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Abstract Background Due to its key role in various biological processes, RNA secondary structures have always been the focus of in-depth analyses, with great efforts from mathematicians and biologists, to find a suitable abstract representation for modelling its functional and structural properties. One contribution is due to Kauffman and Magarshak, who modelled RNA secondary structures as mathematical objects constructed in link theory: tangles of the Brauer Monoid. In this paper, we extend the tangle-based model with its minimal prime factorization, useful to analyze patterns that characterize the RNA secondary structure. Results By leveraging the mapping between RNA and tangles, we prove that the prime factorizations of tangle-based models share some patterns with RNA folding’s features. We analyze the E. coli tRNA and provide some visual examples of interesting patterns. Conclusions We formulate an open question on the nature of the class of equivalent factorizations and discuss some research directions in this regard. We also propose some practical applications of the tangle-based method to RNA classification and folding prediction as a useful tool for learning algorithms, even though the full factorization is not known.

De novo CLTC mutations underlie a spectrum of early-onset neurodevelopmental phenotypes having developmental delay/intellectual disability (ID), epilepsy, and movement disorders (MD) as major clinical features. CLTC encodes the widely expressed heavy polypeptide of clathrin, a major component of the coated vesicles mediating endocytosis, intracellular trafficking, and synaptic vesicle recycling. The underlying pathogenic mechanism is largely unknown. Here, we assessed the functional impact of the recurrent c.2669C > T (p.P890L) substitution, which is associated with a relatively mild ID/MD phenotype. Primary fibroblasts endogenously expressing the mutated protein show reduced transferrin uptake compared to fibroblast lines obtained from three unrelated healthy donors, suggesting defective clathrin-mediated endocytosis. In vitro studies also reveal a block in cell cycle transition from G0/G1 to the S phase in patient’s cells compared to control cells. To demonstrate the causative role of the p.P890L substitution, the pathogenic missense change was introduced at the orthologous position of the Caenorhabditis elegans gene, chc-1 (p.P892L), via CRISPR/Cas9. The resulting homozygous gene-edited strain displays resistance to aldicarb and hypersensitivity to PTZ, indicating defective release of acetylcholine and GABA by ventral cord motor neurons. Consistently, mutant animals show synaptic vesicle depletion at the sublateral nerve cords, and slightly defective dopamine signaling, highlighting a generalized deficit in synaptic transmission. This defective release of neurotransmitters is associated with their secondary accumulation at the presynaptic membrane. Automated analysis of C. elegans locomotion indicates that chc-1 mutants move slower than their isogenic controls and display defective synaptic plasticity. Phenotypic profiling of chc-1 (+/P892L) heterozygous animals and transgenic overexpression experiments document a mild dominant-negative behavior for the mutant allele. Finally, a more severe phenotype resembling that of chc-1 null mutants is observed in animals harboring the c.3146 T > C substitution (p.L1049P), homologs of the pathogenic c.3140 T > C (p.L1047P) change associated with a severe epileptic phenotype. Overall, our findings provide novel insights into disease mechanisms and genotype–phenotype correlations of CLTC-related disorders.

