Search Results (79)

Background: According to scientific literature, some 99% of patients affected by Alzheimer’s disease (AD) suffer from behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms (NPSs). In particular, agitation is one of the most difficult disorders to treat. States of agitation represent a very serious problem as they make these subjects dangerous for themselves and others and worsen as the disease advances. To date, there are no specific solutions for treating agitation. The only authorized drug is risperidone (as well as brexpiprazole, approved by the FDA on 11 May 2023), which can be used for no longer than 6–12 weeks because it increases the risk of death—owing to cardiocerebrovascular accidents—by 1.6–1.7 times. Methods: In order to address the latter noteworthy unmet medical need, NanoBEO was produced. The aim of the present work is to generate the health technology assessment (HTA) of this nanotechnological device. The latter consists of a controlled release system, based on solid lipid nanoparticles loaded with bergamot essential oil (BEO). Results: The results of the present research assessed the current evidence in the field of non-pharmacological treatments for this condition, including relevant primary preclinical and clinical data studies supporting the use of this device and the production of the operative plan for its launch on the market. The findings offer recommendations for decision-making on its implementation in dementia. Conclusions: NanoBEO represents a public-worth innovation in this neglected area, marking a significant advancement in the history of dementia, moving from academic research to product development. Full article

Background: The abuse of psychoactive substances presents challenges in clinical and forensic toxicology. The emergence of novel and potent drugs that pose significant health risks, in particular towards frequent abusers and users unaware of the ingredients, further complicates the situation. Designer benzodiazepines have become a fast-growing subgroup of these new psychoactive substances (NPSs), and their overdose may potentially turn fatal, especially when combined with other central nervous system depressants. In 2021, flubrotizolam, a potent thieno-triazolo designer benzodiazepine, emerged on the illicit market, available online as a “research chemical”. The identification of markers of consumption for this designer benzodiazepine is essential in analytical toxicology, especially in clinical and forensic cases. Methods: We therefore aimed to identify biomarkers of flubrotizolam uptake in ten-donor-pooled human hepatocytes, applying liquid chromatography high-resolution mass spectrometry and software-aided data mining supported by in silico prediction tools. Results: Prediction studies resulted in 10 and 13 first- and second-generation metabolites, respectively, mainly transformed through hydroxylation and sulfation, methylation, and glucuronidation reactions. We identified six metabolites after 3 h human hepatocyte incubation: two hydroxylated metabolites (α- and 6-hydroxy-flubrotizolam), two 6-hydroxy-glucuronides, a reduced-hydroxy-N-glucuronide, and an N-glucuronide. Conclusions: We suggest detecting flubrotizolam and its hydroxylated metabolites as markers of consumption after the glucuronide hydrolysis of biological samples. The results are consistent with the in vivo metabolism of brotizolam, a medically used benzodiazepine and a chloro-phenyl analog of flubrotizolam. Full article

New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae. Full article

The global rise of new psychoactive substances (NPSs) poses challenges for their analysis in biological matrices due to their complex chemistries and short market lifespan. A comparative study for the simultaneous extraction, separation, and detection of 19 NPSs was conducted. Six solid-phase extraction (SPE) methods and one supported liquid extraction method (SLE) were compared for the extraction of analytes from blood, serum, plasma, and urine. Comparisons of four derivatization agents were conducted, at four temperatures and two incubation times. Extraction methods were assessed by precision, sensitivity, and extraction efficiency. Derivatizing agents were assessed on their selectivity and sensitivity, and a three-way ANOVA was conducted to determine statistical significance. CSDAU SPE cartridges were shown to be the most efficient when extracting analytes from blood, serum, and plasma, whereas Xcel I cartridges performed the strongest when extracting analytes from urine. SPE extraction efficiencies, when utilizing the best-performing cartridges, ranged from 49 to 119%. SLE successfully extracted all analytes from all matrices (ranging from 22 to 120%). Pentafluoropropionic anhydride: ethyl acetate was the most successful derivatizing agent, allowing all analytes to be detected, with the highest peak area responses and more unique spectra. The optimum temperature for incubation was 37 °C, with no statistical difference found between the two incubation times. Full article

