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To better understand the location and help in the conservation of buried structures in the ancient site of Tusculum, in Central Italy, archaeological and multi-methodological geophysical studies were developed in the recent last years. These studies included geophysical surveys, which were combined with topographical survey and direct archaeological excavations. Tusculum is one of the largest Roman archaeological sites in the Alban Hills, located in the Latium region (Italy), about 25 km South-East of Rome. This settlement was inhabited since pre-Roman times, up to the middle ages. The objective of the Tusculum Project is to verify the town-planning of Tusculum and to obtain information about the location, shape, depth and size of the hypothesised buried buildings. With these aims, multi-methodological geophysical surveys have been carried out in the time range 2016–2019 to locate the archaeological remains in different portions of the studied area and to verify the orientation of the underground aqueduct system. GPR and gradiometric surveys were carried out to investigate the archaeological remains, while ERT surveys, were employed to find evidence of undiscovered parts of the underground aqueduct system. These results, along with geological studies and historic evidence, are being examined by archaeologist to understand the limits of the town and how water was supplied to such a large, populated settlement. The obtained results show very good correspondence between the buried architecture, the geophysical anomalies and the archaeological excavations. A number of unexpected buried buildings were discovered, which were excavated in 2017 and 2018, which showed remains of buried public thermal bath and a large church with surrounding funerary area built in the Middle Ages. [ABSTRACT FROM AUTHOR]

This paper deals with classical solutions of some initial boundary value problems involving the quasilinear parabolic equation where are given functions. In the case of one space variable, i.e. when , we establish a maximum principle for the auxiliary function where a is an arbitrary nonnegative parameter. In some cases this maximum principle may be used to derive explicit exponential decay bounds for and . Some extensions in space dimensions are indicated. This work may be considered as a continuation of previous works by Payne and Philippin (Mathematical Models and Methods in Applied Sciences, 5 (1995), 95–110; Decay bounds in quasilinear parabolic problems, In: Nonlinear Problems in Applied Mathematics, Ed. by T.S. Angell, L. Pamela, Cook, R.E., SIAM, 1997).

Background and Aims: Metabolic syndrome (MetS) is currently considered to raise the risk for type 2 diabetes and cardiovascular events. It has been suggested that part of this risk excess may be due to a cluster of additional factors associated with MetS. We aimed to investigate the role of inflammation on the ventricular-vascular coupling in patients with MetS.Methods and Results: We enrolled a total of 227 hypertensive patients (106 with MetS and 121 without MetS) matched for age and gender. Aortic pulse wave velocity (aPWV), intima-media thickness (IMT) and high sensitivity C-reactive protein (CRP) increased according to the number of MetS components. Patients with MetS showed increased aPWV (11.5 ± 3.7 vs. 10.3 ± 2.5 m/s, P = 0.03) compared with controls. In a model adjusted for age, sex, heart rate and mean blood pressure, aPWV resulted increased in patients with CKD (beta 1.29 m/s, 95%CI 0.61-1.96 m/s, P < 0.001) and MetS (beta 0.89 m/s, 95%CI 0.28-1.51 m/s, P = 0.005). After additional adjustment for CRP and IMT, the slope of aPWV was respectively reduced by 16% and 62%, suggesting that inflammation and intima-media thickening could contribute to aortic stiffening in patients with MetS. In these patients, aPWV was also associated with left-ventricular mass index (beta 0.79 g/m2.7, 95%CI 0.05-1.52 g/m2.7, P = 0.05).Conclusion: MetS is characterized by an inflammation-dependent acceleration in cardiovascular ageing. This pattern of pathophysiological abnormalities may contribute to amplify the burden of cardiovascular risk in patients with MetS. [ABSTRACT FROM AUTHOR]

Background and Aims: Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT).Methods and Results: We screened 1575 lipid profiles and included for genetic analysis adults with a low-density lipoprotein (LDL) cholesterol >190 mg/dL and triglycerides <200 mg/dL and first-degree child relatives with LDL cholesterol >160 mg/dL and triglycerides <200 mg/dL. The diagnosis of FH was presumed by Dutch Lipid Clinic Network (DLCN) criteria and confirmed by the presence of the genetic variant. Mean common carotid intima-media thickness (IMT) was assessed using consensus criteria. After confirming LDL cholesterol value and excluding secondary hypercholesterolemia, 56 subjects with a DLCN ≥4 performed genetic analysis. Of these, 26 had an FH genetic variant. The proportion of patients with a mutation having a DLCN score of 6-8 was 75%; in individuals with a DLCN score >8 it was 100%. Mean IMT was higher in FH patients compared to non FH (0.73 [0.61-0.83] vs 0.71 [0.60-0.75] mm, p < 0.01). Moreover, we detected two mutations not previously described. Finally, simple regression analysis showed a correlation of IMT with LDL cholesterol >190 mg/dL and corneal arcus (p < 0.01 and p < 0.001, respectively).Conclusions: A hospital screening was useful to detect FH subjects with increased atherosclerosis. Also, next-generation sequencing was able to detect new FH mutations. [ABSTRACT FROM AUTHOR]

