Genomic and Personalized Medicine Approaches for Substance Use Disorders (SUDs) Looking at Genome-Wide Association Studies.

Drug addiction, or substance use disorder (SUD), is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behaviour persist despite serious negative consequences. Drug abuse represents a problem that deserves great attention from a social point of view, and focuses on the importance of genetic studies to help in understanding the genetic basis of addiction and its medical treatment. Despite the complexity of drug addiction disorders, and the high number of environmental variables playing a role in the onset, recurrence, and duration of the symptoms, several studies have highlighted the non-negligible role of genetics, as demonstrated by heritability and genome-wide association studies. A correlation between the relative risk of addiction to specific substances and heritability has been recently observed, suggesting that neurobiological mechanisms may be, at least in part, inherited. All these observations point towards a scenario where the core neurobiological factors of addiction, involving the reward system, impulsivity, compulsivity, stress, and anxiety response, are transmitted, and therefore, genes and mutations underlying their variation might be detected. In the last few years, the development of new and more efficient sequencing technologies has paved the way for large-scale studies in searching for genetic and epigenetic factors affecting drug addiction disorders and their treatments. These studies have been crucial to pinpoint single nucleotide polymorphisms (SNPs) in genes that affect the reaction to medical treatments. This is critically important to identify pharmacogenomic approaches for substance use disorder, such as OPRM1 SNPs and methadone required doses for maintenance treatment (MMT). Nevertheless, despite the promising results obtained by genome-wide association and pharmacogenomic studies, specific studies related to population genetics diversity are lacking, undermining the overall applicability of the preliminary findings, and thus potentially affecting the portability and the accuracy of the genetic studies. In this review, focusing on cannabis, cocaine and heroin use, we report the state-of-the-art genomics and pharmacogenomics of SUDs, and the possible future perspectives related to medical treatment response in people that ask for assistance in solving drug-related problems.

Sorption of benzene derivatives onto a humic acid-zeolitic tuff adduct.

The sorption of some benzene derivatives: o-xylene, toluene, phenol, benzyl alcohol, resorcinol and hydroquinone onto a zeolitic tuff-humic acid adduct (PCT-ImHA) was analysed by batch technique at 25 °C and neutral pH. PCT-ImHA was prepared by binding leonardite-extracted humic acids (HA) to a zeolitic tuff sample rich in phillipsite and chabazite and enriched with Ca2+ by cation exchange (Ca-PCT). The HA calcium salts were gently mixed with wet Ca-PCT; then, the mixture was heated at 330 °C for 1.5 h. An adduct with almost 2% of HA was obtained. The experimental data were well fitted by the Langmuir adsorption isotherm and showed that saturation capacity (qMax) increased with the octanol-water repartition coefficient (KO-W). The comparison with previous data on sorption onto immobilised HA highlights that qMax values for PCT-ImHA are far higher than the sum of the contributions of the two separate components.

Impact assessment of PM10 cement plants emissions on urban air quality using the SCIPUFF dispersion model.

The Second-order Closure Integrated Puff (SCIPUFF) model was used to study the impact on urban air quality caused by two cement plants emissions located near the city of Caserta, Italy, during the entire year of 2015. The simulated and observed PM10 concentrations were compared using three monitoring stations located in urban and sub-urban area of Caserta city. Both simulated and observed concentrations are shown to be highest in winter, lower in autumn and spring and lowest in summer. Model results generally follow the pattern of the observed concentrations but have a systematic under-prediction of the concentration values. Measures of the bias, NMSE and RMSE indicate a good correlation between observed and estimated values. The SCIPUFF model data analysis suggest that the cement plants are major sources for the measured PM10 values and are responsible for the deterioration of the urban air quality in the city of Caserta.

Modelling the biphasic sorption of simazine, imidacloprid, and boscalid in water/soil systems.

The sorption kinetics of simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine), imidacloprid (1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine), and boscalid (2-chloro-N-(4'-chlorobiphenyl-2-yl)nicotinamide), three pesticides of wide use in agriculture, was determined in five different water/soil systems over a time interval from the initial few seconds to about 1 month. In all the experiments, sorption kinetics showed a biphasic pattern characterized by an initial, relatively short phase with a high sorption rate and a later phase with much a lower sorption rate. Initial sorption capacity increased with soil organic carbon content and with sorbate hydrophobicity. We postulate that the first phase of the process involves a fast second-order sorption reaction on superficial sites of soil particles, whereas the second phase depends on diffusion-controlled migration to internal binding sites. A kinetic equation based on this hybrid model accurately fitted all data sets. Less satisfactory results were obtained employing the pseudo-first order, pseudo-second order, Elovich, two site non-equilibrium, or Weber-Morris equation. The superior performance of the hybrid model for describing boscalid sorption probably reflects the high hydrophobic character and consequent low diffusion rates of this compound. The accuracy of modelling was in any case strongly dependent on the time interval considered.

Effects of stimulation of autophagy on the urinary excretion of biomarkers of the oxidative status.

