Synthetic Cooling Agents in Australian-Marketed E-cigarette Refill Liquids and Disposable E-cigarettes: Trends Follow the U.S. Market.

INTRODUCTION: E-cigarettes are becoming increasingly popular in Australia, especially amongst the younger population. The synthetic cooling molecules WS-3 and WS-23 have been identified in e-cigarette products from the United States and Europe. The extent of inclusion of these synthetic coolants in Australian e-liquids is unknown, particularly in newer disposable e-cigarettes. AIMS AND METHODS: E-cigarettes and e-liquids were purchased within Australia and anonymously donated by Australian users. Nicotine, WS-3, WS-23, and menthol were quantified in the e-liquids using gas chromatography-mass spectrometry (GC-MS). RESULTS: WS-23 and nicotine were detected in all of the disposable e-cigarettes with WS-23 often present in high concentrations. There was no correlation between cooling terms in the flavor name and the inclusion of cooling agents. Only three bottled e-liquids were found to contain WS-23 while none contained WS-3 above the limit of detection. CONCLUSIONS: Synthetic coolants were a common addition in disposable e-cigarettes while rarely added to e-liquid bottle refills. Their inclusion in these products is reflective of trends observed in United States and European e-cigarette products. IMPLICATIONS: The increase in synthetic cooling agents as components of e-liquids, particularly disposable e-cigarette devices, has been observed within Australian samples across a range of brands and flavors. WS-23 was present in every disposable e-cigarette analyzed in this study, often in relatively high concentrations. Its inhalational toxicology should be considered when evaluating the safety of these products.

A Wide Range of Flavoring-Carrier Fluid Adducts Form in E-Cigarette Liquids.

A range of flavoring molecules are used in electronic cigarette liquids (e-liquids), some of which have been shown to form cyclic acetal adducts with e-liquid solvent components propylene glycol (PG) and vegetable glycerine (VG). The objective of this study was to identify the range of flavoring molecules which form adducts in e-liquid products. Common e-liquid flavoring molecules (N = 36) from a range of chemical class groups were exposed to PG, VG, or methanol and analyzed by GC-MS over a time frame of 4 weeks to identify possible reaction products. Adduct formation was observed, with 14 of the flavoring molecules reacting with methanol, 10 reacting with PG, and 10 reacting with VG. Furfural PG and VG acetals, valeraldehyde PG and VG acetals, veretraldehyde PG and VG acetals, p-anisaldehyde PG and VG acetals, and piperonal VG acetal were confirmed for the first time. Adducts formed by reaction with ketone-containing flavoring molecules were also observed for the first time. The presence of these acetals was confirmed in 32% of commercial e-liquid products analyzed (N = 142). This study has established a range of flavoring molecules which are able to react with solvent components PG and VG in e-liquids under standard storage conditions. These newly identified adducts need to be further assessed to determine their toxicological safety.

STRIDES - STudying Risk to Improve DisparitiES in Cervical Cancer in Mississippi - Design and baseline results of a Statewide Cohort Study.

Cervical cancer rates in Mississippi are disproportionately high, particularly among Black individuals; yet, research in this population is lacking. We designed a statewide, racially diverse cohort of individuals undergoing cervical screening in Mississippi. Here, we report the baseline findings from this study. We included individuals aged 21 years and older undergoing cervical screening with cytology or cytology-human papillomavirus (HPV) co-testing at the Mississippi State Health Department (MSDH) and the University of Mississippi Medical Center (UMMC) (December 2017-May 2020). We collected discarded cytology specimens for future biomarker testing. Demographics and clinical results were abstracted from electronic medical records and evaluated using descriptive statistics and chi-square tests. A total of 24,796 individuals were included, with a median age of 34.8 years. The distribution of race in our cohort was 60.2% Black, 26.4% White, 7.5% other, and 5.9% missing. Approximately 15% had abnormal cytology and, among those who underwent co-testing at MSDH (n = 6,377), HPV positivity was 17.4% and did not vary significantly by race. Among HPV positives, Black individuals were significantly less likely to be HPV16/18 positive and more likely to be positive for other high-risk 12 HPV types compared to White individuals (20.5% vs. 27.9%, and 79.5% and 72.1%, respectively, p = 0.011). Our statewide cohort represents one of the largest racially diverse studies of cervical screening in the U.S. We show a high burden of abnormal cytology and HPV positivity, with significant racial differences in HPV genotype prevalence. Future studies will evaluate cervical precancer risk, HPV genotyping, and novel biomarkers in this population.

