BACKGROUND: Harm reduction strategies at music festivals seek to create a safer environment for patrons. The Emerging Drugs Network of Australia-Victoria (EDNAV) project is a state-wide toxicosurveillance network that derives drug intelligence from a sample of patients presenting to hospital with illicit drug-related toxicity. This publication describes the preliminary outcomes of conducting toxicosurveillance for critically unwell festival patrons within on-site medical facilities.
METHODS: Blood samples were collected from patrons who presented with severe illicit drug-related toxicity across three festivals (2022/2023). Blood samples were analysed via liquid chromatography-tandem mass spectrometry for over 700 pharmaceutical and illicit drugs.
RESULTS: There were 1603 individual medical encounters across the festivals, 228 of which were illicit drug related. A blood sample was collected for 24 patients, with a median age of 22 years (range 18-39 years). A median of two drugs (range 1-5 drugs) were reported and four drugs (range 0-8 drugs) were analytically confirmed per patient. The most frequently reported exposures were congruent with analytical results, 3,4-methylenedioxymethamphetamine (reported n = 17, detected n = 20), ketamine (reported n = 9, detected n = 13) and cocaine (reported n = 9, detected n = 12). An unreported illicit drug and/or new psychoactive substance (NPS) was detected in 18 patients, including methylamphetamine (n = 10), a cathinone (n = 7), benzodiazepine-type NPS (n = 6), N-ethylamphetamine (n = 1), 3-hydroxyphencyclidine (n = 1) and/or 4-hydroxy-N-methyl-N-isopropyltryptamine (n = 1).
CONCLUSIONS: EDNAV toxicosurveillance serves as an additional tool within a multi-faceted approach to harm reduction at festivals. Continued data collection will allow for the characterisation of high-risk drug use patterns to provide evidence-based messaging to festival patrons and key stakeholders.

In this study, Brassica chinensis L seedlings after 6 weeks of soil cultivation were treated with foliar application of TiO2 NPs (20 mg/L) for different times. Transcriptomics analysis was employed to investigate the impact of TiO2 NPs on the physiology, growth, and yield of B. chinensis L. Results showed that TiO2 NPs\' exposure significantly increased the biomass, total phosphorus, and catalase enzyme activity by 23.60, 23.72, and 44.01%, respectively, compared to the untreated ones (not bulk or ion).TiO2 NPs increased the leaf chlorophyll content by 4.9% and photosynthetic rate by 16.62%, which was attributed to the upregulated expression of seven genes (PetH, PetF, PsaF, PsbA, PsbB, PsbD, and Lhcb) associated with electron transport in photosystem I and light-harvesting in leaves. The water balance of B. chinensis was improved correlating with the altered expressions of 19 aquaporin genes (e.g., PIP2;1 and NIP6;1). The expressions of 58 genes related to plant hormone signaling and growth were dysregulated, with notable downregulations in GA20, SnRK2, and PP2C and upregulations of DELLAs, SAM, and ETR. Moreover, the 11 tricarboxylic acid cycle genes and 13 glycolysis genes appear to stimulate pathways involved in promoting the growth and physiology of B. chinensis. This research contributes valuable insights into new strategies for increasing the yield of B. chinensis.

OBJECTIVE: To investigate the feasibility of standardizing RT simulation CT scanner protocols between vendors using target-based image quality (IQ) metrics.
METHODS: A systematic assessment process in phantom was developed to standardize clinical scan protocols for scanners from different vendors following these steps: (a) images were acquired by varying CTDIvol and using an iterative reconstruction (IR) method (IR: iDose and model-based iterative reconstruction [IMR] of CTp-Philips Big Bore scanner, SAFIRE of CTs-Siemens biograph PETCT scanner), (b) CT exams were classified into body and brain protocols, (c) the rescaled noise power spectrum (NPS) was calculated, (d) quantified the IQ change due to varied CTDIvol and IR, and (e) matched the IR strength level. IQ metrics included noise and texture from NPS, contrast, and contrast-to-noise ratio (CNR), low contrast detectability (d\'). Area under curve (AUC) of the receiver operation characteristic curve of d\' was calculated and compared.
RESULTS: The level of change in the IQ ratio was significant (>0.6) when using IMR. The IQ ratio change was relatively low to moderate when using either iDose in CTp (0.1-0.5) or SAFIRE in CTs (0.1-0.6). SAFIRE-2 in CTs showed a closer match to the reference body protocol when compared to iDose-3 in CTp. In the brain protocol, iDose-3 in CTp could be matched to the low to moderate level of SAFIRE in CTs. The AUC of d\' was highest when using IMR in CTp with lower CTDIvol, and SAFIRE in CTs performed better than iDose in CTp CONCLUSION: It is possible to use target-based IQ metrics to evaluate the performance of the system and operations across various scanners in a phantom. This can serve as an initial reference to convert clinical scanned protocols from one CT simulation scanner to another.