(1) Background: Alcohol consumption during pregnancy is a major concern, particularly in Europe and North America. Its prevalence has so far been under-researched. In most studies, the determination of this consumption may be underestimated, as it is based on the information obtained from questionnaires rather than from biomarkers, which will provide a much more reliable approach. The main objective of this study was to compare the prevalence of consumption during pregnancy as assessed by a questionnaire and a hair biomarker. (2) Method: A cross-sectional study with a random sample of 425 pregnant women treated in public hospital consultations in Seville (Spain) and in the 20th week of their pregnancy, orally interviewed using an elaborated ad hoc questionnaire that evaluated variables of sociodemographic, obstetric, and alcohol consumption. Furthermore, the ethyl glucuronide metabolite (EtG) was tested on a hair sample in 252 pregnant women who agreed to facilitate it. Once the data obtained through the questionnaire and hair test were analyzed, the level of metabolites and self-reported alcohol consumption were compared. (3) Results: The prevalence of self-reported alcohol consumption (questionnaire) was 20.7%, and the real consumption (metabolite analysis) was 20.2%. In 16.8% of pregnant women who declared not consuming alcohol during their pregnancy, noticeable consumption was detected according to the metabolite test. No relevant level of variability in estimated alcohol consumption was detected in the biomarker with respect to the sociodemographic and obstetric variables studied. (4) Conclusions: The prevalence of alcohol consumption during pregnancy obtained through both questionnaires and metabolite analyses was similar and high. There is no association between consumption and sociodemographic factors in this sample. The determination of consumption through biomarkers allows for a more accurate approximation of the prevalence of consumption than estimated through questionnaires. Larger sample-sized studies are needed to determine consumption patterns and thus guide the adoption of more precise policies fostering abstinence from alcohol consumption since the preconception period.

Resumen: Introducción: La identificación temprana de los neonatos expuestos a drogas de abuso permite realizar un manejo clínico más preciso. Objetivos: Describir las características clínicas e identificar factores de riesgo asociados a la detección precoz de neonatos expuestos a drogas de abuso en una Unidad de Cuidados Intensivos e Intermedios Neonatales. Métodos: Estudio observacional prospectivo de neonatos con y sin sospecha clínica de exposición prenatal a drogas de abuso. Se analizó meconio empleando técnicas cromatográficas estandarizadas. Se realizaron análisis estadísticos univariante y multivariante. Resultados: Se incluyeron 372 neonatos. En 49 (13,2%) casos se detectó exposición a alguna droga de abuso; en 41 (83,7%) a una, y en ocho (16,3%) a más de una. La somatometría al nacimiento objetivó: a) menor percentil de longitud en expuestos a alguna droga, a más de una y a cannabis; b) menor percentil de peso en expuestos a cannabis, y de éstos en comparación con los expuestos a alcohol. En mayores de 34 semanas de gestación (SG): a) menor percentil de longitud en expuestos a alguna droga; b) menor percentil de longitud y peso en expuestos a más de una. Los factores de riesgo independientes clínicamente útiles para detectar casos de exposición prenatal a drogas de abuso fueron (odds ratio [IC 95%]): motivo de ingreso distinto a prematuridad (5,52 [2,55-1,93]), percentil de longitud menor a 33 (1,95 [1,05-3,60]) y (2,14 [1,04-3,40]) en mayores de 34 SG y distocia social/embarazo no controlado en mayores a 34SG (4,47 [1,03-19,29]). Conclusiones: Existen alteraciones somatométricas y factores de riesgo que pueden ayudar a detectar precozmente a los neonatos expuestos a drogas de abuso. Las alteraciones somatométricas identificadas pueden servir para ampliar su diagnóstico diferencial y el estudio de sus causas. Abstract: Introduction: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management. Objectives: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit. Methods: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed. Results: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)). Conclusions: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.