This six-year multicentre study investigated acute intentional poisoning with substances of abuse in adolescents to identify changes and patterns in substance use. Data from 562 adolescents were collected from three paediatric poison centres in Romania between January 2017 and December 2022. This study analysed the epidemiological and sociodemographic characteristics of the adolescents, including age, gender, place of residence, history of substance abuse, psychiatric history, and history of institutionalised care. The findings revealed that cannabis and new psychoactive substances (NPSs) are the most commonly implicated substances, each with distinct profiles among adolescents. Cannabis was involved in 46.1% of cases, with a significant association with urban residency. NPSs were identified as the second most prevalent substance, accounting for 39.3% of cases. These were more prevalent in rural areas and among patients with psychiatric disorders. Cannabis and NPSs were also the most commonly implicated substances in acute intentional poisoning cases with substances of abuse. These substances have distinct profiles among adolescents, including age, gender, residency area, history of substance abuse, psychiatric history, and institutional care. These findings underscore the necessity of targeted public health interventions and integrated care approaches to address substance use and related mental health issues in adolescents. Full article

Computational models of turbofans that are oriented to assist the design and testing of innovative components are of fundamental importance in order to reduce their environmental impact. In this paper, we present an effective method for developing numerical turbofan models that allows reliable steady-state turbofan performance calculations. The main difference between the proposed method and those used in various commercial algorithms, such as GasTurb, GSP 12 and NPSS, is the use of neural networks as a multidimensional interpolation method for rotational component maps instead of classical $\beta$ parameter. An additional aspect of fundamental importance lies in the simplicity of implementing this method in Matlab and the high degree of customization of the turbofan components without performing any manipulation of variables for the purpose of reducing the dimensionality of the problem, which would normally lead to a high condition number of the Jacobian matrix associated with the nonlinear turbofan system (and, thus, to significant error). In the proposed methodology, the component behavior can be modeled by analytical relationships and through the use of neural networks trained from component bench test data or data obtained from CFD simulations. Generalization of rotational component maps by feedforward neural networks leads to an average interpolation error up to around $1\%$, for all variables. The resulting nonlinear system is solved by a combined genetic algorithm and least squares algorithm approach, instead of the standard Newton’s method. The turbofan numerical model turns out to be convergent, and results suggest that the trend in overall turbofan performance, as flight conditions change, is in agreement with the outputs of the GSP 12 software. Full article

Despite emerging evidence indicating that molecular SARS-CoV-2 tests performed on saliva have diagnostic sensitivity and specificity comparable to those observed with nasopharyngeal swabs (NPSs), most in vivo follow-up studies on the efficacy of drugs against SARS-CoV-2 have been performed on NPSs, not considering saliva as a possible alternative matrix. For this reason, in this study, we used, in parallel, saliva and NPS samples for the detection of SARS-CoV-2 by real-time RT-PCR in patients receiving Tixagevimab/Cilgavimab, Nirmatrelvir/Ritonavir, or Sotrovimab as a treatment against SARS-CoV-2. Our results showed a good correlation between the NPS and saliva samples for each drug; moreover, comparable changes in the cycle threshold (Ct) levels in saliva and NPSs were observed both 7 days and 30 days after treatment, thus confirming that the saliva represents a good matrix for in vivo follow-up studies verifying the effectiveness of treatments against SARS-CoV-2. Full article

The widespread use of novel psychoactive substances (NPSs)—defined as new narcotic or psychotropic agents not classified under the Single Convention on Narcotic Drugs of 1961 or the Convention on Psychotropic Substances of 1971—poses a significant challenge to contemporary mental health paradigms due to their impact on psychiatric disorders. This study revisits and expands upon the theory of mental automatism as proposed by Gaëtan Gatian de Clérambault, aiming to elucidate the psychopathological mechanisms underlying substance-induced psychoses (SIP) and their distinction from non-induced psychoses (schizophrenia and related disorders). Through a phenomenological and clinical investigation, we explore the relevance of mental automatism in the development of toxic psychoses, drawing upon the historical and contemporary literature. This research highlights the psychopathological distinctions between induced and non-induced psychoses and the transition mechanisms from acute to chronic psychosis states. De Clérambault’s theory, supplemented by Janet, Jackson, and Bonhoeffer’s contributions, provides a foundational framework for understanding the genesis of SIP. Our findings suggest that NPS consumption, particularly among adolescents and psychiatric patients, significantly correlates with increased risks of SIP, marked by a transition to chronicity influenced by biological lesions triggered by substance use. Furthermore, we propose a comprehensive framework for SIP, integrating mental automatism, psychopathological distinctions, and transition mechanisms. This framework aims to refine diagnostic criteria and therapeutic approaches, addressing gaps in clinical practice and research. The study underscores the need for a nuanced understanding of SIP, advocating for a paradigm shift in psychiatric assessment and treatment approaches to better address the complexities of substance-induced mental health disorders. Full article

