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35 pages, 2538 KB  
Review
Carbon Nanotube-Based Biosensors for Non-Invasive Biofluid Analysis
by Samriddha Dutta and Ashok Mulchandani
Biosensors 2026, 16(8), 431; https://doi.org/10.3390/bios16080431 - 7 Aug 2026
Viewed by 81
Abstract
Carbon nanotube (CNT)-based biosensors have emerged as promising platforms for non-invasive biofluid analysis because of their high electrical conductivity, large surface area, tunable optical properties, and versatile surface chemistry, enabling miniaturized, flexible sensing devices. Sweat, saliva, tears, and urine are increasingly recognized as [...] Read more.
Carbon nanotube (CNT)-based biosensors have emerged as promising platforms for non-invasive biofluid analysis because of their high electrical conductivity, large surface area, tunable optical properties, and versatile surface chemistry, enabling miniaturized, flexible sensing devices. Sweat, saliva, tears, and urine are increasingly recognized as attractive alternatives to blood for point-of-care diagnostics because they enable repeated, non-invasive sampling while containing clinically relevant metabolites, electrolytes, proteins, hormones, nucleic acids, pathogens, and other biomarkers. However, the low abundance of many analytes, matrix complexity, biofouling, and biofluid-specific variability present significant analytical challenges. This review critically examines the different CNT-based sensor architectures, and their recent advances in non-invasive analysis of sweat, saliva, tears, and urine. It integrates sensor architecture, biofluid-specific analytical challenges, sample-validation level, and translational readiness within a single comparative framework. Representative applications are discussed for metabolic monitoring, renal health assessment, infectious disease testing, and other clinically relevant uses. Beyond clinical diagnostics, emerging non-clinical applications, including drug-of-abuse detection, forensic body-fluid identification, and occupational or environmental exposure assessment, are also highlighted. Finally, we discuss key barriers limiting real-world translation of CNT biosensors, including material reproducibility issues, biofouling, physiological interpretation of biofluid biomarkers, scalable manufacturing, and long-term operational stability, and outline future strategies to advance these platforms toward robust, reliable, and widely deployable biosensing technologies. Full article
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24 pages, 10228 KB  
Article
Involvement of NLRP3 Inflammasome in Methamphetamine Augmentation of SARS-CoV-2 N-Protein-Induced Neuroinflammation in Rat Microglial Cells
by Debashis Dutta, Jianuo Liu and Huangui Xiong
Int. J. Mol. Sci. 2026, 27(15), 6960; https://doi.org/10.3390/ijms27156960 - 3 Aug 2026
Viewed by 234
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes an immune-mediated neurological syndrome, which persists long after infection. Mechanisms for SARS-CoV-2-associated neurological complications are multifactorial, with an increased risk of drug abuse such as methamphetamine (meth). SARS-CoV-2 infection and its viral proteins play [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes an immune-mediated neurological syndrome, which persists long after infection. Mechanisms for SARS-CoV-2-associated neurological complications are multifactorial, with an increased risk of drug abuse such as methamphetamine (meth). SARS-CoV-2 infection and its viral proteins play pivotal roles in coronavirus disease 2019 (COVID-19)-associated neuroinflammation, which can lead to long COVID. We hypothesize that meth augments activation of the microglial NOD-, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome by the SARS-CoV-2 nucleocapsid (N) protein, resulting in neuroinflammation. To test this hypothesis, we investigated the effect of N-protein and meth on NLRP3 inflammasome activation in primary rat microglial cultures using enzyme-linked immunosorbent assay (ELISA), Reverse Transcription quantitative Polymerase Chain reaction (RT-qPCR), western blot (WB), and immunofluorescence assay (IFA). Our results showed that meth augmented N-protein-induced microglial activation, as evidenced by increased ionized calcium-binding adapter 1 (Iba-1) expression. The addition of meth to the microglial cultures treated with N-protein increased proinflammatory cytokine production. Meth augmentation of N-protein-induced neuroinflammation was further supported by increased inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) production. The effects of meth on N-protein-associated inflammatory responses were significantly attenuated by MCC950, a specific NLRP3 inhibitor. Moreover, meth-associated NLRP3 activation was either blocked by the opioid sigma1-receptor (σ1-R) inhibitor BD1047 or by σ1R siRNA knockdown. Taken together, these results demonstrated that meth augmented SARS-CoV-2 N-protein-induced neuroinflammation via microglial σ1-R and the NLRP3 inflammasome, which may underlie the pathogenesis of neurological manifestations in COVID-19, such as long COVID with meth abuse. These results may also underscore the impact of drug abuse on long COVID and provide targets for the development of therapeutic strategies to control the neurological outcomes of long COVID. Full article
(This article belongs to the Special Issue Molecular Research on Inflammasome Signaling)
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14 pages, 321 KB  
Article
Perinatal Deaths: Autopsy Findings and Medico-Legal Evaluation from a Forensic Medicine Perspective
by Sertac Dalgic, Abuzer Gulderen, Murat Kamalak and Ibrahim Uzun
Diagnostics 2026, 16(15), 2341; https://doi.org/10.3390/diagnostics16152341 - 27 Jul 2026
Viewed by 201
Abstract
Background: Perinatal deaths remain a major public health concern and present unique medico-legal challenges. Forensic autopsy plays a crucial role in determining the cause of death, distinguishing live birth from stillbirth, assessing fetal viability, and identifying traumatic or non-natural causes of death. [...] Read more.