Introduction: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management. Objectives: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit. Methods: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed. Results: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)). Conclusions: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes. Resumen: Introducción: La identificación temprana de los neonatos expuestos a drogas de abuso permite realizar un manejo clínico más preciso. Objetivos: Describir las características clínicas e identificar factores de riesgo asociados a la detección precoz de neonatos expuestos a drogas de abuso en una Unidad de Cuidados Intensivos e Intermedios Neonatales. Métodos: Estudio observacional prospectivo de neonatos con y sin sospecha clínica de exposición prenatal a drogas de abuso. Se analizó meconio empleando técnicas cromatográficas estandarizadas. Se realizaron análisis estadísticos univariante y multivariante. Resultados: Se incluyeron 372 neonatos. En 49 (13,2%) casos se detectó exposición a alguna droga de abuso; en 41 (83,7%) a una, y en ocho (16,3%) a más de una. La somatometría al nacimiento objetivó: a) menor percentil de longitud en expuestos a alguna droga, a más de una y a cannabis; b) menor percentil de peso en expuestos a cannabis, y de éstos en comparación con los expuestos a alcohol. En mayores de 34 semanas de gestación (SG): a) menor percentil de longitud en expuestos a alguna droga; b) menor percentil de longitud y peso en expuestos a más de una. Los factores de riesgo independientes clínicamente útiles para detectar casos de exposición prenatal a drogas de abuso fueron (odds ratio [IC 95%]): motivo de ingreso distinto a prematuridad (5,52 [2,55-1,93]), percentil de longitud menor a 33 (1,95 [1,05-3,60]) y (2,14 [1,04-3,40]) en mayores de 34 SG y distocia social/embarazo no controlado en mayores a 34SG (4,47 [1,03-19,29]). Conclusiones: Existen alteraciones somatométricas y factores de riesgo que pueden ayudar a detectar precozmente a los neonatos expuestos a drogas de abuso. Las alteraciones somatométricas identificadas pueden servir para ampliar su diagnóstico diferencial y el estudio de sus causas.

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.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting 32 million individuals worldwide, particularly the elderly. It is the main cause of ischemic strokes. Oral anticoagulation (OAC) is the gold standard strategy for stroke prevention. Still, there is a not negligible share of patients who have contraindications to this therapy, more frequently due to an increased risk of bleeding. AF is often associated with moderate-severe mitral regurgitation (MR), the second most frequent valvular disease in elderly patients. Data from the literature reported that more than half of patients with severe mitral regurgitation are not suitable candidates for cardiac surgery. Given the progressive aging of the population and the simultaneous increase in the number of patients with comorbidities, the advent of new therapeutic strategies, such as the combined approach of Left Atrial Appendage Occlusion (LAAO) and MitraClip procedure, is acquiring great interest. At present, the category of patients who may benefit from combined percutaneous therapies and the long-term risks and benefits might not have been identified. Despite the efforts of researchers, the correct selection of patients is a very important clinical need that has not yet been met to avoid committing human and financial resources to interventions that may be unnecessary. It is conceivable that the most modern and recent innovations in cardiovascular imaging, particularly three-dimensional echocardiography and new methods of volume imaging, could improve our ability to select patients appropriately. Since data in the literature are scarce, future studies will be needed to evaluate the efficacy and safety of combined MitraClip and LAA occlusion.

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.

(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.

For the first time, the present study employed hair testing to investigate the prevalence of classical drugs of abuse and new psychoactive substances use during gestation in a cohort of 300 Mexican pregnant women. An interview was conducted to collect data on sociodemographic aspects of the patients, and a 9 cm-long hair strand was taken from the back of the head of each mother one month after delivery. A validated ultra-high-performance liquid chromatography–high-resolution mass spectrometry method was used for the screening of classic drugs, new psychoactive substances, and medications in maternal hair. Out of 300 examined hair samples from pregnant women, 127 (42.3%) resulted positive for psychoactive substances: 45 (35.4%) for cannabis only, 24 (18.9%) for methamphetamine only, 13 (10.2%) for cocaine only, 1 (0.3%) for heroin, 1 for N-N-dimethyltryptamine (0.3%), 1 for ketamine (0.8%), and 35 (16.3%) for more than one psychoactive substance. Furthermore, seven samples (2.3%) resulted positive for new psychoactive substances (NPS): two samples for synthetic cannabinoids, two for synthetic cathinones, and three for nor-fentanyl, and 3.3% of women hair resulted positive for anticonvulsant, antidepressant, and antipsychotic medications. Finally, 83 women hair samples (27.7%) tested positive for nicotine. Nonsteroidal anti-inflammatory drugs (NSAIDs) and other painkillers (60.0%), medications for the treatment of nausea and vomiting (12.3%), antihistamines (8.7%) and nasal/sinus decongestants (6.7%), cough suppressants (5.0%), and bronchodilator agents (5.0%) were also detected in pregnant women hair. The gestational use of psychoactive substances and exposure to tobacco smoke, assessed by hair testing, were associated with a significantly younger age and with a low education grade of the mothers (p < 0.005). This study provides a significant preliminary indication of the under-reported gestational consumption of licit and illicit psychoactive and pharmacologically active drugs in a Mexican environment, showing the value of toxicological and forensic analyses in the global effort to determine the health risks caused by classic drugs and new psychoactive substances during pregnancy.

