An inexpensive "do-it-yourself" device for rapid generation of uniform tumor spheroids.

Three-dimensional (3D) cancer cell culture models such as tumor spheroids better recapitulate in vivo tumors than conventional two-dimensional (2D) models. However, two major challenges limit the routine use of 3D tumor spheroids. Firstly, most existing methods of generating tumor spheroids are not high-throughput. Secondly, tumor spheroids generated using current methods are highly variable in dimension. Here, we describe a simple 'Do-It-Yourself (DIY)' device that can be assembled for less than $7 of parts and generate uniform tumor spheroids in a high-throughput manner. We used a simple phone coin vibrating motor to superimpose the vibration for breaking a laminar jet of cell-loaded alginate solution into equally sized spherical beads. We generated 3,970 tumor spheroids/min, which exhibited a hypoxic core recapitulating in vivo tumors and could be used to test the diffusion efficacy of anticancer drugs. Such low-cost, easy-to-fabricate, simple-to-operate systems with high-throughput outcomes are essential to democratize and standardize cancer research.

Delays in blood collection and drug toxicology results among crash-involved drivers arrested for impaired driving.

OBJECTIVE: The concentration of drugs in a driver's system can change between an impaired driving arrest or crash and the collection of a biological specimen for drug testing. Accordingly, delays in specimen collection can result in the loss of critical information that has the potential to affect impaired driving prosecution. The objectives of the study were: (1) to identify factors that influence the time between impaired-driving violations and specimen collections (time-to-collection) among crash-involved drivers, and (2) to consider how such delays affect measured concentrations of drugs, particularly with respect to common drug per se limits. METHOD: Study data included blood toxicology results and crash-related information from 8,923 drivers who were involved in crashes and arrested for impaired driving in Wisconsin between 2019 and 2021. Analyses examined how crash timing and severity influenced time-to-collection and the effects of delays in specimen collection on blood alcohol concentrations (BACs) and blood delta-9-tetrahydrocannabinol (THC) concentrations. RESULTS: The mean time-to-collection for the entire sample was 1.80 h. Crash severity had a significant effect on time-to-collection with crashes involving a fatality having the longest duration (M = 2.35 h) followed by injury crashes (M = 2.06 h) and noninjury crashes (M = 1.69 h). Time of day also affected time-to-collection; late night and early morning hours were associated with shorter durations. Both BAC (r = -0.11) and blood THC concentrations (r = -0.16) were significantly negatively correlated with time-to-collection. CONCLUSIONS: Crash severity and the time of day at which a crash occurs can result in delays in the collection of blood specimens after impaired driving arrests. Because drugs often continue to be metabolized and eliminated between arrest and biological specimen collection, measured concentrations may not represent the concentrations of drugs that were present at the time of driving. This has the potential to affect drug-impaired driving prosecution, particularly in jurisdictions whose laws specify per se impairment thresholds.

A well plate-based GelMA photo-crosslinking system with tunable hydrogel mechanical properties to regulate the PTH-mediated osteogenic fate.

Versatile and efficient regulation of the mechanical properties of the extracellular matrix is crucial not only for understanding the dynamic changes in biological systems, but also for obtaining precise and effective cellular responses in drug testing. In this study, we developed a well plate-based hydrogel photo-crosslinking system to effectively control the mechanical properties of hydrogels and perform high-throughput assays. We improved cell biocompatibility by using gelatin methacryloyl (GelMA) with a visible light photo-crosslinking method. Multiple cell-laden GelMA hydrogels were simultaneously and uniformly created using multi-arrayed 520 nm light-emitting diodes in a well plate format. The elastic modulus of the hydrogels can be widely adjusted (0.5-30 kPa) using a photo-crosslinking system capable of independently controlling the light intensity or exposure time for multiple samples. We demonstrate the feasibility of our system by observing enhanced bone differentiation of human mesenchymal stem cells (hMSCs) cultured on stiffer hydrogels. Additionally, we observed that the osteogenic fate of hMSCs, affected by the different mechanical properties of the gel, was regulated by parathyroid hormone (PTH). Notably, in response to PTH, hMSCs in a high-stiffness microenvironment upregulate osteogenic differentiation while exhibiting increased proliferation in a low-stiffness microenvironment. Overall, the developed system enables the generation of multiple cell-laden three-dimensional cell culture models with diverse mechanical properties and holds significant potential for expansion into drug testing.

