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BackgroundPatient safety is a fundamental aspect of health care practice across global health systems. Safe practices, which include incident reporting systems, have proven valuable in preventing the recurrence of safety incidents. However, the accessibility of this tool for health care discipline students is not consistent, limiting their acquisition of competencies. In addition, there is no tools to familiarize students with analyzing safety incidents. Gamification has emerged as an effective strategy in health care education. ObjectiveThis study aims to develop an incident reporting system tailored to the specific needs of health care discipline students, named Safety Incident Report System for Students. Secondary objectives included studying the performance of different groups of students in the use of the platform and training them on the correct procedures for reporting. MethodsThis was an observational study carried out in 3 phases. Phase 1 consisted of the development of the web-based platform and the incident registration form. For this purpose, systems already developed and in use in Spain were taken as a basis. During phase 2, a total of 223 students in medicine and nursing with clinical internships from universities in Argentina, Brazil, Colombia, Ecuador, and Spain received an introductory seminar and were given access to the platform. Phase 3 ran in parallel and involved evaluation and feedback of the reports received as well as the opportunity to submit the students’ opinion on the process. Descriptive statistics were obtained to gain information about the incidents, and mean comparisons by groups were performed to analyze the scores obtained. ResultsThe final form was divided into 9 sections and consisted of 48 questions that allowed for introducing data about the incident, its causes, and proposals for an improvement plan. The platform included a personal dashboard displaying submitted reports, average scores, progression, and score rankings. A total of 105 students participated, submitting 147 reports. Incidents were mainly reported in the hospital setting, with complications of care (87/346, 25.1%) and effects of medication or medical products (82/346, 23.7%) being predominant. The most repeated causes were related confusion, oversight, or distractions (49/147, 33.3%) and absence of process verification (44/147, 29.9%). Statistically significant differences were observed between the mean final scores received by country (P

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of commonly targeted receptors. Unspecific chemotherapy is currently the main therapeutic option, with poor results. Another major challenge is the frequent appearance of brain metastasis (BM) associated with a significant decrease in patient overall survival. The treatment of BM is even more challenging due to the presence of the blood-brain barrier (BBB). Here, we present a dual-acting peptide (PepH3-vCPP2319) designed to tackle TNBC/BM, in which a TNBC-specific anticancer peptide (ACP) motif (vCPP2319) is joined to a BBB peptide shuttle (BBBpS) motif (PepH3). PepH3-vCPP2319 demonstrated selectivity and efficiency in eliminating TNBC both in monolayers (IC50≈5.0 µM) and in spheroids (IC50≈25.0 µM), with no stringent toxicity toward noncancerous cell lines and red blood cells (RBCs). PepH3-vCPP2319 was also able to cross the BBB in vitro and penetrate the brain in vivo, and was stable in serum with a half-life above 120 min. Tumor cell-peptide interaction is fast, with quick peptide internalization via clathrin-mediated endocytosis without membrane disruption. Upon internalization, the peptide is detected in the nucleus and the cytoplasm, indicating a multi-targeted mechanism of action that ultimately induces irreversible cell damage and apoptosis. In conclusion, we have designed a dual-acting peptide capable of brain penetration and TNBC cell elimination, thus expanding the drug arsenal to fight this BC subtype and its BM.

Tomato leaf curl New Delhi virus (ToLCNDV) is a begomovirus causing significant melon (Cucumis melo) crop losses globally. This study aims to map the ToLCNDV resistance in the PI 414723 melon accession, previously identified and characterized through phenotypic studies, thereby exploring shared genomic regions with the established resistant source WM-7. In the present study, WM-7 and PI 414723 were crossed with the susceptible accessions ‘Rochet’ and ‘Blanco’ respectively, to generate F1 hybrids. These hybrids were self-pollinated to generate the populations for mapping the ToLCNDV resistance region and designing markers for marker-assisted selection. Disease evaluation included visual symptom scoring, viral-load quantification and tissue printing. Genotyping-by-sequencing and SNP markers were used for quantitative trait loci (QTL) mapping. For genetic analysis, qPCR and bulked segregant RNA-seq (BSR-seq) were performed. Gene expression was assessed using RNA-seq, and qRT-PCR was used for confirmation. The research narrows the candidate region for resistance in WM-7 and identifies overlapping QTLs on chromosome 11 in PI 414723, found in the region of the DNA primase large subunit. BSR-seq and expression analyses highlight potential regulatory roles of chromosome 2 in conferring resistance. Differential expression was confirmed for six genes in the candidate region on chromosome 2. This study confirms the existence of common resistance genes in PI 414723 and WM-7.

This article presents the EasyComVi Tool, an interactive application developed to facilitate the study of Computer Vision for students enrolled in an Engineering Master degree with a Distance Learning methodology. The main objective of this tool is to enable students in subjects related to Computer Vision with a distance learning methodology, to acquire a better understanding of different concepts about the subject studied in a theoretical way, through its interactive visual illustration, in an autonomous way. This tool offers the students the possibility to visualize the results of applying different image processing operations to various example images selecting the value of a set of input parameters. The usefulness and applicability of the tool has been evaluated by means of a questionnaire disseminated among the students of a subject on Computer Vision in a Master's degree in Industrial Engineering. This paper presents the preliminary results obtained in the study carried out, which are very promising and encourage further research in this work.

The Green Pact signed by the European Union establishes a trend towards renewable energies to combat the greenhouse gas emissions. Among the technologies used to produce this type of energy, wind power generation technology stands out, which, in countries such as Spain, already has significant installed power. The main problems posed by this technology plans are the uncertainty intervals of wind power and its inclusion in the electricity market, due to the complex price system that does not always favor the producers. The main purpose of this research is to promote the installation of more wind power plants. For this, the installation of cryptocurrency mining equipment is proposed, which will be powered by the generation produced by these wind power plants. The article analyzes the production of cryptocurrencies is a growing business. In the research process, the latest cryptocurrency mining equipment is evaluated. It is analyzed which equipment is the most suitable for its installation in the wind power plant and an economic study is made for the construction project of a large wind power plant. Finally, it will be seen that in this way the amortization time of the facilities decreases and also the project is more attractive for the investor since they can decide between injecting energy into the electrical network or mining cryptocurrencies. If a wind power plant invests in cryptocurrency mining in parallel to the production of electrical energy for the grid, it can decide when to enter the electricity market pool or engage in mining. In this way, the idea of building many more wind power plants becomes more attractive. This would lead to a market where this renewable energy would be much more abundant and the price curve would shift to a lower price, as well as a significant reduction in greenhouse emissions.

