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Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating avatars (herein defined as an extension of digital twins) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges. As the practically unlimited source of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CM) is now mostly resolved, there are great efforts to improve their quality and applicability by overcoming their intrinsic limitations. The greatest bottleneck in the field is the in vitro ageing of hiPSC-CMs to reach a maturity status that closely resembles that of the adult heart, thereby allowing for more appropriate drug developmental procedures as there is a clear correlation between ageing and developing cardiovascular diseases. Here, we review the current state-of-the-art techniques in the most realistic heart models used in disease modelling and toxicity evaluations from hiPSC-CM maturation through heart-on-a-chip platforms and in silico models to the in vitro models of certain cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Drug testing plays a key role in youth substance use treatment in Sweden. Young people treated for substance use problems are routinely required to leave urine samples, and there is often controversy between patients and staff around its relevance. Still, there is a lack of research on how young people make sense of this practice. This article contributes to this knowledge through an ANT-inspired (Actor Network Theory) analysis of how youth enact urine testing in their treatment experiences. We attempt to tease out what kind of sociomaterial object urine testing is according to youth, and how it affects their lives. The study is based on interviews with 25 previous patients (mean age 17). The analysis shows that the participants enacted urine testing as both a stable object that creates binaries in knowledge networks (use or nonuse), and as a flickering object that appears in and affects diverse drug-body-treatment assemblages (even outside the clinic). The participants had internalized the importance of leaving negative samples to get discharged and avoid adult surveillance. They described a practice that made substance use a demarcated, individual and treatable problem, and also, often contrary to their own self-understandings, devalued their ability to be honest about and regulate their conduct. Through establishing substance use as a simplified either/or phenomenon and through attributing patients with the agency to become nonusers only, urine testing appears counter-productive if treatment is to strengthen informed decision making and responsibility among soon to be adults. [ABSTRACT FROM AUTHOR]

Tumor behavior, including its response to treatments, is influenced by interactions between mesenchymal and malignant cells, as well as their spatial arrangement. To study tumor biology and evaluate anticancer drugs, accurate 3D tumor models are essential. Here, we developed an in vitro biomimetic hepatoma microenvironment model by combining an extracellular matrix (3DM-7721). Initially, the internal grid structure, composed of 10/6 % GelMA/gelatin loaded with SMMC-7721 cells, was printed using 3D bioprinting. The external component consisted of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. A control model (3DP-7721) lacked external cell loading. GelMA/gelatin hydrogels provided robust structural support and biocompatibility. The SMMC-7721 cells in the 3DM-7721 model exhibit superior tumor-associated gene expression and proliferation characteristics when compared to the 3DP-7721 model. Furthermore, the 3DM-7721 type exhibited increased resistance to anticancer agents. SMMC-7721 cells in the 3DM-7721 model exhibit significant tumorigenicity in nude mice. The 3DM-7721 model group showed pathological characteristics of malignant tumors, with a high degree of deterioration, and a significant positive correlation between malignant tumor-related gene pathways. This high-fidelity 3DM-7721 tumor microenvironment model is invaluable for studying tumor progression, devising effective treatment strategies, and discovering drugs. 1. A hepatoma microenvironment model (3DM-7721) incorporating an extracellular matrix that is designed to establish solid tumor models in vitro. 2. This model contains a 3D-printed internal tumor component of liver cancer cells loaded with 10/6 % gelatin methacrylate (GelMA)/gelatin (the 3DP-7721 model) and an external extracellular-matrix component of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. 3. The 3DM-7721 model outperforms the 3DP-7721 model in terms of the SMMC-7721 cell proliferation characteristics and tumorigenicity, tumor-related gene expression, anticancer drug resistance, and malignant tumor characteristics. [Display omitted] [ABSTRACT FROM AUTHOR]

Urine-derived stem cells (USCs) are a promising source of adult stem cells for cell therapy, drug testing for renal toxicity, and biomarker discovery in kidney disease. USCs can be non-invasively isolated from the donor's own urine, making them a good candidate for precision medicine. Preclinical studies have shown that USCs and exosomes can be used to repair damaged tissues (particularly urinary tract tissues and organs, including the kidneys), to test the toxicity of new drugs, and to identify biomarkers for kidney disease. Further research is needed to fully understand the potential of USCs and to develop safe and effective ways to explore their full potential in precision medicine. Urine-derived stem cells (USCs) are a promising source of stem cells for cell therapy, renal toxicity drug testing, and renal disease biomarker discovery. Patients' own USCs can be used for precision medicine. In this review we first describe the isolation and characterization of USCs. We then discuss preclinical studies investigating the use of USCs in cell therapy, exploring the utility of USCs and USC-derived induced pluripotent stem cells (u-iPSCs) in drug toxicity testing, and investigating the use of USCs as biomarkers for renal disease diagnosis. Finally, we discuss the challenges of using USCs in these applications and provide insights into future research directions. USCs are a promising tool for advancing renal therapy, drug testing, and biomarker discovery. Further research is needed to explore their potential. [ABSTRACT FROM AUTHOR]