Background After the coronavirus disease 2019 outbreak, social isolation measures were introduced to contain infection. Although there is currently a slowing down of the infection, a reduction of hospitalizations, especially for myocardial infarction, was observed. The aim of our study is to evaluate the impact of the infectious disease on ST‐segment–elevation myocardial infarction (STEMI) care during the coronavirus disease 2019 pandemic, through the analysis of recent cases of patients who underwent percutaneous coronary intervention. Methods and Results Consecutive patients affected by STEMI from March 1 to 31, 2020, during social restrictions of Italian government, were collected and compared with patients with STEMI treated during March 2019. During March 2020, we observed a 63% reduction of patients with STEMI who were admitted to our catheterization laboratory, when compared with the same period of 2019 (13 versus 35 patients). Changes in all time components of STEMI care were notably observed, particularly for longer median time in symptom‐to‐first medical contact, spoke‐to‐hub, and the cumulative symptom‐to‐wire delay. Procedural data and in‐hospital outcomes were similar between the 2 groups, whereas the length of hospitalization was longer in patients of 2020. In this group, we also observed higher levels of cardiac biomarkers and a worse left ventricular ejection fraction at baseline and discharge. Conclusions The coronavirus disease 2019 outbreak induced a reduction of hospital access for STEMI with an increase in treatment delay, longer hospitalization, higher levels of cardiac biomarkers, and worse left ventricular function.

Background: The accurate assessment of fetal exposure to psychoactive substances provides the basis for appropriate clinical care of neonates. The objective of this study was to identify maternal socio-demographic profiles and risk factors for prenatal exposure to drugs of abuse by measuring biomarkers in neonatal matrices. Methods: A prospective, observational cohort study was completed. Biomarkers of fetal exposure were measured in meconium samples. The mothers were interviewed using a questionnaire. Univariate and multivariate logistic regression analyses were performed. Results: A total of 372 mothers were included, 49 (13.2%) testing positive for psychoactive substances use: 24 (49.0%) for cannabis, 11 (22.5%) for ethyl glucuronide, six (12.2%) for cocaine, and in eight (16.3%) more than one psychoactive substance. Mothers who consumed any psychoactive substance (29.7 ± 6.6 years) or cannabis (27.0 ± 5.7 years) were younger than non-users (32.8 ± 6.2 years, p < 0.05). Cocaine (50.0% vs. 96.9%, p < 0.05) and polydrug users (37.5% vs. 96.9%, p < 0.05) showed a lower levels of pregnancy care. Previous abortions were associated with the use of two or more psychoactive substances (87.5% vs. 37.8%, p < 0.05). Single-mother families (14.3% vs. 2.5%, p < 0.05) and mothers with primary level education (75.5% vs. 55.1%, p < 0.05) presented a higher consumption of psychoactive substances. Independent risk factors that are associated with prenatal exposure include: maternal age < 24 years (odds ratio: 2.56; 95% CI: 1.12–5.87), lack of pregnancy care (odds ratio: 7.27; 95%CI: 2.51–21.02), single-mother families (odds ratio: 4.98; 95%CI: 1.37–8.13), and active tobacco smoking (odds ratio: 8.13; 95%CI: 4.03–16.43). Conclusions: These results will allow us to develop several risk-based drug screening approaches to improve the early detection of exposed neonates.

