Hard Drugs Research Articles

Exploring acetaminophen prodrugs and hybrids: a review.

This critical review highlights the advances in developing new molecules for treating pain syndrome, an important issue for human health. Acetaminophen (APAP, known as paracetamol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical practice despite their adverse effects. Research is being conducted to develop innovative drugs with improved pharmaceutical properties to mitigate these effects. A more practical way to achieve that is to study well-known and time-tested drugs in their molecular combinations. Accordingly, the present work explores APAP and their combined chemical entities, i.e., prodrugs (soft drugs), codrugs (mutual prodrugs), and hybrids. Due to their molecular structure, APAP prodrugs or codrugs could be considered merged or conjugated hybrids; all these names are very fluid terms. This article proposed a structural classification of these entities to better analyze their advances. So, the following: carrier-linked O-modified APAP, -linked N-modified APAP derivatives (prodrugs), and direct- and spacer-N,O-linked APAP hybrids (codrugs) are the central parts of this review and are examined, especially ester and amide NSAID-APAP molecules. The C-linked APAP and nitric oxide (NO)-releasing APAP hybrids were also briefly discussed. Prime examples of APAP-based drugs such as propacetamol, benorylate, acetaminosalol, nitroparacetamol, and agent JNJ-10450232 weave well into this classification. The proposed classification is the first and original, giving a better understanding of the SAR studies for new pain relievers research and the design development for the analgesic APAP-(or NSAID)-based compounds.

Piloting a simplified bio-behavioural survey methodology, the BBS-Lite, among people who inject drugs in Georgia

BackgroundDuring 2021 and 2023 two simplified Biological and Behavioural Study (BBS-Lite) surveys, and in 2022 one Standard Integrated Biological and Behavioural Study (IBBS), were conducted among people who inject drugs in seven cities in Georgia. From these, an opportunity to compare the implementation of these survey methods and results was able to be gained. MethodsThe two survey types were compared to find points of similarity and difference in their methodologies. The methodologies of the IBBS and BBS-Lite studies shared many characteristics, including the cities where they were implemented, recruitment criteria, sample sizes, and common questionnaire items. All studies were multi-centre cross-sectional involving administration of a face-to-face behavioural questionnaire and collection of biological specimens for testing of HIV, syphilis, hepatitis B virus (HBV), and hepatitis C virus (HCV). The main differences were in the sampling methods. The IBBS utilised respondent-driven sampling (RDS) while participants of the BBS-Lite studies were enrolled through consecutive recruitment at the harm reduction (HR) programme sites and on outreach and through snowball sampling. We compared the results from each study as well as the implementation modalities modalities such as time taken and budgetary requirements, and the complexity of implementation. ResultsConsiderably less time was required for recruitment, as well as for interviewing, data entry (4 times less) and the analysis for the BSS-Lite studies compared to the IBBS. The BSS-Lite study budgets were at least 2.5 times less than of the IBBS study.The recruited samples were comparable for age distribution, median age at first injection, the last drug injected, sharing of drug injecting equipment or receiving opioid agonist maintenance treatment (OAMT) during the last 12 months. HIV and HCV prevalence were similar including for stratifications by age, client status and city of recruitment. ConclusionOur findings have demonstrated that if implemented on a regular basis, the BBS-Lite can be a complementary solution for systematic data collection, filling surveillance gaps and addressing the challenges that persist in obtaining important data on people who inject drugs (PWID) between IBBS rounds in the country. The methodology is recommended for testing in other settings and in other key populations. In addition, the data collected on a routine base can help the harm reduction (HR) program to better understand the changes in the drug scene and observe new trends in HIV risks and drug injecting behaviours, possible barriers for access to harm reduction, drug treatment, and HIV and/or viral hepatitis testing and treatment services.

Unveiling the power of liquid chromatography in examining a library of degradable poly(2-oxazoline)s in nanomedicine applications.

