EMCDDA framework and practical guidance for naming cathinones.

Cathinones are often sold as "legal" alternatives to controlled stimulants such as amphetamine, MDMA and cocaine. Cathinones are the second largest group of new psychoactive substances (NPS), with close to 170 monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Although all cathinones are related to the parent compound cathinone, one of the psychoactive principles in khat, assigning consistent, informative and user-friendly common names to these substances is challenging. Over time different naming approaches have been applied, leading to cathinones being known by several names. This work provides a framework and practical examples for the consistent naming of cathinones which is easy to understand and can be applied by the forensic community, researchers, clinical practitioners, and policy makers. The scope of the issue and rationale for earlier naming approaches are also discussed. The new naming framework has been developed based on established naming approaches and centered around the common "cathinone," and "phenone" motifs/scaffolds. The proposed framework establishes clear rules to derive the EMCDDA framework names for cathinones. Each name is, in turn, composed by a principal name containing a parent letter, derived after the "cathinone" or the "phenone" scaffold. Additional substitutions are prepended to the principal name. The framework also provides for exceptions for several cathinones and structural analogs scheduled under UN and EU legislation.

Multi-lingual multi-platform investigations of online trade in jaguar parts.

We conducted research to understand online trade in jaguar parts and develop tools of utility for jaguars and other species. Our research took place to identify potential trade across 31 online platforms in Spanish, Portuguese, English, Dutch, French, Chinese, and Vietnamese. We identified 230 posts from between 2009 and 2019. We screened the images of animal parts shown in search results to verify if from jaguar; 71 posts on 12 different platforms in four languages were accompanied by images identified as definitely jaguar, including a total of 125 jaguar parts (50.7% posts in Spanish, 25.4% Portuguese, 22.5% Chinese and 1.4% French). Search effort varied among languages due to staff availability. Standardizing for effort across languages by dividing number of posts advertising jaguars by search time and number of individual searches completed via term/platform combinations changed the proportions the rankings of posts adjusted for effort were led by Portuguese, Chinese, and Spanish. Teeth were the most common part; 156 posts offered at least 367 teeth and from these, 95 were assessed as definitely jaguar; 71 of which could be linked to a location, with the majority offered for sale from Mexico, China, Bolivia, and Brazil (26.8, 25.4, 16.9, and 12.7% respectively). The second most traded item, skins and derivative items were only identified from Latin America: Brazil (7), followed by Peru (6), Bolivia (3), Mexico (2 and 1 skin piece), and Nicaragua and Venezuela (1 each). Whether by number of posts or pieces, the most commonly parts were: teeth, skins/pieces of skins, heads, and bodies. Our research took place within a longer-term project to assist law enforcement in host countries to better identify potential illegal trade and presents a snapshot of online jaguar trade and methods that also may have utility for many species traded online.

From JWH-018 to OXIZIDS: Structural evolution of synthetic cannabinoids in the European Union from 2008 to present day.

With new synthetic cannabinoids (SCs) appearing on the European drug market every year, early warning systems are key to detect, monitor, and respond to threats posed by them. The European Union Early Warning System (EU EWS) implemented by the European Monitoring Centre for Drugs and Drug Addiction has monitored these substances since their first European detection in 2008. Since then, national and international responses have been implemented, aimed at tackling risks posed by SCs. Throughout this time, new SCs have emerged on the European market containing diverse structural moieties, appearing to be designed in a way that circumvents existing legal controls, contributing to a complex public health scenario. This study provides an inventory of the SCs detected in the EU from 2008 to 2022, describing their structural evolution by analysing separately four structural features: their core, tail, linker, and linked groups. The range of structural changes is analysed considering key milestones, including the year of first report by the European Union Early Warning System to the key legislative changes that have occurred since. The analysis shows that from June 2021 to July 2022, 20 out of 23 newly emerged SCs evade the generic SC legislation introduced in China in May 2021. This supports the hypothesis that the protection of public health benefits from timely information exchange and careful assessment of the risks associated with these substances. Additionally, the introduction of legal responses, albeit an important instrument to reduce the availability of dangerous substances on the market, may also be accompanied by unintended consequences.