Be aware of (R)-methamphetamine: Negative immunoassay versus positive confirmation analysis.

The amphetamine-type stimulant methamphetamine exists in two enantiomeric forms, (S)-methamphetamine and (R)-methamphetamine, which are both psychoactive but with the (S)-enantiomer being more potent than the (R)-enantiomer. Illicit methamphetamine encountered in Europe is typically a racemic mixture of both enantiomers and enantiopure (S)-methamphetamine, respectively. However, herein we report two cases with proven enantiopure (R)-methamphetamine consumption with moreover both cases remaining undetected by immunoassay screening. Inconspicuous immunoassay findings can be traced back to a considerably higher sensitivity and concentration-dependent cross-reactivity of the applied drug of abuse assay for the (S)-enantiomer of methamphetamine compared with the (R)-enantiomer, and this limitation should be well known by users of immunoassay drug tests.

Immunoassay Urine Drug Testing among Patients Receiving Opioids at a Safety-Net Palliative Medicine Clinic.

BACKGROUND: Few studies have examined the use of immunoassay urine drug testing of cancer patients in palliative care clinics. OBJECTIVES: We examined the frequency of immunoassay urine drug test (UDT) abnormalities and the factors associated with aberrancy at a safety-net hospital palliative medicine clinic. METHODS: A retrospective review of the electronic medical records of consecutive eligible patients seen at the outpatient palliative medicine clinic in a resource-limited safety-net hospital system was conducted between 1 September 2015 and 31 December 2020. We collected longitudinal data on patient demographics, UDT findings, and potential predictors of aberrant results. RESULTS: Of the 913 patients in the study, 500 (55%) underwent UDT testing, with 455 (50%) having the testing within the first three visits. Among those tested within the first three visits, 125 (27%) had aberrant UDT results; 44 (35%) of these 125 patients were positive for cocaine. In a multivariable regression model analysis of predictors for aberrant UDT within the first three visits, non-Hispanic White race (odds ratio (OR) = 2.13; 95% confidence interval (CI): 1.03-4.38; p = 0.04), history of illicit drug use (OR = 3.57; CI: 1.78-7.13; p < 0.001), and history of marijuana use (OR = 7.05; CI: 3.85-12.91; p < 0.001) were independent predictors of an aberrant UDT finding. CONCLUSION: Despite limitations of immunoassay UDT, it was able to detect aberrant drug-taking behaviors in a significant number of patients seen at a safety-net hospital palliative care clinic, including cocaine use. These findings support universal UDT monitoring and utility of immunoassay-based UDT in resource-limited settings.

Guilty or not guilty? - False positive results of common medicines in drug tests: review and practical guide.

Drug-abuse detection tests are becoming increasingly commonplace in patient care today and provide a rapid and effective method for identifying illicit substances. Occasionally, they may yield a positive result, indicating the presence of a substance, even though the individual has not consumed the suspected drug what sometimes can significantly impact both medical and legal decisions. The study outlines the substances that can lead to false-positive drug test results for amphetamines, cannabinoids, and benzodiazepines. The study's findings have revealed pivotal insights for patients receiving chronic treatment and their primary care physicians. Notably, amphetamine assays appear to be most prone to cross-reactivity with other substances. The beta-blocker group of medications, confirmed by various studies to interfere with amphetamine assays, could pose a substantial challenge in drug screening given its widespread use. Efavirenz also warrants mention, as it frequently triggers positive results for both benzodiazepine and cannabinoid assays among its users. This research helps highlight new areas for further investigation and aims to guide clinicians in their daily practice, especially when interpreting questionable positive drug-abuse test results. This comprehensive review serves as a valuable resource for clinicians to navigate false-positive scenarios effectively and maintain the highest standard of patient care.