The use of the new psychoactive substances is continuously growing and the implementation of accurate and sensible analysis in biological matrices of users is relevant and fundamental for clinical and forensic purposes. Two different analytical technologies, high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) were used for a screening analysis of classic drugs and new psychoactive substances and their metabolites in urine of formed heroin addicts under methadone maintenance therapy. Sample preparation involved a liquid-liquid extraction. The UHPLC-HRMS method included Accucore™ phenyl Hexyl (100 × 2.1 mm, 2.6 μm, Thermo, USA) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2 mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2 mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode for substances identification (mass range 100–1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m, 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40–550 m/z). Urine samples from 296 patients with a history of opioid use disorder were examined. Around 80 different psychoactive substances and/or metabolites were identified, being methadone and metabolites the most prevalent ones. The possibility to screen for a huge number of psychotropic substances can be useful in suspected drug related fatalities or acute intoxication/exposure occurring in emergency departments and drug addiction services.

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.

Background and Objectives: The use of synthetic cannabinoids has increased around the world. As a result, the implementation of accurate analysis in human biological matrices is relevant and fundamental. Two different analytical technologies, ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) and high-sensitivity gas chromatography-mass spectrometry (GC-MS) were used for the determination of three synthetic cannabinoids JWH-122, JWH 210, UR-144 and their metabolites in urine of consumers. Materials and Methods: Sample preparation included an initial hydrolysis with β-glucuronidase and liquid-liquid extraction. The UHPLC-HRMS method included a Kinetex 2.6 u Biphenyl 100A (100 × 2.1 mm, 2.6 μm) (Phenomenex, Italy) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode was used (mass range 100–1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m × 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40–550 m/z). Results: Both methods have been successfully used for screening of parent synthetic cannabinoids and their metabolites in urine samples of consumers. Conclusions: The screening method applied JWH-122, JWH-210, UR-144 and their metabolites in urine of consumers can be applied to other compounds of the JWH family.

OBJECTIVE: Percutaneous mitral valve repair with the MitraClip system is an alternative procedure for high-risk patients not suitable for conventional surgery. The MitraClip can be safely performed under general anesthesia (GA) or deep sedation (DS) with spontaneous breathing using a combination of propofol and remifentanil. This study aimed to evaluate the benefits of target-controlled infusion (TCI) of remifentanil and administration of propofol during DS compared with manual administration of total intravenous anesthesia (TIVA) medication during GA in patients undergoing MitraClip. We assessed the impact of these procedures in terms of remifentanil dose, hemodynamic profile, adverse events, and days of hospital stay after the process. PATIENTS AND METHODS: From March 2013 to June 2015 (mean age 73.5 ± 9,54), patients underwent transcatheter MitraClip repair, 27 received DS via TCI and 27 GA with TIVA. RESULTS: Acute procedural success was 100%. DS-TCI group, in addition to a significant reduction of remifentanil dose administrated (249 μg vs. 2865, p < 0.01), resulted in a decrease in vasopressor drugs requirement for hemodynamic adjustments (29.6% vs. 63%, p = 0.03) during the procedure and a reduction of hypotension (p = 0.08). The duration of postoperative hospitalization did not differ between the two groups (5.4 days vs. 5.8 days, p = 0.4). CONCLUSIONS: Administration of remifentanil by TCI for DS in spontaneously breathing patients offers stable anesthesia conditions, with a lower amount of drugs, higher hemodynamic stability, and decreased side effects. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Synthetic cathinones (SCs) are new psychoactive substances with sympathomimetic effects, which emerged into the illegal drug market to replace controlled stimulants. Since every year more powerful and toxic substances enter the illicit market, there is the need for analytical methodologies able to detect these new compounds in conventional and non-conventional biological matrices. We sought to develop and validate a targeted screening and quantification method for thirty-two parent SCs and two metabolites in hair samples by ultra-high-performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS). MATERIALS AND METHODS: 20 mg hair samples were soaked in 250 µL of 2 mM ammonium formate, methanol and acetonitrile mixture (50/25/25, v/v/v) and incubated overnight at 40°C. After incubation, the samples were evaporated to dryness under nitrogen stream and reconstituted with 100 µL of mobile phase mix (A:B, 80:20) and 10 µL were injected into UHPLC-HRMS. A Q ExactiveTM Focus Orbitrap Mass spectrometer with full scan and targeted data-dependent MS/MS scan acquisition was used for the screening and quantitation analysis. RESULTS: The assay was linear from 5 to 500 pg/mg hair for all the analytes under investigation. Intra-day and inter-day precision were always < 15% and matrix effect and analytical recovery were always within acceptable criteria (±25% and >50%, respectively). The developed method was applied to authentic hair samples from SCs consumers. The most prevalent found SCs were 3,4-Methylenedioxy-a-Pyrrolidinohexanophenone with a concentration range of 6.0-1,000.0 pg/mg along with a-Pyrrolidinohexiophenone (54.0 and 554.0 pg/mg, respectively), 3-Methylmetcathinone (556.0 and 5,000.0 pg/mg) and 4-Methylethcathinone (11.5 and 448.0 pg/mg). CONCLUSIONS: The developed method showed good selectivity, specificity, an easy and low-cost sample preparation and an analysis time compatible with a high throughput laboratory. [ABSTRACT FROM AUTHOR]

