression coefficient = −0.24, 95% CI = −0.47 to −0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81–1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63–1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49–1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57–1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75–1.43). Interpretation: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702–712. © 2018 American Neurological Association

Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA). 3243 A>G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75-98%) and macular dystrophy (54% vs 86%) was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A>G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants.

Background. Laparoscopic adjustable gastric banding (LAGB) results in significant lasting weight loss and improved metabolism in obese patients. To evaluate whether epigenetic factors could concur to these benefits, we investigated the subcutaneous adipose tissue (SAT) microRNA (miRNA) profile before (T0) and three years (T1) after LAGB in three morbidly obese women. Case Reports. SAT miRNA profiling, evaluated by TaqMan Array, showed four downexpressed (miR-519d, miR-299-5p, miR-212, and miR-671-3p) and two upexpressed (miR-370 and miR-487a) miRNAs at T1 versus T0. Bioinformatics predicted that these miRNAs regulate genes belonging to pathways associated with the cytoskeleton, inflammation, and metabolism. Western blot analysis showed that PPAR-alpha, which is the target gene of miR-519d, increased after LAGB, thereby suggesting an improvement in SAT lipid metabolism. Accordingly, the number and diameter of adipocytes were significantly higher and lower, respectively, at T1 versus T0. Bioinformatics predicted that the decreased levels of miR-212, miR-299-5p, and miR-671-3p at T1 concur in reducing SAT inflammation. Conclusion. We show that the miRNA profile changes after LAGB. This finding, although obtained in only three cases, suggests that this epigenetic mechanism, by regulating the expression of genes involved in inflammation and lipid metabolism, could concur to improve SAT functionality in postoperative obese patients.

Background: Significant and sustained excess weight loss (EWL) appears to reduce the risk of obesity-related comorbidities (insulin resistance, hyperlipidemia, and inflammation), but this has been primarily shown in adult diabetic obese patients. We evaluated whether the EWL obtained 3 years after laparoscopic adjustable gastric banding (LAGB) improves the metabolic phenotype in nondiabetic morbidly obese (NDMO) individuals from south Italy. Methods: Serum and subcutaneous adipose tissue (SAT) samples from 20 obese individuals (median BMI = 41.5 kg/m2) before (T0) and after LAGB (T1) and from 10 controls (median BMI = 22.8 kg/m2) were taken. Serum leptin, adiponectin, C reactive protein (CRP), and main analyte levels were evaluated by routine methods or immunoassay. In SAT, adipocyte size was measured by hematoxylin/eosin staining, cluster of differentiation 68 (CD68) macrophage infiltration marker by immunohistochemistry, and adiponectin, adiponectin receptors 1 and 2, and interleukin 6 (IL6) messenger RNAs by qRT-PCR. Results: The average EWL was 66.7 %, and CRP, triglycerides, hepatic markers, leptin levels, homeostasis model assessment, and the leptin/adiponectin ratio were lower (p < 0.05) at T1 than at T0. The expression of small adipocytes and adiponectin was increased (p < 0.05), and inflammation markers (CD68 and IL6) decreased (p < 0.05) at T1 vs. T0. At linear regression multivariate analysis, over 90 % (R2 = 0.905) of EWL (dependent variable) was explained by CD68, adiponectinemia, triglyceridemia, CRP, and total protein levels. Conclusions: The EWL obtained 3 years after LAGB resulted in an improvement of lipid metabolism and a reduction of inflammation in NDMO patients, thereby decreasing the risk of obesity-associated diseases.

Mitochondrial DNA (mtDNA) haplogroups have been associated with the expression of mitochondrial-related diseases and with metabolic alterations, but their role has not yet been investigated in morbid obese Caucasian subjects. Therefore, we investigated the association between mitochondrial haplogroups and morbid obesity in patients from southern Italy. The mtDNA D-loop of morbid obese patients (n=500; BMI > 40 kg/m2) and controls (n=216; BMI < 25 kg/m2) was sequenced to determine the mtDNA haplogroups. The T and J haplogroup frequencies were higher and lower, respectively, in obese subjects than in controls. Women bearing haplogroup T or J had twice or half the risk of obesity. Binomial logistic regression analysis showed that haplogroup T and systolic blood pressure are risk factors for a high degree of morbid obesity, namely, BMI > 45 kg/m2and in fact together account for 8% of the BMI. In conclusion, our finding that haplogroup T increases the risk of obesity by about two-fold, suggests that, besides nuclear genome variations and environmental factors, the T haplogroup plays a role in morbid obesity in our study population from southern Italy.

