Wastewater surveillance to assess cocaine and methylenedioxymethamphetamine use trends during a major music festival in Brazil.

Wastewater-based epidemiology was applied in northeastern Brazil during a dance festival, revealing that cocaine consumption doubled during the event days. The daily drug loads were 0.95 ± 0.03 to 11.4 ± 0.4 g/day for BE, 1.8 ± 0.4 to 7.6 ± 0.3 g/day for COC, 0.04 ± 0.02 to 0.19 ± 0.02 g/day for COE, and 0.08 ± 0.02 to 0.80 ± 0.02 g/day for MDMA.

This study employed the wastewater­based epidemiology (WBE) strategy to investigate cocaine (COC) and ecstasy (MDMA) usage during Carnatal festival in Rio Grande do Norte, Brazil. Wastewater samples were collected over the four festival days (December 12­15, 2019), as well as during corresponding days before and after the event. The samples underwent filtration, acidification, solid­phase extraction (SPE) for pre­concentration, and analysis using ultra­high­performance liquid chromatography­tandem mass spectrometry (UHPLC­MS/MS) with calibration using deuterated internal standards. The measured concentration ranges in the wastewater samples were as follows: benzoylecgonine (BE, a metabolite of COC use) ranged from 760 ± 30 to 8914 ± 252 ng/L, COC (non­metabolized or directly discharged) ranged from 1182 ± 25 to 6,760 ± 95 ng/L, cocaethylene (COE, a metabolite of alcohol­COC use) ranged from 21 ± 10 to 161 ± 10 ng/L, and MDMA (ecstasy) ranged from 18 ± 5 to 613 ± 15 ng/L. Daily wastewater loads were estimated as 0.81 ± 0.03 to 11.69 ± 0.33 g/day for BE, 1.42 ± 0.03 to 8.06 ± 0.11 g/day for COC, 0.02 ± 0.01 to 0.21 ± 0.01 g/day for COE, and 0.02 ± 0.01 to 0.80 ± 0.02 g/day for MDMA. Notably, COE and MDMA were only detected above the quantification limit during the festival days. The data enable estimating that COC consumption doubled during the event days. The COC/BE ratio indicated likely drug disposals on the event's last day and the subsequent week. The study's findings shed light on illicit substance consumption, assisting in public health programs and combating drug trafficking efforts.

Lacticaseibacillus casei decrease long-chain fatty acids and most substances in an experimental model of intestinal mucositis.

PURPOSE: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. METHODS: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. RESULTS: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. CONCLUSIONS: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.

Challenges encountered by natural repellents: Since obtaining until the final product.

Vector-borne diseases, particularly the arboviruses dengue, Zika, chikungunya, and yellow fever caused by the Aedes aegypti mosquito, have been driving the use of repellents worldwide. The most representative synthetic repellent, DEET stands out as the market's oldest and most efficient repellent. It is considered a reference standard but presents considerable toxicity, not recommended for children up to 6 months old and pregnant women. For this reason, alternatives have been sought, and natural repellents derived mainly from essential oils have been studied, highlighting the essential oils of lemon (Corymbia citriodora), citronella (Cympobogon sp.), Andiroba (Carapa guianensis). However, the development and commercialization of products containing natural repellents are significantly lower when compared to DEET and other synthetic repellents. In order to understand the reasons, aspects related to safety, mechanism of action, efficacy as well development and complexity of the products were evaluated. It is concluded that, as for safety, there is lacking information in the literature regarding the effects on non-target organisms and robust toxicity data. The mechanism of action is based on theories, with less information on the exact mode of action, molecular targets, and interaction with the olfactory and taste receptors of insects. Despite being a current trend to search for actives from natural sources highly present in essential oils, however they reduced action time because due to rapid evaporation after application to the skin, thus requiring repellent vehicles. The development and complexity related to these products bring challenging aspects, beginning on the plant cultivation and extraction processes to produce essential oils with a more homogeneous chemical composition towards the formulation stabilization processes due to fast evaporation and short action time, with the use of pharmaceutical technology such as encapsulation techniques.

Lacticaseibacillus casei decrease long-chain fatty acids and most substances in an experimental model of intestinal mucositis

Purpose: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. Methods: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. Results: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. Conclusions: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.

Erythrina velutina Willd. alkaloids: Piecing biosynthesis together from transcriptome analysis and metabolite profiling of seeds and leaves.

Introduction: Natural products of pharmaceutical interest often do not reach the drug market due to the associated low yields and difficult extraction. Knowledge of biosynthetic pathways is a key element in the development of biotechnological strategies for plant specialized metabolite production. Erythrina species are mainly used as central nervous system depressants in folk medicine and are important sources of bioactive tetracyclic benzylisoquinoline alkaloids (BIAs), which can act on several pathology-related biological targets. Objectives: In this sense, in an unprecedented approach used with a non-model Fabaceae species grown in its unique arid natural habitat, a combined transcriptome and metabolome analyses (seeds and leaves) is presented. Methods: The Next Generation Sequencing-based transcriptome (de novo RNA sequencing) was carried out in a NextSeq 500 platform. Regarding metabolite profiling, the High-resolution Liquid Chromatography was coupled to DAD and a micrOTOF-QII mass spectrometer by using electrospray ionization (ESI) and Time of Flight (TOF) analyzer. The tandem MS/MS data were processed and analyzed through Molecular Networking approach. Results: This detailed macro and micromolecular approach applied to seeds and leaves of E. velutina revealed 42 alkaloids, several of them unique. Based on the combined evidence, 24 gene candidates were put together in a putative pathway leading to the singular alkaloid diversity of this species. Conclusion: Overall, these results could contribute by indicating potential biotechnological targets for modulation of erythrina alkaloids biosynthesis as well as improve molecular databases with omic data from a non-model medicinal plant, and reveal an interesting chemical diversity of Erythrina BIA harvested in Caatinga.