Reconsidering the use of urine drug testing in reproductive settings.

The urine drug test is ubiquitous within reproductive healthcare settings. Although the test can have evidence-based use for a patient and clinician, in practice, it is often applied in ways that are driven by bias and stigma, do not correctly inform decisions about clinical aspects of patient care, and cause devastating ripple effects through social and legal systems. This paper proposes a framework of guiding questions to prompt reflection on (1) the question the clinical team is trying to answer, (2) whether a urine drug test answers the question at hand, (3) how testing benefits compare with the associated risks, (4) a more effective tool for clinical decision-making if the urine drug test does not meet the standards for use, and (5) individual and institutional biases affecting decision-making. We demonstrate the use of this framework using 3 common uses of the urine drug test within abortion care and labor and delivery settings.

Reliability of urine drug testing among patients on buprenorphine transdermal patch.

BACKGROUND: Urine drug testing (UDT) plays a significant role in monitoring patients on chronic opioid therapy (COT) for non-medical opioid use (NMOU). UDT, at times, can be inconsistent and misleading. We present a case where a patient on a buprenorphine patch had false negative results. CASE DESCRIPTION: A female in her 70s with metastatic breast cancer presented with uncontrolled pain from a T6 compression fracture. She had no relief with tramadol 50 mg every 6 hours as needed. Due to an allergic reaction to hydromorphone, our team prescribed a buprenorphine patch of 5 µg/h. Subsequently, she expressed excellent pain control, and the clinician confirmed the patch placement on examination. She underwent a UDT during the visit. The UDT was negative for both buprenorphine and its metabolites. The literature review showed that false negative UDT results are relatively common among patients with low-dose buprenorphine patches. The combination of a thorough physical examination, a review of the Prescription Drug Monitoring Program, and reassuring scores on screening tools placed her at low risk for NMOU. DISCUSSION: Buprenorphine has a ceiling effect on respiratory depression and a lower risk for addiction. However, when used in low doses, the drug might not have enough metabolites in the urine, leading to a false negative UDT. Such results might affect patient-physician relationships. CONCLUSION: In addition to the UDT, a thorough history, screening for NMOU, physical exam, a review of PDMP, and a good understanding of opioid metabolism are necessary to help guide pain management.

Ethnoracial differences in workplace drug testing and policies on positive drug tests in the United States.

BACKGROUND: Drug testing is widely implemented as a work-based prevention strategy for employee substance use. However, it has raised concerns about its potential use as a punitive measure in the workplace where racialized/ethnic workers are over-represented. This study examines the rates of exposure to workplace drug testing among ethnoracial workers in the United States and the potential differences in the employers' responses to positive test results. METHODS: A nationally-representative sample of 121,988 employed adults was examined using the 2015-2019 National Survey on Drug Use and Health data. The rates of exposure to workplace drug testing were estimated separately for ethnoracial workers. Then we used multinomial logistic regression to test differences in employers' responses to the first positive drug test results across ethnoracial subgroups. RESULTS: Since 2002, Black workers reported 15-20% points higher rates of having a workplace drug testing policy than Hispanic or White workers. When tested positive for drug use, Black and Hispanic workers were more likely to be fired than White workers. When tested positive, Black workers were more likely to be referred to treatment/counseling services while Hispanic workers were less likely to be referred compared to White workers. CONCLUSION: Black workers' disproportionate exposure to drug testing and punitive responses in the workplace may potentially place individuals with substance use problems out of the workforce, limiting their access to treatment/other resources available via their workplaces. Also, Hispanic workers' limited accessibility to treatment and counseling services when tested positive for drug use requires attention to address unmet needs.