Hair is the matrix of choice for investigating a subject's drug history over time, usually with specific forensic applications (license renewal, workplace drug testing, toxicological evaluation), and it is generally considered difficult to be tampered with. Nevertheless, some treatments promising to lower drug concentrations in hair are described online as how to "pass" a drug test. We selected three of these practices, claiming to be effective in decreasing drug concentrations—Treatment 1: (A) baking soda, (B) salicylic acid, (C) bleach; Treatment 2: (A) bleaching and (B) dyeing; Treatment 3: (A) white vinegar, (B) salicylic acid moisturizer, (C) liquid cleanser, and (D) dyeing. Quantitative results were compared with those of untreated hair strands, used as reference. We evaluated the efficacy of the treatment on drugs of abuse and benzodiazepines. Treatment 1 proved to be the most effective, since drug concentrations in treated hair were significantly lower than in untreated ones, although methadone and tetrahydrocannabinol (THC) seemed to be less affected than cocaine and 6‐monoacetylmorphine (MAM). The mean percentage values of treatment‐induced decrease were up to 90% for cocaine, 81% for benzoylecgonine, 77% for morphine, 89% for MAM, 37% for methadone, 67% for ketamine, 80% for MDMA, 76% for methamphetamine, and 60% for THC, compared with the reference samples. There was no noticeable damage or discoloration of the keratin matrix, making it difficult for the technicians to determine if there was a treatment. This could be an issue for the application of cutoffs or when low concentrations of drugs are incorporated into the keratinic matrix. [ABSTRACT FROM AUTHOR]

3D cancer cell cultures have enabled new opportunities for replacing compound testing in experimental animals. However, most solid tumors are composed of multiple cell types, including fibroblasts. In this study we developed multicellular tumor heterospheroids composed of cancer and fibroblasts cell lines. We developed heterospheroids by combining HT-29, MCF-7, PANC-1 or SW480 with 1BR.3.G fibroblasts, which we have previously reported support spheroid formation. We also tested fibroblast cell lines, MRC-5, GM00498 and HIF, but 1BR.3.G was found to best form heterospheroids with morphological similarity to in vivo tumor tissue. The architectural organization of heterospheroids was based on histological examination using immunohistochemistry. We found that HT-29 and MCF-7 cells developed spheroids with the cancer cells surrounding the fibroblasts, whereas PANC-1 cells interspersed with the fibroblasts and SW480 cells were surrounded by fibroblasts. The fibroblasts also expressed collagen-1 and FAP-α, and whole transcriptomic analysis (WTA) showed abundant ECMand EMT-related expression in heterospheroids, thus reflecting a representative tumor-like microenvironment. The WTA showed that PANC-1 heterospheroids possess a strong EMT profile with abundant Vimentin and CDH2 expression. Drug testing was evaluated by measuring cytotoxicity of 5FU and cisplatin using cell viability and apoptosis assays. We found no major impact on the cytotoxicity when fibroblasts were added to the spheroids. We conclude that the cancer cell lines together with fibroblasts shape the architectural organization of heterospheroids to form tumor-like morphology, and we propose that the various 3D tumor structures can be used for drug testing directed against the cancer cells as well as the fibroblasts. [ABSTRACT FROM AUTHOR]

Drug testing is a common practice for community supervision in the U.S., despite limited research on its effectiveness at deterring future drug use. The present study explores the purpose of drug testing by examining the relationship between drug test frequency and positive test results. The impact of the type of drug tested (any vs. serious) and the risk and need level of the individuals tested are also examined. Results indicate that after controlling for risk and substance abuse need, more frequent testing schedules are associated with an increased rate of positive drug tests, suggesting more frequent testing detects rather than deters drug use. Policy implications for community corrections' purpose and use of drug testing are discussed. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has claimed millions of lives since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and lung disease appears the primary cause of death in COVID-19 patients. However, the underlying mechanisms of COVID-19 pathogenesis remain elusive, and there is no existing model where human disease can be faithfully recapitulated and conditions for the infection process can be experimentally controlled. Herein we report the establishment of an ex vivo human precision-cut lung slice (hPCLS) platform for studying SARS-CoV-2 pathogenicity and innate immune responses, and for evaluating the efficacy of antiviral drugs against SARS-CoV-2. We show that while SARS-CoV-2 continued to replicate during the course of infection of hPCLS, infectious virus production peaked within 2 days, and rapidly declined thereafter. Although most proinflammatory cytokines examined were induced by SARS-CoV-2 infection, the degree of induction and types of cytokines varied significantly among hPCLS from individual donors. Two cytokines in particular, IP-10 and IL-8, were highly and consistently induced, suggesting a role in the pathogenesis of COVID-19. Histopathological examination revealed focal cytopathic effects late in the infection. Transcriptomic and proteomic analyses identified molecular signatures and cellular pathways that are largely consistent with the progression of COVID-19 in patients. Furthermore, we show that homoharringtonine, a natural plant alkaloid derived from Cephalotoxus fortunei, not only inhibited virus replication but also production of pro-inflammatory cytokines, and thus ameliorated the histopathological changes caused by SARS-CoV-2 infection, demonstrating the usefulness of the hPCLS platform for evaluating antiviral drugs. IMPORTANCE Here, established an ex vivo human precision-cut lung slice platform for assessing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral replication kinetics, innate immune response, disease progression, and antiviral drugs. Using this platform, we identified early induction of specific cytokines, especially IP-10 and IL-8, as potential predictors for severe coronavirus disease 2019 (COVID-19), and uncovered a hitherto unrecognized phenomenon that while infectious virus disappears at late times of infection, viral RNA persists and lung histopathology commences. This finding may have important clinical implications for both acute and post-acute sequelae of COVID-19. This platform recapitulates some of the characteristics of lung disease observed in severe COVID-19 patients and is therefore a useful platform for understanding mechanisms of SARS-CoV-2 pathogenesis and for evaluating the efficacy of antiviral drugs. [ABSTRACT FROM AUTHOR]

