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In Europe, concentrations of ∆9-tetrahydrocannabinol (THC) in cannabis resin (also known as hash) have risen markedly in the past decade, potentially increasing risks of mental health disorders. Current approaches to international drug monitoring cannot distinguish between different types of cannabis resin which may have contrasting health effects due to THC and cannabidiol (CBD) content. Here, we compared concentrations of THC and CBD in different types of cannabis resin collected in Europe (either Moroccan-type, or Dutch-type). We then tested the ability of machine learning algorithms to classify the type of cannabis resin (either Moroccan-type, or Dutch-type) using routinely collected monitoring data on THC and CBD. Finally, we applied the optimal algorithm to new samples collected in countries where the type of cannabis resin was unknown, the UK and Denmark. Results showed that overall, Dutch-type samples had higher THC (Hedges' g = 2.39) and lower CBD (Hedges' g = 0.81) than Moroccan-type samples. A Support Vector Machine algorithm achieved classification accuracy exceeding 95%, with little variation in this estimate, good interpretability, and plausibility. It made contrasting predictions about the type of cannabis resin collected in the UK (94% Moroccan-type; 6% Dutch-type) and Denmark (36% Moroccan-type; 64% Dutch-type). In conclusion, we provide proof-of-concept evidence for the potential of machine learning to inform international drug monitoring. Our findings should not be interpreted as objective confirmatory evidence but suggest that Dutch-type cannabis resin has higher THC concentrations than Moroccan-type cannabis resin, which may contribute to variation in drug markets and health outcomes for people who use cannabis in Europe.
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The study of subcellular targets and biochemical processes within a living cell is valuable for biological and medical research. Secretory vesicles, one such important intracellular target, are nanoscale lipid structures that are capable of storage, transport, and secretion of, for example, neurotransmitters, hormones, proteins or waste products. Vesicles play an essential role in intercellular communication systems, as they facilitate the release of chemical messaging agents. If deregulated, these communication processes can be a central part in the pathogenesis of some neurodegenerative diseases or diabetes. Generally, due to their nanometer size and intracellular location, the analysis of single vesicles and their content is a great challenge. It requires sensitive techniques, micro/nanoscale tools and sensitive instruments with extreme spatio-temporal resolution. This review focuses on electrochemical sensors to study the biochemistry and quantification of messenger molecules and other species (e.g., reactive oxygen and nitrogen species) stored in organelles, providing new trends and developments in this field. Furthermore, we review the effect of the chemical environment of single cells (e.g., treatment with chemicals, drugs, lipids, and ions) on regulation of the physical and chemical properties of vesicles. Finally, unsolved challenges of and perspectives on vesicle electroanalysis are discussed.
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Investigación Biomédica , Técnicas Biosensibles , Comunicación Celular , Nitrógeno , OrgánulosRESUMEN
BACKGROUND: European drug checking services exchange information on drug trends within the Trans European Drug Information (TEDI) network, allowing monitoring and coordination of responses. Starting in Spring 2020, several services detected the synthetic cannabinoid receptor agonist MDMB-4en-PINACA in adulterated low-THC cannabis products. METHODS: Cannabis products suspected of adulteration were analyzed for the presence of MDMB-4en-PINACA by 9 services in 8 countries within the TEDI network. If available, phytocannabinoid analysis was also performed. RESULTS: 1142 samples sold as cannabis in herbal, resin and e-liquid form were analyzed, of which 270 were found to contain MDMB-4en-PINACA. All cannabis samples contained low THC (<1%), except the e-liquids which contained no phytocannabinoids. Three serious health incidents requiring hospitalization after use of an adulterated cannabis sample were reported. CONCLUSION: Adulteration of cannabis with synthetic cannabinoid receptor agonists is a new phenomenon that carries risk for people who use it. Given that cannabis consumers are not a usual target group for drug checking services, services and associated harm reduction interventions could be reconfigured to include them.
