Little red riding hood in the social forest. Online grooming as a public health issue: a narrative review.

INTRODUCTION: Online grooming is a manipulative process through which an adult attempts to arrange a sexual interaction with a minor using internet. Children are constantly exposed to the online world, posing online grooming as a public health issue. OBJECTIVES: The aim of this narrative review is to describe the state of online grooming preventive strategies in recent literature through an overview of online grooming phenomenon. METHODS: Our literature review included research articles and reviews published between January 2014 and March 2019, as well as reference lists of included studies. RESULTS: The analysis provides a picture of online grooming phenomenon, identify recurrent features of perpetrators and victims. Several preventive strategies have been implemented, but they lack any kind of efficacy evaluation and miss a theory driven approach. Fragmentation of preventive initiatives is a critical issue, in contrast with the need of an institutional public health strategy. CONCLUSIONS: While the attention around online grooming is growing, there is still the need of further sensitizing the involved stakeholders and developing evidence based preventive strategies under an institutional guidance.

The quest for an effective and safe personalized cell therapy using epigenetic tools.

In the presence of different environmental cues that are able to trigger specific responses, a given genotype has the ability to originate a variety of different phenotypes. This property is defined as plasticity and allows cell fate definition and tissue specialization. Fundamental epigenetic mechanisms drive these modifications in gene expression and include DNA methylation, histone modifications, chromatin remodeling, and microRNAs. Understanding these mechanisms can provide powerful tools to switch cell phenotype and implement cell therapy. Environmentally influenced epigenetic changes have also been associated to many diseases such as cancer and neurodegenerative disorders, with patients that do not respond, or only poorly respond, to conventional therapy. It is clear that disorders based on an individual's personal genomic/epigenomic profile can rarely be successfully treated with standard therapies due to genetic heterogeneity and epigenetic alterations and a personalized medicine approach is far more appropriate to manage these patients. We here discuss the recent advances in small molecule approaches for personalized medicine, drug targeting, and generation of new cells for medical application. We also provide prospective views of the possibility to directly convert one cell type into another, in a safe and robust way, for cell-based clinical trials and regenerative medicine.

Predicting rapid herbicide leaching to surface waters from an artificially drained headwater catchment using a one dimensional two-domain model coupled with a simple groundwater model.

Pesticide losses to water can present problems for environmental management, particularly in catchments where surface waters are abstracted for drinking water supply. The relative role of different transfer pathways (spray drift, spills, overland flow and leaching from soils) is often uncertain, and there is a need for experimental observation and modelling to ensure that processes are understood under a range of conditions. Here we examine the transport of propyzamide and carbetamide in a small (15.5 ha) headwater sub-catchment dominated by an artificially drained field with strongly undulating topography (topographic gradients >1:10). Specifically, we explore the validity of the "field-scale lysimeter" analogy by applying the one dimensional mathematical model MACRO. Although one dimensional representation has been shown to be reasonable elsewhere, the scale and topography of the monitored system challenge many of the underlying assumptions. MACRO considers two interacting flow domains: micropores and macropores. The effect of subsurface drains can also be included. A component of the outflow from the main drain was identified as originating from an upslope permeable shallow aquifer which was represented using a simple groundwater model. Predicted herbicide losses were sensitive to drain spacing and the organic carbon to water partition coefficient, K(OC). The magnitude of the peak water and herbicide transport and their timing were simulated satisfactorily, although model performance was poor following a period of one month when snow covered the ground and precipitation was underestimated by the rain gauge. Total herbicide loads were simulated adequately by MACRO, suggesting that the field-scale lysimeter analogy is valid at this scale, although baseflow contributions to flow needed to be accounted for separately in order to adequately represent hydrological response.

Measurement and conceptual modelling of herbicide transport to field drains in a heavy clay soil with implications for catchment-scale water quality management.

