Tambjamines as Fast-Acting Multistage Antimalarials.

Well-tolerated and novel antimalarials that can combat multiple stages of the parasite life cycle are desirable but challenging to discover and develop. Herein, we report results for natural product-inspired novel tambjamine antimalarials. We show that they are potent against liver, asexual erythrocytic, and sexual erythrocytic parasite life cycle stages.

Mechanistic Rationale for Ketene Formation during Dabbing and Vaping.

Ketene is one of the most toxic vaping emissions identified to date. However, its high reactivity renders it relatively challenging to identify. In addition, certain theoretical studies have shown that realistic vaping temperature settings may betoo low to produce ketene.

A Review of the Toxicity of Ingredients in e-Cigarettes, Including Those Ingredients Having the FDA's "Generally Recognized as Safe (GRAS)" Regulatory Status for Use in Food.

Some firms and marketers of electronic cigarettes (e-cigarettes; a type of electronic nicotine delivery system (ENDS)) and refill liquids (e-liquids) have made claims about the safety of ingredients used in their products based on the term "GRAS or Generally Recognized As Safe" (GRAS). However, GRAS is a provision within the definition of a food additive under section 201(s) (21 U.S.

Kinetics of Aldehyde Flavorant-Acetal Formation in E-Liquids with Different E-Cigarette Solvents and Common Additives Studied by H NMR Spectroscopy.

Flavorants, nicotine, and organic acids are common additives found in the e-liquid carrier solvent, propylene glycol (PG) and/or glycerol (GL), at various concentrations. Some of the most concentrated and prevalent flavorants in e-liquids include -cinnamaldehyde, vanillin, and benzaldehyde. Aldehyde flavorants have been shown to react with PG and GL to form flavorant-PG and -GL acetals that have unique toxicity properties in e-liquids before aerosolization.

Effects of Common e-Liquid Flavorants and Added Nicotine on Toxicant Formation during Vaping Analyzed by H NMR Spectroscopy.

A broad variety of e-liquids are used by e-cigarette consumers. Additives to the e-liquid carrier solvents, propylene glycol and glycerol, often include flavorants and nicotine at various concentrations. Flavorants in general have been reported to increase toxicant formation in e-cigarette aerosols, yet there is still much that remains unknown about the effects of flavorants, nicotine, and flavorants + nicotine on harmful and potentially harmful constituents (HPHCs) when aerosolizing e-liquids.

Emerging ENDS products and challenges in tobacco control toxicity research.

Electronic nicotine delivery systems (ENDS) continue to rapidly evolve. Current products pose unique challenges and opportunities for researchers and regulators. This commentary aims to highlight research gaps, particularly in toxicity research, and provide guidance on priority research questions for the tobacco regulatory community.

Meeting the Moment: Impact of TEACH Grant on US Undergraduate Education Degree Completion in High-Need Content Areas.

Unlabelled: As part of the College Cost Reduction and Access Act (2007), the USA funded the TEACH Grant to incentivize earning a degree in a high-need content area (e.g., STEM fields, language-related areas, and Special Education) and to help meet teacher supply needs in low-income schools.

Adverse Reactions in a Phase 1 Trial of the Anti-Malarial DM1157: An Example of Pharmacokinetic Modeling and Simulation Guiding Clinical Trial Decisions.

Introduction: There is an urgent need to develop new drugs to treat malaria due to increasing resistance to first-line therapeutics targeting the causative organism, Plasmodium falciparum (P. falciparum). One drug candidate is DM1157, a small molecule that inhibits the formation of hemozoin, which protects P.

Ratio of Propylene Glycol to Glycerol in E-Cigarette Reservoirs Is Unchanged by Vaping As Determined by H NMR Spectroscopy.

E-cigarette liquids (e-liquids) contain propylene glycol (PG) and/or glycerol (GL) to deliver flavorants/nicotine. It has recently been suggested that the PG:GL ratio in e-cigarette reservoirs changes during vaping, leaving almost entirely GL after aerosolizing much of a 30:70 PG:GL mixture. To evaluate this directly, we analyzed e-liquids from e-cigarettes before and after aerosolization using 4 different coils, and aerosol samples generated using high and low e-liquid levels.

Barriers, Facilitators, and Cost of Integrating HIV-Related Activities Into Sexually Transmitted Disease Partner Services in Jackson, Mississippi.

Background: Many US health departments now integrate HIV-related outcomes (e.g., relinkage to HIV care and preexposure prophylaxis [PrEP]) into sexually transmitted disease (STD) partner services (PS) programs.

Preservice Observation in Special Education: A Validation Study.

Advancing teacher candidates' overall competence through use of valid teacher observation systems should be an essential element of teacher preparation. Yet, the field of special education has not provided observation protocols designed specifically for preservice teachers that are founded in theoretical perspectives and research on effective instruction for students with learning and other high-incidence disabilities (SWDs). To address this need, a group of researchers in special education teacher preparation and measurement developed the Preservice Observation Instrument for Special Education (POISE).

Unsymmetrical Bisquinolines with High Potency against Malaria.

Quinoline-based scaffolds have been the mainstay of antimalarial drugs, including many artemisinin combination therapies (ACTs), over the history of modern drug development. Although much progress has been made in the search for novel antimalarial scaffolds, it may be that quinolines will remain useful, especially if very potent compounds from this class are discovered. We report here the results of a structure-activity relationship (SAR) study assessing potential unsymmetrical bisquinoline antiplasmodial drug candidates using in vitro activity against intact parasites in cell culture.