A library of degradable poly(2-alkyl-2-oxazoline) analogues (dPOx) with different length of the alkyl substituents was characterized in detail by gradient elution liquid chromatography. The hydrophobicity increased with increased side chain length as confirmed by a hydrophobicity row, established by reversed-phase liquid chromatography. Those dPOx were cytocompatible and formed colloidally stable nanoparticle (NP) formulations with positive zeta potential. Dynamic light scattering (DLS) revealed that dPOx with increased hydrophobicity tended to form NPs with increased sizes. NPs created from the most hydrophobic polymer, degradable poly(2-nonyl-2-oxazoline) (dPNonOx), showed tendency for aggregation at pH 5.0, and in the presence of protease in solution, in particular for NPs formulated without surfactant. Liquid chromatography revealed enzymatic degradation of dPNonOx NPs, clearly demonstrating the disappearance of polymer signals and the appearance of hydrophilic degradation products eluting close to the chromatographic void time. The degradation process was confirmed by 1H NMR spectroscopy. dPNonOx NPs containing the anti-inflammatory drug BRP-201 as payload reduced 5-lipoxygenase activity in human neutrophils. Thereby, composition analysis of the resultant NPs, including drug quantification, was also enabled by liquid chromatography. The results indicate the importance of a detailed analysis of the final polymer-based NP formulations by a multimethod approach, including, next to standard applied techniques such as DLS/ELS, the underexplored potential of liquid chromatography. The latter is demonstrated to resolve a fine structure of solution composition, together with an assessment of possible degradation pathways and is versatile in determining hydrophobicity/hydrophilicity of polymer materials. Our study underscores the power of liquid chromatography for characterization of soft matter drug carriers.

Selection of DNA aptamers for detecting metronidazole and ibuprofen: two common additives in soft drinks.

To enhance the effects of some functional soft drinks, drugs, especially metronidazole (MNZ) and ibuprofen (IBF), are often illegally added. This poses a serious threat to the health of consumers. Therefore, developing simple and rapid detection methods for these additives is crucial. In this study, DNA aptamers of metronidazole and ibuprofen were selected using the library-immobilized method. The best aptamer for metronidazole, named MNZ-1, has a dissociation constant (Kd) value of 4.9 μM and the aptamer for ibuprofen, named IBF-1, shows a Kd of 9.3 μM, as determined by the thioflavin T (ThT) fluorescence assay. The Kd values measured using isothermal titration calorimetry (ITC) were 17.0 μM and 66.7 μM for these two aptamers, respectively. Selectivity experiments indicate that MNZ-1 demonstrates very weak binding to structurally similar drugs, whereas IBF-1 exhibits binding capability to some structurally similar compounds comparable to ibuprofen, enabling the simultaneous detection of these types of drugs. Neither MNZ-1 nor IBF-1 binds to other common drugs. Using ThT, a label-free fluorescent detection method was developed for metronidazole and ibuprofen in soft drinks, showing limits of detection (LODs) of 0.6 μM and 4.7 μM, respectively. Owing to their small size and well-defined secondary structures, these aptamers are expected to be utilized in analytical applications for food and environmental monitoring.

Responsive soft actuator: harnessing multi-vapor, light, and magnetic field stimuli.

Bioinspired soft actuators, capable of undergoing shape deformation in response to external triggers, hold great potential in fields such as soft robotics, artificial muscles, drug delivery, and smart switches. However, their widespread application is hindered by limitations in responsiveness, durability, and complex fabrication processes. In this study, we propose a new approach to tackle these challenges by developing a single-layer soft actuator that responds to multiple stimuli using a straightforward solution-casting method. This actuator comprises bio-polymer gelatin, bio-compatible PEDOT:PSS, and iron oxide (Fe3O4) nanoparticles. Our actuator exhibits responsiveness to a range of organic solvent vapors, including water vapor, light, and magnetic fields. Notably, it exhibits rapid and reversible bending in distinct directions in response to different vapors, bending upwards in the presence of water vapor and downwards in the presence of alcohol vapor. Moreover, exposure to infrared (IR) light induces a bending toward the light source. The incorporation of magnet-responsive Fe3O4 nanoparticles induces multi-functionality in the actuator. The actuation characteristics of the actuator are controlled by leveraging its responsiveness to dual stimuli, such as water vapor and magnetic fields, as well as light and magnetic fields. For the proof of concept, we showcase several potential applications of our multi-stimuli responsive soft actuator, including magnet-triggered electrical switches, cargo transportation, soft grippers, targeted drug delivery, energy harvesting, and bio-mimicry.