Background: High potency synthetic opioids like fentanyl have continued to replace or contaminate the supply of illicit drugs in North America, with fentanyl test strips (FTSs) often used as a harm reduction tool for overdose prevention. The available evidence to support FTS for harm reduction has yet to be summarized. Methods: A search of PubMed, Ovid Embase, and Web of Science was conducted in March 2023. A 2-stage review was conducted to screen by title and abstract and then by full text by 2 reviewers. Data were extracted from each study using a standardized template. Results: A total of 91 articles were included, mostly from North America, predominantly reporting on FTS along with other harm reduction tools, and all conducted after 2016. No randomized controlled trials are reported. Robust evidence exists supporting the sensitivity and specificity of FTS, along with their acceptability and feasibility of use for people who use drugs and as a public health intervention. However, limited research is available on the efficacy of FTS as a harm reduction tool for behavior change, engagement in care, or overdose prevention. Conclusions: Though FTSs are highly sensitive and specific for point of care testing, further research is needed to assess the association of FTS use with overdose prevention. Differences in FTS efficacy likely exist between people who use opioids and nonopioid drugs, with additional investigation strongly needed. As drug testing with point-of-care immunoassays is embraced for nonfentanyl contaminants such as xylazine and benzodiazepines, increased investment in examining overdose prevention is necessary. [ABSTRACT FROM AUTHOR]

Abstract and ARP Position Statement: Based on the available body of scientific evidence and with the goals of promoting safety of combat sports athletes and striving for the advancement of clean sport, the Association of Ringside Physicians recommends the following regarding cannabis: • Use of marijuana or synthetic cannabinoids by combat sports athletes is discouraged due to unproven benefits and many known adverse effects. Acute use can impair cognition and complex motor function, which likely leads to reduced performance in combat sports. Chronic use can increase risk for heart and lung disease, several cancers, schizophrenia, and can reduce testosterone in men and impair fertility. Benefits from cannabis in most contexts, including athletic performance, have not been proven. • Use of topical purified CBD is neither encouraged nor discouraged. • Since acute cannabis intoxication can impair complex cognitive and motor function, any athlete suspected of acute intoxication at the time of competition – based on clinical judgment – should be banned from that competition. • Wide-scale regulation of cannabis based on quantitative testing has limited usefulness in combat sports, for the following reasons: ∘ Cannabis is not ergogenic and is likely ergolytic. ∘ Concentrations in body fluids correlate poorly with clinical effects and timing of use. ∘ Access to testing resources varies widely across sporting organizations. [ABSTRACT FROM AUTHOR]

Background: Young farm animals are susceptible to the opportunistic infections which may cause economic losses due to mortality and poor weight gain. Development of antimicrobial resistance and desire to improve therapy efficacy and safety are the reasons to seek for new antibacterial drugs ensuring rapid recovery with minimum adverse events. Aim: To estimate the efficacy of DOKSI AVZ 500 in respiratory pathologies in young pigs. Methods: The study was conducted in 65–70-day old Yorkshire piglets with the signs of bacterial respiratory pathologies. The animals were treated with the test drug for 3 or 5 days. The reference group received TETRAMAX 500 which is similar to the test drug in terms of chemical structure, mechanism of action and spectrum. The animal status was assessed using clinical examination, CBC and bacteriological tests. Results: Both test and reference drugs were well tolerated and ensured the animal recovery within about 4 days. The recovery was accompanied with normalization of hematological parameters and flora composition. The bacteria associated with the disease development, Streptococcus suis, was virtually completely eliminated in all groups. No adverse events were noted. After the treatment, all the animals readily gained the weight and live market quality. Conclusion: DOKSI AVZ 500 was a highly efficient therapy for respiratory pathologies caused by the resident opportunistic flora in piglets. It also has shown noninferiority vs. TETRAMAX 500 in terms of all the health-related parameters and thus can be recommended for introduction in veterinary practice in pig farms. [Open Vet J 2024; 14(5.000): 1098-1102]

Abstract The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs’ potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