Variation in Nevada primary care clinicians' use of urine drug testing to mitigate opioid harm.

INTRODUCTION: The prescription opioid epidemic led to federal, state, and health system guidelines and policies aimed at mitigating opioid misuse, including presumptive urine drug testing (UDT). This study identifies whether a difference exists in UDT use among different primary care medical license types. METHODS: The study used January 2017-April 2018 Nevada Medicaid pharmacy and professional claims data to examine presumptive UDTs. We examined correlations between UDTs and clinician characteristics (medical license type, urban/rural status, care setting) along with clinician-level measures of patient mix characteristics (proportions of patients with behavioral health diagnoses, early refills). Adjusted odds ratios (AORs) and predicted probabilities (PPs) from a logistic regression with a binomial distribution are reported. The analysis included 677 primary care clinicians (medical doctors [MD], physician assistants [PA], nurse practitioners [NP]). RESULTS: Of those in the study, 85.1 % of clinicians did not order any presumptive UDTs. NPs had the highest proportion of UDT use (21.2 % of NPs), followed by PAs (20.0 % of PAs), and MDs (11.4 % of MDs). Adjusted analyses showed that being a PA or NP was associated with higher odds of UDT (PA: AOR: 3.6; 95 % CI: 3.1-4.1; NP: AOR: 2.5; 95 % CI: 2.2-2.8) compared to being an MD. PAs had the highest PP for ordering UDTs (2.1 %, 95 % CI: 0.5 %-8.4 %). Among clinicians who ordered UDTs, midlevel clinicians had higher mean and median UDT use (PA and NP mean: 24.3 % vs. MDs: 19.4 %; PA and NP median: 17.7 % vs. MDs: 12.5 %). CONCLUSION: In Nevada Medicaid, UDTs are concentrated among 15 % of primary care clinicians who are frequently non-MDs. More research should include PAs and NPs when examining clinician variation in mitigating opioid misuse.

Positivo a opiáceos en análisis de drogas de abuso en orina tras consumo de semillas de amapola. A propósito de un caso / Positive for opiates in urine drug of abuse test after poppy seed consumption. A case report

Antecedentes y objetivos: las semillas de amapola, cuyo consumo solas o contenidas en ciertos alimentos es considerado seguro en España desde el punto de vista toxicológico, presentan cierta cantidad de alcaloides opiáceos que pueden originar resultados «falsos positivos» en los análisis de drogas de abuso en muestras de orina, como los realizados de forma rutinaria, entre otros colectivos, al personal de las Fuerzas Armadas. A raíz de un caso detectado en el Instituto de Toxicología de la Defensa de resultado positivo a opiáceos en una persona que reportó el consumo de un pan con semillas de amapola, se propuso realizar un estudio de esta problemática y cómo abordarla desde el punto de vista analítico. Material y método: se estudió en dos voluntarios cómo afectó el consumo de dicho pan, analizándose muestras de orina, tanto por métodos de cribado como de confirmación, y se apoyó en una revisión bibliográfica empleando distintas bases de datos especializadas en referencia a la interferencia del consumo de semillas de amapola con las analíticas de drogas de abuso en muestras de orina. Resultados: aplicando el punto de corte de 300 ng/ml recomendado por la European Workplace Drug Testing Society (EWDTS) resultaron presuntamente positivos a opiáceos el 62,5% de los análisis de cribado. En ciertas muestras, el análisis de confirmación identificó codeína por encima del límite de detección establecido en la técnica analítica. La bibliografía apoyó estos resultados. Conclusiones: para abordar analíticamente esta problemática se ha propuesto incrementar, en la técnica analítica de confirmación, el punto de corte de confirmación y, asimismo, como otras posibles medidas a implementar se ha planteado la detección de tebaína como biomarcador específico del consumo de semillas de amapola y/o el incremento del punto de corte hasta los 2000 ng/ml. (AU)