Background: Perinatal deaths remain a major public health concern and present unique medico-legal challenges. Forensic autopsy plays a crucial role in determining the cause of death, distinguishing live birth from stillbirth, assessing fetal viability, and identifying traumatic or non-natural causes of death. Methods: This retrospective study included all perinatal cases referred to the Gaziantep Forensic Medicine Group Presidency between 2021 and 2024. Demographic characteristics, gestational age, autopsy findings, histopathological and toxicological examinations, hydrostatic lung test results, and final forensic diagnoses were evaluated. Results: Seventeen of 339 infant forensic cases met the inclusion criteria. Fourteen underwent complete forensic autopsy, whereas three were evaluated by external postmortem examination and medical records. Despite a multidisciplinary forensic investigation that included external examination, complete forensic autopsy, systematic macroscopic organ evaluation, routine histopathological examination, hydrostatic lung flotation testing, toxicological analysis when indicated, review of maternal medical and obstetric records, judicial investigation records, and placental and umbilical cord histopathology whenever available, no definitive cause of death could be established in six cases. Advanced decomposition prevented determination in two cases. One case was classified as an undiagnosed natural death, whereas no specific cause of death could be assigned in the remaining three cases. Placental examination was available in only a minority of cases, whereas umbilical cord histopathology was performed in nearly all autopsied cases. Causes of death included traumatic injury, pulmonary immaturity, intrauterine infection, congenital anomalies, maternal drug exposure, placental abruption, maternal disease, and umbilical cord pathology. Conclusions: Perinatal death investigations require a multidisciplinary forensic approach integrating autopsy, histopathology, toxicology, placental examination, and clinical information. Beyond determining the cause of death, forensic evaluation is essential for assessing live birth, fetal viability, suspected abuse, maternal violence, medical malpractice, and criminal investigations. Full article
(This article belongs to the Section Forensic Diagnostics)
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13 pages, 5276 KB  
Article
Development of a Quantum Dot-Based Immunochromatographic Assay for Rapid and Sensitive Detection of Non-Medical Etomidate Abuse
by Xin Yan, Liwei Jiang, Xiaolong Zhang, Yizhe Zhao, Zixin Wan, Jun Ma, Chunhui Song, Yikai Wang and Xingliang Liu
Biosensors 2026, 16(8), 404; https://doi.org/10.3390/bios16080404 - 24 Jul 2026
Viewed by 271
Abstract
Etomidate is an ultrashort-acting imidazole-derived intravenous anesthetic. The non-medical abuse of etomidate as a new psychoactive substance has emerged as a critical public health challenge globally, particularly among adolescents, necessitating sensitive, rapid detection methods for forensic analysis. This study developed a quantum dot-based [...] Read more.
Etomidate is an ultrashort-acting imidazole-derived intravenous anesthetic. The non-medical abuse of etomidate as a new psychoactive substance has emerged as a critical public health challenge globally, particularly among adolescents, necessitating sensitive, rapid detection methods for forensic analysis. This study developed a quantum dot-based immunochromatographic test strip and a corresponding rapid detection method for the sensitive detection of etomidate acid in urine. CdSe/ZnS fluorescent quantum dot microspheres were used as labeling probes combined with specific monoclonal antibodies, and the detection protocol utilized a portable fluorescence reader. The method’s validation demonstrated a linear range of 10–2000 ng/mL (y = −0.231lnx + 0.5241, r = −0.991), with intra-batch and inter-batch coefficients of variation below 12%. The spike recovery rates ranged from 88.24% to 95.69%. Cross-reactivity testing against 12 common drugs and structural analogs showed no interference. The detection limit of 10 ng/mL represents a substantial improvement over conventional colloidal gold strips and approaches LC-MS/MS sensitivity. Assays of real urine specimens confirmed that the immunochromatographic test strip and detection method possess favorable accuracy and reliability. This fluorescent quantum dot-based immunochromatographic assay provides rapid, quantitative, and highly specific etomidate screening suitable for on-site forensic applications, effectively bridging front-end rapid testing with confirmatory laboratory analysis. Full article
(This article belongs to the Special Issue Biosensing Technologies in Medical Diagnosis—2nd Edition)
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20 pages, 698 KB  
Article
Predictors of Psychoactive and Nootropic Substance Use Among Romanian University Healthcare Students: The Interplay Between Academic Anxiety and Educational Advancement
by Ioana-Cezara Caba, Magdalena Iorga, Iustina-Gabriela Mihăianu, Luminița Agoroaei, Alexandra Jităreanu and Raluca Ortensia Cristina Iurcov
Healthcare 2026, 14(14), 2079; https://doi.org/10.3390/healthcare14142079 - 11 Jul 2026
Viewed by 403
Abstract
Background: The use of cognitive enhancers (CEs) is becoming increasingly widespread among students, especially in health fields, with significant implications for both academic performance and student well-being. The aim of the study was to investigate the use of CEs among healthcare university students [...] Read more.