Resumen: La rotura del seno de Valsalva es una fístula que conecta un seno de Valsalva aórtico con una cavidad cardiaca generalmente derecha, la aurícula o el ventrículo, ocasionando un cortocircuito I-D que puede resultar en insuficiencia cardiaca. Se diagnostica por ecocardiograma y requiere cirugía para evitar complicaciones como la insuficiencia cardiaca congestiva. Presentamos un caso diagnosticado al nacer tras un embarazo normal, parto eutócico y ecografías fetales normales. Al 2.° día de vida se ausculta soplo continuo y se aprecia en ecocardiograma la presencia de un túnel de 5 mm de diámetro con flujo pulsátil que se origina del seno coronariano derecho y termina en orejuela derecha. El paciente fue intervenido a los 3 meses de vida. Se realizó abordaje combinado por aurícula derecha y aorta ascendente. Se practicó cierre del orificio distal y resección parcial de la pared del aneurisma con resutura. Postoperatorio sin incidencias. Ecocardiograma de control normal. La rotura del seno de Valsalva es una cardiopatía rara que puede provocar cortocircuito I-D significativo e insuficiencia cardiaca. La cirugía restaura la normalidad respetando la válvula aórtica y la arteria coronaria derecha. Es el caso más joven reportado en la literatura. Abstract: Rupture of a sinus of Valsalva is a fistula connecting an aortic sinus of Valsalva with a cardiac chamber, generally right either the atrium or the ventricle, resulting in L-R shunt that may induce congestive heart failure. The lesion is diagnosed by echocardiogram and early surgery is always granted due to the high risk of complications like congestive heart failure. We present a case diagnosed at birth after normal pregnancy and delivery and normal fetal echocardiograms. At 2 nd day of life, a continuous murmur was evident. Echocardiogram showed a 5mm-diameter tunnel-like structure with pulsatile flow originating from the right sinus of Valsalva and ending at the right atrial appendage. At the age of 3 months, the patient was operated upon. A combined approach was used through the ascending aorta and the right atrium. It consisted on closure of the distal orifice in the atrium and partial resection of the aneurysm wall and suture. Postoperative course was uneventful with normal postoperative echocardiogram. Rupture of a sinus of Valsalva is a rare congenital lesion that may result in significant L-R shunt and congestive heart failure. Surgery restores normalcy preserving aortic valve function and coronary flow. This is the youngest reported case in the literature.

Methylone is one of the most common synthetic cathinones popularized as a substitute for 3,4-methylenedioxymethamphetamine (MDMA, midomafetamine) owing to its similar effects among users. Both psychostimulants exhibit similar chemistry (i.e., methylone is a β-keto analog of MDMA) and mechanisms of action. Currently, the pharmacology of methylone remains scarcely explored in humans. Herein, we aimed to evaluate the acute pharmacological effects of methylone and its abuse potential in humans when compared with that of MDMA following oral administration under controlled conditions. Seventeen participants of both sexes (14 males, 3 females) with a previous history of psychostimulant use completed a randomized, double-blind, placebo-controlled, crossover clinical trial. Participants received a single oral dose of 200 mg of methylone, 100 mg of MDMA, and a placebo. The variables included physiological effects (blood pressure, heart rate, oral temperature, pupil diameter), subjective effects using visual analog scales (VAS), the short form of the Addiction Research Center Inventory (ARCI), the Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire (VESSPA-SSE), and the Sensitivity to Drug Reinforcement Questionnaire (SDRQ), and psychomotor performance (Maddox wing, psychomotor vigilance task). We observed that methylone could significantly increase blood pressure and heart rate and induce pleasurable effects, such as stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone exhibited an effect profile similar to MDMA, with a faster overall onset and earlier disappearance of subjective effects. These results suggest that abuse potential of methylone is comparable to that of MDMA in humans.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT05488171; Identifier: NCT05488171.

Given the current load and power density limitations in electric vehicle (EV) storage systems, it is necessary to study hybrid and control systems in order to optimize their performance and present themselves as a real alternative to internal combustion engine (ICE) vehicles. This implies the development of legislation and specific regulations that enable the research and development of these storage and management systems for hybrid systems. The research presented here aims to analyze the implementation of the SMES (Superconducting Magnetic Energy Storage) energy storage system for the future of electric vehicles. To do this, the need for a hybrid storage system has been taken into account, with several regulatory options, such as the reduction of rates or the promotion of private investments, which allow the technological development of EVs. What is sought is to achieve the market share proposed by the different countries to reduce Greenhouse Gases (GHG), according to their objectives. This approach must be taken from the legislative and regulatory perspective, specific to EVs and charging points, of several countries or regions with different cultures, management models and implementation potential, such as the United States of America (USA), Europe and China. This analysis is associated with the economic study of costs that this storage system may involve in the implementation of EVs to replace ICE vehicles, resulting in possible economic benefits as well as the environmental benefits of the use of EVs. In this analysis, the current high cost of using a hybrid system of these characteristics can be observed with the comparison of three EVs, as well as current data on GHG emissions produced by transport. All this leads to a series of advantages and disadvantages that must be taken into account in order to achieve the objectives that countries have in the coming decades of EV diffusion.

Cannabis is the most widely consumed illegal drug in the world and synthetic cannabinoids are increasingly gaining popularity and replacing traditional cannabis. These substances are a type of new psychoactive substance that mimics the cannabis effects but often are more severe. Since, people with opioids use disorder use widely cannabis, they are a population vulnerable to use synthetic cannabinoids. In addition, these substances are not detected by the standard test used in the clinical practice and drug-checking is more common in recreational settings. A cross-sectional study with samples of 301 opioid use disorder individuals was carried out at the addiction care services from Barcelona and Badalona. Urinalysis was performed by high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high –resolution mass spectrometry (UHPLC-HRMS). Any synthetic cannabinoid was detected in 4.3% of the individuals and in 23% of these samples two or more synthetic cannabinoids were detected. Among the 8 different synthetic cannabinoids detected, most common were JWH-032 and JWH-122. Natural cannabis was detected in the 18.6% of the samples and only in the 0.7% of them THC was identified. Several different synthetic cannabinoids were detected and a non-negligible percentage of natural cannabis was detected among our sample. Our results suggest that the use of synthetic cannabinoids may be related to the avoidance of detection. In the absence of methods for the detection of these substances in clinical practice, there are insufficient data and knowledge making difficult to understand about this phenomenon among opioid use disorder population.

This study presents a validated GC-MS/MS method for the detection and quantification of 4-chloromethcathinone or clephedrone (4-CMC), N-ethyl Pentedrone (NEP), and N-ethyl Hexedrone (NEH, also named HEXEN) in oral fluid and sweat and verifies its feasibility in determining human oral fluid concentrations and pharmacokinetics following the administration of 100 mg of 4-CMC orally and 30 mg of NEP and NEH intranasally. A total of 48 oral fluid and 12 sweat samples were collected from six consumers. After the addition of 5 μL of methylone-d3 and 200 μL of 0.5 M ammonium hydrogen carbonate, an L/L extraction was carried out using ethyl acetate. The samples, dried under a nitrogen flow, were then derivatized with pentafluoropropionic anhydride and dried again. One microliter of the sample reconstituted in 50 μL of ethyl acetate was injected into GC-MS/MS. The method was fully validated according to international guidelines. Our results showed how, in oral fluid, the two cathinones taken intranasally were absorbed very rapidly, within the first hour, when compared with the 4-CMC which reached its maximum concentration peak in the first three hours. We observed that these cathinones were excreted in sweat in an amount equivalent to approximately 0.3% of the administered dose for 4-CMC and NEP. The total NEH excreted in sweat 4 h after administration was approximately 0.2% of the administered dose. Our results provide, for the first time, preliminary information about the disposition of these synthetic cathinones in the consumers’ oral fluid and sweat after controlled administration.