In defence of the decriminalisation of drug possession in the UK

In this review article, we develop the case for the decriminalisation of drug possession in the UK by describing our ‘modest proposal’ to repeal the relevant sections of the Misuse of Drugs Act 1971 and its advantages. We defend this proposal against possible critiques from both conservative and radical positions. On the conservative side, these criticisms include that it would increase drug use and harm and that it would be illegal under international law. From the more radical position, we anticipate the criticisms that decriminalisation of possession would leave the harm associated with illegal drug supply to continue, that it would leave in place restrictions on the rights to use drugs, that it would forego the possible tax income from a legally regulated market, and that the drug laws would continue to act as tools of social control. In response, we argue that decriminalisation offers a feasible first step towards reducing the harm of drug control which would not increase drug-related harm.

Efficacy of therapeutic intervention with NanoBEO to manage agitation and pain in patients suffering from severe dementia: a pilot clinical trial.

An estimated 57.4 million people live with dementia worldwide, with the social burden of the disease steadily growing. Despite the approval of lecanemab and ongoing trials, there is still a lack of effective and safe treatments for behavioral and psychological symptoms of dementia (BPSD), which affect 99% of patients. Agitation is one of the most disabling BPSD, with a cross-sectional prevalence of ≥50% in nursing homes, and refers to help-seeking behavior in response to various sources of discomfort, among which pain is a crucial component. This pilot phase of the BRAINAID (NCT04321889) trial aimed to assess the effectiveness of the patented nanotechnological device NanoBEO in older (≥65 years) people with severe dementia. This randomized placebo-controlled trial, with quadruple masking that involved all operators and participants, followed the SPIRIT and CONSORT statements. A total of 29 patients completed the trial. The patients were randomly allocated in a 1:1 ratio to the NanoBEO or placebo group, and the corresponding product was applied on both arms once daily for 4weeks, with a 4-week follow-up period. The primary endpoint was efficacy against agitation. The secondary endpoints were efficacy against agitation at follow-up and efficacy against pain. Any adverse events were reported, and biochemical analyses were performed. The NanoBEO intervention reduced the frequency (28%) and level of disruptiveness of agitated behaviors. The effect on frequency was statistically significant after 2weeks of treatment. The efficacy of NanoBEO on agitated behaviors lasted for the entire 4-week treatment period. No additional psychotropic drugs were prescribed throughout the study duration. The results after 1week of treatment demonstrated that NanoBEO had statistically significant analgesic efficacy (45.46% improvement in pain intensity). The treatment was well tolerated. This trial investigated the efficacy of NanoBEO therapy in managing agitation and pain in dementia. No need for rescue medications was recorded, strengthening the efficacy of NanoBEO in prolonged therapy for advanced-stage dementia and the usefulness of the intervention in the deprescription of potentially harmful drugs. This study provided a robust rationale for the application of NanoBEO in a subsequent large-scale pivotal trial to allow clinical translation of the product. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04321889.

Problematic Social Media Use and Lifestyle Behaviors in Adolescents: Cross-Sectional Questionnaire Study.