Objective: Workplace drug testing for public transport drivers is required to apply or renew their driver’s certificate as well as a psychological evaluation according to the decision taken by the Adana Municipality Transportation Coordination Center in May 2015. In the context of this study, our objective is to safeguard both the rights of public transportation drivers who have tested positive for illicit substances and the safety of passengers. To this end, we aimed to corroborate the presence of these substances in urine or hair samples through liquid chromatography/tandem mass spectrometry and to provide a nuanced interpretation of the results. Methods: The sample of the study consisted of 35 drivers who applied to the Forensic Toxicology Laboratory of Çukurova University, Department of Forensic Medicine, for confirmation analysis between January 2019 and December 2022. Opioids, cocaine, marijuana, amphetamines and their derivatives, benzodiazepine, buprenorphine, and synthetic cannabinoids were confirmed by liquid chromatography/tandem mass spectrometry in the urine or hair samples of 35 drivers. Results: All of 35 public transport drivers were male in this study and the mean age was 48.8±9.1 years old. The most detected substance in urine by immunoassay test were benzodiazepine, amphetamine and opiate, respectively. However, 91.5% of drivers showed false positive results in confirmatory methods. Benzodiazepine was detected in only 5% by liquid chromatography/tandem mass spectrometry while more than half of the 35 samples were positive for benzodiazepine in screening test. Conclusion: Immunoassay tests are susceptible to generating false positive results due to the cross-reactivity of analytes.

To create a review of the published scientific literature on the benefits and potential perspectives of the use of 3D bio-nitrification in the field of pharmaceutics. This work was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting meta-analyses and systematic reviews. The scientific databases PubMed, Scopus, Google Scholar, and ScienceDirect were used to search and extract data using the following keywords: 3D bioprinting, drug research and development, personalized medicine, pharmaceutical companies, clinical trials, drug testing. The data points to several aspects of the application of bioprinting in pharmaceutics were reviewed. The main applications of bioprinting are in the development of new drug molecules as well as in the preparation of personalized drugs, but the greatest benefits are in terms of drug screening and testing. Growth in the field of 3D printing has facilitated pharmaceutical applications, enabling the development of personalized drug screening and drug delivery systems for individual patients. Bioprinting presents the opportunity to print drugs on demand according to the individual needs of the patient, making the shape, structure, and dosage suitable for each of the patient's physical conditions, i.e., print specific drugs for controlled release rates; print porous tablets to reduce swallowing difficulties; make transdermal microneedle patches to reduce patient pain; and so on. On the other hand, bioprinting can precisely control the distribution of cells and biomaterials to build organoids, or an Organ-on-a-Chip, for the testing of drugs on printed organs mimicking specified disease characteristics instead of animal testing and clinical trials. The development of bioprinting has the potential to offer customized drug screening platforms and drug delivery systems meeting a range of individualized needs, as well as prospects at different stages of drug development and patient therapy. The role of bioprinting in preclinical and clinical testing of drugs is also of significant importance in terms of shortening the time to launch a medicinal product on the market. [ABSTRACT FROM AUTHOR]

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes. [ABSTRACT FROM AUTHOR]

Recent research has yielded important insight into the characteristics and behaviours of officers who commit misconduct across the UK, USA and Australia. However, there remains little research into illicit substance use by sworn police. Considering substance use by police through the lens of police misconduct, this paper employs correlation and regression analyses using a sample of 489 sworn officers, to analyse whether individual types of misconduct, or the overall volume of misconduct committed, were predictive of an officer returning a positive drug test during departmental random drug testing. Findings suggested that neither individual types of misconduct, or the overall number of complaints received by officers were useful in predicting a positive drug test. However, a current or historical association with a known offender held a strong relationship with returning a positive drug test. Pivotally, holding a second job (outside of the agency) was also a significant predictor of a positive drug test. The findings of this research hold important implications for drug testing policy and procedure of policing agencies, and for understanding which factors may suggest that an officer is at risk of drug use. [ABSTRACT FROM AUTHOR]

Background: Young farm animals are susceptible to opportunistic infections which may cause economic losses due to mortality and poor weight gain. The development of antimicrobial resistance and the desire to improve therapy efficacy and safety are the reasons to seek for new antibacterial drugs ensuring rapid recovery with minimum adverse events. Aim: To estimate the efficacy of DOKSI AVZ 500 in respiratory pathologies in young pigs. Methods: The study was conducted in 65-70-day-old Yorkshire piglets with signs of bacterial respiratory pathologies. The animals were treated with the test drug for 3 or 5 days. The reference group received TETRAMAX 500 which is similar to the test drug in terms of chemical structure, mechanism of action, and activity spectrum. The animal's status was assessed using clinical examination, clinical blood count, and bacteriological tests. Results: Both test and reference drugs were well tolerated and ensured the animal recovery within about 4 days. The recovery was accompanied by normalization of hematological parameters and flora composition. The bacterium associated with the disease development, Streptococcus suis, was virtually completely eliminated in all groups. No adverse events were noted. After the treatment, all the animals readily gained weight and live market quality. Conclusion: DOKSI AVZ 500 was a highly efficient therapy for respiratory pathologies caused by the resident opportunistic flora in piglets. It has also shown noninferiority vs. TETRAMAX 500 in terms of all the health-related parameters and thus can be recommended for introduction in veterinary practice in pig farms. [ABSTRACT FROM AUTHOR]

Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes enriched in melanin which are responsible for skin, eye and hair pigmentation. They also have different functions in photoprotection, immunity and sound perception. Melanocyte dysfunction can cause pigmentary disorders, hearing and vision impairments or increased cancer susceptibility. This review focuses on the role of melanocytes in homeostasis and disease, before discussing their potential in regenerative medicine applications, such as for disease modeling, drug testing or therapy development using stem cell technologies, tissue engineering and extracellular vesicles. [ABSTRACT FROM AUTHOR]