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Cannabinoides , Cannabis , Alucinógenos , Analgésicos , Agonistas de Receptores de Cannabinoides , Dronabinol , HumanosRESUMEN
BACKGROUND: Osteoarthritis of the knee is characterized by progressive cartilage deterioration causing pain and function loss. Symptoms develop late with limited disease-modifying opportunities. Osteoarthritis is a major cause of immobility, with a higher prevalence above 60 years. This age-related increase in prevalence is further amplified by the female gender. Imaging and biochemical analyses for detection of osteoarthritis of the knee are expensive and labor-intensive. Continuous movement tracking could aid in detecting onset and/or worsening of symptoms. METHODS: We used portable technology to investigate kinematic differences in female patients with knee osteoarthritis, weight-matched healthy female volunteers and obese female patients with osteoarthritis of the knee. Knee osteoarthritis was established radiographically and corroborated using magnetic resonance imaging. FINDINGS: The total amount, type and level of activity did not differ significantly between groups. The temporal activity pattern during the day was however significantly different with a bimodal signature in healthy volunteers only. Sequence analyses revealed more time to recuperate after dynamic activity in both patient groups. Analysis of walking bouts revealed significant differences in stride interval dynamics, indicative of gait naturalness, only in healthy volunteers. Temporal activity, sequence and walking patterns were independent of body weight. INTERPRETATION: We thus provide for the first-time evidence of temporal specific kinematic signatures in amount and quality of movement also in stride interval dynamics between people with and without osteoarthritis of the knee independent of body weight. These findings could allow early and non-intrusive diagnosis of osteoarthritis enabling concordant treatment.
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Fractales , Marcha , Osteoartritis de la Rodilla/fisiopatología , Adulto , Anciano , Fenómenos Biomecánicos , Peso Corporal , Estudios de Casos y Controles , Femenino , Humanos , Articulación de la Rodilla/fisiopatología , Persona de Mediana EdadRESUMEN
The lockdown measures implemented to curb the spread of SARS-CoV-2 may affect (illicit) drug consumption patterns. This rapid response study investigated changes in cannabis use in a non-probability sample of cannabis users in the Netherlands during the early lockdown period. We fielded an online cross-sectional survey 4-6 weeks after implementation of lockdown measures in the Netherlands on March 15, 2020. We measured self-reported \motives for changes in use, and assessed cannabis use frequency (use days), number of joints per typical use day, and route of administration in the periods before and after lockdown implementation. 1,563 cannabis users were recruited. Mean age was 32.7 ± 12.0 years; 66.3% were male and 67.9% used cannabis (almost) daily. In total, 41.3% of all respondents indicated that they had increased their cannabis use since the lockdown measures, 49.4% used as often as before, 6.6% used less often, and 2.8% stopped (temporarily). One-third of those who were not daily users before the lockdown became (almost) daily users. Before the lockdown, most respondents (91.4%) used cannabis in a joint mixed with tobacco and 87.6% still did so. Among users of joints, 39.4% reported an increase in the average number consumed per use day; 54.2% stayed the same and 6.4% used fewer joints. This rapid response study found evidence that during the lockdown more users increased rather than decreased cannabis consumption according to both frequency and quantity. These data highlight the need to invest more resources in supporting cessation, harm reduction, and monitoring longer term trends in cannabis use.
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Análisis de la Célula Individual/métodos , Animales , Línea Celular Tumoral , Espectroscopía Dieléctrica/métodos , Técnicas Electroquímicas/métodos , Humanos , Dispositivos Laboratorio en un Chip , Espectrometría de Masas/métodos , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Microscopía Electroquímica de Rastreo/métodosRESUMEN
We suspended a single nanoskived gold nanowire in a microfluidic channel. In this preliminary report, a 200 nm-diameter nanowire was used as an electrode to perform hydrodynamic voltammetry in the center of solution flow. Suspended nanowires exhibit superior current response due to highly efficient mass transport in the area of fastest flow.
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Osteoarthritis is one of the major causes of immobility and its current prevalence in elderly (>60 years) is 18% in women and 9.6% in men. Patients with osteoarthritis display altered movement patterns to avoid pain and overcome movement limitations in activities of daily life, such as sit-to-stand transfers. Currently, there is a lack of evidence that distinguishes effects of knee osteoarthritis on sit-to-stand performance in patients with and without obesity. The purpose of this study was therefore to investigate differences in knee and hip kinetics during sit-to-stand movement between healthy controls and lean and obese knee osteoarthritis patients. Fifty-five subjects were included in this study, distributed over three groups: healthy controls (n=22), lean knee osteoarthritis (n=14), and obese knee OA patients (n=19). All subjects were instructed to perform sit-to-stand transfers at self-selected, comfortable speed. A three-dimensional movement analysis was performed to investigate compensatory mechanisms and knee and hip kinetics during sit-to-stand movement. No difference in sit-to-stand speed was found between lean knee OA patients and healthy controls. Obese knee osteoarthritis patients, however, have reduced hip and knee range of motion, which is associated with reduced peak hip and knee moments. Reduced vertical ground reaction force in terms of body weight and increased medial ground reaction forces indicates use of compensatory mechanisms to unload the affected knee in the obese knee osteoarthritis patients. We believe that an interplay between obesity and knee osteoarthritis leads to altered biomechanics during sit-to-stand movement, rather than knee osteoarthritis alone. From this perspective, obesity might be an important target to restore healthy sit-to-stand biomechanics in obese knee OA patients.