Most common prostaglandin analogs, bimatoprost, latanoprost and travoprost, are licensed for the reduction of elevated intraocular pressure in patients with open angle glaucoma and ocular hypertension, but their non approved use as eyelash enhancers is becoming popular, especially in patients with eyelashes hypotrichosis. A fast and sensitive high performance liquid chromatography tandem mass spectrometry method was developed for the measurement of bimatoprost, latanoprost and travoprost in cosmetic serums freely web-sold to increase eyelash length, thickness and darkness. The analytes and the internal standard (reserpine) were separated by reversed phase chromatography with 5 mM ammonium acetate with 0.02% formic acid (mobile phase A) and 5 mM ammonium acetate in acetonitrile/water (95/5; v/v) with 0.02% formic acid (mobile phase B) by gradient elution and detected with tandem mass spectrometry operated in multiple reaction monitoring mode. Linearity between 1 and 500 μg/g shows good correlation coefficients (r2 = 0.99) for all substances. Analytical recovery of analytes under investigation were always higher than 90% and intra-assay and inter-assay precision and accuracy always better than 11%. This method was successfully applied to analyze cosmetic serums freely sold on the Internet websites.

OBJECTIVE: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder associated with vascular complications including acute myocardial infarction (AMI). AMI pathogenesis in APS is considered to be acute thrombosis of coronary arteries, in contrast to typical AMI where the pathogenesis is atherosclerotic plaque rupture. Therapeutic management is therefore a clinical challenge. There is no consensus among experts about optimal antithrombotic therapy in secondary prevention. The role of coronary stents is still to be determined, due to the higher rates of stent thrombosis after percutaneous coronary intervention (PCI) in APS patients. CASE REPORT: We described the case of a 51-year-old male, smoker, that presented with anterior ST elevation myocardial infarction (STEMI) as first manifestation of APS. The patient underwent primary PCI on left main and ostial left anterior descending artery. RESULTS: We discussed antithrombotic therapy management after PCI in our patient and reviewed literature on current therapeutic management of this specific population. CONCLUSIONS: APS patients with STEMI should undergo PCI, usually associated with thrombus aspiration, and in select cases stent implantation in the culprit lesion. In the latter case, triple antithrombotic therapy with shortterm dual antiplatelet therapy and long-term anticoagulant therapy is recommended. Clinicians should include autoimmune etiologies in the differential diagnosis of underlying causes of AMI. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the meta-analysis was to assess post-procedural outcome of the new generation of transcatheter aortic valve implantation (TAVI) devices, focusing on the transfemoral and balloon-expandable SAPIEN 3 (Edwards Lifesciences Inc., Irvine, CA, USA), the self-expanding CoreValveTM Evolut series R and PRO (R/PRO)TM (Medtronic Inc., Minneapolis, MN, USA) and ACURATE neo™ transcatheter aortic valve (Symetis SA, a Boston Scientific company, Ecublens, Switzerland). MATERIALS AND METHODS: All observational studies were retrieved through PubMed computerized database from January 2014 until June 30th, 2019. The risk difference (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. The primary end point was 30-day