This study investigated the effects of hexahydrocannabinol (HHC) and other unclassified cannabinoids, which were recently introduced to the recreational drug market, on cannabis drug testing in urine and oral fluid samples. After the appearance of HHC in Sweden in 2022, the number of posts about HHC on an online drug discussion forum increased significantly in the spring of 2023, indicating increased interest and use. In parallel, the frequency of false positive screening tests for tetrahydrocannabinol (THC) in oral fluid, and for its carboxy metabolite (THC-COOH) in urine, rose from <2% to >10%. This suggested that HHC cross-reacted with the antibodies in the immunoassay screening, which was confirmed in spiking experiments with HHC, HHC-COOH, HHC acetate (HHC-O), hexahydrocannabihexol (HHC-H), hexahydrocannabiphorol (HHC-P), and THC-P. When HHC and HHC-P were classified as narcotics in Sweden on 11 July 2023, they disappeared from the online and street shops market and were replaced by other unregulated variants (e.g. HHC-O and THC-P). In urine samples submitted for routine cannabis drug testing, HHC-COOH concentrations up to 205 (mean 60, median 27) µg/L were observed. To conclude, cannabis drug testing cannot rely on results from immunoassay screening, as it cannot distinguish between different tetra- and hexahydrocannabinols, some being classified but others unregulated. The current trend for increased use of unregulated cannabinols will likely increase the proportion of positive cannabis screening results that need to be confirmed with mass spectrometric methods. However, the observed cross-reactivity also means a way to pick up use of new cannabinoids that otherwise risk going undetected. [ABSTRACT FROM AUTHOR]

Drug testing—either random, scheduled, or for-cause—is a common condition of community supervision. This study investigates the utility of drug testing measures in predicting arrest or revocation outcomes for individuals on probation. Results were generated during the development of a set of new risk classification algorithms for individuals on probation or parole in Georgia. Multiple analytic approaches and predictive factors were tested in the development of these models that were built using data for approximately 154,000 individuals who began probation or parole between January 1, 2016, and December 31, 2019. Accuracy at predicting rearrest was improved by implementing time-period-specific models; using recent rather than lifetime criminal history; and incorporating dynamic measures of both protective and risk factors, including drug test results and absence of testing. Models were estimated separately for men and women, for different supervision statuses (probation-only, split-sentence probation, and parole), and for three consecutive time periods (first quarter, next three quarters, one-plus years). Positive test results were predictive of future arrest or revocation, while negative results and absence of testing in latter-period models were associated with reduced risk. Results are presented for the probation-only models for men and women, but similar results obtained for the split-probation and parole models. [ABSTRACT FROM AUTHOR]

The criminal justice system is enthralled with drug testing. It is a billion dollar industry fueled by drug courts, swift certain, and fair strategies, and the idea that probation is a privilege. It has become so pervasive that even people without an identified drug problem are often tested on a regular basis. While the field has accepted drug testing as a key component, this paper suggests that the data, while limited, is not as pervasive as the practice itself. This paper will explore the current research on drug testing, how effective it is for people without an identified substance use issue, and what are some of the collateral consequences to testing that may offset any perceived or real benefit to the practice. [ABSTRACT FROM AUTHOR]

This paper examines the multilayered dynamics behind the drivers of overdose deaths, criminal legal-system involvement, and the drug war infiltration of people's everyday lives—especially for people under community supervision. While incarceration receives more media and academic attention because of its particular cruelty, almost twice as many people—3.7 million, or one in every sixty-nine U.S. adults—are under community supervision. Probation and parole are commonly understood as "alternatives to incarceration" or "lenient sentences," but people on supervision must endure constant monitoring, perpetually under the threat of incarceration. Drug war policies and practices have profoundly shaped probation and parole. Regardless of someone's original sentence, abstinence from drugs, drug testing, submission to warrantless searches, and court-ordered treatment are routine features of supervision. The putative goal of community supervision is to ensure successful reintegration; yet drug war surveillance enacts extensive barriers, while not reducing drug use or drug-related harms like overdose. In order to ensure health, financial security, and overall well-being of those under supervision, policymakers, probation and parole officers, clinicians, service providers, and researchers must work to identify and remove barriers to care, including routine drug testing, substandard or forced substance use disorder treatment, and poor-quality services and support. [ABSTRACT FROM AUTHOR]

Observers of the criminal legal system in the U.S. have increasingly looked beyond prisons to map the expansion and consequences of mass supervision, or the role of probation and parole in people's lived experiences of correctional control. In this commentary, I reflect on the lessons learned from a decade of research on mass probation, focusing in particular on how drug testing helps us understand the risks and potential benefits of supervision. In light of the concerns about the harms of supervision, I argue that scholars and advocates should reconsider the fundamental purpose of probation and ask what it might look like to abolish supervision as we know it. [ABSTRACT FROM AUTHOR]