EMCDDA framework and practical guidance for naming synthetic cannabinoids.

Synthetic cannabinoids (SCs), often sold as "legal" replacements for cannabis, are the largest group of new psychoactive substances monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Currently, close to 240 structurally heterogeneous SCs are monitored through the European Union (EU) Early Warning System, and attributing consistent, informative, and user-friendly names to SCs has been a challenge in the past. Over time, several naming conventions have been employed with the aim of making SCs more easily recognizable by non-chemists, including regulators. To achieve this, the names assigned need to contain detailed information on the structural features present in the substance. This work provides a theoretical framework and a practical hands-on guideline for consistent naming of SCs, which is easy to understand and can be applied by the forensic community, researchers, clinical practitioners, and policy-makers. The proposed framework builds on the established letter code system for molecular building blocks (core, linker, linked group, and tail) implemented by the EMCDDA in 2013 and has been expanded to incorporate additional structural features through substitution. The scope of the issue of attributing semi-systematic code names is illustrated, and earlier approaches used for naming SCs are discussed. The concepts and rules of the EMCDDA framework are described through a flowchart that provides a basis for naming new SCs, a graphical overview of the chemical diversity of SCs, and a detailed list of the SCs identified in the EU by the Early Warning System of the EMCDDA for reference.

Factores quirúrgicos, emocionales y cuidado integral tras la cirugía del pie diabético / Surgical, emotional factors and comprehensive care after diabetic foot surgery

El abordaje de un problema de salud tan importante, frecuente y de no fácil solución como es el pie diabético, mejora cuando se constituye un equipo multidisciplinar, ya que en general son varios los profesionales sanitarios implicados en el diagnóstico y tratamiento de este síndrome, cirujanos, endocrinólogos, infecciosos, ortopedas, podólogos y enfermeros; del entendimiento y colaboración de todos ellos debe surgir la mejor manera de encauzarlo correctamente. Objetivo: Analizar los factores quirúrgicos, emocionales y cuidado integral tras la cirugía del pie diabético. Material y método: Revisión bibliográfica con características de estudio de abordaje cualitativo, descriptivo, transversal. Se revisaron serie de revistas con artículos cuyas variables se situaran en pacientes diagnosticados con diabetes mellitus. Resultados: Mujeres 55 y en hombres 45 años, edad media fue 54 años. Sin embrago, la asociación de la edad con el cumplimiento de las conductas de autocuidado en la muestra de pacientes con DM tipo 2 amputados no fue estadísticamente significativa. Así mismo, estos factores influyen en la adherencia al autocuidado de la diabetes, específicamente con las prácticas relacionadas con el cuidado de los pies, correspondiente con una mayor dificultad en la comprensión de las indicaciones. Conclusiones: Se observa en forma general un cumplimiento inadecuado a las conductas de autocuidado para la prevención del pie diabético en la muestra de pacientes diabéticos amputados a pesar de que, la mayoría de las conductas son de bajo costo y requieren poco esfuerzo, evidenciándose escaso acompañamiento por parte del personal sanitario a esta población(AU)

The approach to a health problem as important, frequent and difficult to solve as the diabetic foot, improves when a multidisciplinary team is constituted, since in general there are several health professionals involved in the diagnosis and treatment of this syndrome. surgeons, endocrinologists, infectious, orthopedists, podiatrists and nurses; from the understanding and collaboration of all of them, the best way to channel it correctly must emerge. Objective: To analyze the surgical, emotional and comprehensive care factors after diabetic foot surgery. Material and Method: Bibliographical review with study characteristics of a quantitative, descriptive, cross-sectional approach. A series of journals with articles whose variables were located in patients diagnosed with diabetes mellitus were reviewed. Results: Women 55 and men 45 years, mean age was 54 years. However, the association of age with compliance with self-care behaviors in the sample of amputated patients with type 2 DM was not statistically significant. Likewise, these factors influence adherence to diabetes self- care, specifically with practices related to foot care, related to greater difficulty in understanding the indications. Conclusions: Inadequate compliance with self-care behaviors for the prevention of diabetic foot is generally observed in the sample of amputated diabetic patients, despite the fact that most of the behaviors are low-cost and require little effort, showing little follow-up. by health personnel to this population(AU)

DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles.