Free-Base Nicotine Fraction α in Non-Aqueous versus Aqueous Solutions: Electronic Cigarette Fluids Without versus With Dilution with Water.

An important design aspect of electronic cigarettes ("e-cigarettes") is the nature of the acid/base chemistry in the e-liquid phase. E-liquids having formulations similar to those of early products are mixes of propylene glycol/glycerol (PG/GL) plus free-base (fb) nicotine and (usually) flavor chemicals that are either rather weak or non-acid/base actors in PG/GL. The fraction of nicotine in the fb form is denoted (α), with a possible range of 0 < (α) < 1.

Nicotine in tobacco product aerosols: 'It's déjà vu all over again'.

Introduction: The distribution of nicotine among its free-base (fb) and protonated forms in aerosolised nicotine affects inhalability. It has been manipulated in tobacco smoke and now in electronic cigarettes by the use of acids to de-freebase nicotine and form 'nicotine salts'.

Methods: Measurements on electronic cigarette fluids (e-liquids) were carried out to determine (1) the fraction of nicotine in the free-base form () and (2) the levels of organic acid(s) and nicotine.

Free-Base Nicotine Is Nearly Absent in Aerosol from IQOS Heat-Not-Burn Devices, As Determined by H NMR Spectroscopy.

Heat-not-burn products, eg, I quit ordinary smoking (IQOS), are becoming popular alternative tobacco products. The nicotine aerosol protonation state has addiction implications due to differences in absorption kinetics and harshness. Nicotine free-base fraction (α) ranges from 0 to 1.

Sucralose-Enhanced Degradation of Electronic Cigarette Liquids during Vaping.

Electronic cigarette liquids (e-liquids) with sweetener additives such as sucralose, a synthetic chlorinated disaccharide, are popular among some e-cigarette consumers; sucralose can be added either by the manufacturer or by the consumer. The prevalence of sucralose in commercial e-liquids is not known, nor is the typical concentration of sucralose when present; labels are not required to disclose ingredient information. Here, we report the effects of sucralose on e-liquid degradation upon e-cigarette vaping as studied using H NMR spectroscopy, ion chromatography, and gas chromatography coupled with detection by mass spectrometry or flame ionization detector.

Integrating Human Immunodeficiency Virus Testing Into Syphilis Partner Services in Mississippi to Improve Human Immunodeficiency Virus Case Finding.

Background: Mississippi has the 10th highest rate of new human immunodeficiency virus (HIV) infections in the United States. The Mississippi State Department of Health (MSDH) integrated partner HIV testing into syphilis partner services (PS) in 2014, but the effectiveness of this as an HIV case finding strategy has not been evaluated.

Methods: We identified all early syphilis (primary, secondary, and early latent) case records reported from July 1, 2014, to December 31, 2016, excluding case records for people concurrently newly diagnosed with HIV.

Boiling points of the propylene glycol + glycerol system at 1 atmosphere pressure: 188.6-292 °C without and with added water or nicotine.

In electronic cigarettes ("electronic nicotine delivery systems", ENDS), mixtures of propylene glycol (PG) and/or glycerol (GL; aka "vegetable glycerin", VG) with nicotine are vaporized to create a nicotine-containing aerosol. For a given composition, the temperature required to boil the liquid at 1 atmosphere must be at least somewhat greater than the boiling point (BP). The use of ENDS is increasing rapidly worldwide, yet the BP characteristics of the PG + GL system have been characterized as the mixtures; here we re-do this, but significantly, also study the effects of added water and nicotine.

Dihydroxyacetone levels in electronic cigarettes: Wick temperature and toxin formation.

Recently, we reported the presence of dihydroxyacetone (DHA), the active ingredient in sunless tanners, in the aerosol of an electronic cigarette. DHA has been shown to react with DNA . The FDA restricts the use of DHA to external application only.

Triacetin Enhances Levels of Acrolein, Formaldehyde Hemiacetals, and Acetaldehyde in Electronic Cigarette Aerosols.

The health effects of inhaled electronic cigarette (e-cigarette) flavoring compounds are largely unknown. Earlier reports of their chemical reactivity have been conflicting, with some claiming, for example, that the degradation of flavoring chemicals in e-cigarettes to aldehydes is statistically insignificant. It is thus important to understand how these molecules react to afford enhanced aerosol products.

Free-Base Nicotine Determination in Electronic Cigarette Liquids by H NMR Spectroscopy.

E-liquids usually contain significant nicotine, which will exist primarily in two forms, monoprotonated and free-base, the proportions of which are alterable through the effective pH of the medium. The fraction of nicotine in the free-base form is α, with 0 ≤ α ≤ 1. When dosed via aerosol, the two nicotine forms have different mechanisms and kinetics of delivery, as well as differing implications for harshness of the inhaled aerosol, so α is relevant regarding abuse liability.

E-cigarettes can emit formaldehyde at high levels under conditions that have been reported to be non-averse to users.

E-cigarette aerosol emission studies typically focus on benchmarking toxicant levels versus those of cigarettes. However, such studies do not fully account for the distinct chemical makeup of e-liquids and their unique properties. These approaches often conclude that there are fewer and lower levels of toxins produced by e-cigarettes than by cigarettes.