Antecedents and objectives: Poppy seeds, whose consumption alone or contained in certain foods is considered safe in Spain from the toxicological point of view, have different amounts of opioid alkaloids that can cause «false positive» results in the analysis of drugs of abuse in urine samples, such as those routinely performed, among other groups, on Armed Forces personnel. Following a case detected at the Institute of Toxicology of the Defense of a positive result to opiates in a person who reported the consumption of a bread containing poppy seeds, it was proposed to carry out a study of this problem and how to approach it from the analytical point of view. Material and methods: We studied how the consumption of this bread affected to two volunteers, analyzing urine samples by both screening and confirmation methods, and was supported by a literature review using different specialized databases in reference to the interference of the consumption of poppy seeds and products containing them with the analysis of drugs of abuse in urine samples. Results: Using the 300 ng/ml cut-off point, 62% of the screening tests were presumably positive to opiates. In certain samples the confirmatory analysis identified codeine above the established detection limit. The literature supported these results. Conclusions: In order to deal with this problem analytically, it has been proposed to increase the confirmation cut-off level in the analytical confirmatory technique. In addition, the detection of thebaine as a specific biomarker for poppy seed consumption and/or the increase of the cut-off point to 2000 ng/ml has been proposed as other possible measures to be implemented. (AU)

Urine Drug Tests Indicate Higher Prevalence of Combined Alcohol and Cocaine Use Compared to Alcohol Together with Cannabis or Amphetamine-A Possible Link to Cocaethylene.

AIM: This retrospective study examined the prevalence of combined ethanol and cocaine use, which produces an enhanced psychoactive effect through formation of the active metabolite cocaethylene, compared to combined use of ethanol and two other common recreational drugs, cannabis and amphetamine, based on urine drug test results. METHODS: The study was based on >30,000 consecutive samples from routine urine drug testing in 2020, and 2627 samples from acute poisonings in the STRIDA project (2010-2016), in Sweden. Drug testing for ethanol (i.e. ethyl glucuronide and ethyl sulfate), cocaine (benzoylecgonine), cannabis (Δ9-THC-COOH) and amphetamine was done by routine immunoassay screening and LC-MS/MS confirmatory methods. Seven samples testing positive for cocaine and ethyl glucuronide were also analyzed for cocaethylene by LC-HRMS/MS. RESULTS: Among routine samples for which testing of ethanol and cocaine had been requested, 43% tested positive for both substances, compared with 24% for ethanol and cannabis and 19% for ethanol and amphetamine (P < 0.0001). Among the drug-related intoxications, 60% of cocaine-positive samples were also positive for ethanol, compared to 40% for cannabis and ethanol and 37% for amphetamine and ethanol. Cocaethylene was detected (range 1.3-150 µg/L) in all randomly selected samples testing positive for ethanol and cocaine use. CONCLUSIONS: These results, which were based on objective laboratory measures, indicated that combined ethanol and cocaine exposure was more prevalent than expected from drug use statistics. This may relate both to the common use of these substances in party and nightlife settings, and the amplified and prolonged pharmacological effect by the active metabolite cocaethylene.

Reporting of unknown drug test results in the Fatality Analysis Reporting System and associated factors, 2000-2020.

OBJECTIVE: To investigate how the percentage of unknown drug test results among drug-tested drivers in the Fatality Analysis Reporting System (FARS) has trended over the past 2 decades and to evaluate factors that may affect a drug-tested driver having unknown test results in FARS. METHODS: The percentage of unknown test results among fatally injured drivers who were tested for drugs in FARS was assessed from 2000 to 2020. Trends in annual FARS drug testing data were compared with those for alcohol testing. In addition, the percentage of unknown drug test results was regressed on several factors that have been shown to be associated with higher risk of drug-involved crash fatalities. RESULTS: The percentage of unknown drug test results in FARS has decreased drastically over the past 2 decades, and the percentage of unknown drug test data gradually matched that of alcohol data over the study period. Multiple factors such as the fatally injured drivers' age and whether the crash occurred in an urban/rural area were found to be statistically significantly associated with the percentage of unknown drug test results in FARS. CONCLUSIONS: The percentage of unknown test results in FARS drug data is decreasing, and the significant associated factors found in this study may help identify additional strategies for reducing unknown drug test results. Future research should focus on continued improvement of FARS data, given the importance of FARS in understanding fatal crashes and informing strategies for prevention of crash-related injuries and fatalities in the United States.