Etonitazene and related 2-benzylbenzimidazoles are potent analgetics invented in the research laboratories of the Swiss pharmaceutical giant CIBA in the late 1950s. Though the unprecedented structure distinguishes this class of compounds from poppy-derived and other synthetic analgetics, a range of studies indicate that these drugs are selective µ opioid receptor agonists possessing morphine-like pharmacotoxicological properties in animals as well as humans. Several unscheduled members of this synthetically readily accessible class of opioids that are not controlled under the international and national drug control systems have recently emerged on the illicit drug market. Among them, isotonitazene has been implicated in at least 200 fatalities in Europe and North America. None of the 2-benzylbenzimidazole derivatives have been developed into medicines, but etonitazene and some of its derivatives have been used as receptor probes and in addiction behavior studies in animals. The unique structure has inspired research on such benzimidazoles and related benzimidazolones of which "brorphine" made its debut as one of the newest psychoactive substance to emerge on the illicit opioid drug market in mid-2019. This in-depth review provides a historical introduction, an overview on the chemistry, pharmacological profiles, adverse effects, addiction liability, regulatory status, and the impact on chemical neuroscience of the 2-benzylbenzimidazoles. Structurally related benzimidazoles with opioid and/or analgesic properties are also discussed briefly.

Geometrical structure data of nanoporous carbon systems obtained from computer simulated pyrolysis.

This article contains data on nanoporous carbon materials coming from lignocellulosic components. Such data is directly related to the research paper "Insights into the design of carbon electrodes coming from lignocellulosic components pyrolysis with potential application in energy storage devices: A combined in silico and experimental study" [1]. In this work, the geometrical parameters of nanoporous carbon systems were found with Molecular Dynamics (MD) simulations at the ReaxFF level. The tridimensional structures of such carbon systems are given in Cartesian coordinates. They were computed at different heating rates, simulating the conditions observed in pyrolysis processes of Agave angustifolia leaves, which were carried out in a solar furnace. Nanoporous carbon systems are characterized with radial distribution functions (RDF) and ring distribution profiles.

Bone mineral density changes in lactating adolescent mothers during the first postpartum year.

OBJECTIVES: This study aimed to compare changes in whole body bone mineral density (wbBMD) during the first postpartum year in adolescent mothers with those of nulliparous adolescents. METHODS: The study included 21 adolescent mothers and 16 nulliparous adolescent non-indigenous Mexican women (State of Sonora) from a low income level. All mothers were assessed at 15 days (0.5 months), 3 months, and 6 months postpartum; 16 were measured at 12 months postpartum. Nulliparous adolescents were assessed in the same periods. Multiple regression models was used to assess adjusted associations of changes in wbBMD (by DPX-MD+ densitometer) with dietary calcium and physical activity assessments (estimated using pre-tested questionnaires), post menarche years, and number of breast feedings. RESULTS: At baseline, no differences were observed between nulliparous and adolescent mothers regarding age, post-menarche years, or BMD values. Changes in wbBMD of -0.56% and 0.77% were observed in mothers and nulliparous adolescents, respectively, after the first 3 months (P = 0.006). Changes in wbBMD in mothers were associated with number of breast feedings and changes in BMI. At 12 months postpartum, the BMD of adolescent mothers was similar to that of nulliparous adolescents. CONCLUSIONS: At 1 year postpartum, adolescent mothers exhibited BMD similar to those of nulliparous adolescents. This result is likely attributable to the breastfeeding practices adopted by mothers during late adolescence.

Computer-aided (in silico) approaches in the mode-of-action analysis and safety assessment of ostarine and 4-methylamphetamine.