Background: The use of cognitive enhancers (CEs) is becoming increasingly widespread among students, especially in health fields, with significant implications for both academic performance and student well-being. The aim of the study was to investigate the use of CEs among healthcare university students in relationship with stimulant intake, academic progression, and academic anxiety. Material and Methods: The cross-sectional study included 402 students enrolled in medical studies (general medicine, pharmacy, dentistry, and physiotherapy). Socio-demographic characteristics, health-related and academic data, lifestyle behaviors, and the consumption of different CEs were collected. The Academic Anxiety Scale was used to evaluate university students’ perceived stressors that contribute to academic anxiety. Data processing analysis was performed using IBM Statistical Package for Social Sciences. Results: The frequency of cognitive compound intake exhibits a positive correlation with the consumption of group B vitamins (r = 0.170, p = 0.001), tea (r = 0.158, p = 0.003), and coffee (r = 0.113, p = 0.031). Lecithin and Ginkgo biloba were significant independent predictors (p < 0.05) of enhanced alertness, memory, and academic performance. The only significant independent predictor of cardiovascular events (palpitations, tachycardia) is caffeine consumption, which increases the risk by nearly three times (OR = 2.96; p = 0.001). In terms of addictive risk, drinking caffeine raises the likelihood of being addicted by 4.78 times (p = 0.014). It has been demonstrated that the probability of using synthetic nootropics (piracetam/cerebrolysin) increases by 1.86 times (OR = 1.86, p = 0.021) as university education progresses (nN= 335). Academic anxiety had a mean score of 23.27 ± 7.38. Unemployed students exhibit markedly elevated anxiety levels compared to employed students. Respondents who justify the use of stimulants by feeling stressed or overwhelmed present the highest levels of academic distress, in contrast to those who use them to combat fatigue or out of curiosity. A large majority (95.0%) do not consider use of CEs as a form of cheating on examinations, and 88.9% are against its prohibition. Conclusions: The findings of this study highlight that many university students in the healthcare field use cognitive stimulants during periods of intellectual overload, with more than 40% of participants utilizing CEs daily or weekly in periods of academic stress. Overload schedule, academic stress, the knowledge about their positive effects, and psychosocial contexts influence consumption. Full article
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12 pages, 1599 KB  
Article
Large-Scale Forensic Surveillance of Seized E-Liquids Reveals an Emerging Etomidate-Analog-Centered Vaping Trend in Eastern Taiwan
by Huei-Ru Lin
Toxics 2026, 14(7), 604; https://doi.org/10.3390/toxics14070604 - 10 Jul 2026
Viewed by 607
Abstract
The growing use of e-cigarettes as vehicles for illicit drug delivery has created an urgent challenge for forensic surveillance and public health in East Asia. This study analyzed 496 e-liquid samples seized by law-enforcement agencies in Eastern Taiwan (January–July 2025) using a full-scan [...] Read more.