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Obesidad/fisiopatología , Osteoartritis de la Rodilla/fisiopatología , Anciano , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/patología , Osteoartritis de la Rodilla/patología , Rango del Movimiento Articular , Posición de PieRESUMEN
In this work, the use of fused deposition modeling (FDM) in a (bio)analytical/lab-on-a-chip research laboratory is described. First, the specifications of this 3D printing method that are important for the fabrication of (micro)devices were characterized for a benchtop FDM 3D printer. These include resolution, surface roughness, leakage, transparency, material deformation, and the possibilities for integration of other materials. Next, the autofluorescence, solvent compatibility, and biocompatibility of 12 representative FDM materials were tested and evaluated. Finally, we demonstrate the feasibility of FDM in a number of important applications. In particular, we consider the fabrication of fluidic channels, masters for polymer replication, and tools for the production of paper microfluidic devices. This work thus provides a guideline for (i) the use of FDM technology by addressing its possibilities and current limitations, (ii) material selection for FDM, based on solvent compatibility and biocompatibility, and (iii) application of FDM technology to (bio)analytical research by demonstrating a broad range of illustrative examples.
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Materiales Biocompatibles/química , Polímeros/química , Impresión Tridimensional , Diseño de Equipo , Dispositivos Laboratorio en un Chip , Microfluídica/instrumentación , Impresión Tridimensional/instrumentaciónRESUMEN
Oxygen is essential in the energy metabolism of cells, as well as being an important regulatory parameter influencing cell differentiation and function. Interest in precise oxygen control for in vitro cultures of tissues and cells continues to grow, especially with the emergence of the organ-on-a-chip and the desire to emulate in vivo conditions. This was recently discussed in this journal in a Critical Review by Brennan et al. (Lab Chip (2014). DOI: ). Microfluidics can be used to introduce flow to facilitate nutrient supply to and waste removal from in vitro culture systems. Well-defined oxygen gradients can also be established. However, cells can quickly alter the oxygen balance in their vicinity. In this Tutorial Review, we expand on the Brennan paper to focus on the implementation of oxygen analysis in these systems to achieve continuous monitoring. Both electrochemical and optical approaches for the integration of oxygen monitoring in microfluidic tissue and cell culture systems will be discussed. Differences in oxygen requirements from one organ to the next are a challenging problem, as oxygen delivery is limited by its uptake into medium. Hence, we discuss the factors determining oxygen concentrations in solutions and consider the possible use of artificial oxygen carriers to increase dissolved oxygen concentrations. The selection of device material for applications requiring precise oxygen control is discussed in detail, focusing on oxygen permeability. Lastly, a variety of devices is presented, showing the diversity of approaches that can be employed to control and monitor oxygen concentrations in in vitro experiments.
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Técnicas de Cultivo de Célula/instrumentación , Procedimientos Analíticos en Microchip/métodos , Oxígeno , Técnicas de Cultivo de Tejidos/instrumentación , Humanos , Oxígeno/química , Oxígeno/farmacologíaRESUMEN
This paper describes the fabrication of millimeter-long gold nanowires that bisect the center of microfluidic channels. We fabricated the nanowires by nanoskiving and then suspended them over a trench in a glass structure. The channel was sealed by bonding it to a complementary poly(dimethylsiloxane) structure. The resulting structures place the nanowires in the region of highest flow, as opposed to the walls, where it approaches zero, and expose their entire surface area to fluid. We demonstrate active functionality, by constructing a hot-wire anemometer to measure flow through determining the change in resistance of the nanowire as a function of heat dissipation at low voltage (<5 V). Further, passive functionality is demonstrated by visualizing individual, fluorescently labeled DNA molecules attached to the wires. We measure rates of flow and show that, compared to surface-bound DNA strands, elongation saturates at lower rates of flow and background fluorescence from nonspecific binding is reduced.