Modern agriculture has boosted the production of food based on the use of pesticides and fertilizers and improved plant varieties. However, the impact of some such technologies is high and not sustainable in the long term. Although the importance of rhizospheres in final plant performance, nutrient cycling, and ecosystems is well recognized, there is still a lack of information on the interactions of their main players. In this paper, four accessions of pepper are studied at the rhizosphere and root level under two farming systems: organic and conventional. Variations in soil traits, such as induced respiration, enzymatic activities, microbial counts, and metabolism of nitrogen at the rhizosphere and bulk soil, as well as measures of root morphology and plant production, are presented. The results showed differences for the evaluated traits between organic and conventional management, both at the rhizosphere and bulk soil levels. Organic farming showed higher microbial counts, enzymatic activities, and nitrogen mobilization. Our results also showed how some genotypes, such as Serrano or Piquillo, modified the properties of the rhizospheres in a very genotype-dependent way. This specificity of the soil–plant interaction should be considered for future breeding programs for soil-tailored agriculture.

A two-dimensional (2D) Sb-modified screen-printed carbon nanofibers electrode (2D Sbexf-SPCNFE) was developed to improve the stripping voltammetric determination of Cd(II) and Pb(II), taking advantage of the synergistic effect between the two nanomaterials. The surface morphology of the 2D Sbexf-SPCNFE was investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Raman spectroscopy. The analytical performance of 2D Sbexf-SPCNFE was compared to those presented by screen-printed carbon electrodes modified with 2D Sbexf (2D Sbexf-SPCE) and the corresponding bare electrodes: screen-printed carbon nanofibers electrode (SPCNFEbare) and screen-printed carbon electrode (SPCEbare). After optimizing the experimental conditions, the 2D Sbexf-SPCNFE exhibited much better analytical parameters compared to the other assessed sensors. Analysis in 0.01 mol L−1 HCl (pH = 2) using 2D Sbexf-SPCNFE showed excellent linear behavior in the concentration range of 2.9 to 85.0 µg L−1 and 0.3 to 82.0 µg L−1 for Cd(II) and Pb(II), respectively. The limits of detection after 240 s deposition time for Cd(II) and Pb(II) were 0.9 and 0.1 µg L−1, and sensitivities between 1.5 and 3 times higher than those displayed by SPCEbare, SPCNFEbare, and 2D Sbexf-SPCE were obtained. Finally, the 2D Sbexf-SPCNFE was successfully applied to the determination of Cd(II) and Pb(II) traces in a certified estuarine water sample.

The aim of this study was to determine the excretion of methylone and its metabolites in sweat following the ingestion of increasing controlled doses of 50, 100, 150 and 200 mg of methylone to twelve healthy volunteers involved in a clinical trial. Methylone and its metabolites 4-hydroxy-3-methoxy-N-methylcathinone (HMMC) and 3,4-methylenedioxycathinone (MDC) were analyzed in sweat patches by liquid chromatography–tandem mass spectrometry. Methylone and MDC were detected in sweat at 2 h and reached their highest accumulation (Cmax) at 24 h after the administration of 50, 100, 150 and 200 mg doses. In contrast, HMMC was not detectable at any time interval after each dose. Sweat proved to be a suitable matrix for methylone and its metabolites’ determination in clinical and toxicological studies, providing a concentration that reveals recent drug consumption.

The aim of this study was to investigate methylone and its metabolites concentration in oral fluid following controlled increasing doses, focusing on the effect of oral fluid pH. Samples were obtained from a clinical trial where twelve healthy volunteers participated after ingestion of 50, 100, 150 and 200 mg of methylone. Concentration of methylone and its metabolites 4-hydroxy-3-methoxy-N-methylcathinone (HMMC) and 3,4-methylenedioxycathinone in oral fluid were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Pharmacokinetic parameters were estimated, and the oral fluid-to-plasma ratio (OF/P) at each time interval was calculated and correlated with the oral fluid pH using data from our previous study in plasma. Methylone was detected at all time intervals after each dose; MDC and HMMC were not detectable after the lowest dose. Oral fluid concentrations of methylone ranged between 88.3–503.8, 85.5–5002.3, 182.8–13,201.8 and 214.6–22,684.6 ng/mL following 50, 100, 150 and 200 mg doses, respectively, peaked between 1.5 and 2.0 h, and were followed by a progressive decrease. Oral fluid pH was demonstrated to be affected by methylone administration. Oral fluid is a valid alternative to plasma for methylone determination for clinical and toxicological studies, allowing for a simple, easy and non-invasive sample collection.

Las películas comerciales se utilizan cada vez más como método de enseñanza en muchas disciplinas universitarias. En medicina son un recurso importante para enseñar algunos aspectos médicos al ser ilustrados usando el lenguaje cinematográfico. La relación médico-paciente, los dilemas éticos o el profesionalismo son alguno de los temas más presentes en las películas comerciales. En el presente manuscrito tratamos del interés del cine comercial en el campo de la farmacología, cuyo conocimiento está en la frontera de los campos básicos y clínicos. Revisamos el uso de películas para mejorar la enseñanza y aprendizaje de la farmacología y la farmacología clínica. Por ello describimos algunas películas que son especialmente útiles para este propósito, como Awakenings / Despertares de 1990, Lorenzo’s oil / El aceite de Lorenzo de 1992, The constant gardener / El jardinero fiel de 2005 y más recientemente Dallas Buyers Club (2013). Se incluyen algunas recomendaciones para su uso óptimo en la enseñanza de farmacología y farmacología clínica.

The picophytoplankton Synechococcus is a globally abundant autotroph that contributes significantly to primary production in the oceans and coastal areas. These cyanobacteria constitute a diverse genus of organisms that have developed independent niche spaces throughout aquatic environments. Here, we use the 16S V3–V4 rRNA gene region and flow cytometry to explore the diversity of Synechococcus within the picophytoplankton community in the Gullmar Fjord, on the west coast of Sweden. We conducted a station-based 1-year time series and two transect studies of the fjord. Our analysis revealed that within the large number of Synechococcus amplicon sequence variants (ASVs; 239 in total), prevalent ASVs phylogenetically clustered with clade representatives in both marine subcluster 5.1 and 5.2. The near-surface composition of ASVs shifted from spring to summer, when a 5.1 subcluster dominated community developed along with elevated Synechococcus abundances up to 9.3 × 104 cells ml–1. This seasonal dominance by subcluster 5.1 was observed over the length of the fjord (25 km), where shifts in community composition were associated with increasing depth. Unexpectedly, the community shift was not associated with changes in salinity. Synechococcus abundance dynamics also differed from that of the photosynthetic picoeukaryote community. These results highlight how seasonal variations in environmental conditions influence the dynamics of Synechococcus clades in a high latitude threshold fjord.