The growing use of e-cigarettes as vehicles for illicit drug delivery has created an urgent challenge for forensic surveillance and public health in East Asia. This study analyzed 496 e-liquid samples seized by law-enforcement agencies in Eastern Taiwan (January–July 2025) using a full-scan GC–MS workflow validated in accordance with ANSI/ASB forensic toxicology standards. Overall, 80.8% of samples (n = 401) tested positive for psychoactive substances, with 35.4% (n = 142) containing polydrug mixtures. Etomidate dominated detections (87.0% of positive cases), followed by isopropoxate (25.4%), ketamine (9.7%), metomidate (8.5%), propoxate (7.2%), and methamphetamine (7.2%); cannabinoids (Δ9-THC and Δ8-THC) were comparatively rare (2.0% each). Predominant polydrug profiles included sedative–analog, sedative–dissociative, and sedative–stimulant combinations of acute toxicological concern. The present Eastern Taiwan dataset revealed a distinct etomidate-analog-centered adulterant profile, in marked contrast to the cannabinoid-dominated patterns reported in published seizure datasets from North America, Europe, and the Middle East. To our knowledge, seized-e-liquid surveillance data of this scale have not previously been reported for Eastern Taiwan. These findings highlight the value of seized-material toxicology as an early-warning component of forensic surveillance and support adaptive, class-level regulatory responses to the rapidly evolving landscape of designer-anesthetic vaping. Full article
(This article belongs to the Special Issue Current Issues and Research Perspectives in Forensic Toxicology)
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25 pages, 2732 KB  
Review
Initial Drug Sensitivity and Vulnerability to Substance Use Disorders: A Review of Individual Influences
by Shaun Smith and Judith Grisel
Biology 2026, 15(13), 1077; https://doi.org/10.3390/biology15131077 - 5 Jul 2026
Viewed by 501
Abstract
Individual differences in the sensitivity and response to drugs of abuse are reliably associated with later patterns of substance use and, for some, progression to a substance use disorder diagnosis. This review synthesizes human drug challenge, longitudinal, and translational animal evidence to characterize [...] Read more.
Individual differences in the sensitivity and response to drugs of abuse are reliably associated with later patterns of substance use and, for some, progression to a substance use disorder diagnosis. This review synthesizes human drug challenge, longitudinal, and translational animal evidence to characterize how early or initial sensitivity to drugs, shaped by heritable and developmental factors, may relate to subsequent risk. These initial responses, through associative learning, may influence how drug-paired cues acquire motivational significance over time. Ample evidence suggests that early response variability is a biologically grounded and measurable correlate of SUD vulnerability, detectable well before chronic neuroadaptation, with potential utility for targeted prevention and intervention efforts. Full article
(This article belongs to the Section Behavioural Biology)
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21 pages, 2967 KB  
Article
Examining Current Trends in Addictive Substance Abuse Among Youth: Study on Prevalence of Emergency Service Interventions and Drug-Related Crime in the Slovak Republic
by Samuel Hubočan, Lukáš Valla, Katarína Kampová and Eva Sventeková
Youth 2026, 6(3), 86; https://doi.org/10.3390/youth6030086 - 4 Jul 2026
Viewed by 221
Abstract
Youth substance abuse represents a complex social and security problem which cannot be adequately captured solely through crime statistics. In the context of the Slovak Republic, there is a lack of systematic research linking healthcare data on intoxications with criminological indicators, which limits [...] Read more.
Youth substance abuse represents a complex social and security problem which cannot be adequately captured solely through crime statistics. In the context of the Slovak Republic, there is a lack of systematic research linking healthcare data on intoxications with criminological indicators, which limits the effective design of preventive measures. The research analyses substance abuse (according to ICD 10 F10–F19) among youth in the NUTS 3 regions of the Slovak Republic during 2019–2024 and their descriptive association with drug-related crime. Analysis is based on data provided by public administration entities—the National Health Information Centre of the Slovak Republic (data on youth hospitalisation), the Operational Centre of the Emergency Medical Service of the Slovak Republic (data on EMS call-outs) and the Ministry of Interior of the Slovak Republic (data on crime). The provided data represent the whole population of the Slovak Republic. To enable comparison between datasets, two standardised indices are constructed: an EMS index representing a number of EMS call-outs and urgent hospitalisations per 100,000 inhabitants of the respective youth age group and a crime index representing a number of drug-related criminal offences per 100,000 total regional inhabitants. A total of 4486 emergency interventions with F10–F19 diagnoses were identified, with the highest proportion being disorders caused by alcohol (F10), more common among juveniles (14–17) than in minors (6–13). The analysis identifies a moderate positive association between the regional EMS index for F10 and F11–F19 diagnoses (correl youth = 0.66; correl juveniles = 0.55) and a weak negative association between the F11–F19 EMS index and the drug-related crime index (correl youth = −0.28; correl minors = −0.52). The Pearson correlation coefficients are reported as descriptive indicators. Formal statistical inference was not the aim of this study. The findings suggest that crime statistics alone inadequately reflect the health risks of youth substance abuse, underscoring the need to link healthcare, criminological, and demographic data and to develop regionally targeted prevention. Full article
(This article belongs to the Special Issue Alcohol Use in Young People)
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23 pages, 1121 KB  
Article
The Emerging Burden of Opioid Poisoning in Brazil, 2019–2025: A Nationwide Epidemiological and Toxicovigilance Analysis
by Luíza Siqueira Lima, Diancarlos Pereira de Andrade, Viviane Serra Melanda, Ana Tereza Bittencourt Guimarães and Cláudia Sirlene Oliveira
Pharmaceuticals 2026, 19(7), 994; https://doi.org/10.3390/ph19070994 - 26 Jun 2026
Viewed by 405
Abstract
Background: Despite increasing opioid use in Brazil, the national epidemiological profile of opioid-related poisonings remains insufficiently characterized. Objective: To characterize opioid-notified poisonings reported in the Sistema de Informações sobre Agravos de Notificação (SINAN—Notifiable Diseases Information System), accessed through Departamento de Informática do Sistema [...] Read more.