The St. John Lateran Basilica is the Pope's Cathedral and the first public building constructed for Christian worship. The complex has been the focus of sundry excavations since the 1730s. These have revealed traces of the earliest phases of the building, along with parts of the Castra Nova of the Imperial Horseguard, a bath complex and palatial housing. Interpretation of these excavations is, however, difficult; and most of them are either undocumented or only partially recorded. The geophysical prospection is generally considered as the attempt to locate structures of archaeological interest buried in the natural subsoil, but in many cases, when applied in urban centres, this attempt could fail due to the effect and disturbances caused by recent man-made structures in the subsoil, covering any signal related to possible archaeological structures. In the present paper the ground penetrating radar (GPR) surveys carried out in the urban archaeological site of St. John Lateran Basilica, in Rome, characterised by different targets and environmental conditions, are presented and discussed. This site is characterized by artificial medium as road pavement, outside the basilica, and ancient buildings, below the current basilica. The paper illustrates the ground penetrating radar GPR surveys and the obtained results. [ABSTRACT FROM AUTHOR]

Background and Aims: Modern diets are high in advanced glycation end-products (dAGEs), derived from processing methods, exerting a pivotal role in promoting atherosclerotic risk. In this cross-sectional study we investigate the relationship between dAGE intake, arterial stiffness, inflammatory profile and macronutrient composition, in subjects with type 2 diabetes without overt cardiovascular disease.Methods and Results: Arterial stiffness, carboxy-methyl-lysine, endogenous secretory receptor for AGEs (esRAGE), high sensitivity C reactive protein (hs-CRP), S100A12 and macronutrient intake were evaluated in 85 subjects with type 2 diabetes. The subjects were stratified into two groups according to dAGE consumption: high and low dAGE intake (≥ or <15.000 kU/day, respectively). Subjects with high dAGE intake (n = 45) showed a higher augmentation, augmentation index and pulse wave velocity (PWV) compared with those subjects with low dAGE intake (18 ± 5.4 vs 12.2 ± 6.3 mmHg, P < 0.05; 38.3 ± 5.4 vs 29.3 ± 10%; 9.2 ± 1.4 m/sec vs 7.9 ± 1.7, P < 0.05, respectively). hs-CRP were higher in subjects with high dAGE intake [0.42 (0.18-0.54) vs 0.21 (0.14-0.52) mg/dL, P < 0.05] whereas esRAGE plasma levels were lower [0.16 (0.23-0.81) vs 0.2 (0.14-0.54) ng/dL, P < 0.05]. Simple regression analysis showed a correlation between dAGEs and fat intake. Multivariate analysis showed an independent association between augmentation, systolic blood pressure (BP) and dAGE consumption; BMI and esRAGE were the major determinants of PWV.Conclusions: Our data suggests that a chronic high dAGE diet could lead to a vascular dysfunction and inflammatory activation, contributing to the development of vascular complications in subjects with type 2 diabetes. Testing this hypothesis may represent a direction of future research. [ABSTRACT FROM AUTHOR]

Background& Aims: Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers.Methods and Results: We profiled the expression of 754 cellular and medium-secreted human miRNAs in HepG2 cells after lipotoxic (Palmitate, model of NASH) or not-lipotoxic stimuli (Oleate-Palmitate, model of NAFLD). Results were validated through Single TaqMan assays. We performed computational analysis of miRNA targets and pathways. Oleate-palmitate treatment induced a variation of 2.8% and 10% of total miRNAs in cells and medium, respectively; palmitate treatment caused 10% and 19% intracellular and extracellular miRNA deregulation, respectively. We validated miR-126, miR-150, miR-223, miR-483-3p, miR-1226*, and miR-1290 deregulation. Through computational analysis, we observed that targets of both intracellular and extracellular DE miRNAs were involved in processes associated with the onset and progression of NAFLD and NASH, such as fatty acid metabolism, apoptosis and inflammation.Conclusions: These data would be useful to elucidate the role of miRNAs in the pathogenesis and progression of the NAFLD spectrum, but they also allow the identification of novel potential biomarkers for differential diagnosis to be tested in vivo. [ABSTRACT FROM AUTHOR]