Awareness survey on drug crime scene investigation and drug detection kits among drug-related police officers.

This questionnaire-based study aimed to investigate the drug crime scene experienced by drug-related police officers and the perceptions of drug test kits by them before initiating the development of drug test kits to detect 16 types of drugs. The subjects were 57 drug-related police officers. Most of the respondents (96.5%) had <10 years of experience in drug-related work. Respondents were questioned about the drug scene investigation and perceptions of drug test kits. The questionnaire about drug test kits included the question on 'simple/rapid drug test kit' and 'electronic portable drug analyzer' regarding the disadvantages of existing kits and expecting features when a new kit is developed. First, in the on-site survey, the drug-related crime occurred at the suspect's house (47.8%), and methamphetamine (35.0%) and γ-hydroxybutyric acid (19.5%) were mainly found. In the awareness survey on drug test kits, most respondents (67.2%) had an experience of using 'simple/rapid drug test kits', whereas 17.5% for the 'electronic portable drug analyzer'. In the case of 'simple/rapid drug test kit', the false-positive rate reached 53.8% by a misinterpretation due to ambiguous color change (47.6%). The inaccuracy of the result (33.3%) was the most concern in 'electronic portable drug analyzer'. Respondents most favored pipette type for sample collector when a new kit is developed. In addition, they preferred the smaller kit with short detection times in both kit types. This survey could be applied to the development of efficient and practical kits for police officers working in drug-related fields.

Establishment of a human 3D pancreatic adenocarcinoma model based on a patient-derived extracellular matrix scaffold.

Pancreatic cancer is likely to become one of the leading causes of cancer-related death in many countries within the next decade. Surgery is the potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC), although only 10%-20% of patients have a resectable disease after diagnosis. Despite recent advances in curative surgery the current prognosis ranges from 6% to 10% globally. One of the main issues at the pre-clinical level is the lacking of model which simultaneously reflects the tumour microenvironment (TME) at both structural and cellular levels. Here we describe an innovative tissue engineering approach applied to PDAC starting from decellularized human biopsies in order to generate an organotypic 3D in vitro model. This in vitro 3D system recapitulates the ultrastructural environment of native tissue as demonstrated by histology, immunohistochemistry, immunofluorescence, mechanical analysis, and scanning electron microscopy. Mass spectrometry confirmed a different extracellular matrix (ECM) composition between decellularized healthy pancreas and PDAC by identifying a total of 110 non-redundant differently expressed proteins. Immunofluorescence analyses after 7 days of scaffold recellularization with PANC-1 and AsPC-1 pancreatic cell lines, were performed to assess the biocompatibility of 3D matrices to sustain engraftment, localization and infiltration. Finally, both PANC-1 and AsPC-1 cells cultured in 3D matrices showed a reduced response to treatment with FOLFIRINOX if compared to conventional bi-dimensional culture. Our 3D culture system with patient-derived tissue-specific decellularized ECM better recapitulates the pancreatic cancer microenvironment compared to conventional 2D culture conditions and represents a relevant approach for the study of pancreatic cancer response to chemotherapy agents.