The use of social media by adolescents has increased considerably in the past decade. With this increase in social media use in our daily lives, there has been a rapidly expanding awareness of the potential unhealthy lifestyle-related health effects arising from excessive, maladaptive, or addictive social media use. This study aims to assess the association between adolescents' social media use and health-related behaviors. We used a cross-sectional research approach and analyzed data from 96,919 adolescents at high schools throughout the Netherlands. A structured 43-item questionnaire was used to gather data on sociodemographics, dietary and lifestyle factors, and the degree of social media use based on the Compulsive Internet Use Scale. Logistic regression analyses were performed to assess the association between problematic social media use (PSMU) and lifestyle behaviors while adjusting for sociodemographic factors. Of the 96,919 included adolescents, 7.4% (n=7022) were identified as at risk for PSMU. Furthermore, logistic regression results showed that adolescents who are at risk for PSMU were more likely to report alcohol consumption and smoking while simultaneously having significantly lower levels of health-promoting behavior such as healthy eating habits (eating fruits, vegetables, and breakfast regularly) and physical activity. This study confirms that adolescents at risk of PSMU were more likely to exhibit an unhealthy lifestyle. Being at risk for PSMU was a determinant of soft drug use, alcohol consumption, smoking, poor eating habits, and lower physical activity independent of the additional adjusted covariates including demographic variables and remaining lifestyle variables. Future research is needed to confirm this observation in an experimental setting.

Pelaksanaan Program Kerja KKN-Sains Tematik Desa Berbasis Sosialisasi Peran Keluarga Sebagai Salah Satu Pencegahan Bahaya Narkoba Di Desa Mojodowo

Implementation of KKN-Science is one of the community services aimed at solving a problem in the region. In the implementation of this KKN-Science the main focus is to know the role of families towards the dangers of narcotic abuse and the prevention of narcotic dangers in Mojodowo Village. The KKN-Science activities of Mayjen Sungkono Mojokerto University conducted by students and DPL were held on 09-16 December 2023 at Mojodowo Village office, Kembagi, Mojokerto. The benefits of this service activity are aimed at adding insight and education to the public in the prevention of the dangers of narcotics and the relationship of criminal offenses to narcotic abuse. This study uses destriptive research methods with quantitative approach as well as data collection sourced from primary data using socialization and documentation. The study was conducted on parents with teenage children in the vicinity of Mojodowo Village. The results of the study and discussion show that the role of the family is very important in providing broad information, knowledge and understanding of the dangers of drugs and their negative impact on all aspects of life. Obstacles in the prevention of drug harm in the family are differences in the personality of the child, the child's lack of openness to parents, and exposure to a negative social environment. The study's recommendation is that each family supervise and guide adolescents to avoid falling into narcotics.

A strategy for the detection of benzodiazepine drugs using low-resolution paper-spray mass spectrometry for harm reduction drug checking.

The ability to detect newly emerging substances is of great importance in reducing harms for people who use drugs. New psychoactive substances including novel benzodiazepines in the illicit drug supply have been linked to high rates of overdose deaths while complicating drug checking as an overdose prevention strategy. Paper-spray mass spectrometry (PS-MS) has emerged as a novel strategy to rapidly detect trace components in street drug samples. While targeted, low-resolution PS-MS methods have proven effective, newly emerging substances are often missed. To address this, a method was applied to low-resolution full-scan PS-MS data to aid in the early detection and identification of novel benzodiazepines in the unregulated drug supply. Using the developed method, true positives rates of 0.89 and 0.75 were achieved for bromazolam and etizolam in street samples obtained in a community drug checking service. The applicability of the method was further demonstrated for a novel benzodiazepine, desalkylgidazepam, that has recently emerged in the illicit drug supply.