Background: Despite increasing opioid use in Brazil, the national epidemiological profile of opioid-related poisonings remains insufficiently characterized. Objective: To characterize opioid-notified poisonings reported in the Sistema de Informações sobre Agravos de Notificação (SINAN—Notifiable Diseases Information System), accessed through Departamento de Informática do Sistema Único de Saúde (DATASUS—Department of Informatics of the Unified Health System), between 2019 and 2025. Methods: This retrospective descriptive study used secondary national surveillance data from publicly accessible databases. Records of exogenous poisonings related to medications and drugs of abuse were screened, and notifications involving opioid analgesics were identified and standardized. Descriptive analyses were performed for demographic, clinical, and exposure-related variables. Bivariate analyses and multivariable logistic regression, regression models were conducted for selected outcomes. Incidence rates were estimated by year and federative unit, and temporal trends were assessed using generalized linear mixed models. Results: Between 2019 and 2025, 1,127,265 poisonings related to medications and drugs of abuse were reported in Brazil, of which 12,645 involved opioids. The opioids most frequently implicated in notifications were codeine (38.65%), tramadol (33.98%), and morphine (17.86%). Most cases occurred in women (70.3%), in individuals aged 26–50 years (47.8%), and in residences (85.6%). Digestive exposure predominated (92.3%), and suicide attempt was the main circumstance (73.5%). Most patients recovered without sequelae (75.1%), whereas 1.6% died due to exogenous intoxication. Co-exposure information was classifiable in 9573 records, most commonly involving opioids and medications. In multivariable analyses, suicide attempts were associated with female sex (aOR = 1.98; 95% CI: 1.68–2.34), residence-based exposure (aOR = 8.95; 95% CI: 6.29–12.72), and co-exposure (aOR = 2.17; 95% CI: 1.82–2.60). Hospitalization was less likely among females (aOR = 0.83; 95% CI: 0.75–0.91) and more likely with co-exposure (aOR = 1.14; 95% CI: 1.02–1.27). Serious outcomes were associated with older age (aOR = 1.017; 95% CI: 1.009–1.026), while residence-based exposure and suicide attempt showed lower odds. A significant increasing temporal trend was identified, with higher reported notification rates observed in the South and Southeast regions. Discussion: The predominance of suicide attempts and residential digestive exposures suggests that the notification profile captured by SINAN/DATASUS is predominantly shaped by intentional self-poisoning and household medication availability, while still representing a broader toxicovigilance scenario involving abuse, habitual use, adverse reactions, and other exposure contexts. The contrast between the most frequent notification profile and the profile associated with serious outcomes indicates that occurrence and severity may follow different epidemiological patterns. Therefore, these findings should be interpreted as a toxicovigilance signal reflecting multiple exposure contexts rather than as evidence of a single opioid-use pattern. Conclusions: Reported opioid-notified poisonings in Brazil increased over the study period and were predominantly associated with domestic exposure, suicide attempts, and co-exposure to other substances. These findings highlight the clinical and public health relevance of opioid-notified poisonings and support the need for strengthened surveillance, improved reporting quality, and preventive strategies addressing both opioid use and mental health. Limitations: Underreporting, missing data, regional reporting differences, and possible misclassification in SINAN/DATASUS records; therefore, associations, temporal increases, and projections should be interpreted as exploratory, and hypothesis generating. Full article
(This article belongs to the Special Issue Pharmacology and Toxicology of Opioids, 2nd Edition)
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20 pages, 433 KB  
Article
“To Survive in This Society like a Normal Person”: Social Reintegration Challenges of Young People Who Use Drugs During Community-Based Drug Rehabilitation in China
by Zhihao Wei, Nazirah Hassan, Nur Saadah Mohamad Aun, Ezarina Zakaria, Sheng Chen and Xiaojin Liu
Societies 2026, 16(7), 202; https://doi.org/10.3390/soc16070202 - 24 Jun 2026
Viewed by 261
Abstract
Youth drug abuse is a persistent public health concern in China. Community-based drug rehabilitation (CBDR), the final three-year stage of China’s official rehabilitation system, aims to help people who use drugs (PWUD) reintegrate into society, but reintegration remains limited, particularly among young PWUD. [...] Read more.