Propyzamide and carbetamide are essential for blackgrass control in oilseed rape production. However, both of these compounds can contaminate surface waters and pose compliance problems for water utilities. The transport of propyzamide and carbetamide to an instrumented field drain in a small clay headwater tributary of the Upper Cherwell catchment was monitored over a winter season. Despite having very different sorption and dissipation properties, both herbicides were transported rapidly to the drain outlet in the first storm event after application, although carbetamide was leached more readily than propyzamide. A simple conceptual model was constructed to represent solute displacement from mobile pore water and preferential flow to drains. The model was able to reproduce the timing and magnitude of herbicide losses well, lending support to its conceptual basis. Measured losses in drainflow in the month following application were 1.1 and 8.1%, respectively, for propyzamide and carbetamide. Differences were due to a combination of differences in herbicide mobility and due to the fact that the monitoring period for carbetamide was hydrologically more active. For both compounds, losses were greater than those typically reported elsewhere for other herbicides. The data suggest that drainflow is the dominant pathway for the transfer of these herbicides to the catchment outlet, where water is abstracted for municipal supply. This imposes considerable constraints on the management options available to reduce surface water concentrations of herbicides in this catchment.

Randomized controlled trial of early compared with delayed use of inhaled nitric oxide in newborns with a moderate respiratory failure and pulmonary hypertension.

OBJECTIVE: To evaluate whether early treatment with inhaled nitric oxide (iNO) will prevent newborns with moderate respiratory failure from developing severe hypoxemic respiratory failure (oxygenation index (OI)>or=40). STUDY DESIGN: A total of 56 newborns with moderate respiratory failure (OI between 10 and 30) were randomized before 48 h after birth to early treatment with 20 p.p.m. of iNO (Early iNO group, n=28) or conventional mechanical ventilation with FiO(2) 1.0 (Control group, n=28). Infants received iNO and/or high-frequency oscillatory ventilation (HFOV) if they developed an OI>40. RESULT: 7 of 28 early iNO patients (25%) compared to 17 of 28 control patients (61%) developed an OI>40 (P<0.05). In the Early iNO group mean OI significantly decreased from 22 (baseline) to 19 at 4 h (P<0.05) and remained lower over time: 19 (12 h), 18 (24 h) and 16 at 48 h. In contrast, OI increased in the Control group and remained significantly higher than the Early iNO group during the first 48 h of study: 22 (baseline), 29, 35, 32 and 23 at 4, 12, 24 and 48 h, respectively (P<0.01). Of 17, 6 control patients who developed an OI>40 were successfully treated with iNO. Nine of the remaining eleven control patients and six of seven Early iNO patients who had an OI>40 despite use of iNO responded with the addition of HFOV. One patient of the Early iNO group and two of the Control group died. Median (range) duration of oxygen therapy was significantly shorter in the Early iNO group: 11.5 (5 to 90) days compared to 18 (6 to 142) days of the Control group (P<0.03). CONCLUSION: Early use of iNO in newborns with moderate respiratory failure improves oxygenation and decreases the probability of developing severe hypoxemic respiratory failure.

A comparison of river water quality sampling methodologies under highly variable load conditions.

When river water quality fluctuates over relatively short periods of time with respect to the sampling frequency, the collection of grab samples may be inappropriate for characterising average water quality. This paper presents the results of a water quality monitoring study carried out on a stretch of the river Lambro (northern Italy) dominated by a periodically overloaded sewage treatment works (STW) located near its upstream end. Water quality was strongly influenced by a pronounced diurnal cycle in pollutant loads caused by the regular emission of untreated waste water during periods of high domestic flow (daytime). Two different sampling techniques were employed: grab sampling and 24-h composite sampling using automatic samplers. Samples were collected at the plant overflow and at several sites along the river and analysed for two common ingredients of household detergents, linear alkylbenzene sulphonate (LAS) and boron (B) and for routine water quality variables. The results obtained show that: (1) The diurnal variability of point-source-derived chemical concentrations in the river downstream of the undersized STW increased with increasing removal efficiency in sewage treatment. (2) The shape of the diurnal concentration signal remained relatively intact for a considerable distance downstream of the STW for several water quality variables, suggesting that hydrodynamic dispersion plays a relatively minor role in controlling concentration patterns in this river. (3) In-stream degradation of LAS was consistent with first order kinetics with a rate constant of 0.05-0.06 h(-1). (4) Grab sampling is a relatively inefficient methodology for capturing mean concentrations for rivers subjected to highly variable loads, especially when it is restricted to office hours. The inefficiency of grab sampling is more marked for substances (e.g. LAS) which are effectively removed during sewage treatment than for substances which are not. (5) For LAS, diurnal variability in the concentration signal decreases with distance downstream, making grab sampling an increasingly reliable methodology for estimating mean concentrations. (6) 24-h composite sampling is an efficient way of eliminating the effect of diurnal variations in load strength.