Autophagy, a health-promoting lysosomal degradation pathway that controls the quality of the cytoplasm by eliminating protein aggregates and damaged organelles including 8-OHdG-rich mitochondria, is under investigation as a target for prevention and/or treatment of several human diseases and decelerating aging. Stimulation of autophagy was shown to rescue older liver cells from accumulation of 8-OHdG-rich mitochondria and to increase urinary 8-OHdG levels. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a recently recommended biomarker for monitoring oxidative status over time. In order to rule out the possibility that the in vivo stimulation of autophagy may cause an increase in the oxidative status, in this study we compared the effects of the stimulation of autophagy by two different procedures (the administration of antilipolytic drug and everolimus, an mTOR inhibitor in clinical use) on the urinary levels of 8-OHdG and 15-isoprostane F2t, another well-known biomarker of the oxidative status. Results show that both procedures increased the urinary 8-OHdG levels without any change in urinary 15-isoprostane F2t; this increase in urinary 8-OHdG levels after the antilipolytic drug was fully suppressed by the simultaneous injection of glucose to make rats transiently incompetent for the endocrine stimulation of autophagy. Conclusions are that the in vivo stimulation of autophagy does not affect the oxidative status and that the increasing effect on urinary 8-OHdG may be secondary to an increased degradation of previously accumulated 8-OHdG-rich (mt)DNA. The authors are aware that findings may open the way to a safe, easy, highly desirable non-invasive test for successful in vivo activation of autophagy after pharmacological stimulation.

Sorption of non-ionic organic pollutants onto a humic acids-zeolitic tuff adduct: thermodynamic aspects.

Sorption isotherms from water solutions for toluene, cyclohexane, o-xylene, benzyl alcohol, phenol and cyclohexanol onto a humic acid-zeolite adduct were determined at 4, 14, 24 and 34 °C and utilized to calculate the isosteric enthalpy (ΔadsHi) and isosteric entropy (ΔadsSi) of the process. For hydrocarbon compounds, toluene, cyclohexane and o-xylene, both ΔadsHi and ΔadsSi were negative, the process was exothermic. In contrast, for hydroxyl compounds, benzyl alcohol, phenol and cyclohexanol, ΔadsHi and ΔadsSi were positive, the increase in entropy possibly reflecting the release of water molecules during sorption. The results suggest that sorption/desorption of either class of compounds could be controlled by operating on the temperature.

Contribution of vehicular traffic and industrial facilities to PM10 concentrations in a suburban area of Caserta (Italy).

PM10 levels have been recorded in the suburban area of Caserta (Italy) from February to October 2012. The daily limit was exceeded in 13 % of the determinations, with no significant difference between weekdays and weekends. Benzo[a]pyrene concentrations were in the range 0.01-0.46 ng/m(3), thus, never exceeding the National Standard. The B(a)P-eq was 0.20 ng/m(3). PM10 peaks were associated with wind from east-northeast. The same was observed for Ca concentrations, whereas no relation with wind direction was observed for organic pollutants. The results point to a local limestone quarry and cement factory as the likely major source of PM10 pollution in the area investigated.

TVT SECUR System: Final results of a prospective, observational, multicentric study.

INTRODUCTION AND HYPOTHESIS: This is an observational multicentre prospective study into the complications and effectiveness of TVT SECUR™. METHODS: One hundred forty-seven patients with urodynamic or occult Stress Urinary Incontinence (SUI) were enrolled. Outcome measures at 6, 12 and 24 months were: objective cough test; subjective responses to PGI-S questionnaire and Visual Analogue Score. STATISTICAL ANALYSIS: Wilcoxon Test; Monte Carlo Exact Test. RESULTS: Ninety-five urodynamic SUI and 41 occult SUI patients were treated using transobturator (H-position) or retropubic (U-position) approach (110 vs. 26 patients). Cure rates at 6, 12, and 24 months were 87.5%, 88.6% and 89.5%. Failure rates at all follow-ups were similar for urodynamic and occult SUI. The U-position failure rate was comparable to H-position at short-term but significantly higher at mid-term. Familiarity with the technique brought significantly higher success rates. CONCLUSIONS: TVT SECUR is safe, effective and versatile, but has an appreciable learning curve.

Radial artery pseudoaneurysm after a single arterial puncture for blood-gas analysis: a case report.

We report a case of a radial artery pseudoaneurysm complicating a single arterial puncture for blood-gas analysis that was treated with excision of pseudoaneurysm and suture of the defect of wall of radial artery. The puncture for continuous blood pressure monitoring and serial blood gas analysis have been reported in critically ill patients, but, to the best of our knowledge, there are no cases reported of pseudoaneurysm after a single arterial puncture for blood-gas analysis. In the reported case we think that the main cause of the pseudoaneurysm onset was an incorrect compression and/or a too much short time of compression of the radial artery after the puncture. Minor sequelae and rare complications may be minimized by careful attention to detail in the performance of such procedures and care of the patient also after a single arterial puncture.