Cannabis Legalization: Social Risk Assessment and Economic Forecast

Abstract The paper considers the problem of the economic feasibility of cannabis legalization in the Russian Federation. The paper also analyzes attitudes towards cannabis legalization among 584 residents (291 female and 293 male, 18.8 ± 1.4 for men, 18.3 ± 1.6 for women) from two different Russian regions (with the highest (Republic of Khakassia, Chelyabinsk Region, Moscow Region, Amur Region, and Saint-Petersburg) and lowest (Chukotka Autonomous District, Nenets Autonomous District, Chechen Republic, Arkhangelsk Region, and Orel Region) per capita drug use in the Russian Federation). All participants were interviewed via the Internet. In the first stage, a keyword analysis categorized articles into medical (48 %) and non-medical (52 %) cannabis use, revealing varied perspectives on its benefits and risks. The second stage surveyed Russian citizens, indicating regional differences in attitudes toward cannabis legalization based on per capita drug use. The third stage conducted a PEST analysis, highlighting economic consequences and offering recommendations. Practical implications include the need for targeted prevention programs, effective curriculum modules, and collaborative efforts to address the complex challenges associated with cannabis legalization. The study found that the public attitude towards the legalization of drugs for non-medical purposes is negative. In regions with the highest per capita soft drug use, the legalization of non-medical cannabis is unlikely to cause an increase in the level of usage. Teenagers living in regional centers tend to be more engaged in trying and using cannabis (11.9 %) compared to other cities (8.8 %, p ≤ 0.05) and rural areas, where the rate of cannabis use was the lowest (5.4 %, p ≤ 0.05). This research underscores the importance of tailored interventions and educational strategies to address diverse attitudes toward cannabis legalization. The findings contribute valuable insights for policymakers, educators, and health professionals, guiding the development of informed approaches to substance use prevention. The recommendations emphasize the necessity of proactive measures, such as outreach programs and collaborative efforts, to navigate the multifaceted implications of cannabis legalization and promote overall societal well-being.

RURAL OLDER ADULTS’ VIEWS OF DEPRESCRIBING AND NONPHARMACOLOGICAL METHODS IN PAIN TREATMENT

Abstract Proper pain management is essential to quality of life. Due to the risks of harmful drug interactions, there has been an increasing effort to reduce medication that may be harmful or ineffective (i.e., deprescribing) and to promote non-medication based (i.e., non-pharmacological) strategies in pain management. The purpose of this qualitative study is to understand the views of deprescribing and non-pharmacological methods in pain management among community-dwelling older adults with multiple chronic health conditions. Eligibility criteria included: 65+, Alabama resident living outside of nursing homes, cognitively intact, have two or more chronic health conditions and chronic pain, and take medications for their health conditions including pain medications. Participants were recruited through the Area Agency on Aging across the state of Alabama as well as other community venues serving older adults. Individual, open-ended interviews were conducted by phone to explore their concerns about medications, their views of deprescribing and using non-pharmacological pain management as well as their needs in doing so. Thematic analysis of the interview data revealed various barriers and needs: concerns about various side effects while also worrying about missing out benefits from the medications if reduced or stopped, uncertainty or skepticism toward non-pharmacological pain treatment, lacking financial and logistical access to non-pharmacological options, and lack of knowledge about available non-pharmacological options and their benefits. These findings have implications for future education and advocacy efforts to promote older adults’ knowledge and self-efficacy so that they can consider deprescribing and non-pharmacological methods in managing their pain.

C3N4-interlayer-mediated interfacial polymerization of homopolymer nanofiltration membranes for efficient water purification

Interlayered thin film composite (TFNi) membranes have been shown to achieve high-quality polyamide (PA) skin layers with enhanced permeability and selectivity. Herein, we demonstrate the construction of a hydrophilic interlayer by polymeric graphitic carbon nitride (g-C3N4) for optimizing the interfacial polymerization of the nanofiltration membrane. Due to the effective enrichment and the slowed diffuse rate of amine monomer solutions, g-C3N4 modification decreases the thickness of the PA skin layer and increases the electronegativity of membranes. The best TFNi membrane exhibits a high water permeance of 31.82 L m−2 h−1 bar−1, nearly twice as high as that of the membrane without g-C3N4 interlayer, while maintaining a comparably Na2SO4 rejection efficiency. The stronger hydrophilicity and more negatively charged surface of the TFNi membrane effectively retarded membrane fouling, contributing to the high-efficiency removal of harmful drugs from actual surface water, with more than two times higher water flux that of commercialized NF270 membrane. This work provides a facile strategy to synthesize TFNi membranes with great application potential for high-performance nanofiltration.