Youth drug abuse is a persistent public health concern in China. Community-based drug rehabilitation (CBDR), the final three-year stage of China’s official rehabilitation system, aims to help people who use drugs (PWUD) reintegrate into society, but reintegration remains limited, particularly among young PWUD. This study explores the social reintegration challenges faced by young PWUD aged 18 to 35 during the CBDR stage in Guangzhou, China. Semi-structured interviews were conducted with 16 participants and analyzed using reflexive thematic analysis (RTA). Three themes were identified: stigma and relational struggles, socioeconomic marginalization and daily life disruption, and limitations of the CBDR service model. These challenges were not separate but reinforced one another, with difficulties in one domain spilling into others and narrowing the space in which reintegration could occur. These findings suggest that addressing the reinforcing linkages between stigma, economic hardship, and service limitations requires a more coordinated approach to CBDR service provision, one that integrates vocational support into relapse prevention, builds flexibility into surveillance procedures, and provides participants and their families with realistic, evidence-based information about the prospects of recovery. Full article
(This article belongs to the Collection Community-Based Rehabilitation and Community Rehabilitation)
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22 pages, 27777 KB  
Article
Subthreshold Thermal Stress Aggravates Methamphetamine-Induced Cardiomyocyte Pyroptosis via the Mitochondrial ROS/BAX/mtDNA/NLRP3 Pathway
by Mengmeng Wang, Congcong Hou, Menglian Hu, Dan Zhou, Xintao Wang, Mingyang Jin, Chunling Ma, Jianhong Shi and Zhiyu Ni
Int. J. Mol. Sci. 2026, 27(11), 5000; https://doi.org/10.3390/ijms27115000 - 31 May 2026
Viewed by 536
Abstract
Methamphetamine (METH)-induced cardiomyocyte injury is the leading cause of mortality beyond acute intoxication. METH abuse often occurs in crowded, poorly ventilated environments, and even moderately high ambient temperatures exacerbate METH-related cardiovascular emergencies. However, the underlying mechanisms by which environmental factors drive the progression [...] Read more.
Methamphetamine (METH)-induced cardiomyocyte injury is the leading cause of mortality beyond acute intoxication. METH abuse often occurs in crowded, poorly ventilated environments, and even moderately high ambient temperatures exacerbate METH-related cardiovascular emergencies. However, the underlying mechanisms by which environmental factors drive the progression of cardiac diseases remain poorly understood. This study modeled the real-world scenario in vivo by exposing mice to METH under normothermic condition (NC, 22 °C) or subthreshold thermal stress (STS, 28 °C, a mild thermal challenge for mice) conditions, and in vitro by using H9c2 cardiomyocytes exposed to METH at 37 °C or 39 °C. STS significantly potentiated METH-induced cardiac dysfunction, mitochondrial ultrastructural damage, and oxidative stress (p < 0.05). Mechanistically, the co-exposure impaired mitochondrial respiratory chain complex I and led to excessive mitochondrial ROS (mtROS) production, activating the pro-apoptotic protein BAX, causing mitochondrial outer membrane (MOM) permeabilization and the cytosolic release of mitochondrial DNA (mtDNA). Cytosolic mtDNA-mediated NLRP3 inflammasome activation subsequently executed cardiomyocyte pyroptosis via caspase-1/Gasdermin D (p < 0.05). Crucially, the mitochondria-targeted antioxidant mitoquinone (MitoQ) substantially attenuated the aggravated cardiotoxicity by scavenging the initial mtROS (p < 0.05), thereby preventing the activation of the downstream BAX/mtDNA/NLRP3 axis. These findings provide evidence for a defined signaling basis for this drug-environment interaction and highlight mitochondrial redox modulation as a potential therapeutic strategy for psychostimulant-associated cardiovascular injury. Full article
(This article belongs to the Special Issue Environmental Pollutants Exposure and Toxicity)
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17 pages, 961 KB  
Article
Detection of Nitazenes (2-Benzylbenzimidazoles)—Novel Synthetic Opioids in Coronial Casework in Victoria, Australia
by Lachlan Scully, Jared W. Castle, Matthew Di Rago, Hans H. de Boer, Jennifer Schumann, Kerryn Crump, Linda Glowacki and Dimitri Gerostamoulos
Metabolites 2026, 16(6), 358; https://doi.org/10.3390/metabo16060358 - 26 May 2026
Viewed by 892
Abstract
Background: The 2-benzylbenzimidazoles or nitazenes are an evolving class of highly potent mu-opioid receptor agonists. Nitazenes were originally developed in the late 1950s for pharmaceutical use as analgesics; however, due to their extreme potency and the risk of adverse health outcomes, pharmaceutical [...] Read more.