OBJECTIVE: This study exemplifies computer-aided (in silico) approaches in assessing the risks of new psychoactive substances emerging in the European Union. In this work, we (i) consider the potential of Ostarine exhibiting psychoactivity and (ii) anticipate potential activities and toxicities of 4-methylamphetamine. METHOD: The approach, termed in silico target prediction, suggests potential protein targets modulated by compounds given their chemical structure. This is achieved by first establishing the associations between chemical structure and protein targets using data from the bioactivity database, ChEMBL, via the use of two different computational algorithms. On the basis of the associations, protein targets and consequently the mode of action of novel compounds were predicted. RESULTS: For Ostarine, none of the targets anticipated are currently known to elicit psychoactivity. Furthermore, Ostarine is unlikely to cross the blood-brain barrier to reach relevant target sites on the basis of its physicochemical properties. For 4-methylamphetamine, toxicities were anticipated, that is, serotonin syndrome (based on the prediction of SERT) and other effects similar to related substances, that is, methamphetamine. CONCLUSION: From the two case studies, we showed that in silico target prediction appears to have potential in assessing new psychoactive compounds where experimental data are scarce. The applicability domain of target predictions when applied to psychoactive compounds needs to be established in future work.

The pharmacology and toxicology of the synthetic cathinone mephedrone (4-methylmethcathinone).

Mephedrone (4-methylmethcathinone) is a synthetic cathinone that is used as a recreational drug. It has been available since 2007 but its availability and use increased significantly during 2009 and 2010. In this review article we will summarize the available literature on the sources, availability, and prevalence of the use of mephedrone. We will also discuss the pharmacology of mephedrone, the patterns of acute toxicity associated with its use, the reports of fatalities associated with its use, and the potential for mephedrone dependence.

Khat use and monitoring drug use in Europe: the current situation and issues for the future.

AIM OF THE STUDY: To review the information available on the use of khat (Catha edulis) in the EU, and to assess the future use of this drug and related substances. MATERIAL AND METHODS: Khat is not controlled by international law and it has not been systematically included in the list of illicit drugs monitored in the EU. The current principal source of information on khat use in Europe is the early-warning system set up to monitor new and emerging drugs. Further information was obtained from official national reports to the EMCDDA and from the scientific literature. RESULTS: Across Europe, the use of khat is low. Khat use is limited to countries with immigrant communities from countries where khat use is common (such as Ethiopia, Somalia and Kenya). Information on the prevalence of khat use in the general population is scarce. Data on seizures provide an insight on the situation, though these may be difficult to interpret. The most recent estimates suggest that Europe accounts for about 40% of the khat seized worldwide. CONCLUSION: The shortage of data on the use and patterns of use of khat in Europe does not allow an evaluation of the needs for health and social interventions in communities in which the drug is used. But seizures of the plant are increasing in the EU, and more synthetic derivatives of the pharmacologically active ingredients of the plant (cathine and cathinone) are appearing on the market. Some of these, like mephedrone, have significant potential for future diffusion, and are likely to play a greater role on the European drug scene of the future.

Notes on quantitative structure-properties relationships (QSPR) (1): A discussion on a QSPR dimensionality paradox (QSPR DP) and its quantum resolution.

Classical quantitative structure-properties relationship (QSPR) statistical techniques unavoidably present an inherent paradoxical computational context. They rely on the definition of a Gram matrix in descriptor spaces, which is used afterwards to reduce the original dimension via several possible kinds of algebraic manipulations. From there, effective models for the computation of unknown properties of known molecular structures are obtained. However, the reduced descriptor dimension causes linear dependence within the set of discrete vector molecular representations, leading to positive semi-definite Gram matrices in molecular spaces. To resolve this QSPR dimensionality paradox (QSPR DP) here is proposed to adopt as starting point the quantum QSPR (QQSPR) computational framework perspective, where density functions act as infinite dimensional descriptors. The fundamental QQSPR equation, deduced from employing quantum expectation value numerical evaluation, can be approximately solved in order to obtain models exempt of the QSPR DP. The substitution of the quantum similarity matrix by an empirical Gram matrix in molecular spaces, build up with the original non manipulated discrete molecular descriptor vectors, permits to obtain classical QSPR models with the same characteristics as in QQSPR, that is: possessing a certain degree of causality and explicitly independent of the descriptor dimension.

Unrevealed structural requirements for auxin-like molecules by theoretical and experimental evidences.