Gambaran Tingkat Pengetahuan Tenaga Kefarmasian Tentang Penyerahan Obat Keras Tanpa Resep Dokter di Apotek Desa Waimital

Introduction Hard drugs are drugs that have hard properties and if used carelessly or not according to the rules, can cause dangerous side effects and even poison the body, aggravate the disease, trigger the emergence of other diseases, to cause damage to body organs and death. Hard drugs are drugs that can only be obtained by prescription. Its characteristics are marked with a red round circle with a black border with the letter K in the middle that touches the border. This drug should only be sold in pharmacies and must be prescribed by a doctor at the time of buying it. While Mandatory Pharmacy Drugs (OWA) are some hard drugs that can be submitted without a doctor's prescription, but must be submitted by a Pharmacist at the pharmacy. This research method uses qualitative descriptive research design. What was used was total sampling with the measuring instrument used, namely a questionnaire with the number of samples being 15 respondents who became pharmaceutical personnel at the pharmacy. The results of the study showed that for the variable level of knowledge of pharmaceutical personnel with good categories amounted to 12 respondents with a percentage (80.0%) and enough 3 respondents with a percentage (20.0%), Kesimplant from the results of the level of knowledge of pharmaceutical personnel at pharmacies Waimital Village, Kairatu District, West Seram was good because pharmaceutical personnel knew information about hard drugs without a prescription and it was known that the pharmacist profession and the pharmacist assistant have the same level of understanding.

Multi-stimuli responsive, shape deformation, and synergetic biomimetic actuator

Hydrogel actuators with controllable deformation and excellent biocompatibility are widely used in soft robot, valve, drug delivery and lenses. However, the stimulation response performance of existing hydrogel actuators mostly focuses on a single active layer, which greatly affects its driving performance and service life. In this work, we integrate temperature-responsive hydrogel (Poly (N-isopropyl acrylamide), PNIPAM) and pH-responsive hydrogel (polyacrylic acid, PAAc) into one system to fabricate a dual active layer composite hydrogel actuator with high performance. Based on the PAAc hydrogels achieving contract or expand at different pH values, the obtained actuator exhibits admirable bidirectional bending characteristics. In addition, the anisotropic bamboo sheet endows the hydrogel actuator with programmable 3 D complex deformation. Benefitting from the synergy and different responsiveness between the two active layers, the hydrogel actuator not only has multiple response performance, but also greatly improves its deformation degree and response speed. More importantly, these promising properties of the actuator have broad application prospects in the development of pattern design and intelligent switch. This work proposes a promising strategy for the structural design of hydrogel actuators with excellent performance, and encourages more exploration of the application range of the actuator.

Pertanggungjawaban Pidana Bagi Pihak Marketplace dan Penjual dalam Jual Beli Obat Ilegal Jenis Cytotec Secara Online

Indonesian society, especially those in urban areas, is inseparable from the internet, because almost all activities always involve the internet and information technology. So, it is not surprising that the internet has now become a basic necessity for some groups, especially for those who use the internet for business purposes (E-commerce). One of the online suggestions for selling illegal drugs is E-commerce as access to transactions via online media. Through these trade transactions, conventional buying and selling is no longer valid, and E-commerce has become an alternative trade for consumers. What is the responsibility of the marketplace and sellers in the illegal buying and selling of Cytotec hard drugs online. The type of research used is normative juridical (legal research). using a statutory approach and a case approach. In this research, researchers found that the marketplace has criminal responsibility for buying and selling illegal drugs such as misoprostol online. Based on an analysis of applicable laws and regulations, it was found that the marketplace has an obligation to monitor and prevent illegal drug buying and selling transactions on its platform. This research concludes that the marketplace is criminally responsible for buying and selling illegal drugs such as misoprostol online. Research findings show that marketplaces have an obligation to monitor and prevent illegal drug sales transactions on their platforms. However, in several cases studied, there is strong evidence that marketplaces do not take adequate steps to prevent the sale of illegal drugs, such as a lack of seller verification mechanisms, monitoring of unlawful advertisements, and a disinterest in removing illegal drug offers.