Simulation supported scenario analysis for water resources planning: a case study in northern Italy.

The work presents the results of a comprehensive modelling study of surface and groundwater resources in the Muzza-Bassa Lodigiana irrigation district, in Northern Italy. It assesses the impact of changes in land use and irrigation water availability on the distribution of crop water consumption in space and time, as well as on the groundwater resources. A distributed, integrated surface water-groundwater simulation system was implemented and applied to the study area. The system is based on the coupling of a conceptual vadose zone model with the groundwater model MODFLOW. To assess the impact of land use and irrigation water availability on water deficit for crops as well as on groundwater system in the area, a number of management scenarios were identified and compared with a base scenario, reflecting the present conditions. Changes in land use may alter significantly both total crop water requirement and aquifer recharge. Water supply is sufficient to meet demand under present conditions and, from the crop water use viewpoint, a reduction of water availability has a positive effect on the overall irrigation system efficiency; however, evapotranspiration deficit increases, concentrated in July and August, when it may be critical for maize crops.

GREAT-ER: a new tool for management and risk assessment of chemicals in river basins. Contribution to GREAT-ER #10.

The GREAT-ER (Geo-referenced Regional Exposure Assessment Tool for European Rivers) project team has developed and validated an accurate aquatic chemical exposure prediction tool for use within environmental risk assessment schemes. The software system GREAT-ER 1.0 calculates the distribution of predicted environmental concentrations (PECs) of consumer chemicals in surface waters, for individual river stretches as well as for entire catchments. The system uses an ARC/INFO-ArcView (ESRI) based Geographical Information System (GIS) for data storage and visualization, combined with simple mathematical models for prediction of chemical fate. At present, the system contains information for four catchments in Yorkshire, one catchment in Italy, and two in Germany, while other river basins are being added. Great-ER 1.0 has been validated by comparing simulations with the results of an extensive monitoring campaign for two 'down-the-drain' chemicals, i.e. the detergent ingredients boron and Linear Alkylbenzene Sulphonate (LAS). GREAT-ER 1.0 is currently being expanded with models for the terrestrial (diffuse input), air and estaurine compartments.

Tartronates: a new generation of drugs affecting bone metabolism.

In the search for a new class of bone-sparing agents for treating osteopenic disorders, we hypothesized that tartronic acid derivatives, sharing the chemical characteristics both of bisphosphonates and of Gla residues contained in matrix proteins such as osteocalcin, could positively affect bone metabolism. A series of tartronates was therefore tested for their ability to affect bone metabolism. In vitro resorption tests were performed examining pit formation by freshly isolated rat and rabbit osteoclasts plated onto bone slices and exposed to the drugs for 48 h. Tartronates bearing a linear side-chain (DF 1222 and DF 1363A) were the most effective in inhibiting pit excavation in the pM-nM range. Tartronates did not affect osteoclast viability, number, adhesion, or tartrate resistant acid phosphatase activity. Transient cell retraction was observed in osteoclasts plated onto glass and exposed to DF 1222. The maximal effect was seen in cells treated for 4 h at a concentration of 1 pM. DF 1222 accelerated mineralization in cultures of periosteal cells without affecting other osteoblast-like functions. This product was therefore tested in vivo in ovariectomized mice. Bone mass in femur was evaluated, by ash gravimetry, 21 days after ovariectomy. Unfortunately, DF 1222, the most active of tartronates in vitro, was inactive in this test because of its high hydrophilicity and the subsequent too short residence time. On the contrary, its tetrahydropyranyl ether derivative, DF 1363A, endowed with a significantly higher lipophilicity, showed a dose-dependent bone-sparing effect when administered subcutaneously at 10, 30, and 100 mg/kg/die, thus confirming the activity seen in in vitro tests. Because of their feasible parallel effect on both bone resorption and formation, tartronate derivatives may be tested to candidate this class of products for clinical studies.

N-acyl-2-substituted-1,3-thiazolidines, a new class of non-narcotic antitussive agents: studies leading to the discovery of ethyl 2-[(2-methoxyphenoxy)methyl]-beta-oxothiazolidine-3-propanoate.