Bovine mastitis caused by infectious pathogens, mainly Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), constitutes a major destructive challenge for the dairy industry and public health. Berberine chloride (BER) and Cyperus rotundus possess a broad spectrum of anti-inflammatory, antioxidant, antibacterial, and antiproliferative activities; however, their bioavailability is low. This research aimed first to prepare an ethanolic extract of Cyperus rotundus rhizomes (CRE) followed by screening its phytochemical contents, then synthesis of BER and CRE loaded chitosan nanoparticles (NPs) (BER/CH-NPs and CRE/CH-NPs), afterward, the analysis of their loading efficiency in addition to the morphological and physicochemical characterization of the formulated NPs employing Scanning Electron Microscopy (SEM), Zeta Potential (ZP), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) assessments compared to their crude forms to evaluate the enhancement of bioavailability and stability. Isolation of bacterial strains from the milk of mastitic cows, used for induction of mammary gland (MG) inflammation in female albino rats, and a preliminary investigation of the prophylactic oral doses of the prepared NPs against S. aureus-induced mastitis in female rats. The minimal inhibitory concentration (MIC) of BER/CH-NPs and CRE/CH-NPs is 1 mg/kg b.w. BER/CH-NPs and CRE/CH-NPs alone or in combination show significant (P ≤ 0.05) DPPH radical scavenging activity (69.2, 88.5, and 98.2%, respectively) in vitro. Oral administration of BER/CH-NPs and CRE/CH-NPs to mastitis rats significantly (P ≤ 0.05) attenuated TNF-α (22.1, 28.6 pg/ml), IL-6 (33.4, 42.9 pg/ml), IL-18 (21.7, 34.7 pg/ml), IL-4 (432.9, 421.6 pg/ml), and MPO (87.1, 89.3 pg/ml) compared to mastitis group alongside the improvement of MG histopathological findings without any side effect on renal and hepatic functions. Despite promising results with BER and CRE nanoparticles, the study is limited by small-scale trials, a focus on acute administration, and partially explored nanoparticle-biological interactions, with no economic or scalability assessments. Future research should address these limitations by expanding trial scopes, exploring interactions further, extending study durations, and assessing economic and practical scalability. Field trials and regulatory compliance are also necessary to ensure practical application and safety in the dairy industry. In conclusion, the in vitro and in vivo results proved the antioxidant and anti-inflammatory efficacy of BER/CH-NPs and CRE/CH-NPs in low doses with minimal damage to the liver and kidney functions, supposing their promising uses in mastitis treatment.

BPSD is relatively common but profoundly disturbing to persons with dementia, their family, and caregivers. Growing recognition of the impact of BPSD on quality of life has improved recently, but assessment and management approaches are still lacking. Considerable controversy surrounding the label of BPSD has garnered a great deal of attention, with implications of its contribution to the already pervasive dementia-related stigma experienced by persons with dementia and their caregivers. This brief review aims to summarize salient viewpoints, controversies, and considerations of the assessment, management, and perception of BPSD, in an effort to offer potential recharacterizations of BPSD to promote and prioritize personhood in persons with dementia.

UNASSIGNED: Protonitazene is an opioid belonging to the 2-benzylbenzimidazole structural class. We describe two cases of opioid toxicity involving the reported inhalation of a delta-9-tetrahydrocannabinol vape product in which protonitazene was detected.
UNASSIGNED: Case 1 was a young male found unconscious after the reported use of a delta-9-tetrahydrocannabinol vape. He suffered two subsequent apnoeic episodes requiring bag-valve-mask ventilation before eventual recovery. Only protonitazene was detected in blood at a concentration of 0.74 µg/L. Case 2 was a young male who died shortly after being found unresponsive. The postmortem femoral blood concentrations of protonitazene and delta-9-tetrahydrocannabinol were 0.33 µg/L and 2 µg/L, respectively. Analysis of a pod vaping device found in the decedent\'s hand and a separate e-liquid bottle labelled as delta-9-tetrahydrocannabinol showed a mixture of protonitazene and delta-9-tetrahydrocannabinol.
UNASSIGNED: The opioid effects of protonitazene are mediated through β-arrestin2 and mu opioid receptor signalling pathways. Benzimidazole opioids are lipophilic and, when mixed with a suitable solvent, can be used in a vape device. It is anticipated that naloxone would have provided effective reversal of toxicity in our cases.
UNASSIGNED: Novel routes of opioid administration, like vaping, may appear relatively innocuous in comparison to intravenous administration, but opioids may still be absorbed at high concentrations, resulting in severe opioid toxicity or death.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. This has been attributed to the complex pathophysiological mechanisms that accompany individuals with several co-morbidities and symptoms and signs of HFpEF. Natriuretic peptides have been recognized as playing an important role in the diagnosis and monitoring of patients with heart failure with reduced ejection fraction (HFrEF), but their role in HFpEF remains controversial, driven by the different pathophysiological characteristics of these patients. The type of diet consumed has shown various modifying effects on plasma levels of NPs, irrespective of pharmacological treatment.