Drug-Drug Interactions Between COVID-19 Treatments and Psychotropic Medications: An Updated Study.

The recent evolution of coronavirus disease 2019 (COVID-19) treatments has created challenges for healthcare providers in terms of new potential interactions between these COVID-19 treatments and psychotropic drugs in patients with psychiatric disorders. Current clinical practice guidelines on managing interactions between psychotropic medications and COVID-19 treatments do not account for the newer COVID-19 medications. There is a need for updated patient management recommendations that take into account drug interactions between psychotropic drugs and the latest pharmacological approaches to COVID-19 treatment. Asearch of literature pertaining to drug interactions and outcomes in patients concurrently prescribed COVID-19 treatments and psychotropic medications was conducted. Drug databases were also analyzed to screen for interactions.Our review focuses on the most recent and effective COVID-19 treatments, including PaxlovidTM (nirmatrelvir/ritonavir), remdesivir, dexamethasone, tocilizumab, and baricitinib. The study provides condensed and easily interpretable tables for healthcare providers to screen for potentially harmful drug interactions. We discuss the implications of our findings on appropriate treatment plan selection by healthcare providers for patients taking select antipsychotics, antidepressants, mood stabilizers, and benzodiazepines while receiving COVID-19 treatments.Notably, PaxlovidTMmay interact with several medications, particularly antipsychotics and anxiolytics, necessitating close monitoring and, in some cases, reconsideration of use. We find that dexamethasone, remdesivir, tocilizumab, and baricitinib have fewer reported interactions with psychotropics, and while some monitoring is necessary, no major adjustments are recommended for their administration in conjunction with psychotropic medications.These findings underscore the importance of careful consideration and monitoring when combining COVID-19 treatments with other medications to mitigate the risk of adverse interactions and ensure patient safety.

Drug-related deaths at Australian music festivals

BackgroundIllicit drug use is overrepresented in music festival attendees compared with the general population. Drug use often involves a wide range of substances with the potential to cause drug toxicity. Law enforcement-centred strategies intended to deter drug use and supply at these mass gatherings have been implemented throughout Australia. However, many have been criticised for their lack of effectiveness, with evidence suggesting that they can inadvertently increase the risk of drug harm. Drug deaths are often multifactorial, providing added challenges in the development of prevention strategies. This study aimed to determine the frequency of deaths involving alcohol and other drugs at music festivals in Australia and to identify potential risk factors that may inform future harm reduction strategies. MethodsA descriptive case series study was conducted using the National Coronial Information System (NCIS) to investigate drug-related deaths at music festivals throughout Australia between 1 July 2000 (Queensland from 1 January 2001) and 31 December 2019, using a list of keywords comprising music festival names and terms. ResultsThere were 64 deaths, of which most involved males (73.4%) aged in their mid-20s (range 15-50 years). Drug toxicity was the most common primary cause of death (46.9%) followed by external injuries (37.5%). The drug most commonly detected or reported as being used was MDMA (65.6%), followed by alcohol (46.9%) and cannabis (17.2%), with most cases reporting the use of two or more drugs (including alcohol) and 36% reporting a history of drug misuse in the coroner's findings. Most deaths were unintentional, with less than a fifth of cases (17.2%) involving intentional self-harm. Clinical intervention was involved in 64.1% of cases and most festivals occurred in inner city locations (59.4%). ConclusionsThe findings suggest that drug-related deaths at music festivals in Australia typically involve young people using multiple illicit substances in combination with alcohol. Most are unintentional and could potentially be prevented through the implementation of a range of harm reduction strategies, including mobile medical care, drug checking services, and increased consumer education and awareness.