Immunochromatography screening devices for cannabinoids in oral fluid sample

Abstract Cannabis sativa L. is one of the most consumed drugs in the world and recent studies have associated its use with an increase in the number of traffic accidents in different countries. In many countries, like Brazil, simple and reliable methodologies are still needed for the detection of drugs on site, mainly cannabinoids, considering its prevalence of use and oral fluid (OF) has been proved as an appropriate biological matrix for this purpose. Considering that, this work aims to review previous studies on immunochromatographic devices for on-site detection of cannabinoids in OF, discussing their sensitivity, specificity, cut-offs values and confirmatory methods. This data shows the importance of choosing a screening device and it reinforces the need for its implementation in Brazil. The research was conducted on 5 databases and all original articles, published in the last 10 years, were selected. A total of 32 articles were found, providing data for 17 screening devices of distinct brands. Only 2 screening devices showed satisfactory sensitivity and specificity in the evaluated studies (≥80% and ≥90% respectively). However, it should be considered that the screening devices still have some limitations, such as a higher cut-off than those recommended by international guidelines (cut-off > 2 ng/mL), therefore demonstrating the need for more studies in the area and the importance of confirmatory analysis usually fulfilled by LC-MS/MS, GC-MS/MS or GC-MS. Thus, the screening analyzes should not be evaluated by itself, but in association with confirmatory results and observational traits (behavioral changes), for a better understanding of the traffic scenario

Investigation on the use of new types of drugs among HIV/AIDS patients in Ningbo City / 预防医学

Objective@#To investigate the use of new types of drugs among HIV/AIDS patients in Ningbo City, Zhejiang Province, so as to provide insights into surveillance and interventions for use of new types of drugs among HIV/AIDS patients.@*Methods@#The HIV/AIDS patients in Ningbo City were randomly sampled from the HIV/AIDS Prevention and Control Information System of Chinese Disease Prevention and Control Information System. Patients' demographics, use of new types of drugs and sexual behaviors were collected using questionnaire surveys. Patients' hair samples were collected, and new types of drugs were determined in hair using liquid chromatography-mass spectrometry (LC-MS). In addition, factors affecting the use of new types of drugs were identified using a multivariable logistic regression model.@*Results@#A total of 254 HIV/AIDS patients were enrolled, including 214 men (84.25%), 31 cases aged under 25 years (12.20%), 66 cases aged 25 to 30 years (25.98%), and 157 cases aged 31 to 75 years (61.81%). There were 30 cases reported previous use of new drugs (11.81%), including 27 cases reported previous use of methamphetamine (90.00%). There were 48 cases tested positive of new types of drugs, with a positive rate of 18.90%, including 44 cases tested positive for methamphetamine (91.67%). Multivariable logistic regression analysis identified age (25 to 30 years, OR=6.926, 95%CI: 1.412-33.969), occupation (students/teachers/cadres/employees/retirees, OR=6.971, 95%CI: 2.123-22.889; housekeeping and housework servants/unemployed, OR=3.356, 95%CI: 1.289-8.739; business/public place servants, OR=2.447, 95%CI: 1.033-4.448) and syphilis infection during recent six months (OR=3.491, 95%CI: 1.664-7.326) as factors affecting the use of new types drugs among HIV/AIDS patients. @*Conclusions @#The use of new types of drugs exists in HIV/AIDS patients in Ningbo City. Age, occupation and syphilis infection were associated with the use of new types of drugs among HIV/AIDS patients.

Assessing the Efficacy of Anti-Cancer Drugs on Organoid Models Derived from Prostate Cancer.

It was proven that tumor organoids effectively mirror the phenotypic and genetic traits of the original biomaterial. It was reported that outcomes from drug testing in organoid cultures can accurately represent the clinical response observed in patients. In this study, an organoid culture was derived from biopsy material of prostate cancer (PC). Subsequently, clinical practice drugs, docetaxel and enzalutamide, were tested on this organoid culture. Various techniques for evaluating the efficacy of drugs in vitro were compared. The half-maximal inhibitory concentration of docetaxel was found to be markedly lower compared to that of enzalutamide. However, when tested at clinically relevant concentrations and incubation times, enzalutamide was more effective than docetaxel. Therefore, it is crucial to optimize the testing conditions for drugs on in vitro cultures for their subsequent application in clinical practice.