mortality. Safety end points included: (i) stroke, (ii) moderate/severe paravalvular leak, and (iii) the need for new permanent pacemaker implantation. RESULTS: Meta-analysis demonstrated no significant differences as regards to either 30-day mortality or stroke for all the groups of prostheses under comparison. ACURATE neo was associated with significantly less new permanent pacemaker implantation compared to SAPIEN 3 (RD: -0.06; 95% CI -0.08 to -0.03; p<0.0001; I2=0%) or to EVOLUT R/PRO (RD: -0.06; 95% CI -0.09 to -0.02; p=0.0009; I2=0%). A significant reduction of new permanent pacemaker need was observed in the group of patients implanted with SAPIEN 3 compared to EVOLUT R/PRO (RD: -0.07; 95% CI -0.09 to -0.04; p<0.00001; I2=7%). The occurrence of moderate/severe leak was significantly increased in the group of patients implanted with ACURATE neo vs. SAPIEN 3 (RD: 0.04; 95% CI 0.02 to 0.05; p<0.00001; I2=0%). No significant differences were found between ACURATE neo vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.02; p=0.69; I2=0%) and between SAPIEN 3 vs. EVOLUT R/PRO (RD: -0.01; 95% CI -0.04 to 0.01; p=0.28; I2=73%). CONCLUSIONS: The results of the meta-analysis show that: (1) ACURATE neo was associated with significantly less new permanent pacemaker implantation than SAPIEN 3 and EVOLUT R/PRO; (2) SAPIEN 3 had significantly lower occurrence of moderate/severe valvular leak than ACURATE neo. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We studied the impact of transcatheter aortic valve implantation (TAVI) compared to the surgical aortic valve replacement (SAVR) on 30-day and one-year mortality from randomized controlled trials (RCTs) in patients with severe aortic stenosis at high or low-intermediate surgical risk. MATERIALS AND METHODS: All RCTs were retrieved through PubMed computerized database and the site https://www.clinicaltrials.gov from January 2010 until March 31st, 2019. The absolute risk reduction (RD) with the 95% confidence interval (CI) was used to assess the effectiveness of the intervention under comparison. We evaluated overall mortality rates at 30-day and one-year follow-up in the comparison between TAVI vs. SAVR. We also evaluated the role played by the site access for TAVI performed through the femoral or subclavian artery (TV-TAVI) vs. SAVR, or transapically (TA-TAVI) vs. SAVR. RESULTS: In the "as-treated population" the overall 30-day mortality was significantly lower in TAVI (p=0.03) with respect to SAVR. However, the analysis for TAVI subgroups showed that 30-day mortality was (1) significantly lower in TV-TAVI vs. SAVR (p=0.006), (2) increased, not significantly, in TA-TAVI vs. SAVR (p=0.62). No significant differences were found between TAVI vs. SAVR at one-year follow-up. CONCLUSIONS: The results of our meta-analysis suggest that TV-TAVI is a powerful tool in the treatment of severe aortic stenosis at high or low-intermediate surgical risk, with a significant lower mortality with respect to SAVR. On the contrary, SAVR seems to provide better results than TA-TAVI. [ABSTRACT FROM AUTHOR]

The article offers information on the importance of gamma-hydroxybutyric acid (GHB) detection in biological matrices of unconscious and conscious consumers in many forensic and clinical settings because of its recreational use purposes in 2019. The primary issue in the analytical determination of GHB concentrations in keratin matrices and biological fluids derives from the significance to be able to identify endogenous GHB of an illegal drug from exogenous administration.