Because metformin affects glucose and free fatty acid (FFA) metabolism in peripheral insulin target tissues, we investigated the effect of this drug in restoring a normal secretory pattern in rat pancreatic islets whose function has been impaired by chronic exposure to elevated FFA or glucose concentrations. We cultured rat pancreatic islets with or without FFA (2 mmol/l oleate/palmitate 2:1) or high glucose (16.7 mmol/l) concentrations in the presence or absence of metformin (0.25-12.5 microg/ml) and then measured insulin release, glucose utilization, glucose, and FFA oxidation. When compared with control islets, islets exposed to high FFA or glucose concentrations showed an increased basal and a decreased glucose-induced insulin release. In islets cultured for an additional 24 h with FFA or glucose in the presence of metformin (2.5 microg/ml), both basal and glucose-induced insulin secretions were restored. Both glucose utilization and glucose oxidation were altered in islets pre-exposed to high FFA or glucose concentrations. In particular, regarding control islets, glucose utilization was increased at 2.8 mmol/l glucose and decreased at 16.7 mmol/l glucose; glucose oxidation was similar to control islets at 2.8 mmol/l glucose but decreased at 16.7 mmol/l glucose. In contrast, oleate oxidation was increased in islets pre-exposed to FFA. All of these abnormalities were reversed in islets cultured for an additional 24 h with high FFA or glucose concentrations in the presence of metformin (2.5 microg/ml). In conclusion, our data show that metformin is able to restore the intracellular abnormalities of glucose and FFA metabolism and to restore a normal secretory pattern in rat pancreatic islets whose secretory function has been impaired by chronic exposure to elevated FFA or glucose levels. These data raise the possibility that, in diabetic patients, metformin (in addition to its peripheral effects) may have a direct beneficial effect on the beta-cell secretory function. [ABSTRACT FROM AUTHOR]

Chronic exposure to high leucine impairs glucose-induced insulin release by lowering the ATP-to-ADP ratio. Am J Physiol Endocrinol Metab 281: E1082-E1087, 2001.--Exposure of rat pancreatic islets to 20 mM leucine for 24 h reduced insulin release in response to glucose (16.7 and 22.2 mM). Insulin release was normal when the same islets were stimulated with leucine (40 mM) or glyburide (1 [micro]M). To investigate the mechanisms responsible for the different effect of these secretagogues, we studied several steps of glucose-induced insulin secretion. Glucose utilization and oxidation rates in leucine-precultured islets were similar to those of control islets. Also, the ATP-sensitive K+ channel-independent pathway of glucose-stimulated insulin release, studied in the presence of 30 mM [K.sup.+] and 250 [micro]M diazoxide, was normal. In contrast, the ATP-to-ADP ratio after stimulation with 22.2 mM glucose was reduced in leucine-exposed islets with respect to control islets. The decrease of the ATP-to-ADP ratio was due to an increase of ADP levels. In conclusion, prolonged exposure of pancreatic islets to high leucine levels selectively impairs glusoce-induced insulin release. This secretory abnormality is associated with (and might be due to) a reduced ATP-to-ADP ratio. The abnormal plasma amino acid levels often present in obesity and diabetes may, therefore, affect pancreatic islet insulin secretion in these patients. adenosine triphosphate; adenosine diphosphate; [Beta]-cell desensitization; amino acids; adenine nucleotides; adenosine triphosphate potassium channel-independent pathway

Abstract: Background and aims: We aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. Methods and results: Ninety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39–46mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT. Conclusions: Subjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases. [Copyright &y& Elsevier]

For most archaeological prospections with GPR, detection is the most important aspect of the surveys. If enough density of profiles is recorded across a site, structural information can also be obtained regarding the buried features. Shallow and narrow features may require a very fine line density to get detected. If the profile spacing is large, shallow areas can have no microwaves penetrating the region. At greater penetration depths however, the unsampled region decreases. If small targets are buried close to the ground surface, detection of these features may require a finer line spacing then objects which are buried slightly deeper and within the penetration depth of the antenna. A method for presenting GPR data from archaeological sites is needed to show these minute changes. Rather than showing the changes in reflected energies along the vertical -- radargram -- slices of the ground, it is more useful to map horizontal changes of reflected energy across a site. In this case small, but consistent reflections above the background noise can be visualized by using time slice analysis. There are a variety of imaging and analyses that must be implemented to solve the multitude of subsurface conditions in the archaeological field survey. Among a few of the necessary imaging techniques and analysis to be briefly introduced in this presentation: Time slices, Isosurface rendering and Overlay Analysis. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aims: Metabolic syndrome (MS) has been mainly related to insulin resistance, but the role of changes in insulin secretion has not been thoroughly investigated. Methods and Results: Using an oral glucose tolerance test (OGTT) we studied beta-cell function and insulin sensitivity in subjects with normal fasting glucose with and without MS, and their relationship to fatty liver which was evaluated by abdominal-ultrasonography. In MS early phase insulin secretion, as measured by insulinogenic index (IG30), was increased (p <0.05) independently from insulin sensitivity. Furthermore IG30 was progressively higher as the number of factors needed for the diagnosis of MS increased (p <0.01). Insulin and C-peptide AUC were also increased (p <0.01 and p <0.05, respectively) but, in contrast to IG30, these differences disappeared when ISI was used as a covariate. After OGTT, 51% of the subjects with MS had altered post-load glucose tolerance compared to 24.9% without MS (p <0.01). In both groups, the altered glucose tolerance was associated with a similar IG30 reduction. In normo-tolerant subjects with MS the IG30 was higher (+54.1%, p <0.01), and this elevation occurred irrespective of ISI; however, the beta-cell compensatory capacity for insulin resistance (disposition index) was impaired (p <0.001). Fatty liver was more frequent (p <0.001) and more severe (p <0.01) in MS, and it was significantly related to total AUC-insulin (p <0.001), independently from ISI. Conclusion: These findings indicate that the prevalence of altered tolerance is more frequent in subjects with normal fasting glucose and MS. The hyperinsulinemia might not only be an adaptive response to insulin resistance, but a primary defect of beta-cell function contributing to glucose intolerance. [Copyright &y& Elsevier]