The synthesis of a novel class of antitussive agents is described. The compounds were examined for antitussive activity in guinea pig after cough induction by electrical or chemical stimulation. Ethyl 2-[(2-methoxyphenoxy)methyl]-beta-oxothiazolidine-3-propanoate (BBR 2173, moguisteine, 7) and other structurally related compounds showed a significant level of activity, comparable to that of codeine and dextromethorphan. The compounds presented in this paper are characterized by the N-acyl-2-substituted-1,3-thiazolidine moiety, which is a novel entry in the field of antitussive agents. The serendipitous discovery of the role played by the thiazolidine moiety in determining the antitussive effect promoted extensive investigations on these structures. This optimization process on N-acyl-2-substituted-1,3-thiazolidines led to the initial identification of 2-[(2-methoxypheoxy)methyl]-3-[2-(acetylthio)acetyl]- 1,3-thiazolidine (18a) as an interesting lead compound. The careful study of the rapid and very complicated metabolism of 18a provided further insights for the design of newer related derivatives. The observation that the metabolic oxidation on the lateral chain's sulfur of 18a to sulfoxide maintained the antitussive properties suggested the introduction of isosteric functional groups with respect to the sulfoxide moiety. Subsequent structural modifications showed that hydrolyzable malonic residues in the 3-position of the thiazolidine ring were able to assure high antitussive activity. This optimization ultimately led to the selection of moguisteine (7) as the most effective and safest representative of the series. Moguisteine is completely devoid of unwanted side effects (such as sedation and addiction), and its activity was demonstrated also in clinical studies.

Chromophore-modified antitumor anthracenediones: synthesis, DNA binding, and cytotoxic activity of 1,4-bis[(aminoalkyl)amino]benzo[g]-phthalazine-5,10-diones.

As part of a program aimed at exploring the effect of the introduction of heteroatoms into the anthracene-9,10-dione chromophore, we have synthesized novel 1,4-bis[(aminoalkyl)amino]-benzo[g]phthalazine-5,10-diones (BPDs) 1 which are related to the antitumor agents ametantrone and mitoxantrone. Derivatives 1 were prepared by chromic acid oxidation of acylated benzo[g]phthalazines 5 followed by acid hydrolysis or by silylation-amination of 5,10-dihydroxybenzo[g]phthalazine-1,4-dione (8). The 1-[(aminoalkyl)amino]-4-amino congeners 2 were isolated in low yields as byproducts from the oxidation of 5. Against a panel of human tumor cell lines, the benzo[g]phthalazine-5,10-diones 1 and 2 exhibited cytotoxic activity comparable or even superior to that of mitoxantrone. In compounds 1, structure-activity relationships different than those operative in the carbocyclic series appeared to emerge. DNA-binding studies with the ametantrone-like compound 1c and its single-armed congener 2c indicated that the introduction of a 2,3-diaza subunit into the anthracene-9,10-dione chromophore reduces the affinity of the drug for DNA in comparison with ametantrone. On the other hand, the number of side-chain groups does not affect binding to a great extent. These findings seem to suggest mechanisms of cell death other than those induced by simple interaction of the 1,4-BPDs 1 and 2 with DNA.

Hepatitis B in children in Italy: incidence and risk factors: SEIEVA Collaborating Group. Sistema Epidemiologico Integrato dell'Epatite virale Acuta.

The objectives of the present report were to give a baseline picture of hepatitis B notification incidence rates in children before the campaign of mass vaccination for newborns and adolescents (12-13 years old), and to study the role of different risk factors. Data from a specific national surveillance system of acute viral hepatitis (SEIEVA, Sistema Epidemiologico Integrato dell'Epatite Virale Acuta) were used and acute hepatitis B cases were compared to acute hepatitis A patients with the case-control study method to estimate the associations with the considered risk factors. Since the system began, one hundred and sixty-three local health departments have joined SEIEVA covering 30% of the Italian population. The incidence of acute hepatitis B notifications among 0-14 aged children was 9 per 100,000 in 1985 and 1 per 100,000 in 1990. Such decline in incidence was observed in both the North and the South of Italy. Surgical interventions, dental therapy and household contacts with a HBsAg chronic carrier were found to be associated with acute hepatitis B. The point estimate of the odds ratio was 10 for the latter risk factor. Other preventive measures in addition to vaccination are needed to control the risk of hepatitis B infection and other parenteral diseases due to surgical intervention and dental therapy.