Nicotine in electronic cigarette fluid: importation pathways to unequal harm.

The Australian Government recently walked away from changes to the importation of nicotine-containing electronic cigarette fluids, originally due to come into force on 1 January 2021. Additionally, the Therapeutic Goods Administration is in the process of rescheduling nicotine for use in e-fluids. We are concerned that the 270 000 daily vapers in Australia will purchase high concentrations of nicotine (≥100 mg/mL) for mixing with nicotine-free locally purchased e-fluids, which is a pathway of increased relative harm. We would like to see regulation of these products to limit the maximum concentration of nicotine, ensure appropriate child-resistant containers and compulsory labelling for all nicotine-containing e-fluid bottles.

Endogenous doesn't always mean innocuous: a scoping review of iron toxicity by inhalation.

Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with in vitro, in vivo and epidemiological studies involving PM containing Fe or iron oxide following inhalation or instillation. The major findings from these investigations are summarized and tabulated. Epidemiological studies showed that exposure to Fe oxide is correlated with an increased incidence of cancer, cardiovascular diseases, and several respiratory diseases. Iron PM was found to induce inflammatory effects in vitro and in vivo and to translocate to remote locations including the brain following inhalation. A potential pathway for the PM-containing Fe-mediated toxicity by inhalation is via the generation of ROS which leads to lipid peroxidation and DNA and protein oxidation. Our recommendations include an expansion of epidemiological, in vivo and in vitro studies, integrating research improvements outlined in this review, such as the method of particle preparation, cell line type, and animal model, to enhance our understanding of the complex biological interactions of these particles.

Risk versus regulation: an update on the state of e-cigarette control in Australia.

E-cigarettes are increasingly common around the world, particularly among youth. Ingestion of nicotine-containing e-liquid, while relatively rare, is the major toxicological risk associated with their use. Current Australian regulation has nicotine for use in e-cigarettes listed as a dangerous poison in Schedule 7, with its supply or sale illegal in all states and territories, while regulation on the sale of e-cigarettes and accessories varies by state. However, with increasing evidence that e-cigarettes produce far fewer toxic by-products than their combustible counterparts perhaps it is time to review this regulation.

Narrative Review of the Pharmacodynamics, Pharmacokinetics, and Toxicities of Illicit Synthetic Cannabinoid Receptor Agonists.

BACKGROUND: Synthetic cannabinoid receptor agonists (SCRAs) are the most diverse class of new psychoactive substances worldwide, with approximately 300 unique SCRAs identified to date. While the use of this class of drug is not particularly prevalent, SCRAs are associated with several deaths every year due to their severe toxicity. METHODS: A thorough examination of the literature identified 15 new SCRAs with a significant clinical impact between 2015 and 2021. RESULTS: These 15 SCRAs have been implicated in 154 hospitalizations and 209 deaths across the US, Europe, Asia, and Australasia during this time period. CONCLUSION: This narrative review provides pharmacodynamic, pharmacokinetic, and toxicologic data for SCRAs as a drug class, including an in-depth review of known pharmacological properties of 15 recently identified and emerging SCRAs for the benefit of researchers, policy makers, and clinicians who wish to be informed of developments in this field.

Labelling and composition of contraband electronic cigarettes: Analysis of products from Australia.

BACKGROUND: The sale of nicotine-containing electronic cigarettes (e-cigarettes) is prescription only in Australia, regulated under the Standard for Nicotine Vaping Products (TGO110). Australian e-cigarette users, however, are purchasing e-cigarette products outside of the intended pathways. METHODS: The labelling of e-cigarette packaging (N = 388 boxes) and the chemical composition of disposable e-cigarettes and pods (N = 428) were analysed for adherence to the current Australian regulations. These samples were confiscated from over-the-counter retailers in NSW by the NSW Ministry of Health during 2022 for non-compliance with Australian regulations. RESULTS: Following the announcement of the prescription only model for nicotine-containing e-cigarettes in Australia in mid-2021 there was a clear shift in the labelling of products. Any mention of the word 'nicotine' was removed from e-cigarette packaging by early 2022 and nicotine warnings were replaced with generic underage sale warnings. Despite this labelling, the vast majority (98.8 %) of devices analysed contained nicotine, most (89 %) at high concentration (>30 mg/mL) and 4.2 % contained at least one chemical prohibited by the TGO110. CONCLUSIONS: It appears that manufacturers have removed any mention of nicotine from the original packaging of nicotine-containing disposable e-cigarettes to circumvent restrictions on nicotine-containing products and continue their sale. The packaging of e-cigarette products in Australia is generally not indicative of their contents, particularly nicotine, and most did not display required warnings. Ingredients with associated health risks, prohibited in legal vapes by the TGO110, were found in samples. Consequently, the risks of e-cigarette use cannot be appropriately identified from the information supplied on the packaging or device.