BackgroundMajor depressive disorder (MDD) and cocaine use disorder (CUD) are related with disability and high mortality rates. The assessment and treatment of psychiatric comorbidity is challenging due to its high prevalence and its clinical severity, mostly due to suicide rates and the presence of medical comorbidities. The aim of this study is to investigate differences in brain derived neurotrophic factor (BDNF) and cortisol plasmatic levels in patients diagnosed with CUD-primary-MDD and CUD-induced-MDD and also to compare them to a sample of MDD patients (without cocaine use), a sample of CUD (without MDD), and a group of healthy controls (HC) after a stress challenge.MethodsA total of 46 subjects were included: MDD (n = 6), CUD (n = 15), CUD-primary-MDD (n = 16), CUD-induced-MDD (n = 9), and 21 HC. Psychiatric comorbidity was assessed with the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders IV (PRISM-IV), and depression severity was measured with the Hamilton Depression Rating Scale (HDRS). Patients were administered the Trier Social Stress Test (TSST) before and after the biological measures, including BDNF, and cortisol levels were obtained.ResultsAfter the TSST, Cohen's d values between CUD-primary-MDD and CUD-induced-MDD increased in each assessment from 0.19 post-TSST to 2.04 post-90-TSST. Pairwise differences among CUD-induced-MDD and both MDD and HC groups had also a large effect size value in post-30-TSST and post-90-TSST. In the case of the BDNF concentrations, CUD-primary-MDD and CUD-induced-MDD in post-90-TSST (12,627.27 ± 5488.09 vs.17,144.84 ± 6581.06, respectively) had a large effect size (0.77).ConclusionResults suggest a different pathogenesis for CUD-induced-MDD with higher levels of cortisol and BDNF compared with CUD-primary-MDD. Such variations should imply different approaches in treatment.

The methodological strategy of project-based learning has been implemented in Analytical Chemistry laboratories, specifically in the subject of Basic Analytical Chemistry Laboratory of the Chemistry Degree, with the aim of contextualizing the practices, improving the critical evaluation of the results obtained and promoting collaborative work. For this purpose, five different topics have been proposed for students to elaborate a project, setting out its objective and the analytical determinations (parameters and samples) necessary to achieve it. The implementation of these projects has facilitated the generation of a greater volume of interrelated results that has allowed the students to work on the critical evaluation of the results in greater depth. The achievement of the objectives proposed for the implementation of the PBL has been demonstrated by means of anonymous surveys to the students and by comparison with other four groups of the same subject taught during the same academic year.

ABSTRACT A considerable fraction of organic matter derived from photosynthesis in the euphotic zone settles into the ocean’s interior and, as it progresses, is degraded by diverse microbial consortia that utilize a suite of extracellular enzymes and membrane transporters. Still, the molecular details that regulate carbon cycling across depths remain little explored. As stratification in fjords has made them attractive models to explore patterns in biological oceanography, we here analyzed bacterial and archaeal transcription in samples from five depth layers in the Gullmar Fjord, Sweden. Transcriptional variation over depth correlated with gradients in chlorophyll a and nutrient concentrations. Differences in transcription between sampling dates (summer and early autumn) were strongly correlated with ammonium concentrations, which potentially was linked with a stronger influence of (micro-)zooplankton grazing in summer. Transcriptional investment in carbohydrate-active enzymes (CAZymes) decreased with depth and shifted toward peptidases, partly a result of elevated CAZyme transcription by Flavobacteriales, Cellvibrionales, and Synechococcales at 2 to 25 m and a dominance of peptidase transcription by Alteromonadales and Rhodobacterales from 50 m down. In particular, CAZymes for chitin, laminarin, and glycogen were important. High levels of transcription of ammonium transporter genes by Thaumarchaeota at depth (up to 18% of total transcription), along with the genes for ammonia oxidation and CO2 fixation, indicated that chemolithoautotrophy contributed to the carbon flux in the fjord. The taxon-specific expression of functional genes for processing of the marine pool of dissolved organic matter and inorganic nutrients across depths emphasizes the importance of different microbial foraging mechanisms over spatiotemporal scales for shaping biogeochemical cycles. IMPORTANCE It is generally recognized that stratification in the ocean strongly influences both the community composition and the distribution of ecological functions of microbial communities, which in turn are expected to shape the biogeochemical cycling of essential elements over depth. Here, we used metatranscriptomics analysis to infer molecular detail on the distribution of gene systems central to the utilization of organic matter in a stratified marine system. We thereby uncovered that pronounced shifts in the transcription of genes encoding CAZymes, peptidases, and membrane transporters occurred over depth among key prokaryotic orders. This implies that sequential utilization and transformation of organic matter through the water column is a key feature that ultimately influences the efficiency of the biological carbon pump.

Resumen: Presentamos un caso clínico de coartación de aorta compleja. Fue intervenida a los 15 días de vida realizando resección de coartación y anastomosis término-terminal extendida. Al alta presentaba un gradiente de 20 mm Hg. En el seguimiento se hizo evidente la presencia de recoartación con hipertensión proximal y gradiente de 55 mm Hg. La aortografía confirmó la hipoplasia del arco transverso entre la arteria carótida y subclavia izquierdas. Se reintervino a los 3 meses. Se realizó ampliación del arco con flap de subclavia invertido dirigido al arco transverso y el origen de la carótida izquierda. Se respetó la zona yuxtaductal que estaba bien resuelta. El resultado fue satisfactorio. La técnica de flap de subclavia invertido es una alternativa eficaz para la reparación de coartación de aorta asociada a hipoplasia de arco. Abstract: We present a case report of a newborn with complex aortic coarctation. She was operated upon at the age of 15 days. Repair consisted of coarctation resection and extended end-to-end anastomosis. At discharge, a 20-mmHg gradient was present. At follow-up, it was evident the presence of re-coarctation with proximal hypertension and 55 mmHg gradient. Angiography confirmed hypoplasia of the transverse aortic arch between left carotid and subclavian arteries. At 3 months of age, she underwent a reintervention. The hypoplastic aortic arch was enlarged with an inverted subclavian flap: the incision was carried out through the subclavian artery and the transverse arch entering the proximal left carotid artery. The previous end-to-end suture was left untouched. The outcome was satisfactory. Inverted subclavian flap technique is a good alternative when dealing with aortic coarctation associated to aortic arch hypoplasia

The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0–24 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 h·ng/mL and T1/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10–14-fold lower and an AUC0–24 value that was 21–29-fold lower. Methylone pharmacokinetics was linear across 50–200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50–200 mg.

The crosstalk between obesity, diabetes, steatohepatitis, and dementia creates a controversial scenario when also studied using animal models. In the present work, this crosstalk was investigated in male and female 3xTg-AD mice for Alzheimer’s disease (AD) at different ages/stages and compared to sex- and age-matched counterparts with normal aging. The relevance of the genetic background and classical intrinsic factors (AD genotype and sex) were determined using a retrospective analysis of population data and an experimental design. Age/stage of disease was considered a source of stochastic and non-stochastic factors. Data from two different colonies of 3xTg-AD mice with distinct genetic backgrounds were analyzed to verify the functional interplay between the studied factors. Data from asymptomatic/prodromal to early/advanced stages of the disease were screened. Then, all factors’ relationships were studied in an experimental design using the same set of animals. The population data unveiled that the genetic background and sex effects were confirmed with regards to the variable body weight, with changes during disease development and progress. Sexual dimorphism was found as an important factor in glucose metabolism. Statistically significant differences in glucose tolerance and behavioral assessment (exploration, anxiety, and cognition in a two-days open-field paradigm) were found when all the factors were analyzed. In summary, the present study shows that all the studied factors should always be considered when assessing the outcome of the research interventions in the field because they have a distinct functional interplay through the process of normal and AD-pathological aging and from a gendered perspective.

Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects of SCs usually is available from intoxication cases and surveys, and few studies on humans after controlled administration or observational/naturalistic studies using standardized measures of cardiovascular and subjective effects are available. The aim of this study was to evaluate the acute pharmacological effects of JWH-122 and JWH-210 recreational consumption in a 4 h observational study and assess their disposition in oral fluid (OF). Sixteen volunteers self-administered 1 mg dose of JWH-122 (n = 8) or 2.25 mg mean dose of JWH-210 (range 2–3 mg, n = 8) by inhalation (smoking). Physiological parameters including blood pressure (systolic and diastolic), heart rate (HR), and cutaneous temperature were measured. A set of visual analog scales, the 49-item short-form version of the Addiction Research Center Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were used for the evaluation of subjective effects. OF was collected at baseline and at 10, 20, and 40 min and 1, 2, 3, and 4 h after self-administration. Statistically significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR were observed after JWH-122 self-administration but not after JWH-210 self-administration. JWH-210 self-administration produced significant changes in subjective drug effects, similar to those induced by THC (intensity, high, good effects, and hunger). The subjective effects following JWH-122 consumption were minimal. The maximal effects were mostly observed 20 min after intake. JWH-122 and JWH 210 OF concentration reached a peak 20 min after administration and could not be detected after 3 h. The results demonstrated a different pattern of effects of these two SCs. Due to the limitations of our observational study, further research with a larger sample and controlled studies are needed to better define the acute pharmacological effect and health risk profile of JWH-122 and JWH-210.

Ctn[15-34], the C-terminal section of crotalicidin (Ctn), a cathelicidin from a South American pit viper, is an antimicrobial and antitumoral peptide with remarkably longer stability in human serum than the parent Ctn. In this work, a set of topoisomers of both Ctn and Ctn[15-34], including the retro, enantio, and retroenantio versions, were synthesized and tested to investigate the structural requirements for activity. All topoisomers were as active as the cognate sequences against Gram-negative bacteria and tumor cells while slightly more toxic towards normal cells. More importantly, the enhanced serum stability of the D-amino-acid-containing versions suggests that such topoisomers must be preferentially considered as future antimicrobial and anticancer peptide leads.

Background: Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both in vitro and in vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis. Methods: We used an in vitro culturing system of T. pallidum to perform drug susceptibility testing and applied quantitative PCR targeting the tp0574 gene to measure bacterial growth. To confirm in vivo efficacy, fifteen rabbits were infected intradermally with T. pallidum at eight sites each and randomly allocated to an experimental treatment (linezolid, moxifloxacin, clofazimine) or a control arm (benzathine penicillin G [BPG], untreated). The primary outcome was treatment efficacy defined as the time to lesion healing measured from the date of treatment start. Secondary outcomes were absence of treponemes or treponemal mRNA in injection sites, absence of seroconversion, and cerebrospinal fluid (CSF) abnormalities and negative rabbit infectivity tests (RIT). Findings: Linezolid showed in vitro bactericidal activity at concentrations of 0.5 µg/mL or higher. When administered orally to experimentally infected rabbits, it induced healing of early lesions at a time similar to BPG (hazard ratio 3.84; 95% CI 2.05–7.17; p

(1) Background: Since the beginning of the 21st century, the large number and wide chemical variety of new psychoactive substances (NPS) that enter the market every year has become a public health problem. Given the rapidity with which the drug market is changing, many NPS are not clinically investigated and their effects and health risks are unknown. Drug testing is a very useful tool for this purpose, but, unfortunately, it is not very widespread in individuals with opioid-use disorder under detoxification treatment. The aim of this study is to investigate the use of illicit drugs and NPS in opioid-use disorder (OUD) patients on opioid agonist treatment. (2) Methods: A multicenter, descriptive, cross-sectional study was conducted at two addiction care services in Barcelona and Badalona, Spain. Urine samples were collected from OUD individuals attending these two centers, who anonymously donated a urine sample at the time of a periodical visit. Samples were analyzed by high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high –resolution mass spectrometry (UHPLC-HRMS). (3) Results: Out of the 187 collected and analyzed urine samples, 27.3% were positive for any type of NPS and 8.6% were positive for new synthetic opioids, including fentanyl and its derivatives (NSO). Other frequently detected substances were benzodiazepines in 46.0% of samples, antipsychotics in 27.8% of samples, or cocaine and cannabis in 23.5% of samples. (4) Conclusion: A wide number of NPS, including NSO, have been detected in urine samples from an OUD population. A lack of NPS detection in standard drug screening among drug users can hide the identification of a potential public health problem.

A simple, fast, sensitive and low-cost voltammetric method using a screen-printed carbon electrode (SPCE) is presented in this work for the simultaneous determination of ascorbic acid (AA), paracetamol (PA), dextromethorphan (DX) and caffeine (CF) in both pharmaceutical formulations and samples of environmental interest. The oxidative peak current displayed linear dependence on concentration within the range 1.7–60.5, 0.6–40.0, 0.9–8.4 (1st linear part) and 1.8–22.0 mg L−1 for AA, PA, DX and CF, respectively; and detection limits of 0.5, 0.2, 0.3 and 0.5 mg L−1, respectively. The developed differential pulse voltammetric (DPV) method was validated using both a pharmaceutical product and a spiked well water sample. A very good agreement between the determined and the theoretical label drug content and recoveries in the range of 99.5–100.8% were obtained for pharmaceutical product and well water samples, respectively.

Introducción: La COVID 19 es una pandemia que afecta actualmente a 183 países. Hasta el momento ha causado amenazas para la salud física y la vida de las personas. Ha desencadenado variedad de problemas psicológicos y es campo de asistencia e investigación para los profesionales de la Psicología Objetivo: Caracterizar actitudes de una muestra de la población del área de salud del Policlínico “Mario Escalona Reguera” ante la pandemia COVID 19 en tiempo real. Material y Métodos: Investigación cualitativa, desarrollada en el área de salud del Policlínico Docente “Mario Escalona Reguera”, en Alamar, Municipio Habana del Este, durante el mes de abril de 2020. Se utiliza la entrevista, (telefónica) como instrumento de recogida de información, haciendo análisis de contenido de las respuestas. Resultados: Se reconoce como enfermedad letal en primer lugar y se considera muy buena información televisiva, básicamente a partir de conferencia de prensa del MINSAP. Tristeza e irritabilidad son reacciones emocionales frecuentes. Los comportamientos en la familia contribuyen a disfrute familiar y retomar juegos tradicionales con los menores. Es interesante su valoración como aprendizaje en la vida. Conclusiones: Las actitudes hacia la pandemia están caracterizadas por conocimiento sobre esta, reacciones emocionales esperadas ante lo desconocido y acciones favorables hacia el interior de la familia. La confianza en orientaciones de Salud y políticas gubernamentales, pudieran explicar la indisciplina social aún presente en algunos individuos.