An Uncertainty-Guided Deep Learning Method Facilitates Rapid Screening of CYP3A4 Inhibitors.

Cytochrome P450 3A4 (CYP3A4), a prominent member of the P450 enzyme superfamily, plays a crucial role in metabolizing various xenobiotics, including over 50% of clinically significant drugs. Evaluating CYP3A4 inhibition before drug approval is essential to avoiding potentially harmful pharmacokinetic drug-drug interactions (DDIs) and adverse drug reactions (ADRs). Despite the development of several CYP inhibitor prediction models, the primary approach for screening CYP inhibitors still relies on experimental methods. This might stem from the limitations of existing models, which only provide deterministic classification outcomes instead of precise inhibition intensity (e.g., IC50) and often suffer from inadequate prediction reliability. To address this challenge, we propose an uncertainty-guided regression model to accurately predict the IC50 values of anti-CYP3A4 activities. First, a comprehensive data set of CYP3A4 inhibitors was compiled, consisting of 27,045 compounds with classification labels, including 4395 compounds with explicit IC50 values. Second, by integrating the predictions of the classification model trained on a larger data set and introducing an evidential uncertainty method to rank prediction confidence, we obtained a high-precision and reliable regression model. Finally, we use the evidential uncertainty values as a trustworthy indicator to perform a virtual screening of an in-house compound set. The in vitro experiment results revealed that this new indicator significantly improved the hit ratio and reduced false positives among the top-ranked compounds. Specifically, among the top 20 compounds ranked with uncertainty, 15 compounds were identified as novel CYP3A4 inhibitors, and three of them exhibited activities less than 1 μM. In summary, our findings highlight the effectiveness of incorporating uncertainty in compound screening, providing a promising strategy for drug discovery and development.

Structure and Physico-Mechanical Properties of Polyelectrolyte Complexes Based on Sodium Carboxymethylcellulose Polysaccharide and Polyacrylamide

In this paper, the structure and physico-mechanical properties of films of polyelectrolyte complexes (PEC) based on sodium carboxymethylcellulose (Na-CMC) with linear polyacrylamide (PAA) have been studied. Polyelectrolyte complexes were obtained by mixing aqueous solutions of Na-CMC and PAA components in various ratios of components and pH of the medium. The structure of the obtained products was determined using IR spectroscopy and electron microscopy. IR spectra in the range 400–4000 cm-1 were recorded on NIKOLET Magna-560 IR and Specord-75IR spectrophotometers (Carl Zeiss, GDR). The mechanical properties of films of polyelectrolyte complexes were determined by stretching at a constant speed of movement of the lower clamp, 50 mm/min, on an Instron-1100 automatic dynamometer (England) at room temperature. IR spectroscopic data showed that polyelectrolyte complexes based on Na-CMC and PAA were stabilized due to the cooperative ionic bond between Na-CMC carboxylate anions (-COO-) and amine groups (-NH2) of polyacrylamide. It is shown that PEC films with an equimolar ratio of Na-CMC and PAA components have an increased value of mechanical strength (σр = 38 MPa), elastic modulus (Е = 73 MPa) and a minimum relative elongation (ε = 0.5%). And in excess of Na-CMC or PAA leads to a decrease in mechanical strength and elastic modulus, which is associated with a decrease in the frequency of intermolecular bonds. It has been ascertained that water-soluble polyelectrolyte complexes based on Na-CMC and PAA with increased strength properties can be obtained from solutions of components taken at an equimolar ratio of interacting components. By changing the ratio of components, properties such as mechanical strength, modulus of elasticity and elongation can be controlled. This can serve as one of the means of controlling the structure and properties of Na-CMC and PAA polyelectrolyte complexes. The regulation of the physico-mechanical properties of PEC films opens up wide opportunities for their use as a soil structure former in agriculture and water management and as the basis for soft drugs in pharmacy.