Evaluation of Follow-up Colposcopy Procedures After Abnormal Cervical Screening Result Across a Statewide Study in Mississippi.

Purpose: Cervical screening is used to detect and treat precancers to prevent invasive cancers. However, successful prevention also requires adequate follow-up and treatment of individuals with abnormal screening results. The aim was to investigate demographics, clinical characteristics, and follow-up status for individuals needing colposcopy after an abnormal screening result. Methods: The STRIDES (Studying Risk to Improve DisparitiES) cohort comprises individuals undergoing cervical cancer screening and management at a Mississippi Health Department or University of Mississippi clinic. Follow-up status, demographics, and clinical data were assessed from electronic health records and, if necessary, patient navigation on individuals identified as needing a colposcopy after an abnormal screening. Results: Of the 1,458 individuals requiring colposcopy, 43.0% had the procedure within 4 months, 16.4% had a delayed procedure, and 39.5% had no documented follow-up, with significant predictors of follow-up identified as age and cytology diagnosis. Based on age, individuals 30 + were more likely to follow up with a colposcopy compared to individuals < 30 years (49% and 38.7%, respectively; p < .001). Individuals with cytology diagnoses of LSIL (52.9%), ASC-H (51.4%), and HSIL (62.3%) had higher percentages of adherence to follow-up colposcopy guidelines (p < .001). Conclusion: Despite high cervical cancer screening rates among Mississippians, a substantial portion did not have adequate next-step intervention. However, it is encouraging that highest risk individuals were more likely to have a colposcopy. Regardless, continuing to understand the underlying causes for incomplete follow-up is crucial for timely secondary targeted interventions to reduce cervical cancer burden, promote awareness, and improve health outcomes.

Vaping preferences of individuals who vaporise dry herb cannabis, cannabis liquids and cannabis concentrates.

In 2019 an estimated 200 million people aged 15-64 used cannabis, making cannabis the most prevalent illicit substance worldwide. The last decade has seen a significant expansion in the cannabis vaporiser market, introducing cannabis vaporisation as a common administration method alongside smoking and ingestion. Despite reports of increased prevalence of cannabis vaporisation there has been little research into the use of these devices. To remedy the current dearth of data in this area this study utilised an anonymous online survey of individuals who self-reported past cannabis vaporisation. The respondents (N = 557) were predominantly young (<35 years) and male. Most (91.4 %) stated they had ever vaped dry herb cannabis, 59.1 % reported vaporisation of cannabis oil or liquids, and 34.0 % reported vaporisation of cannabis concentrates. This study identifies the types of vaporisation devices (including brands and models) employed by cannabis vapers, as well as the vaporisation temperatures and puff durations commonly used for dry herb, cannabis liquids and cannabis concentrates. To the best of our knowledge, this is the first time the usual operating temperatures of these vaporisation devices and user specific consumption patterns such as puff duration have been reported for cannabis vaping. This information will allow for a more realistic understanding of patterns of recreational use and improve experimental conditions in research settings to reflect the user's context.

Age-specific prevalence of human papillomavirus and abnormal cytology at baseline in a diverse statewide prospective cohort of individuals undergoing cervical cancer screening in Mississippi.