Uniform Tumor Spheroids on Surface-Optimized Microfluidic Biochips for Reproducible Drug Screening and Personalized Medicine.

Spheroids are recognized for resembling the important characteristics of natural tumors in cancer research. However, the lack of controllability of the spheroid size, form, and density in conventional spheroid culture methods reduces the reproducibility and precision of bioassay results and the assessment of drug-dose responses in spheroids. Nonetheless, the accurate prediction of cellular responses to drug compounds is crucial for developing new efficient therapeutic agents and optimizing existing therapeutic strategies for personalized medicine. We developed a surface-optimized PDMS microfluidic biochip to produce uniform and homogenous multicellular spheroids in a reproducible manner. This platform is surface optimized with 10% bovine serum albumin (BSA) to provide cell-repellent properties. Therefore, weak cell-surface interactions lead to the promotion of cell self-aggregations and the production of compact and uniform spheroids. We used a lung cancer cell line (A549), a co-culture model of lung cancer cells (A549) with (primary human osteoblasts, and patient-derived spine metastases cells (BML, bone metastasis secondary to lung). We observed that the behavior of cells cultured in three-dimensional (3D) spheroids within this biochip platform more closely reflects in vivo-like cellular responses to a chemotherapeutic drug, Doxorubicin, rather than on 24-well plates (two-dimensional (2D) model). It was also observed that the co-culture and patient-derived spheroids exhibited resistance to anti-cancer drugs more than the mono-culture spheroids. The repeatability of drug test results in this optimized platform is the hallmark of the reproducibility of uniform spheroids on a chip. This surface-optimized biochip can be a reliable platform to generate homogenous and uniform spheroids to study and monitor the tumor microenvironment and for drug screening.

Use of a Novel EEG-Based Objective Test, the Cognalyzer®, in Quantifying the Strength and Determining the Action Time of Cannabis Psychoactive Effects and Factors that May Influence Them Within an Observational Study Framework.

INTRODUCTION: Current methods to detect recent delta-9-tetrahydrocannabinol (THC) use cannot objectively quantify its psychoactive effects (PE). The Cognalyzer®, an electroencephalography (EEG)-based method, detects and quantifies the strength of THC-induced PE on a scale from 0 to 100%. This study assesses the relationship between the magnitude of Cognalyzer® PE predictions and reported subjective drug effects for 4-h post-cannabis inhalation. METHODS: Seventy-five participants were enrolled in the study. Prior to ad libitum cannabis inhalation, an EEG recording episode was completed. Immediately after inhalation, the Drug Effects Questionnaire (DEQ) was administered and another EEG recording performed. For 25 participants, the study ended. For 50 participants, assessments were repeated at 30-min intervals for 4 h. EEG files were blinded and analyzed using two versions of the Cognalyzer® algorithm. The relationship between the Cognalyzer® PE level results and the DEQ was assessed using generalized linear models and multiple regression. RESULTS: There were significant PE increases from pre-cannabis for up to 3.5 h. Mean reports of feeling drug effects were > 0 at all post-inhalation time points (p ≤ 0.024). Furthermore, there were significant relationships between the Cognalyzer® PE and self-reported perception of drug effects (p ≤ 0.001). Subgroup analysis showed that Cognalyzer® PE levels were impacted by cannabis use history, subjective ratings of drug effects, oral fluid THC concentration and the cannabis product inhaled. CONCLUSION: The findings show that the Cognalyzer® can be used to objectively determine the strength of cannabis psychoactive effects that cannabis products create on consumers and how it changes depending on their experience with cannabis. The Cognalyzer® can be used to conduct scientific consumer research to generate trustworthy informational material about the psychoactive experience of cannabis products. For clinical research, the Cognalyzer® can be used to study the pharmacodynamics of cannabinoids or delivery systems, such as nano-emulsifications.