Cardiovascular activities of the new potent and long-lasting antihypertensive calcium entry blocker (+-)-3-ethyl,5-methyl,2- ([2-(formylamino)-ethyl]- thiomethyl)-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicar box ylate.

BBR 2160 ((+-)3-ethyl,5-methyl,2-([2-(formylamino)-ethyl]- thiomethyl)-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxy late, CAS 118587-22-7) is a new calcium entry blocker (CEB) which completely displaces 3H-nitrendipine from binding sites, is 10 times more potent than amlodipine (A) and equiactive with nifedipine (N). On the rat aorta contracted by 10 mmol/l Ca++, or 45 mmol/l K+, BBR 2160 shows higher CEB activity than N and A, achieving the maximum effect on voltage operated channels-induced contractions in 6 h, while N takes about 2 h. BBR 2160, N and A negatively affect the chronotropism on spontaneously beating, and inotropism on electrically driven guinea pig atria, respectively. In vitro BBR 2160 has marked vasoselectivity. Administered orally to conscious hypertensive rats (SHR) and renal hypertensive dogs (RHD), it caused a dose-dependent reduction in systolic blood pressure with a relatively slow onset, peak effect at 3-6 h and duration over 6 h. BBR 2160 and A have more pronounced activity on SHR than on normotensive rats (NR) (ED20 NR/SHR 3.3 for both compounds), while the antihypertensive and hypotensive activities of N are in the same dose-range (ED20 NR/SHR 1.3). No tolerance develops to the antihypertensive effects of BBR 2160 after five days' dosing up to 3.2 mg/kg in SHR and 1 mg/kg in RHD. In instrumented conscious normotensive dogs BBR 2160, N and A mostly lower diastolic blood pressure and total peripheral resistance, and do not increase total oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of PGI2 and two analogues (FCE 21292 and FCE 21258) in vitro and in vivo.

Two analogues of PGI2, FCE 21258 (5E-13,14-didehydro-carboprostacyclin) and FCE 21292 (5E-13,14-didehydro-20-methyl-carboprostacyclin) have been evaluated in comparison with PGI2 in different in vitro and in vivo screening tests. The rank order of potency was PGI2 greater than FCE 21292 greater than FCE 21258 in the following tests: potentiation of bradykinin-induced increased plasma protein extravasation in the guinea pig skin, inhibition of guinea pig platelet aggregation in vivo where the duration of action of FCE 21292 was longer than that of PGI2, lowering of mean systemic arterial pressure in conscious normotensive and spontaneously hypertensive rats and inhibition of rabbit platelet aggregation in vitro. In the relaxation of bovine coronary artery in vitro the rank order of potency was FCE 21292 greater than PGI2 greater than FCE 21258.

Azaprostaglandin analogues. Synthesis and biological properties of 11-azaprostaglandin derivatives.

New nitrogen analogues of prostaglandins (11, 11a, 12, and 12a) have been synthesized starting from a 4,5-disubstituted 2-pyrrolidinone nucleus (5 and 5a) containing one side chain and a suitable functionality for elaborating the second one. These analogues had no better activity than natural prostaglandins in vitro [guinea pig ileum and trachea, rat stomach fundus strip, uterus and portal vein, ADP-induced guinea pig platelet-rich plasma (PRP) aggregation]. They similarly lacked any interesting activity in vivo [anesthetized rat blood pressure, stress, and acetylsalycilic acid (ASA) induced gastric lesions in rat].

Effects of prostacyclin on aspecifically and specifically induced bronchoconstriction in asthmatic patients.

The efficacy of prostacyclin in preventing aspecifically and specifically induced bronchoconstriction was evaluated in a single-blind cross-over study in 3 groups of asthmatic patients. Prostacyclin was given by inhalation in doses of 250 microgram in women and 500 microgram in men. Ultrasonic mist of H2O (group 1), physical exercise on cycloergometer (group 2) and pneumoallergens (group 3) were used as bronchial stimulant agents. Prostacyclin gave a very good protection in the first 2 groups, but was ineffective in the third. An increase in heart rate was observed immediately after the inhalation of prostacyclin: this effect was particularly evident in women in whom a significant decrease in diastolic pressure was noted too.