Background: The 2-benzylbenzimidazoles or nitazenes are an evolving class of highly potent mu-opioid receptor agonists. Nitazenes were originally developed in the late 1950s for pharmaceutical use as analgesics; however, due to their extreme potency and the risk of adverse health outcomes, pharmaceutical research was discontinued. Since 2019, nitazenes have emerged as illicit drugs of abuse, causing significant concern. From 2021, they have been detected in both coronial and clinical casework in Victoria, Australia. This study examined nitazene-related coronial casework in Victoria from 2021 to 2025 to explore the trends and characteristics of nitazene-related deaths. Methods: Relevant cases were identified from the Victorian Institute of Forensic Medicine’s (VIFM’s) case management system. Data were collated and analysed from all coronial cases where a nitazene was detected by a toxicological analysis between 1 January 2021 and 31 December 2025. Trend comparisons were made with nitazene detections reported in other countries. Results: Nitazenes were detected in 23 deaths from a total of approximately 33,108 coronial cases admitted to the VIFM for investigation over the time period. The age range was 17–45 years, with a median of 32 and with 87% of the deaths being male. The nitazenes detected were protonitazene (n = 14), metonitazene (n = 5), isotonitazene (n = 2), N-pyrrolidino etonitazene (n = 2), N-desethyl isotonitazene (n = 1), methylenedioxynitazene (n = 1) and etodesnitazene (n = 1). Two cases contained more than one nitazene; both involved protonitazene, one involved metonitazene, and the other involved N-desethyl isotonitazene and methylenedioxynitazene. The timeline of detection of these nitazenes displays similarities with emergence trends in other countries. The nitazene concentrations ranged from 0.1 to 33 ng/mL. Broad polydrug usage was evident in all cases, with other drugs co-detected in the blood including stimulants (particularly, methylamphetamine (48%) and cocaine (44%)) as well as pharmaceutical benzodiazepines (43%) and pharmaceutical opioids (22%), and 13% had 6-monoacetylmorphine detected in either blood or urine. Novel benzodiazepines (39%) were also common, including bromazolam, which was co-detected in 35% of cases. Nineteen deaths were attributed solely to nitazene-related mixed-drug toxicity, while the remaining four cases were attributed to cardiac- and pulmonary-related disease, with polydrug use deemed a contributing factor. Conclusions: This novel case series adds comprehensive toxicological information to the body of evidence reinforcing the high risk of harm associated with the use of nitazenes. It is imperative that toxicology services continue to monitor for nitazenes to promote community awareness against nitazene-related harm. Full article
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12 pages, 225 KB  
Review
Exploring Non-Pharmacological Interventions as Part of Multimodal Management to Prevent Opioid Misuse in Adults Prescribed Opioids for Chronic Pain
by Manar A. Alrashid, Maya S. Zumot and Salim Fredericks
J. Clin. Med. 2026, 15(11), 4079; https://doi.org/10.3390/jcm15114079 - 25 May 2026
Viewed by 646
Abstract
In recent years, there has been an unprecedented upsurge in opioid prescriptions for pain management. Consequently, the widespread availability of these medicines has led to an increase in misuse and abuse. This has led to a greater number of overdose-related deaths. The high [...] Read more.
In recent years, there has been an unprecedented upsurge in opioid prescriptions for pain management. Consequently, the widespread availability of these medicines has led to an increase in misuse and abuse. This has led to a greater number of overdose-related deaths. The high prevalence of drug misuse was born of multiple and complex societal factors. However, from a medical perspective, critical contributors to the dire consequences of the crisis have been the need for chronic pain relief, as well as mental health issues within communities. Chronic pain coupled with psychological distress exacerbates patients’ predicaments and thus further fuels the crisis. Anxiety and depression have bidirectional and complex relationships with pain. The somatic symptoms associated with anxiety potentially worsen pain, whilst pain emanating from a chronic condition worsens anxiety. The same relational dynamic applies to depression and pain. Thus, these psychopathological states may be major contributors to the opioid abuse epidemic. Thus, psychosocial management as a first-line treatment instead of starting with drug treatments seems an enlightened approach to this problem. Cognitive behavioral therapy (CBT) has been proven to be effective in managing specific symptoms associated with chronic pain. Similarly, patient education has been shown to be a viable alternative to drugs for certain aspects of chronic pain treatment. We consider that the opioid crisis could be addressed with a greater reliance and emphasis on non-pharmacological approaches to managing chronic pain patients. This mini-review examines non-pharmaceutical and monitoring-based interventions to reduce opioid misuse risk among adults prescribed opioids for chronic non-cancer pain. Studies were identified through PubMed/MEDLINE, Scopus, and Google Scholar using terms related to chronic pain, prescription opioid misuse, opioid use disorder, cognitive behavioral therapy, patient education, prescription drug monitoring programs, digital health, telehealth, and non-pharmacological interventions. Studies were included if they focused on adults with chronic pain who were prescribed opioids or at risk of misuse, and evaluated interventions aimed at reducing unsafe opioid use, misuse risk, or opioid-related harm. Evidence was synthesized narratively to identify key intervention approaches, limitations, and clinical implications. Full article
17 pages, 1370 KB  
Review
Application of Rapid Detection Technology for the Determination of γ-Hydroxybutyric Acid
by Nan Li, Xingliang Liu, Boyuan Shi, Chunhui Song, Teng Zhang, Xin Yan, Yingying Li, Xinyi Li and Jun Ma
Biosensors 2026, 16(5), 288; https://doi.org/10.3390/bios16050288 - 15 May 2026
Viewed by 652
Abstract
The abuse of γ-hydroxybutyric acid (GHB) and its precursors, γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), has increased in recent years, with these substances frequently being illicitly added to beverages. GHB is colorless and odorless and exhibits anesthetic and hypnotic psychoactive effects, which are often [...] Read more.