Maternal obesity is associated to increased fetal risk of obesity and other metabolic diseases. Human amniotic mesenchymal stem cells (hA-MSCs) have not been characterized in obese women. The aim of this study was to isolate and compare hA-MSC immunophenotypes from obese (Ob-) and normal weight control (Co-) women, to identify alterations possibly predisposing the fetus to obesity. We enrolled 16 Ob- and 7 Co-women at delivery (mean/SEM prepregnancy body mass index: 40.3/1.8 and 22.4/1.0 kg/m2, respectively), and 32 not pregnant women. hA-MSCs were phenotyped by flow cytometry; several maternal and newborn clinical and biochemical parameters were also measured. The expression of membrane antigen CD13 was higher on Ob-hA-MSCs than on Co-hA-MSCs (P = 0.005). Also, serum levels of CD13 at delivery were higher in Ob- versus Co-pregnant women and correlated with CD13 antigen expression on Ob-hA-MSCs (r2 = 0.84, P < 0.0001). Adipogenesis induction experiments revealed that Ob-hA-MSCs had a higher adipogenic potential than Co-hA-MSCs as witnessed by higher peroxisome proliferator-activated receptor gamma and aP2 mRNA levels (P = 0.05 and P = 0.05, respectively), at postinduction day 14 associated with increased CD13 mRNA levels from baseline to day 4 postinduction (P < 0.05). Adipogenesis was similar in the two sets of hA-MSCs after CD13 silencing, whereas it was increased in Co-hA-MSCs after CD13 overexpression. CD13 expression was high also in Ob-h-MSCs from umbilical cords or visceral adipose tissue of not pregnant women. In conclusion, antigen CD13, by influencing the adipogenic potential of hA-MSCs, could be an in utero risk factor for obesity. Our data strengthen the hypothesis that high levels of serum and MSC CD13 are obesity markers.

neuromuscular human diseases have been associated with mitochondrial DNA (mtDNA) variations, causing defects of oxidative phosphorylation. These dysfunctions affect preferentially tissues with high energy demands and give arise to several degenerative disorders such as optic neuropathy, cerebellar ataxia, movement disorders, dementia, muscle weakness and deafness. The extremely heterogeneous clinical phenotype is due to the involved tissue, to specific mtDNA mutations and their heteroplasmic level, but also to nuclear DNA alterations, environmental and epigenetic factors. In this study we investigated a child affected by a complex neurological disease whose clinical features were suggestive of a mitochondrial involvement. Methods: mtDNA from proband, her healthy relatives (grandmother, mother and two sisters) and 80 controls were collected and studied by sequencing. The enzymatic activity of specific respiratory chain complex was tested on lymphocytes by spectrophotometric assay. Bioinformatic analysis was performed to predict the pathogenicity of the detected variants. Results: In all subjects we detected 11 known polymorphisms, whereas 1 novel heteroplasmic variant in complex I [ND5:12514G>A (E60K)] was present only in the proband and in her grandmother and absent in controls. The bioinformatics predicted the novel variant to be deleterious. Further, spectrophotometric assay of complex I activity was lower both in the proband and in her relatives than in the controls. Conclusions: We report a novel mtDNA variant detected in a patient affected by a complex neurological disease. The reduction of complex I respiratory chain activity associated to this variant suggests it could exert a pathogenic role in the disease.

Adipose tissues show selective gene expression patterns, to whom microRNAs (miRNAs) may contribute. We evaluated in visceral adipose tissue (VAT) from obese and nonobese females, both miRNA and protein expression profiles, to identify miRNA/protein target pairs associated with obesity (metabolic pathways miRNA-deregulated during obesity). Obese and nonobese females [BMI 42.2 ± 1.6 and 23.7 ± 1.2 kg/m(2) (mean ± SEM), respectively] were enrolled in this study. Notably, most miRNAs were down-expressed in obese tissues, whereas most of the proteins from the investigated spots were up-expressed. Bioinformatics integration of miRNA expression and proteomic data highlighted two potential miRNA/protein target pairs: miR-141/YWHAG (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide) and miR-520e/RAB11A (Ras-related protein RAB-11A); the functional interaction between these miRNAs and their target sequences on the corresponding mRNAs was confirmed by luciferase assays. Both RAB11A and YWHAG proteins are involved in glucose homeostasis; YWHAG is also involved in lipid metabolism. Hence, the identified miRNA/protein target pairs are potential players in the obese phenotype.