An computational-biostatistical approach, supported by ab initio optimizations of auxin-like molecules, was used to find biologically meaningful relationships between quantum chemical variables and fresh bioassay's data. It is proven that the auxin-like recognition requires different molecular assembling states. We suggest that the carboxyl group is not the determining factor in explaining the biological auxin-like conduct. The biological effects depends essentially on the chemical condition of the ring system. The aim to find active molecules (quantum objects) via statistical grouping-analysis of molecular quantum similarity measures was verified by bioactivity assays. Next, this approach led to the discovery of a non-carboxylated active auxin-like molecule (2,6-dibromo-phenol). This is the first publication on structure activity relationship of auxin-like molecules, which relies on highly standardized bioassays of different auxins screened in parallel as well as analysed by multi-dimensional scaling.

Coulomb and overlap self-similarities: a comparative selectivity analysis of structure-function relationships for auxin-like molecules.

Auxins are defined mainly by a set of physiological actions, but the structure-effect relationship still is based on chemical intuition. Currently a well-defined auxin molecular structure is not available. The existence of different auxin binding proteins and mechanisms of auxin action, the wide diversity of the auxin molecules, and the pleiotropic effects of auxin imply a completely different mechanism as described for the animal hormone concept. Here, we present a computational approach dealing with semiempirical optimizations of the auxin molecules themselves, which represent a number of about 250 different chemical structures. Our approach uses molecular quantum similarity measures and additional quantum variables for the analysis of auxin-like molecules. The finding of similarities in molecules by focusing basically on their electron structure results in new insights in the relationship of the different auxin groups. Additional statistical analysis allows the identification of relationships between similarity groups and their biological activity, respectively. It is postulated that the auxin-like molecular recognition depends more on specific molecular assembling states than on a specific ring system or side chain.

Similarity approach to QSAR. Application to antimycobacterial benzoxazines.

The antimycobacterial activity in six series of substituted 3-phenyl-2H-benzoxazine-2,4(3H)-dithiones and 3-(phenyl)-4-thioxo-2H-benzoxazine-2,4(3H)-diones has been studied using a quantum molecular similarity approach. The approach is based on the use of fragment self-similarity measures as new universal molecular descriptors applicable for the design of novel theoretical QSAR models. Using this approach it was possible to show that while traditional QSAR models were able to describe the activity only within each of the six sets of studied molecules individually, the proposed approach is much more general and a single universal QSAR model describing the activity of all the 39 studied molecules in all the studied series together was built. The replacement of the oxo group by the thioxo group in position 4 on the benzoxazine ring of the antitubercular 3-(phenyl)-2H-benzoxazine-2,4(3H)-diones increases the activity, as well as the similar replacement in position 2.

Evaluación de un programa de manejo de factores de riesgo para el consumo de sustancias psicoactivas en mujeres adolescentes escolares de secundaria / Evaluation of a program of handling of factors of risk for the consumption of substances psicoactivas in school adolescent women of secondary

Se evaluaron los efectos de un programa preventivo del consumo de sustancias psicoactivas, basado en el manejo de cinco factores de riesgo: agresividad, habilidades sociales, autocontrol, autoestima y creencias irracionales. Fueron seleccionados al azar dos grupos por cada uno de los tres últimos años de secundaria, cada grupo constaba de 30 alumnas (n igual 180). El programa se aplicó a un grupo de cada año de estudios. Para cada año de estudios, no hubo diferencias significativas entre ambos grupos, en ninguna de las medidas de los factores de riesgo tomadas antes de la aplicación del programa. En cambio, en el postest, los grupos experimentales mostraron significativamente menos agresión; más autoestima; mejores habilidades sociales y mejor autocontrol que los respectivos grupos de control; pero sólo en el quinto año de secundaria se observó que el grupo experimental mostraba un menor nivel de creencias irracionales que el grupo control. No hubo diferencias significativas entre los puntajes pretest y postest de los grupos controles; excepto una reducción significativa en agresión en el quinto año. por otro lado, en los grupos experimentales hubo diferencias significativas en todos los puntajes pretest y postest en las direcciones esperadas.