The characterization of biologically active peptides relies heavily on the study of their efficacy, toxicity, mechanism of action, cellular uptake, or intracellular location, using both in vitro and in vivo studies. These studies frequently depend on the use of fluorescence-based techniques. Since most peptides are not intrinsically fluorescent, they are conjugated to a fluorophore. The conjugation may interfere with peptide properties, thus biasing the results. The selection of the most suitable fluorophore is highly relevant. Here, a comprehensive study with blood–brain barrier (BBB) peptide shuttles (PepH3 and PepNeg) and antimicrobial peptides (AMPs) (vCPP2319 and Ctn[15-34]), tested as anticancer peptides (ACPs), having different fluorophores, namely 5(6)-carboxyfluorescein (CF), rhodamine B (RhB), quasar 570 (Q570), or tide fluor 3 (TF3) attached is presented. The goal is the evaluation of the impact of the selected fluorophores on peptide performance, applying routinely used techniques to assess cytotoxicity/toxicity, secondary structure, BBB translocation, and cellular internalization. Our results show that some fluorophores significantly modulate peptide activity when compared with unlabeled peptides, being more noticeable in hydrophobic and charged fluorophores. This study highlights the need for a careful experimental design for fluorescently labeled molecules, such as peptides.

RESUMEN Introducción: La evaluación comunitaria es una herramienta útil en el trabajo asistencial, y existen pocas referencias de esta en la literatura. Es un reto para los profesionales de la salud recuperar el sentido psicológico de comunidad, esencial para resultados exitosos en la promoción de salud. Se necesita conocer los problemas psicosociales de nuestras comunidades y sus valoraciones al respecto, tarea posible con diagnósticos psicosociales que trasciendan el formalismo. Objetivo: Caracterizar aspectos psicosociales de la comunidad. Métodos: Investigación cuanti-cualitativa, descriptiva, no experimental y transversal desarrollada en la población atendida por tres consultorios médicos del Policlínico Docente "Dr. Mario Escalona Reguera", entre febrero y junio del 2016. Se realizaron entrevistas, se utilizó el Análisis de la Situación de Salud e Historias de Salud Familiar de los consultorios para la información primaria. Resultados: Población mayormente de adultos medios y trabajadores. Se identificaron problemas en la recolección de residuales sólidos. Prevaleció baja percepción de riesgo y comportamientos inadecuados ante algunas orientaciones de salud comunitaria. Se practicaba religión yoruba, católica y protestante. Se reconocieron inicio precoz de relaciones sexuales en adolescentes y patrones de crianza educativa inadecuados. Las familias eran mayormente pequeñas, bigeneracionales y nucleares, con dificultades en la comunicación y el desempeño de roles. Conclusiones: El diagnóstico permitió elaborar planes de acciones educativas efectivas para minimizar las situaciones problemas identificadas. En esta comunidad permitió orientarse a intervenciones psicoeducativas en las escuelas de enseñanza media y en grupos de pacientes con enfermedades crónicas no trasmisibles.

2,5-Dimethoxy-4-ethylphenethylamine (2C-E) is psychedelic phenylethylamine, with a chemical structure similar to mescaline, used as new psychoactive substance (NPS). It inhibits norepinephrine and serotonin uptake and, more relevant, acts as a partial agonist of the serotonin 2A (5-HT2A), 2B (5-HT2B), and (5-HT2C) receptors. Consumers have reported that 2C-E induces mild-moderate psychedelic effects, but its pharmacology in humans, including pharmacological effects and pharmacokinetics, have not yet studied. To assess the acute effects of 2C-E on physiological and subjective effects and evaluate its pharmacokinetics, an observational study was carried-out. Ten recreational users of psychedelics self-administered a single oral dose of 2C-E (6.5, 8, 10, 15, or 25 mg). Blood pressure and heart rate were evaluated at baseline, 2, 4, and 6 h post-administration. Three rating scales were administered to evaluate subjective effects: a set of Visual Analog Scales (VAS), the 49-item short form version of the Addiction Research Centre Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 2, 4, and 6 h after self-administration. To assess 2C-E concentrations oral fluid (saliva) was collected during 6 h. 2C-E induced primarily alterations in perceptions, hallucinations, and euphoric-mood. Saliva maximal concentrations were achieved 2 h after self-administration. Administration of oral 2C-E at recreational doses produces a group of psychedelic-like effects such to 2C-B and other serotonin-acting drugs.

Mephedrone (4-MMC, mephedrone) is a synthetic cathinone derivative included in the class of new psychoactive substances. It is commonly used simultaneously with alcohol (ethanol). The aim of the present study was to evaluate the interactions on subjective, cardiovascular and hormone effects and pharmacokinetics between mephedrone and alcohol in humans. Eleven male volunteers participated as outpatients in four experimental sessions in a double-blind, randomized, cross-over, and placebo-controlled clinical trial. Participants received a single oral dose of 200 mg of mephedrone plus 0.8 g/kg of alcohol (combination condition); 200 mg of mephedrone plus placebo alcohol (mephedrone condition); placebo mephedrone plus 0.8 g/kg of ethanol (alcohol condition); and placebo mephedrone plus placebo alcohol (placebo condition). Outcome variables included physiological (blood pressure, heart rate, temperature, and pupil diameter), psychomotor (Maddox wing), subjective (visual analogue scales, Addiction Research Center Inventory 49 item short form, and Valoración de los Efectos Subjetivos de Sustancias con Potencial de Abuso questionnaire), and pharmacokinetic parameters (mephedrone and ethanol concentrations). The study was registered in ClinicalTrials.gov, number NCT02294266. The mephedrone and alcohol combination produced an increase in the cardiovascular effects of mephedrone and induced a more intense feeling of euphoria and well-being in comparison to the two drugs alone. Mephedrone reduced the sedative effects produced by alcohol. These results are similar to those obtained when other psychostimulants such as amphetamines and 3,4-methylenedioxymethamphetamine are combined simultaneously with alcohol. The abuse liability of mephedrone combined with alcohol is greater than that induced by mephedrone alone.

Here we present new and original data on the endogenous conversion of tyrosol (Tyr) into hydroxytyrosol (OHTyr) in humans and its effects on the cardiovascular system. A randomized, crossover, controlled clinical trial was performed with individuals at cardiovascular risk (n = 33). They received white wine (WW) (females 1, males 2 standard drinks/day), WW plus Tyr capsules (WW + Tyr) (25mg Tyr capsule, one per WW drink), and water (control) ad libitum. Intervention periods were of 4 weeks preceded by three-week wash-out periods. We assessed the conversion of Tyr to OHTyr, its interaction with a polygenic activity score (PAS) from CYP2A6 and CYP2D6 genotypes, and the effects on cardiovascular risk markers. For further details and experimental findings please refer to the article “Cardiovascular benefits of tyrosol and its endogenous conversion into hydroxytyrosol in humans. A randomized, controlled trial” [1]. Keywords: Tyrosol, Hydroxytyrosol, Endogenous conversion, CYP2A6, CYP2D6, Cardiovascular risk

Family physical activity can have beneficial effects on the physical condition of parents and children. Method: Uncontrolled longitudinal intervention study. 152 children aged 3 to 10 years (79 Boys: 5.60 ± 2.20 yr., 73 Girls: 6.90 ± 2.20 yr.) and 112 parents aged 30 to 40 years (36 Parents: 41.87 ± 4.45 yr.; 76 Mothers: 40.01 ± 2.96 yr.). They carried out 2 hours of joint activity on a weekly basis from October to June. Physical fitness was assessed by ALPHA-Fitness and PRE-FIT batteries at the beginning and end of the intervention. A descriptive analysis and a t-student for paired variables were performed. Results: The 3-6-year-old girls improved the Standing long jump (33.50 ± 10.61 vs 78.11 ± 8.64 cm) * and the 20 m shuttle run test (7.00 ± 2, 83 vs. 22.50 ± 0.71) *, (*p

In recent years, the consumption of energy drinks (EDs) has become increasingly popular, especially among adolescents. Caffeine, a psychostimulant, is the main compound of EDs which also contain other substances with pharmacological effects. This review aims to compile current evidence concerning the potential interactions between EDs, medicines, and drugs of abuse as they are frequently consumed in combination. The substances involved are mainly substrates, inductors or inhibitors of CYP1A2, psychostimulants, alcohol and other depressant drugs. Furthermore, intoxications reported with EDs and other substances have also been screened to describe acute toxicity. The results of our review show that the consumption of both EDs alone and in combination is not as safe as previously thought. Health professionals and consumers need to be aware of the potential interactions of these drinks as well as the absence of long-term safety data.

