Phenethylamine-derived new psychoactive substances 2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY: Investigations on their metabolic fate including isoenzyme activities and their toxicological detectability in urine screenings

Psychoactive substances of the 2C‐series are phenethylamine‐based designer drugs that can induce psychostimulant and hallucinogenic effects. The so‐called 2C‐FLY series contains rigidified methoxy groups integrated in a 2,3,6,7‐tetrahydrobenzo[1,2‐b:4,5‐b']difuran core. The aim of the presented work was to investigate the in vivo and in vitro metabolic fate including isoenzyme activities and toxicological detectability of the three new psychoactive substances (NPS) 2C‐E‐FLY, 2C‐EF‐FLY, and 2C‐T‐7‐FLY to allow clinical and forensic toxicologists the identification of these novel compounds. Rat urine, after oral administration, and pooled human liver S9 fraction (pS9) incubations were analyzed by liquid chromatography−high‐resolution tandem mass spectrometry (LC−HRMS/MS). By performing activity screenings, the human isoenzymes involved were identified and toxicological detectability in rat urine investigated using standard urine screening approaches (SUSAs) based on gas chromatography (GC)−MS, LC−MSn, and LC−HRMS/MS. In total, 32 metabolites were tentatively identified. Main metabolic steps consisted of hydroxylation and N‐acetylation. Phase I metabolic reactions were catalyzed by CYP2D6, 3A4, and FMO3 and N‐acetylation by NAT1 and NAT2. Methoxyamine was used as a trapping agent for detection of the deaminated metabolite formed by MAO‐A and B. Interindividual differences in the metabolism of the 2C‐FLY drugs could be caused by polymorphisms of enzymes involved or drug–drug interactions. All three SUSAs were shown to be suitable to detect an intake of these NPS but common metabolites of 2C‐E‐FLY and 2C‐EF‐FLY have to be considered during interpretation of analytical findings

Saberes e práticas de pais ou responsáveis no cuidado de pré-escolares

http://dx.doi.org/10.5902/217976926282Aim: to know the knowledge and practices of parents or guardians in hygiene and health care of preschool children who study in kindergartens in Palmeira das Missões/RS. Method: descriptive, explanatory research with qualitative approach. Data collection was done through questionary with semi-structured questions, composed of socio demographic information and with matters related to hygiene habits and daily care of children and their families. For data analysis, a thematic type of Content analyses was adopted in which two thematic axes emerged. Results: it was evident with the study that parents’ and guardians’ knowledge and practices on hygiene are associated with the families’ culture and economic condition. Conclusion: it is suggested closer approximation of nursing and health staff with families and Kindergarden Schools aiming at promoting health education actions.Objetivo: conocer los saberes y las prácticas de los padres o responsables en el cuidado en relación a la higiene y salud de niños en edad preescolar que estudian en escuelas de educación infantil en Palmeira das Missões/RS. Método: pesquisa exploratoria, descriptiva con abordaje cualitativa. La colecta de datos ocurrió a través de la aplicación de cuestiones semiestructuradas, compuestas por informaciones socio-demográficas relacionadas a los hábitos de higiene y cuidados diarios de los niños y de las familias. Se utilizó el Análisis de Contenidos del tipo temático que salieron dos ejes temáticos. Resultados: evidencio que los conocimientos y prácticas de higiene de los padres o responsables están asociados a las condiciones culturales y económicas de las familias. Conclusión: se sugiere mayor aproximación de la enfermería y de los equipos de salud con las familias y Escuelas de Educación Infantil a fin de promover las acciones de educación para la salud.http://dx.doi.org/10.5902/217976926282Objetivo: conhecer os saberes e práticas de pais ou responsáveis no cuidado à higiene e saúde de pré-escolares, que estudam nas escolas de educação infantil do município de Palmeira das Missões/RS. Método: pesquisa exploratória, descritiva com abordagem qualitativa. A coleta de dados se deu através da aplicação de um questionário com questões semiestruturadas, compostas por informações sociodemográficas relacionadas aos hábitos de higiene e cuidados diários das crianças e das famílias. Para análise dos dados, adotou-se a Análise de Conteúdo do tipo temática em que emergiram dois eixos temáticos. Resultados: evidenciou-se com o estudo que os saberes e práticas de higiene dos pais e ou responsáveis para com as crianças estão associados às condições culturais e econômicas das famílias. Conclusão: sugere-se maior aproximação da enfermagem e das equipes de saúde para com as famílias e Escolas de Educação Infantil, tendo em vista a promoção de ações de educação em saúde

Cell-biological studies of osmotic shock response in Streptomyces spp.

Most bacteria are likely to face osmotic challenges, but there is yet much to learn about how such environmental changes affect the architecture of bacterial cells. Here, we report a cell-biological study in model organisms of the genus Streptomyces, which are actinobacteria that grow in a highly polarized fashion to form branching hyphae. The characteristic apical growth of Streptomyces hyphae is orchestrated by protein assemblies, called polarisomes, which contain coiled-coil proteins DivIVA and Scy, and recruit cell wall synthesis complexes and the stressbearing cytoskeleton of FilP to the tip regions of the hyphae. We monitored cell growth and cell-architectural changes by time-lapse microscopy in osmotic upshift experiments. Hyperosmotic shock caused arrest of growth, loss of turgor, and hypercondensation of chromosomes. The recovery period was protracted, presumably due to the dehydrated state of the cytoplasm, before hyphae could restore their turgor and start to grow again. In most hyphae, this regrowth did not take place at the original hyphal tips. Instead, cell polarity was reprogrammed, and polarisomes were redistributed to new sites, leading to the emergence of multiple lateral branches from which growth occurred. Factors known to regulate the branching pattern of Streptomyces hyphae, such as the serine/threonine kinase AfsK and Scy, were not involved in reprogramming of cell polarity, indicating that different mechanisms may act under different environmental conditions to control hyphal branching. Our observations of hyphal morphology during the stress response indicate that turgor and sufficient hydration of cytoplasm are required for Streptomyces tip growth

