USE OF NOVEL PSYCHOACTIVE SUBSTANCES (NPS) OF NATURAL ORIGIN: AN INTERNATIONAL SURVEY

Aim NPS recreational use are mostly derived and modified from constituents of natural origin. Here we investigated the motivation of natural NPS use, perception of potential associated health risks and demographic factors associated with natural NPS use. Methodology The Bristol Online Survey was in English and advertised on the drug forum Bluelight and social media Facebook pages and via University email between 1 July and 17 November 2018 (812 responses; 458 NPS users). This pharmacoepidemiologic study was evaluated using SPSS software (IBM SPSS Statistics version 24;MacOS Sierra 10.12.3). Results The main motivation (67%) for natural NPS use was curiosity to ‘’experience something new and different’’ with a low perception of health risk (85%). The preferred natural NPS was magic mushrooms (psilocybin, 95%) often in combination with cannabis (63%). Gender, living area, educational background, smoking frequency and employment significantly affected (P<0.001) natural NPS use. Male respondents, residents of suburban and rural areas, smokers and respondents with low educational level represented the majority of natural NPS users as well as the employed, the unable to work and retired groups. Similarly, sexual orientation significantly affected (p<0.05) natural NPS use. Conclusion Users’ low perception of natural NPS safety profile and the fact that natural NPS use correlates with a lower level of education, indicates a need for enhanced statutory targeted prevention interventions in schools. Many users (67%) reported natural NPS make them happier and more optimistic about life emphasizing the need to study the potential application of these substances in appropriate clinical settings for therapeutic purposes in mental health.Peer reviewe

Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses

peer-reviewedUnderstanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 “POSITIVe” to conduct a short-term scientific mission to K.C. at CEBAS-CSIC (A.G.-S. and M.T.G.-C.) during which the data analysis was performed

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790

Pharmaceutical cognitive enhancement in Greek university students: differences between users and non-users in social cognitive variables, burnout and engagement

Pharmaceutical cognitive enhancement (PCE) represents the non-medical use of prescribed medication for the improvement of cognitive functioning and academic performance. Although there are some studies about PCE prevalence, it is less clear how users and non-users of PCE substances differ with respect to their positive and negative student experiences (e.g., academic burnout, engagement with studies) and in social cognitive variables that relate to decision-making and self-regulation of PCE use. The present study assessed whether students with different experiences of PCE substance use displayed differences in academic burnout, study engagement and social cognitive variables relevant to PCE use. Three hundred and forty seven University students (M age = 22.15, SD = 1.69; 54% females) completed a battery of anonymous questionnaires on academic burnout, engagement with studies, social cognitive variables relevant to PCE use, and self-reported use of PCE substances and non-prescribed nutritional supplements. Three user groups emerged, namely, non-users (51.9%, n = 180), single users of non-prescribed dietary supplements (25.4%, n = 88), and dual users of both non-prescribed dietary supplements and PCE (22.8%, n = 79). Multivariate analysis of variance indicated significant differences among the three user groups in intentions, attitudes, social norms, and anticipated regret towards PCE use. No significant differences were observed with respect to academic burnout and work engagement. The findings show that University students may engage in PCE use independently of their student experiences. Rather, a chemically-assisted performance enhancement mindset seems to differentiate users from non-users of PCE substances

Systematic bioinformatic analyses of nutrigenomic modifications by polyphenols associated with cardiometabolic health in humans: Evidence from targeted nutrigenomic studies

Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies

Evaluation and comparative analysis of quantitative structure activity relationships (QSAR) on serine proteases inhibitors. Synthesis and biological evaluation of novel coumarin derivatives as possible anti-inflammatory agents and serine proteases inhibitors (QSARs) on serine proteases inhibitors. Synthesis and biological evaluation of novel coumarin derivatives as possible anti-inflammatory agents and serine proteases inhibitors”