OBJECTIVE: The most commonly associated substance found in Ecstasy tablets is MDMA (3,4-methylenedioxymethamphetamine). In our study, we showed how the composition of psychoactive ingredients in Ecstasy tablets seized on the drug market in Poland has changed in the years 2005-2020.
METHODS: The study material consisted of nearly 20,000 single Ecstasy tablets seized by representatives of law enforcement (the police, prosecutors) from 2005 to 2020 and analysed by the Institute of Forensic Research, Krakow, Poland. The analysis of the tablets was carried out by gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography with diode array detection (HPLC-DAD) and ultra-high-performance liquid chromatography with photodiode array detection (UHPLC-PDA).
RESULTS: Currently, new types of MDMA tablets are introduced onto the market, available in various colours and shapes. Our study showed that tablets sold on the street as Ecstasy have variable purity and sometimes contain little or no MDMA. The mean content of MDMA in one tablet seized in 2005-2011 decreased from 90 to 50 mg. In 2013, Ecstasy tablets with a very high MDMA content (average 195 mg per tablet) appeared on the market, but in the next 2 years, the MDMA content decreased again. From 2016, the average MDMA content began to rise again, ranging from 60 to 280 mg.
CONCLUSIONS: Tablets sold as Ecstasy also contained completely different psychoactive substances, including new psychoactive substances (NPS) (found in almost 20% of all examined tablets sold as Ecstasy) belonging to different chemical groups or their dangerous combinations (i.e. phenylethylamines, piperazines, tryptamines, cathinones, arylalkylamines, arylcyclohexylamines and piperidines). Such a large variety of psychoactive substances in Ecstasy tablets is associated with a high risk for users unaware of their composition.

Significance: Numerous disorders are linked to ferroptosis, a form of programmed cell death triggered by lipid peroxidation accumulation rather than apoptosis. Inflammation is the body\'s defensive response to stimuli and is also caused by inflammatory chemicals that can harm the body. The treatment of inflammatory diseases by focusing on the signaling pathways and mechanisms of ferroptosis has emerged as a new area worthy of extensive research. Recent Advances: Studies in cellular and animal models of inflammatory diseases have shown that ferroptosis markers are activated and lipid peroxidation levels are increased. Natural products (NPs) are gaining importance due to their ability to target ferroptosis pathways, particularly the Nuclear factor E2-related factor 2 signaling pathway, thereby suppressing inflammation and the release of pro-inflammatory cytokines. Critical Issues: This article provides an overview of ferroptosis, focusing on the signaling pathways and mechanisms connecting it to inflammation. It also explores the potential use of NPs as a treatment for inflammatory diseases and ferroptosis. Future Directions: NPs offer unique advantages, including multicomponent properties, multi-bio-targeting capabilities, and minimal side effects. Further research may facilitate the early clinical application of NPs to develop innovative treatment strategies.

Those involved in drug testing continue to grapple with the dynamic nature of emerging psychoactive substances (NPS) and their rapid infiltration into society. The challenge extends beyond merely detecting and measuring NPS using analytical tools; it also encompasses the complexities arising from the formation and presence of metabolites and degradation products. This study utilises liquid chromatography time-of-flight mass spectrometry to investigate the stability of new psychoactive substances in wastewater. Seven NPS compounds including 25C-NBOMe, 5F-APINACA 4-hydroxyphenyl, AB-PINACA, APINACA 4-hydroxyphenyl, fentanyl, norfentanyl and MDPV, along with their corresponding internal standard, were examined. Reference material for each NPS compound was introduced into a wastewater sample from a Wessex water treatment plant. The sample was then exposed to four different environments: room temperature, refrigerator temperature, acidification to pH 2, and the introduction of sodium metabisulfite. The findings highlight the critical dependence of storage conditions on target analytes, emphasizing the paramount importance of the time elapsed between collection and analysis for NPS wastewater analysis. Notably, synthetic cannabinoids exhibit limited stability in wastewater whereas cathinone-like substances demonstrate greater stability. Furthermore, metabolites prove to be more stable in wastewater than the parent drug, suggesting that focusing on metabolite detection may be more favourable for future analysis.