Considered the β-keto analogue of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-Methylenedioxymethcathinone (methylone) is a synthetic cathinone. Over the years, methylone has been used as a substitute for conventional psychostimulants, such as MDMA. To date, little is known about the human pharmacology of methylone; the only available information has been provided by surveys or published intoxication reports. In the present observational–naturalistic study, we evaluate the acute subjective and physiological effects of methylone after oral self-administration in comparison to MDMA in healthy poly-drug users. Fourteen participants (10 males, 4 females) selected their single oral doses of methylone from 100 to 300 mg (n = 8, mean dose 187.5 mg) or MDMA from 75 to 100 mg (n = 6, mean dose 87.5 mg) based on their experience. Study variables were assessed at 0, 1, 2, and 4 h (h) and included vital signs (non-invasive blood pressure, heart rate, cutaneous temperature) and subjective effects using visual analogue scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI) short form, and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) questionnaire. Additionally, oral fluid concentrations of methylone and MDMA were determined. Acute pharmacological effects produced by methylone followed the prototypical psychostimulant and empathogenic profile associated with MDMA, although they were less intense. Methylone concentrations in oral fluid can be considered a useful biomarker to detect acute exposure in oral fluid. Oral fluid concentrations of MDMA and methylone peaked at 2 h and concentrations of MDMA were in the range of those previously described in controlled studies. Our results demonstrate that the potential abuse liability of methylone is similar to that of MDMA in recreational subjects.

Soy beans contain isoflavones, including daidzein and genistein, with biological activities related to therapeutic effects in reducing osteoporosis, decreasing adverse menopausal manifestations, providing protection from cardiovascular diseases, and reducing hormone-dependent cancers and age-related cognitive-decline. Daidzein has been described as inhibiting the aldehyde-dehydrogenase-2 enzyme (ALDH2), and reducing alcohol use in clinical pilot studies. Our aim was to evaluate the possible interactions between a soy extract product and alcohol in a crossover, single blind, randomized study. Ten healthy male volunteers participated in two experimental sessions: one with a single dose of alcohol (0.5 g/kg, Vodka Absolut, Sweden), and the other with four capsules of a soy extract product (Super-Absorbable Soy Isoflavones, Life-Extension, United States) and, 2 h later, the same dose of alcohol. Results showed no differences in vital signs except a slightly higher significative reduction in diastolic blood pressure at 2, 3, 4, and 8 h after administration with alcohol alone in comparison with soy extract+alcohol. Ethanol-induced subjective and adverse effects were similar for both conditions with the exception of headache (higher at 8 h after alcohol alone). Our results demonstrate that a single dose of a soy isoflavone extract did not influence alcohol pharmacokinetics and pharmacological effects and did not induce any disulfiram-reaction symptoms. Soy extract and alcohol did not interact and can be administered safely.

Major depressive disorder (MDD) is the most prevalent comorbid mental disorder among people with substance use disorders. The MDD can be both primary and substance-induced and its accurate diagnosis represents a challenge for clinical practice and treatment response. Recent studies reported alterations in the circulating expression of inflammatory mediators in patients with psychiatric disorders, including those related to substance use. The aim of the study was to explore TNF-α, IL-1β, CXCL12, CCL2, CCL11 (eotaxin-1) and CX3CL1 (fractalkine) as potential biomarkers to identify comorbid MDD and to distinguish primary MDD from substance-induced MDD in patients with substance disorders. Patients diagnosed with cocaine (CUD, n = 64) or alcohol (AUD, n = 65) use disorders with/without MDD were recruited from outpatient treatment programs [CUD/non-MDD (n = 31); CUD/primary MDD (n = 18); CUD/cocaine-induced MDD (N = 15); AUD/non-MDD (n = 27); AUD/primary MDD (n = 16) and AUD/alcohol-induced MDD (n = 22)]. Sixty-two healthy subjects were also recruited as control group. Substance and mental disorders were assessed according to "Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision" (DSM-IV-TR) and a blood sample was collected for determinations in the plasma. The cocaine group showed lower TNF-α (p

The widely spread use of the hanging mercury drop electrode (HMDE) for multi-ion analysis is primarily ascribed to the following reasons: (i) excellent reproducibility owing to the easy renewal of the electrode surface avoiding any hysteresis effect (i.e., a new identical drop is generated for each measurement to be accomplished); (ii) a wide cathodic potential window originating from the passive hydrogen evolution and solvent electrolysis; (iii) the ability to form amalgams with many redox-active metal ions; and (iv) the achievement of (sub)nanomolar limits of detection. On the other hand, the main controversy of the HMDE usage is the high toxicity level of mercury, which has motivated the scientific community to question whether the HMDE deserves to continue being used despite its unique capability for multi-metal detection. In this work, the simultaneous determination of Zn2+, Cd2+, Pb2+, and Cu2+ using the HMDE is investigated as a model system to evaluate the main features of the technique. The analytical benefits of the HMDE in terms of linear range of response, reproducibility, limit of detection, proximity to ideal redox behavior of metal ions and analysis time are herein demonstrated and compared to other electrodes proposed in the literature as less-toxic alternatives to the HMDE. The results have revealed that the HMDE is largely superior to other reported methods in several aspects and, moreover, it displays excellent accuracy when simultaneously analyzing Zn2+, Cd2+, Pb2+, and Cu2+ in such a complex matrix as digested soils. Yet, more efforts are required towards the definitive replacement of the HMDE in the electroanalysis field, despite the elegant approaches already reported in the literature.

Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144.