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3D cancer cell cultures have enabled new opportunities for replacing compound testing in experimental animals. However, most solid tumors are composed of multiple cell types, including fibroblasts. In this study we developed multicellular tumor heterospheroids composed of cancer and fibroblasts cell lines. We developed heterospheroids by combining HT-29, MCF-7, PANC-1 or SW480 with 1BR.3.G fibroblasts, which we have previously reported support spheroid formation. We also tested fibroblast cell lines, MRC-5, GM00498 and HIF, but 1BR.3.G was found to best form heterospheroids with morphological similarity to in vivo tumor tissue. The architectural organization of heterospheroids was based on histological examination using immunohistochemistry. We found that HT-29 and MCF-7 cells developed spheroids with the cancer cells surrounding the fibroblasts, whereas PANC-1 cells interspersed with the fibroblasts and SW480 cells were surrounded by fibroblasts. The fibroblasts also expressed collagen-1 and FAP-α, and whole transcriptomic analysis (WTA) showed abundant ECM- and EMT-related expression in heterospheroids, thus reflecting a representative tumor-like microenvironment. The WTA showed that PANC-1 heterospheroids possess a strong EMT profile with abundant Vimentin and CDH2 expression. Drug testing was evaluated by measuring cytotoxicity of 5FU and cisplatin using cell viability and apoptosis assays. We found no major impact on the cytotoxicity when fibroblasts were added to the spheroids. We conclude that the cancer cell lines together with fibroblasts shape the architectural organization of heterospheroids to form tumor-like morphology, and we propose that the various 3D tumor structures can be used for drug testing directed against the cancer cells as well as the fibroblasts.

The occurrence of vaso-occlusive crisis greatly depends on the competition between the sickling delay time and the transit time of individual sickle cells, i.e., red blood cells from sickle cell disease (SCD) patients, while they are traversing the circulatory system. Many drugs for treating SCD work by inhibiting the polymerization of sickle hemoglobin (HbS), effectively delaying the sickling process in sickle cells (SS RBCs). Most previous studies on screening anti-sickling drugs, such as voxelotor, rely on in vitro testing of sickling characteristics, often conducted under prolonged deoxygenation for up to 1 hour. However, since the microcirculation of RBCs typically takes less than 1 minute, the results of these studies may be less accurate and less relevant for in vitro-in vivo correlation. In our current study, we introduce a computer vision-enhanced microfluidic framework designed to automatically capture the transient sickling kinetics of SS RBCs within a 1-min timeframe. Our study has successfully detected differences in the transient sickling kinetics between vehicle control and voxelotor-treated SS RBCs. This approach has the potential for broader applications in screening anti-sickling therapies. [ABSTRACT FROM AUTHOR]

Chronic inflammation and dysregulated repair mechanisms after epithelial damage have been implicated in chronic obstructive pulmonary disease (COPD). However, the lack of ex vivo-models that accurately reflect multicellular lung tissue hinders our understanding of epithelial-mesenchymal interactions in COPD. Through a combination of transcriptomic and proteomic approaches applied to a sophisticated in vitro iPSC-alveolosphere with fibroblasts model, epithelial-mesenchymal crosstalk was explored in COPD and following SARS-CoV-2 infection. These experiments profiled dynamic changes at single-cell level of the SARS-CoV-2-infected alveolar niche that unveiled the complexity of aberrant inflammatory responses, mitochondrial dysfunction, and cell death in COPD, which provides deeper insights into the accentuated tissue damage/inflammation/remodeling observed in patients with SARS-CoV-2 infection. Importantly, this 3D system allowed for the evaluation of ACE2-neutralizing antibodies and confirmed the potency of this therapy to prevent SARS-CoV-2 infection in the alveolar niche. Thus, iPSC-alveolosphere cultured with fibroblasts provides a promising model to investigate disease-specific mechanisms and to develop novel therapeutics. [ABSTRACT FROM AUTHOR]

The standard protocol in addiction treatment/pain management is to conduct immunoassay screens for major drugs subject to misuse, followed by confirmatory testing of positive results. However, this may miss unscreened or rarely screened drugs that could pose risks, especially to polydrug users. We sought to determine the prevalences of unscreened/rarely screened drugs in a sample of individuals misusing drugs in 7 U.S. states, and to compare the results of urine vs. oral testing for these drugs by direct-to-definitive liquid chromatography/tandem mass spectrometry (LC-MS-MS). The five drugs with the highest prevalences were: gabapentin (16.8%), quetiapine (6.2%), chlorpheniramine (5.3%), hydroxyzine (4.9%), and ephedrine (3.5%). All have clinical significance as indicated by severity of possible side effects, interactions with other drugs, and/or misuse potential. Drugs were generally detected more frequently in oral fluid than urine, but gabapentin was more frequently detected in urine. The prevalences of the included drugs seem high enough, and their clinical significance important enough, to warrant consideration of expanding clinical drug test panels, either by direct-to-definitive testing or the addition of selected immunoassay screens when available. Oral fluid was usually more suitable than urine as the test matrix, given the higher rates of detection in oral fluid for most substances included in this study. [ABSTRACT FROM AUTHOR]