Inflammation is a complex phenomenon involving interrelationships between humoral and cellular reactions through a number of inflammatory mediators. It is an usual symptom covering different pathologies and there are still many questions to be answered in order to understand the inflammatory process, as well as a need for better-tolerated and more efficient anti-inflammatory drugs. Recently it has been clarified that serine proteases are implicated in various inflammatory disorders. Some of the most well known members of serine proteases are trypsin, chymotrypsin, thrombin and Factor Xa. Coumarin derivatives are mostly active compounds. Many of them have been isolated from natural sources and especially from plants. In previous studies many coumarin derivatives have shown significant anti-inflammatory activity as well as antioxidant. Coumarins were found to highly inhibit various enzymes implicated in inflammation. Among them lipoxygenase and serine proteases, especially chymotrypsin and thrombin. In this study a number of new synthesized coumarin Mannich bases is presented. Among them: compound 2 [9-methyl-9,10-dihydro-2H,8H-hromen[8,7-e][1,3]-oxazin-2-one] and compounds 3-15 with the general structure of 7-hydroxy-8-methylene-amine-substituted coumarins. Another group of new coumarin derivatives has also been synthesized. These compounds contain an azomethine group at position 7 of the coumarin ring. The structure of all the new compounds (bases, salts, azomethine derivatives) are confirmed spectrophotometrically and elemental analysis have been performed. Lipophilicity of the compounds was determined experimentally as RM values by RPTLC and theoretically by computational methods (C-QSAR for Clog P and McSpartan). The compounds are novel and in relation to their pharmacological properties are of high interest, since they present major differences to the classical anti-inflammatory agents. All the compounds have been conducted to a preliminary in vitro and in vivo study. The new compounds were studied for their interaction with the stable free radical DPPH and most of them shown high ability to scavenge free radicals. Moreover many of them were found to have a good competition with DMSO for scavenging free hydroxy radicals, which were found to be involved in inflammatory process. A number of enzymes is well known that they are implicated in inflammation. Some of them are lipoxygenase, cyclooxygenase and #-glucuronidase. Most of the new tested coumarin derivatives have shown high inhibitory activity on these enzymes in two different concentrations (0.01 mM and 0.1 mM). Compounds were tested in vitro against various serine proteases. In the case of trypsin and chymotrypsin two different experiments were performed examining their proteolytic activity and their ability to function as esterases. Almost all the compounds presented high inhibitory activity against both enzymic activities Two different experiments were performed to delineate the inhibitory activity of the tested coumarins against thrombin. Some of the compounds presented significant inhibition. All the azomethine - derivatives were studied in vitro for the nitric oxide release in the presence of thiol cofactors. It was found that ##2 - release was dependent on the nature of thiol. Some of them were found to highly release ##2 . For the anti-inflammatory activity of all the new compounds the carraggenin induced rat paw edema has been used. All the tested compounds highly inhibit the carrageen induced rat paw edema at 0.01 mmol/ kg b.w. For some of the synthesized compounds the adjuvant induced arthritis (AID) model has been used. AID is considered to be one of the best experimental models for investigation of anti-inflammatory drugs and quite close to the human rheumatoid arthritis. The examined compounds suppressed very effectively the AID manifestations (inflammation – arthritic score – cachexia impairment of the in vivo drug metabolism). In continuation, we tried to linearly correlate the different biological responses in order to delineate the mechanism of action of these derivatives: in vivo anti-inflammatory and in vitro antioxidant activity, free radical scavenging activity and inhibitory activity of enzymes induced by the tested compounds. The relationships between structure, physicochemical properties and biological activities for several classes of serine proteases (trypsin, thrombin and Factor Xa) inhibitors reported in literature, have been evaluated. An attempt has been also made to correlate all the biological data of this research with the physicochemical properties of the corresponding compounds. The QSAR analysis presented here is an attempt to organize the knowledge available from the compounds able to inhibit trypsin, thrombin and Factor Xa. The C-QSAR methodology of Biobyte can greatly help in this effort being focused on the physicochemical and statistical bases as to extract useful results that can be used in the further design of serine proteases inhibitors

Multitarget Molecular Hybrids of Cinnamic Acids

In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids—2e, 2a, 2g—and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX) inhibition and analgesic activity (IC50 = 0.34 μΜ and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 μΜ) and the highest anti-proteolytic activity (IC50= 5 μΜ). The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91%) and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure–activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding

Monitoring of Frequency and Antimicrobial Susceptibility of Pathogens on the Hands of Healthcare Workers in a Tertiary Hospital

Objective: To monitor microbes, focusing on drug resistance, on the hands of the personnel of four departments of a tertiary hospital (ICU, neonatal unit, internal medicine ward and surgical ward) and explore differences between departments, professions and genders

Socio-demographic Factors Affecting Initiation and Duration of Breastfeeding in a Culturally Diverse Area of North Eastern Greece

Background: Breastfeeding is not only important for the bond between the mother and the child but is also associated with many health benefits. Socio-demographic factors have been found to be important for the initiation and longer duration of breastfeeding. Aim: To record the breastfeeding characteristics and to explore possible associations with socio-cultural and demographic factors in a culturally diverse area in Greece.Materials and methods: A questionnaire including information about breastfeeding characteristics, medical history and demographics was completed by parents of children in the primary schools of the area.Results: The study included 700 school-age children (352 boys), mean age 9.4±1.9 years. Breastfeeding was reported in 54.9% of them, with median (IQR) duration of 120 (range 60-360) days. Prevalence of breastfeeding was slightly higher in semi-urban areas, versus rural or urban settlements, but the duration there was significantly lower (p<0.001). Better educated mothers tended to initiate or sustain breastfeeding for a longer period; however, this difference was not statistically significant. Children of the native Muslim minority had been breastfed for a longer time (median duration 360 vs. 120 days, p<0.001), however, no difference was noted in prevalence.Conclusion: Prevalence of breastfeeding in Greece is approximately 55%, similar to previous reports and along with duration is determined by certain socio-cultural factors