Inhalation by vaporization is a useful application mode for medical cannabis. In this study, we present the disposition of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, and their metabolites in serum, oral fluid, and urine together with the acute pharmacological effects in 14 healthy individuals treated with vaporized medical cannabis. THC and CBD peaked firstly in serum and then in oral fluid, with higher concentrations in the first biological matrices and consequent higher area under the curve AUCs. Acidic precursors Δ-9-tetrahydrocannabinolic acid A (THCA) and cannabidiolic acid (CBDA) showed a similar time course profile but lower concentrations due to the fact that vaporization partly decarboxylated these compounds. All THC and CBD metabolites showed a later onset with respect to the parent compounds in the absorption phase and a slower decrease to baseline. In agreement with serum kinetics, THC-COOH-GLUC and 7-COOH-CBD were the significantly most excreted THC and CBD metabolites. The administration of vaporized medical cannabis induced prototypical effects associated with the administration of cannabis or THC in humans, with a kinetic trend overlapping that of parent compounds and metabolites in serum. The pharmacokinetics of cannabinoids, their precursors, and their metabolites in biological fluids of individuals treated with vaporized medical cannabis preparations showed a high interindividual variability as in the case of oral medical cannabis decoction and oil. Inhaled medical cannabis was absorbed into the organism earlier than decoction and oil. Cannabinoids reached higher systemic concentrations, also due to the fact that the acid precursors decarboxylated to parent cannabinoids at high temperatures, and consequently, the physiological and subjective effects occurred earlier and resulted with higher intensity. No serious adverse effects were observed.

Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100–200 mg; mean 150 mg) or intranasally (n = 5, 50–100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.

The consumption of synthetic cannabinoids (SCs) has significantly increased in the last decade and the analysis of SCs and their metabolites in human specimens is gaining interest in clinical and forensic toxicology. A pilot study has been carried out using a combination of an initial last generation gas chromatography-mass spectrometry (GC-MS) screening method for the determination of JWH-122, JWH-210, UR-144) in oral fluid (OF) of consumers and an ultra-high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) confirmatory method for the quantification of the parent compounds and their metabolites in the same biological matrix. OF samples were simply liquid-liquid extracted before injecting in both chromatographic systems. The developed methods have been successfully validated and were linear from limit of quantification (LOQ) to 50 ng/mL OF. Recovery of analytes was always higher than 70% and matrix effect always lower than 15% whereas intra-assay and inter-assay precision and accuracy were always better than 16%. After smoking 1 mg JWH-122 or UR-144 and 3 mg JWH-210, maximum concentration of 4.00–3.14 ng/mL JWH-122, 8.10–7.30 ng/mL JWH-210 ng/mL and 7.40 and 6.81 ng/mL UR-144 were measured by GC-MS and UHPLC-HRMS respectively at 20 min after inhalation. Metabolites of JWH 122 and 210 were quantified in OF by UHPLC-HRMS, while that of UR144 was only detectable in traces. Our results provide for the first time information about disposition of these SCs and their metabolites in consumers OF. Last generation GC-MS has proven useful tool to identify and quantify parent SCs whereas UHPLC-HRMS also confirmed the presence of SCs metabolites in the OF of SCs consumers.

The use of cannabis flowering tops with standardized amounts of active phytocannabinoids was recently authorized in several countries to treat several painful pathological conditions. The acute pharmacological effects and disposition of Δ-9-tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors and THC metabolites after oil and decoction administration have been already described. In this study, the disposition of CBD metabolites: 7-carboxy-cannabidiol (7-COOH-CBD), 7-hydroxycannabidiol (7-OH-CBD), 6-α-hydroxycannabidiol (6-α-OH-CBD), and 6-β-hydroxycannabidiol (6-β-OH-CBD) in the serum and urine of healthy volunteers was presented. Thirteen healthy volunteers were administered 100 mL of cannabis decoction in the first experimental session and, after 15 days of washout, 0.45 mL of oil. Serum and urine samples were collected at different time points, and the CBD metabolites were quantified by ultra-high-performance liquid chromatography–tandem mass spectrometry. The most abundant serum metabolite was 7-COOH-CBD, followed by 7-OH-CBD, 6-β-OH-CBD, and6-α-OH-CBD, after decoction and oil. Both 7-OH-CBD and the 6-α-OH-CBD showed similar pharmacokinetic properties following administration of both cannabis preparations, whereas 7-COOH and 6-α-OH-CBD displayed a significant higher bioavailability after decoction consumption. All CBD metabolites were similarly excreted after oil and decoction intake apart from 6-α-OH-CBD, which had a significantly lower excretion after oil administration. The pharmacokinetic characterization of CBD metabolites is crucial for clinical practice since the cannabis herbal preparations are increasingly used for several pathological conditions.

Glycine monitoring is gaining importance as a biomarker in clinical analysis due to its involvement in multiple physiological functions, which results in glycine being one of the most analyzed biomolecules for diagnostics. This growing demand requires faster and more reliable, while affordable, analytical methods that can replace the current gold standard for glycine detection, which is based on sample extraction with subsequent use of liquid chromatography or fluorometric kits for its quantification in centralized laboratories. This work discusses electrochemical sensors and biosensors as an alternative option, focusing on their potential application for glycine determination in blood, urine, and cerebrospinal fluid, the three most widely used matrices for glycine analysis with clinical meaning. For electrochemical sensors, voltammetry/amperometry is the preferred readout (10 of the 13 papers collected in this review) and metal-based redox mediator modification is the predominant approach for electrode fabrication (11 of the 13 papers). However, none of the reported electrochemical sensors fulfill the requirements for direct analysis of biological fluids, most of them lacking appropriate selectivity, linear range of response, and/or capability of measuring at physiological conditions. Enhanced selectivity has been recently reported using biosensors (with an enzyme element in the electrode design), although this is still a very incipient approach. Currently, despite the benefits of electrochemistry, only optical biosensors have been successfully reported for glycine detection and, from all the inspected works, it is clear that bioengineering efforts will play a key role in the embellishment of selectivity and storage stability of the sensing element in the sensor.

Background and objective: Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral cannabis containing Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is a promising route of administration but there is still little information about its pharmacokinetics (PK) effects in humans. The purpose of this systematic review is to provide a general overview of the available PK data on cannabis and THC after oral administration. Materials and Methods: A search of the published literature was conducted using the PubMed database to collect available articles describing the PK data of THC after oral administration in humans. Results: The literature search yielded 363 results, 26 of which met our inclusion criteria. The PK of oral THC has been studied using capsules (including oil content), tablets, baked goods (brownies and cookies), and oil and tea (decoctions). Capsules and tablets, which mainly correspond to pharmaceutical forms, were found to be the oral formulations most commonly studied. Overall, the results reflect the high variability in the THC absorption of oral formulations, with delayed peak plasma concentrations compared to other routes of administration. Conclusions: Oral THC has a highly variable PK profile that differs between formulations, with seemingly higher variability in baked goods and oil forms. Overall, there is limited information available in this field. Therefore, further investigations are required to unravel the unpredictability of oral THC administration to increase the effectiveness and safety of oral formulations in medicinal use.

Carbon-nanofiber-based screen-printed electrodes modified with silver nanoparticles (Ag-NP-SPCNFEs) were tested in a pioneering manner for the direct determination of As(V) at low μg L−1 levels by means of differential pulse anodic stripping voltammetry. Screen-printed electrodes were modified with two different types of Ag-NPs, nanoseeds (NS), and nanoprisms (NPr) and characterized both microscopically and electrochemically. Furthermore, after optimizing the direct voltammetric determination of As(V), the analytical performance of considered sensors was compared for the direct determination of As(V). These results suggest that Ag-NS offer a better analytical response compared to Ag-NPr, with a detection and quantification limit of 0.6 and 1.9 µg L−1, respectively. The proposed methodology was validated using a spiked tap water sample with a very high reproducibility and good agreement with inductively coupled plasma-mass spectrometry (ICP-MS) measurements.