Background: Xylazine is an ⍺2 adrenergic receptor agonist and a veterinary sedative that can cause severe health complications yet interventions to detect and treat human exposure remain underdeveloped. Community-based drug checking services (DCS) involve the testing of small amounts of drugs to increase community knowledge of unregulated supplies and decrease harms. This study characterized xylazine awareness, desire, use and exposure among people who use drugs (PWUD) in Rhode Island, US. Methods: We analyzed data from an ongoing PWUD cohort study. In 2023, 125 PWUD were enrolled and surveyed. Using point-of-care Fourier Transform infrared spectroscopy (FTIR-S), we tested a drug sample from each participant onsite and confirmed the results offsite at a laboratory. Results were conveyed in real-time, along with harm reduction education, referrals to resources and care. Results: Virtually all participants (99.2 %) wanted to avoid xylazine exposure. Half (51.2 %) knew what xylazine was, and a quarter (26.1 %) suspected previous exposure. Xylazine exposure was primarily surmised through sedating (45.2 %) and ulcerative (29.0 %) effects. Only 8.8 % of participants submitted a sample that they expected to contain xylazine. Xylazine was detected in 14.5 % of samples using FTIR-S and in 21.4 % of samples using a dual laboratory approach of gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Participants thought that these xylazine-positive samples were fentanyl (78.3 %), heroin (13.0 %), or Percocet® (8.7 %). Conclusion: Implementing point-of-care DCS at harm reduction organizations could be useful in rapidly increasing xylazine awareness and engaging at-risk individuals in prevention, harm reduction, treatment, and rapid care for xylazine-related wounds.

Background: Xylazine is a sedative found increasingly in the illicit fentanyl supply that can cause hypotension, bradycardia, necrosis and death. This pilot examined the real-world performance of BTNX xylazine test strips (XTS) in drug residue samples. Methods: This study was nested within a drug checking service in Rhode Island. We tested unmeasured drug residue dissolved in 5 mL of distilled water using XTS and Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF-MS). Analyses compared XTS and LC-QTOF-MS results to calculate XTS detection of xylazine in residue. Results: Among 41 residue samples, xylazine was detected in 11% by the XTS and 44 % by the laboratory. The LC-QTOF-MS detected xylazine in 18 samples: 4 major, 9 minor, 5 trace by volume relative to the whole sample. The XTS disagreed with the LC-QTOF-MS by indicating a negative result in 77.8 % (N=14) of the samples but never indicated a positive when the LC-QTOF-MS reported xylazine’s absence. The XTS correctly detected xylazine 22 % of the time, however, this increased to 100 % of the time if xylazine was a major active component. Conclusions: In this study, the BTNX XTS often disagreed with LC-QTOF-MS by indicating a negative result, likely due to the dilution levels used and sample composition. The XTS may not be accurate in detecting residual amounts of xylazine, especially if xylazine is not a dominant component of the tested sample. Given the novelty of BTNX’s XTS products, we recommend XTS only be used in conjunction with other advanced drug checking modalities for residue testing.

Julie Rud is the community corrections field services area director for Hennepin County (Minneapolis). Only five states have more people on probation than Minnesota, yet Hennepin County is a leader in reforms to supervision, including eliminating fees and cutting the use of drug testing in half since 2017. Below is an edited and condensed version of remarks delivered by Rud as a panelist at the "Drug Testing and Community Supervision: Interrogating Policy, Practice, and Purpose" convening in Columbus, Ohio, in November 2023. [ABSTRACT FROM AUTHOR]

Diversion of substances from the care of the intended patient is a significant problem in healthcare. Patients are harmed by the undertreatment of pain and suffering, transmission of disease, as well as the risk associated with impaired vigilance. Healthcare providers may be harmed by the physical and mental impact of their addictions. Healthcare systems are placed in jeopardy by the legal impact associated with illegal routes of drug release including sanction and financial liability and loss of public trust. Healthcare institutions have implemented many measures to reduce diversion from the perioperative area. These efforts include education, medical record surveillance, automated medication dispensing systems, urine drug testing, substance waste management systems, and drug diversion prevention teams. This narrative review evaluates strengths, weaknesses, and effectiveness of these systems and provides recommendations for leaders and care providers.

One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges. As the practically unlimited source of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CM) is now mostly resolved, there are great efforts to improve their quality and applicability by overcoming their intrinsic limitations. The greatest bottleneck in the field is the in vitro ageing of hiPSC-CMs to reach a maturity status that closely resembles that of the adult heart, thereby allowing for more appropriate drug developmental procedures as there is a clear correlation between ageing and developing cardiovascular diseases. Here, we review the current state-of-the-art techniques in the most realistic heart models used in disease modelling and toxicity evaluations from hiPSC-CM maturation through heart-on-a-chip platforms and in silico models to the in vitro models of certain cardiovascular diseases.