SARS-CoV-2 is a highly infectious virus responsible for the COVID-19 pandemic. Therefore, it is important to assess the risk of SARS-CoV-2 infection, especially in persistently positive patients. Rapid discrimination between infectious and non-infectious viruses aids in determining whether prevention, control, and treatment measures are necessary. For this purpose, a method was developed and utilized involving a pre-treatment with 50 µM of propidium monoazide (PMAxx, a DNA intercalant) combined with a digital droplet PCR (ddPCR). The ddPCR method was performed on 40 nasopharyngeal swabs (NPSs) both before and after treatment with PMAxx, revealing a reduction in the viral load at a mean of 0.9 Log copies/mL (SD ± 0.6 Log copies/mL). Furthermore, six samples were stratified based on the Ct values of SARS-CoV-2 RNA (Ct < 20, 20 < Ct < 30, Ct > 30) and analyzed to compare the results obtained via a ddPCR with viral isolation and a negative-chain PCR. Of the five samples found positive via a ddPCR after the PMAxx treatment, two of the samples showed the highest post-treatment SARS-CoV-2 loads. The virus was isolated in vitro from both samples and the negative strand chains were detected. In three NPS samples, SARS CoV-2 was present post-treatment at a low level; it was not isolated in vitro, and, when detected, the strand was negative. Our results indicate that the established method is useful for determining whether the SARS-CoV-2 within positive NPS samples is intact and capable of causing infection. Full article

Drug abuse represents a significant public health problem with a growing tendency. As a way of circumventing the strict national and international control of psychoactive substances by regulatory agencies, there is a market release of new substances with psychoactive activity, called New Psychoactive Substances (NPSs). This group of substances encompasses a diverse range of synthetic compounds designed to mimic the effects of traditional illicit substances. As NPSs show stronger psychoactive effects than classical drugs, they pose unique challenges to public health and regulatory frameworks. Additionally, some substances are considered NPSs in some countries but not in others. Therefore, based on a given legal definition, manufacturers can create an NPS that does not fall under that definition and thus is not prohibited. This review critically explores the multifaceted dimensions of the criminal and legal contexts associated with NPSs. It examines the trends of abuse, the intricate network of criminal and legal aspects surrounding these substances, and the crucial warning signs that indicate their emergence, highlighting the health risks posed by these substances. In conclusion, this manuscript addresses the intricate interplay between the pharmacology, risks, and regulatory responses. These multifaceted challenges associated with NPSs will likely provide valuable insights for future research. Full article

Respiratory tract infections (RTIs) pose a substantial health burden worldwide, especially among immunocompromised groups like cancer patients. The aim of this prospective cohort study was to explore lower respiratory tract infections in cancer patients. We followed 107 cases with clinically or radiologically suspected lower respiratory tract infections until discharge or death, comprising 65 males and 42 females across diverse age groups. Clinical evaluations, including patient history, examination, and malignancy diagnosis, were conducted. Nasopharyngeal swabs (NPSs), sputum samples, and blood samples were collected within 24 h of symptom onset. Multiplex Real-Time PCR allowed for the simultaneous detection of viral, bacterial, and fungal infections, while conventional microbiological culture methods were used for bacterial and fungal analysis. SARS-CoV-2 infection was excluded in all of the enrolled patients using real-time RT-PCR. Hematological and biochemical analyses included hemoglobin, lymphocyte, neutrophil, and platelet counts, along with ALT, AST, creatinine, and CRP levels. Significant differences were noted in clinical presentations, management outcomes, and prognostic markers among patients with different hematological malignancies. Distinct clinical profiles were identified for leukemia, lymphoma, and solid tumors, with variations in age distribution and symptom prevalence. ICU admission rates varied significantly, with solid tumor patients exhibiting higher rates. The hematological and biochemical biomarkers differed across malignancies, with notable associations between lymphopenia, thrombocytopenia, and mortality following respiratory episodes. This study highlights the critical role of rapid pathogen detection and infection control measures in safeguarding vulnerable cancer patients from nosocomial transmission. Full article

