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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]

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]

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM. [ABSTRACT FROM AUTHOR]

We deal with the Cauchy problem associated to a class of quasilinear singular parabolic equations with L∞ coefficients whose prototypes are the p-Laplacian (2 N/( N + 1) < p < 2) and the porous medium equation ((( N − 2)/ N) + < m < 1). We prove existence of and sharp pointwise estimates from above and from below for the fundamental solutions. Our results can be extended to general non-negative L1 initial data. [ABSTRACT FROM AUTHOR]

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]

Aims/hypothesis Glucagon-like peptide 1 (GLP-1) is a major incretin, mainly produced by the intestinal L cells, with beneficial actions on pancreatic beta cells. However, while in vivo only very small amounts of GLP-1 reach the pancreas in bioactive form, some observations indicate that GLP-1 may also be produced in the islets. We performed comprehensive morphological, functional and molecular studies to evaluate the presence and various features of a local GLP-1 system in human pancreatic islet cells, including those from type 2 diabetic patients. Methods The presence of insulin, glucagon, GLP-1, proconvertase (PC) 1/3 and PC2 was determined in human pancreas by immunohistochemistry with confocal microscopy. Islets were isolated from non-diabetic and type 2 diabetic donors. GLP-1 protein abundance was evaluated by immunoblotting and matrix-assisted laser desorption–ionisation-time of flight (MALDI–TOF) mass spectrometry. Single alpha and beta cell suspensions were obtained by enzymatic dissociation and FACS sorting. Glucagon and GLP-1 release were measured in response to nutrients. Results Confocal microscopy showed the presence of GLP-1-like and PC1/3 immunoreactivity in subsets of alpha cells, whereas GLP-1 was not observed in beta cells. The presence of GLP-1 in isolated islets was confirmed by immunoblotting, followed by mass spectrometry. Isolated islets and alpha (but not beta) cell fractions released GLP-1, which was regulated by glucose and arginine. PC1/3 (also known as PCSK1) gene expression was shown in alpha cells. GLP-1 release was significantly higher from type 2 diabetic than from non-diabetic isolated islets. Conclusions/interpretation We have shown the presence of a functionally competent GLP-1 system in human pancreatic islets, which resides in alpha cells and might be modulated by type 2 diabetes. [ABSTRACT FROM AUTHOR]

We consider a class of non-autonomous, degenerate parabolic equations and we study the asymptotic behaviour of the solutions. Even if the equation depends explicitly upon the time, we prove that several asymptotic properties, valid for the autonomous case, are preserved in this more general situation. To our knowledge, it is the first time that the asymptotic behaviour of solutions to non-autonomous equations is studied. [ABSTRACT FROM AUTHOR]

We consider the blow-up of the solution to a semilinear heat equation with nonlinear boundary condition. We establish conditions on nonlinearities sufficient to guarantee that u( x, t) exists for all time t > 0 as well as conditions on data forcing the solution u( x, t) to blow up at some finite time t*. Moreover, an upper bound for t* is derived. Under somewhat more restrictive conditions, lower bounds for t* are also derived. [ABSTRACT FROM AUTHOR]

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]

Glycemic control in elderly persons with type 2 diabetes mellitus (T2DM) is challenging because they are more likely to have other age-associated medical conditions and to experience hypoglycemia during intensive therapy. A best therapeutic strategy for these patients has not yet been defined. We investigated the efficacy and safety of adding once-daily insulin glargine to patients’ current oral antidiabetic drugs (OAD) regimen, compared to increasing the OAD doses. The study enrolled patients aged 65 years or more, with poor glycemic control. Patients were randomized to two groups and entered a 3-week titration period in which their actual therapy was adjusted to meet the study’s glycemic goals, by either adding insulin glargine to current therapy (group A, 27 patients) or increasing current OAD dosages (group B, 28 patients). Thereafter, therapies were continued unchanged for a 24-week observation period. The mean therapeutic dosage of insulin glargine in group A was 14.9 IU/day (SD = 5.0 IU/day). During the observation period, mean levels of glycosylated hemoglobin (HbA1c) reduced by 1.5% in group A and 0.6% in group B ( P = 0.381). An HbA1c level <7.0% was achieved by five patients in each group. Mean fasting blood glucose levels reduced by 29 and 15% in groups A and B, respectively ( P = 0.029). Group A had fewer total hypoglycemic events (23 vs. 79, P = 0.030) and fewer patients experiencing any such event (9 vs. 17, P = 0.045). Neither a serious hypoglycemic event nor other adverse event occurred. These results suggest that, compared to increasing OAD dosage, the addition of insulin glargine to current OAD therapy is as effective but safer in terms of the risk for hypoglycemia in elderly patients with T2DM. [ABSTRACT FROM AUTHOR]

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols. [ABSTRACT FROM AUTHOR]

This article continues the derivation of explicit solution and gradient bounds for classes of second order nonlinear parabolic initial-boundary value problems. Earlier results were restricted to domains with boundaries of nonnegative average curvature. The purpose of the present article is to remove the curvature restriction and to extend the results to more general parabolic problems. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Little information is available on the insulin release properties of pancreatic islets isolated from type 2 diabetic subjects. Since mitochondria represent the site where important metabolites that regulate insulin secretion are generated, we studied insulin release as well as mitochondrial function and morphology directly in pancreatic islets isolated from type 2 diabetic patients. Methods: Islets were prepared by collagenase digestion and density gradient purification, and insulin secretion in response to glucose and arginine was assessed by the batch incubation method. Adenine nucleotides, mitochondrial membrane potential, the expression of UCP-2, complex I and complex V of the respiratory chain, and nitrotyro sine levels were evaluated and correlated with insulin secretion. Results: Compared to control islets, diabetic islets showed reduced insulin secretion in response to glucose, and this defect was associated with lower ATP levels, a lower ATP/ADP ratio and impaired hyperpolarization of the mitochondrial membrane. Increased protein expression of UCP-2, complex I and complex V of the respiratory chain, and a higher level of nitrotyrosine were also found in type 2 diabetic islets. Morphology studies showed that control and diabetic beta cells had a similar number of mitochondria; however, mitochondnial density volume was significantly higher in type 2 diabetic beta cells. Conclusions/interpretation: In pancreatic beta cells from type 2 diabetic subjects, the impaired secretory response to glucose is associated with a marked alteration of mitochondrial function and morphology. In particular, UCP-2 expression is increased (probably due to a condition of fuel overload), which leads to lower ATP, decreased ATP/ADP ratio, with consequent reduction of insulin release. [ABSTRACT FROM AUTHOR]

Presents a study which investigated whether chronic exposure of cultured rat pancreatic islets to an elevated leucine concentration might affect insulin secretion stimulated by glucose or other secretagogues. Methodology; Glucose utilization and oxidation; Relationship between insulin release and adenine nucleotide levels.

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