The abuse of γ-hydroxybutyric acid (GHB) and its precursors, γ-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), has increased in recent years, with these substances frequently being illicitly added to beverages. GHB is colorless and odorless and exhibits anesthetic and hypnotic psychoactive effects, which are often exploited in drug-facilitated sexual assault, posing a significant public safety concern. Chromatography–tandem mass spectrometry is a conventional analytical approach for narcotic drug determination due to its high sensitivity and accuracy; however, its large instrumentation footprint and high operational cost limit its suitability for on-site rapid screening. In response to the growing demand for field-deployable analytical tools, rapid detection technologies for GHB have progressively evolved. This review summarizes and compares the advantages and limitations of current rapid detection methods for GHB and discusses their potential future developmental trends, with the aim of providing a reference for researchers and relevant authorities. Full article
(This article belongs to the Special Issue Microfluidics for Sample Pretreatment)
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18 pages, 1602 KB  
Review
ING Proteins and Neural Development in Newborns from Alcohol- and/or Drug-Abusing Pregnant Women
by Sergio Terracina, Luigi Tarani, Mauro Ceccanti, Giovanna Blaconà, Marco Fiore and Giampiero Ferraguti
Int. J. Mol. Sci. 2026, 27(10), 4383; https://doi.org/10.3390/ijms27104383 - 14 May 2026
Viewed by 461
Abstract
Maternal consumption of alcohol and drugs during pregnancy can compromise neural development with long-lasting impact on individuals’ health. The inhibitor of growth (ING) family of proteins is an epigenetic regulator that plays a central role in fetal brain development, contributing to neural stem [...] Read more.
Maternal consumption of alcohol and drugs during pregnancy can compromise neural development with long-lasting impact on individuals’ health. The inhibitor of growth (ING) family of proteins is an epigenetic regulator that plays a central role in fetal brain development, contributing to neural stem cell maintenance, neuronal differentiation, and the regulation of genes involved in brain morphogenesis. Given the susceptibility of the developing nervous system to epigenetic dysregulation induced by alcohol and drugs, this narrative study aims to summarize literature evidence with the hypothesis that ING proteins may represent a critical but understudied mechanistic link between maternal substance dependence and adverse neurodevelopmental outcomes in newborns. We conducted a comprehensive literature search across three databases (PubMed, Scopus, and Web of Science) up to February 2026 to identify relevant studies. Search terms included combinations of “ING proteins”, “neural development”, “alcohol”, “drugs”, “epigenetic”, “oxidative stress” and “neuroinflammation”. The inclusion criteria were limited to original studies published in English that examined neural development in newborns; the exclusion criteria encompassed non-English publications, letters, editorials, and case reports, and those not directly addressing the specified topics. We identified 55 papers; six were excluded per the exclusion criteria, leaving 49 works discussed in this review. ING proteins are epigenetic regulators essential for embryonic and neural development, including neural stem cell fate and neurogenesis, while substances of abuse are disruptors of the essential pathways necessary for the right fetal brain development. Furthermore, substance abuse creates oxidative stress environments and activates pathways that require ING-mediated chromatin regulation. ING proteins likely act as mediators linking oxidative stress, neuroinflammation, and transcriptional reprogramming in the developing brain. Meanwhile, alcohol and drugs induce epigenetic reprogramming that may disrupt ING-mediated chromatin control. There is little evidence directly linking prenatal exposure (e.g., alcohol and drugs) to ING changes during fetal development. However, we hypothesize that ING proteins function as epigenetic stress response regulators whose disruption by oxidative stress, inflammation, and chromatin alterations induced by prenatal alcohol or drug exposure may contribute to impaired fetal neurodevelopment. Although direct experimental evidence remains limited, this could be a promising and relatively unexplored research area. Full article
(This article belongs to the Special Issue Alcohol Use Disorder: From Molecular Mechanisms to Therapeutics)
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