This study reports the first application of in silico methods to assess the toxicity of 4-chloromethcathinone (4-CMC), a novel psychoactive substance (NPS). Employing advanced toxicology in silico tools, it was possible to predict crucial aspects of the toxicological profile of 4-CMC, including acute toxicity (LD₅₀), genotoxicity, cardiotoxicity, and its potential for endocrine disruption. The obtained results indicate significant acute toxicity with species-specific variability, moderate genotoxic potential suggesting the risk of DNA damage, and a notable cardiotoxicity risk associated with hERG channel inhibition. Endocrine disruption assessment revealed a low probability of 4-CMC interacting with estrogen receptor alpha (ER-α), suggesting minimal estrogenic activity. These insights, derived from in silico studies, are critical in advancing the understanding of 4-CMC properties in forensic and clinical toxicology. These initial toxicological findings provide a foundation for future research and aid in the formulation of risk assessment and management strategies in the context of the use and abuse of NPSs. Full article

Novel psychoactive substances (NPSs) are compounds plotted to modify the chemical structures of prohibited substances, offering alternatives for consumption and evading legislation. The prompt emergence of these substances presents challenges in health concerns and forensic assessment because of the lack of analytical standards. A viable alternative for establishing these standards involves leveraging in silico methods to acquire spectroscopic data. This study assesses the efficacy of utilizing infrared spectroscopy (IRS) data derived from density functional theory (DFT) for analyzing NPSs. Various functionals were employed to generate infrared spectra for five distinct NPS categories including the following: amphetamines, benzodiazepines, synthetic cannabinoids, cathinones, and fentanyls. PRISMA software was conceived to rationalize data management. Unsupervised learning techniques, including Hierarchical Cluster Analysis (HCA), Principal Component Analysis (PCA), and t-distributed stochastic neighbor embedding (t-SNE), were utilized to refine the assessment process. Our findings reveal no significant disparities among the different functionals used to generate infrared spectra data. Additionally, the application of unsupervised learning demonstrated adequate segregation of NPSs within their respective groups. In conclusion, integrating theoretical data and dimension reduction techniques proves to be a powerful strategy for evaluating the spectroscopic characteristics of NPSs. This underscores the potential of this combined methodology as a diagnostic tool for distinguishing IR spectra across various NPS groups, facilitating the evaluation of newly unknown compounds. Full article

Ketamine derivatives such as deschloroketamine and deschloro-N-ethyl-ketamine show dissociative and psychoactive properties and their abuse as new psychoactive substances (NPSs) has been reported. Though some information is available on the biotransformation of dissociative NPSs, data on deschloro-N-cyclopropyl-ketamine deschloro-N-isopropyl-ketamine and deschloro-N-propyl-ketamine concerning their biotransformation and, thus, urinary detectability are not available. The aims of the presented work were to study the in vivo phase I and II metabolism; in vitro phase I metabolism, using pooled human liver microsomes (pHLMs); and detectability, within a standard urine screening approach (SUSA), of five deschloroketamine derivatives. Metabolism studies were conducted by collecting urine samples from male Wistar rats over a period of 24 h after their administration at 2 mg/kg body weight. The samples were analyzed using liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) and gas chromatography–mass spectrometry (GC-MS). The compounds were mainly metabolized by N-dealkylation, hydroxylation, multiple oxidations, and combinations of these metabolic reactions, as well as glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected. For the LC-HRMS/MS SUSA, compound-specific metabolites were identified, and suitable screening targets could be recommended and confirmed in pHLMs for all derivatives except for deschloro-N-cyclopropyl-ketamine. Using the GC-MS-based SUSA approach, only non-specific acetylated N-dealkylation metabolites could be detected. Full article

As the management areas for NPS pollution continue to increase, it is essential to conduct a situation analysis considering the regional characteristics and the scope of pollution reduction. In this study, the focus is on differentiating regional (urban, agricultural) characteristics to enhance water quality and reduce pollution loads in the increasing management areas for NPSs. Furthermore, priority management areas are identified based on urgency and vulnerability, and management strategies are proposed. The assessment involved evaluating both streamflow and water quality (T-P) using long-term monitoring data and watershed models (SWAT and HSPF) that take into account regional characteristics. The results indicated notable regional improvements, with T-P pollution reductions ranging from 20.7% to 26.8% and T-P concentration reductions ranging from 16.4% to 24.7% compared to baseline conditions in unmanaged areas. Based on these research findings, it is anticipated that the efficient and effective management of NPS pollution can be implemented on a regional basis. Moreover, the results of this study will not only contribute to the establishment of pollution standards, but also significantly impact the evaluation and proposal of management objectives, thereby making a substantial contribution to national water quality policies. Full article