Background: Humans living near industrial point emissions can experience high levels of exposures to air pollutants. Map Ta Phut Industrial Estate in Thailand is the location of the largest steel, oil refinery, and petrochemical factory complexes in Southeast Asia. Air pollution is an important source of oxidative stress and reactive oxygen species, which interact with DNA and lipids, leading to oxidative damage and lipid peroxidation, respectively. Objective: We measured the levels of malondialdehyde-deoxyguanosine (dG) adducts, a biomarker of oxidative stress and lipid peroxidation, in petrochemical workers, nearby residents, and subjects living in a control district without proximity to industrial sources. Design: We conducted a cross-sectional study to compare the prevalence of malondialdehyde-dG adducts in groups of subjects experiencing various degrees of air pollution. Results: The multivariate regression analysis shows that the adduct levels were associated with occupational and environmental exposures to air pollution. The highest adduct level was observed in the steel factory workers. In addition, the formation of DNA damage tended to be associated with tobacco smoking, but without reaching statistical significance. A nonsignificant increase in DNA adducts was observed after 4-6 years of employment among the petrochemical complexes. Conclusions: Air pollution emitted from the Map Ta Phut Industrial Estate complexes was associated with increased adduct levels in petrochemical workers and nearby residents. Considering the mutagenic potential of DNA lesions in the carcinogenic process, we recommend measures aimed at reducing the levels of air pollution. [ABSTRACT FROM AUTHOR]

We investigate continuous dependence on initial data for solutions of a nonlinear parabolic problem, when Robin conditions are prescribed on the boundary ∂ Ω × (t > 0), Ω a bounded R2 domain. [ABSTRACT FROM AUTHOR]

Abstract: Backgrounds and aims: Non-alcoholic-steatohepatitis (NASH) is closely related to insulin resistance, but it is unknown whether insulin resistance may be localized in hepatocytes. This study investigates insulin signalling in liver tissue from NASH, and the molecular mechanisms by which insulin-resistance could lead to liver damage (apoptosis). Moreover, to investigate the mechanisms of lipid overload we studied key enzymes in hepatocytes lipid metabolism. Methods and Results: In liver specimens from 11 patients with NASH and 7 histological normal livers, we measured total and phosphorylated Akt (active form), Bax and Bcl-2 by Western-blot analysis. In addition, we studied AMP-activated protein Kinase and Carnitine-Palmitoyl-Transferase-1 gene expression, key regulators of non-esterified fatty acid synthesis and oxidation, by reverse transcription polymerase chain reaction. In NASH, phosphorylated Akt was impaired (104.3±10.6 vs 152.6±22.4 AU, p <0.002) and correlated with necroinflammatory score (r =−0.62; p <0.05). Bax/Bcl-2 ratio was increased in NASH. Moreover, we observed a decrease of AMP-activated protein Kinase (10.74±6 vs 144.7±41.6 AU, p <0.0001) and Carnitine-Palmitoyl-Transferase-1 gene expression (38.7±14.6 vs 192.1±26.2 AU, p <0.0001), and both were correlated with steatosis score (r =−0.56, p <0.05, r =−0.87, p <0.05 respectively). Conclusions: Akt, a key molecule of insulin signalling and cell apoptosis is impaired in NASH, suggesting an important role of hepatic insulin resistance in liver failure. Moreover, decreased non-esterified fatty acid oxidation may cause hepatic lipid overload. [Copyright &y& Elsevier]