In drug development, conventional preclinical and clinical testing stages rely on cell cultures and animal experiments, but these methods may fall short of fully representing human biology. To overcome this limitation, the emergence of organ-on-a-chip (OOC) technology has sparked interest as a transformative approach in drug testing research. By closely replicating human organ responses to external signals, OOC devices hold immense potential in revolutionizing drug efficacy and safety predictions. This review focuses on the advancements, applications, and prospects of OOC devices in drug testing. Based on the latest advances in the field of OOC systems and their clinical applications, this review reflects the effectiveness of OOC devices in replacing human volunteers in certain clinical studies. This review underscores the critical role of OOC technology in transforming drug testing methodologies. [ABSTRACT FROM AUTHOR]

The relevance of identifying pathological processes in the context of embryonic development is increasingly gaining attention in terms of professionalized prenatal care. To analyze local effects of prenatally administered drugs during embryonic development, the model organism of the chicken embryo can be used in a first exploratory approach. For the examination of local dexamethasone administration—as an exemplary drug—common bead implantation protocols have been adapted to serve as an in vivo technique for local drug testing during embryonic skin regeneration. For this, acrylic beads were soaked in a dexamethasone solution and implanted into skin incisional wounds of 4-day-old chicken embryos. After further incubation, the effects of the applied substance on the process of embryonic skin regeneration were analyzed using histological and molecular biological techniques. This data descriptor contains a detailed microsurgical protocol, a representative video demonstration, and exemplary results of local glucocorticoid-induced changes during embryonic wound healing. To conclude, this method allows for the analysis of the local effects of a particular substance on a cellular level and can be extended to serve as an in vivo technique for numerous other drugs to be tested on embryonic tissue. Dataset:  https://doi.org/10.3390/biomedicines10123125. Dataset License: CC-BY [ABSTRACT FROM AUTHOR]

Skeletal muscle contributes significantly to human health, which is closely relevant to human locomotion, energy metabolism, immune regulation, and aging. Skeletal muscle holds the potential to recover its healthy condition via self‐repairing after minor damage. However, the capacity of sarcous self‐repair becomes incompetent following massive trauma or some myopathy, which raises a huge demand for skeletal muscle regeneration. Skeletal muscle engineering aims to rebuild muscle tissues in vitro to repair muscle injuries, develop pathological models, advance myopathy‐related research, and explore myopathy‐related medications. This review summarizes the advances in skeletal muscle engineering, including the cell resources that can be used in muscle regeneration, the recent progress of rebuilding methods for skeletal muscle engineering, as well as the biomedical applications of engineered skeletal muscle for tissue repair, drug testing, disease modeling, and soft robots. Finally, the challenges and future perspectives are discussed on improving skeletal muscle engineering by integrating multidisciplinary approaches, thus accelerating the technological innovation and translational application of this area. [ABSTRACT FROM AUTHOR]

The occurrence of vaso-occlusive crisis greatly depends on the competition between the sickling delay time and the transit time of individual sickle cells, i.e., red blood cells from sickle cell disease (SCD) patients, while they are traversing the circulatory system. Many drugs for treating SCD work by inhibiting the polymerization of sickle hemoglobin (HbS), effectively delaying the sickling process in sickle cells (SS RBCs). Most previous studies on screening anti-sickling drugs, such as voxelotor, rely on in vitro testing of sickling characteristics, often conducted under prolonged deoxygenation for up to 1 hour. However, since the microcirculation of RBCs typically takes less than 1 minute, the results of these studies may be less accurate and less relevant for in vitro-in vivo correlation. In our current study, we introduce a computer vision-enhanced microfluidic framework designed to automatically capture the transient sickling kinetics of SS RBCs within a 1-min timeframe. Our study has successfully detected differences in the transient sickling kinetics between vehicle control and voxelotor-treated SS RBCs. This approach has the potential for broader applications in screening anti-sickling therapies.

Background & Aims: Cholangiocarcinoma (CCA) is a primary liver tumour characterised by a poor prognosis and limited therapeutic options. Available 3D human CCA models fail to faithfully recapitulate the tumour niche. We aimed to develop an innovative patient-specific CCA-on-chip platform. Methods: A CCA tumour microenvironment was recapitulated on a microfluidic three-channel chip using primary CCA cells, cancer-associated fibroblasts (CAFs), endothelial cells, and T cells isolated from CCA specimens (n = 6). CAF and CCA cells were co-cultured in the central channel, flanked by endothelial cells in one lateral channel, recreating a tubular structure. An extensive characterisation of this platform was carried out to investigate its diffusion ability, hydrogel properties, and changes in matrix composition. Cell phenotype and functional properties were assessed. Results: Primary cells seeded on the microfluidic device were shown to reproduce the architectural structure and maintain the original phenotype and functional properties. The tumour niche underwent a deep remodelling in the 3D device, with an increase in hydrogel stiffness and extracellular matrix deposition, mimicking in vivo CCA characteristics. T cells were incorporated into the device to assess its reliability for immune cell interaction studies. Higher T cell migration was observed using cells from patients with highly infiltrated tumours. Finally, the drug trial showed the ability of the device to recapitulate different drug responses based on patient characteristics. Conclusions: We presented a 3D CCA platform that integrates the major non-immune components of the tumour microenvironment and the T cell infiltrate, reflecting the CCA niche. This CCA-on-chip represents a reliable patient-specific 3D platform that will be of help to further elucidate the biological mechanisms involved in CCA and provide an efficient tool for personalised drug testing. Impact and implications: An innovative patient-specific cholangiocarcinoma (CCA)-on-chip platform was successfully developed, integrating the major components of the tumour microenvironment (tumour cells, cancer-associated fibroblasts, endothelial cells, and immune infiltrate) and faithfully mimicking the CCA niche. This CCA-on-chip represents a powerful tool for unravelling disease-associated cellular mechanisms in CCA and provides an efficient tool for personalised drug testing.