BACKGROUND: Mississippi (MS) has among the highest rates of cervical cancer incidence and mortality in the United States, with disproportionately higher rates among Blacks compared to Whites. Here, we evaluate the prevalence of high-risk human papillomavirus (HPV) and abnormal cytology in a representative baseline sample from a diverse statewide cohort of individuals attending cervical screening in MS from the STRIDES Study (STudying Risk to Improve DisparitiES in cervical cancer). METHODS: We included individuals aged 21-65 years undergoing screening at the University of Mississippi Medical Center (UMMC) and the Mississippi State Department of Health (MSDH) from May to November 2018. We calculated age-specific HPV prevalence, overall and by partial HPV16/18 genotyping, and abnormal cytology by race. RESULTS: A total of 6871 individuals (mean age 35.7 years) were included. HPV prevalence was 25.6% and higher in Blacks (28.0%) compared to Whites (22.4%). HPV prevalence was significantly higher in Blacks aged 21-24 years (50.2%) and 30-34 years (30.2%) compared to Whites in the same age groups (32.1% and 20.7%; p < 0.0001, respectively). The prevalence of high-grade cytologic abnormalities, a cytologic sign of cervical precancer, peaked earlier in Blacks (ages 25-29) compared to Whites (35-39). For comparison, we also analyzed HPV prevalence data from the National Health and Nutrition Examination Survey (NHANES, 2013-2016) and observed similar racial differences in HPV prevalence among women aged 21-24 years. CONCLUSIONS: Our findings suggest that Blacks undergoing cervical cancer screening in MS have higher prevalence of other high-risk 12 HPV types at younger ages and experience an earlier peak of high-grade cytologic abnormalities compared to Whites.

Synthesis and antibacterial studies of binaphthyl-based tripeptoids. Part 2.

A compact synthesis of 15 new binaphthyl-based dicationic tripeptoids and one biphenyl based dicationic tripeptoid is described. Fourteen of these tripeptoids resulted from variation of the C-2' ether substituent of the binaphthyl unit. An O-iso-butyl ether binaphthyl derivative was found to be the most active against Staphylococcus aureus (MIC 1.95 µg/mL). The biphenyl analogue also showed good activity against S. aureus (MIC 1.95 µg/mL). These compounds, however, were less active against four vancomycin-resistant strains of enterococci (VRE) than some of our previously developed compounds that had an O-iso-pentyl ether substituent on the binaphthyl unit and a C-2 L-Leu moiety.

E-cigarettes-An unintended illicit drug delivery system.

Since the introduction of electronic cigarettes (e-cigarettes) in 2003, the technology has advanced allowing for greater user modifications, with users now able to control voltage, battery power, and constituents of the e-cigarette liquid. E-cigarettes have been the subject of a growing body of research with most research justifiably focused on the chemical makeup and risk analysis of chemicals, metals, and particulates found in e-cigarette liquids and vapor. Little research to date has focused on assessing the risks associated with the drug delivery unit itself and its potential for use as an illicit drug delivery system. In light of this, a range of illicit drugs was researched focusing on pharmacodynamics, usual method of administration, the dosage required for toxicity, toxic effects, and evidence of existing use in e-cigarettes in both literature and online illicit drug forums. A systematic literature search found evidence of current use of e-cigarettes to vape almost all illicit drug types analyzed. This presents both a potential population health risk and a management issue for clinicians. It also raises the issue of policing illicit drugs due to potential altered characteristic smells and storage within e-cigarette fluids. E-cigarettes are a viable illicit drug delivery system with evidence both inside and outside of the formal medical literature detailing their potential use for drug delivery of a wide range of illicit and legal drugs.

Detection of Al(III) and Ga(III) complexes with morin by electrospray ionization mass spectrometry.

The Al(III) and Ga(III) complexes formed by morin (M) in aqueous solution were investigated by means of electrospray ionization mass spectrometry (ESI-MS). In the full scan mass spectra, Al:M showed 1:2 and 2:3 stoichiometric ratios. When (S)-N-acetylserine methyl ester (Ser), as a partial mimic of the serine residue in silk, was added to Al:M and Ga:M complexes in aqueous solution, the mass spectra of Ser:Al:M showed 1:1:1 and 1:1:2 stoichiometric ratios. The patterns of the mass spectra of Ga:M and Ser:Ga:M complexes were similar to those for the corresponding Al(III) complexes. Calculated heats of formation of potential structures of the complexes, with and without bound water, were obtained using semiempirical PM3 calculations.

The role of the HPA axis in psychiatric disorders and CRF antagonists as potential treatments.

An overview of the links between the Hypothalamic-Pituitary-Adrenal (HPA) axis and psychiatric disorders is presented. The current treatments are outlined, indicating that they are insufficient to meet the needs of those that suffer from these affective disorders. Therefore, there is an urgent need for the generation of new therapeutics, in particular, against new targets. The association of the corticotrophin releasing factor (CRF) and the HPA axis indicates that CRF antagonists should be beneficial as potential therapeutics.

Anilinopyrimidines as novel antituberculosis agents.

A selection of novel anilinopyrimidine analogues have been found to have micromolar activity against Mycobacterium tuberculosis. This could potentially generate new lead compounds in the fight against multi-drug resistant tuberculosis.