Phenethylamine-derived new psychoactive substances 2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY: Investigations on their metabolic fate including isoenzyme activities and their toxicological detectability in urine screenings

Psychoactive substances of the 2C-series are phenethylamine-based designer drugs that can induce psychostimulant and hallucinogenic effects. The so-called 2C-FLY series contains rigidified methoxy groups integrated in a 2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran core. The aim of the presented work was to investigate the in vivo and in vitro metabolic fate including isoenzyme activities and toxicological detectability of the three new psychoactive substances (NPS) 2C-E-FLY, 2C-EF-FLY, and 2C-T-7-FLY to allow clinical and forensic toxicologists the identification of these novel compounds. Rat urine, after oral administration, and pooled human liver S9 fraction (pS9) incubations were analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS). By performing activity screenings, the human isoenzymes involved were identified and toxicological detectability in rat urine investigated using standard urine screening approaches (SUSAs) based on gas chromatography (GC)-MS, LC-MSn, and LC-HRMS/MS. In total, 32 metabolites were tentatively identified. Main metabolic steps consisted of hydroxylation and N acetylation. Phase I metabolic reactions were catalyzed by CYP2D6, 3A4, and FMO3 and N-acetylation by NAT1 and 2. Methoxyamine was used as a trapping agent for detection of the deaminated metabolite formed by MAO-A and B. Interindividual differences in the metabolism of the 2C-FLY drugs could be caused by polymorphisms of enzymes involved or drug-drug interactions. All three SUSAs were shown to be suitable to detect an intake of these NPS but common metabolites of 2C-E-FLY and 2C-EF-FLY have to be considered during interpretation of analytical findings

Assessing soil ecosystem processes – biodiversity relationships in a nature reserve in Central Europe

Background and aims: Plant diversity – ecosystem processes relationships are essential to our understanding of ecosystem functioning. We aimed at disentangling the nature of such relationships in a mesotrophic grassland that was highly heterogeneous with regards to nutrient availability. Methods: Rather than targeting primary productivity, like most existing reports do, we focused our study on belowground ecosystem processes. We tested three, largely mutually exclusive, hypotheses of ecosystem processes relationships: the redundancy hypothesis, the insurance hypothesis and the centrifugal model hypothesis. We sampled the grassland twice within a single plant growing season in a spatially explicit way and assayed the soil for nitrification, urease activity, relative bacterial activity and a microbial community profile based on respiration while we simultaneously assessed plant diversity. Results: Results supported the centrifugal model. We justify the lack of support for the other two hypotheses on the basis of having conducted an observational study in an environmentally heterogeneous site. Conclusions: The centrifugal model hypothesis appears to be a very good predictive model for explaining diversity in observational, heterogeneous studies. The specific study represents one of the few observational studies that consider measures of ecosystem functioning other than primary productivity

Elucidating the Role of Ligand Engineering on Local and Macroscopic Charge‐Carrier Transport in NaBiS₂ Nanocrystal Thin Films

Publication status: PublishedFunder: Helmholtz International Research School “Hybrid Integrated Systems for Conversion of Solar Energy”Funder: Agency for Science, Technology and Research, SingaporeFunder: Institute of Materials Research and Engineering; doi: http://dx.doi.org/10.13039/501100001453Funder: Ministry of Education, TaiwanAbstractTernary chalcogenides have emerged as potential candidates for ultrathin photovoltaics, and NaBiS2 nanocrystals (NCs) have gained appeal because of their months‐long phase‐stability in air, high absorption coefficients &gt;105 cm−1, and a pseudo‐direct bandgap of 1.4 eV. However, previous investigations into NaBiS2 NCs used long‐chain organic ligands separating individual NCs during synthesis, which severely limits macroscopic charge‐carrier transport. In this work, these long‐chain ligands are exchanged for short iodide‐based ligands, allowing to understand the macroscopic charge‐carrier transport properties of NaBiS2 and evaluate its photovoltaic potential in more depth. It is found that ligand exchange results in simultaneous improvements in intra‐NC (microscopic) and inter‐NC (macroscopic) mobilities, while charge‐carrier localization still takes place, which places a fundamental limit on the transport lengths achievable. Despite this limitation, the high absorption coefficients enable ultrathin (55 nm thick) solar absorbers to be used in photovoltaic devices, which have peak external quantum efficiencies &gt; 50%. In addition, temperature‐dependent transient current measurements uncover a small activation energy barrier of 88 meV for ion migration, which accounts for the strongly hysteretic behavior of NaBiS2 photovoltaic devices. This work not only reveals how the charge‐carrier transport properties of NaBiS2 NCs over several length and time scales are influenced by ligand engineering, but also unveils the facile ionic transport in this material, which limits the potential of NaBiS2 in photovoltaics. On the other hand, the discovery shows that there are opportunities to use this material in memristors, electrolytes, and other applications requiring ionic conduction.</jats:p