Enhancement of Benzene Emissions in Special Combinations of Electronic Nicotine Delivery System Liquid Mixtures.

Electronic nicotine delivery systems (ENDS) are battery-powered devices introduced to the market as safer alternatives to combustible cigarettes. Upon heating the electronic liquid (e-liquid), aerosols are released, including several toxicants, such as volatile organic compounds (VOCs). Benzene has been given great attention as a major component of the VOCs group as it increases cancer risk upon inhalation. In this study, several basic e-liquids were tested for benzene emissions. The Aerosol Lab Vaping Instrument was used to generate aerosols from ENDS composed of different e-liquid combinations: vegetable glycerin (VG), propylene glycol (PG), nicotine (nic), and benzoic acid (BA). The tested mixtures included PG, PG + nic + BA, VG, VG + nic + BA, 30/70 PG/VG, and 30/70 PG/VG + nic + BA. A carboxen polydimethylsiloxane fiber for a solid-phase microextraction was placed in a gas cell to trap benzene emitted from a Sub-Ohm Minibox C device. Benzene was adsorbed on the fiber during the puffing process and for an extra 15 min until it reached equilibrium, and then it was determined using gas chromatography-mass spectrometry. Benzene was quantified in VG but not in PG or the 30/70 PG/VG mixtures. However, benzene concentration increased in all tested mixtures upon the addition of nicotine benzoate salt. Interestingly, benzene was emitted at the highest concentration when BA was added to PG. However, lower concentrations were found in the 30/70 PG/VG and VG mixtures with BA. Both VG and BA are sources of benzene. Enhanced emissions, however, are mostly noticeable when BA is mixed with PG and not VG.

Aromatic Hydrocarbon Receptor Repressor (AHRR) is a biomarker of ambient air pollution exposure and Coronary Artery Disease (CAD).

Two hundred and twenty subjects were recruited while undergoing cardiac catheterization. AHRR cg05575921 methylation was shown to be significantly decreased in ever smokers compared to never smokers (Mean± SD = 64.2 ± 17.2 vs 80.1 ± 11.1 respectively; P < 0.0001). In addition, higher urinary levels of 2-OHNAP and 2-OHFLU were significantly associated with more AHRR cg05575921 hypomethylation, even after correcting for smoking (ß[95%CI]= -4.161[-7.553, -0.769]; P = 0.016 and -5.190[-9.761, -0.618]; P = 0.026, respectively) but not 1-OHPYR (ß[95%CI]= -3.545 [-10.935, 3.845]; P = 0.345). Additionally, hypomethylation of AHRR ROI was significantly associated with obstructive coronary artery disease (CAD) after adjusting for smoking, age, sex, diabetes and dyslipidemia (OR [95%CI] = 1.024[1.000 - 1.048]; P = 0.046). Results of this study necessitate further validation to potentially consider clinical incorporation of AHRR methylation status as an early predictive biomarker for the potential association between ambient air pollution and CAD.

Influence of nicotine form and nicotine flux on puffing behavior and mouth-level exposure to nicotine from electronic nicotine delivery systems.

BACKGROUND: Nicotine form (freebase/protonated) and nicotine flux (rate at which nicotine is emitted) are two factors that can affect the dose of nicotine inhaled by individuals using electronic nicotine delivery systems (ENDS) because they can influence puffing behavior. The nicotine dose for each puff also is directly proportional to nicotine flux (i.e., dose/puff=nicotine flux*puff duration). This study examines the effect of nicotine form and flux on puffing parameters and mouth-level nicotine exposure. METHODS: Thirty-two dual ENDS and combustible cigarette participants completed five visits that differed by nicotine form (freebase or protonated) and nicotine flux (14 or 35µg/sec); a zero-nicotine condition was a negative control. Participants used a Subox Mini C ENDS, powered at 20W, during a 10-puff directed bout (B1) followed by a one-hour ad libitum bout (B2). Puffing parameters and mouth-level nicotine exposure were assessed using the American University of Beirut REALTIME instrument. RESULTS: Relative to protonated nicotine, freebase nicotine was associated with lower total puff duration (puff duration*number of puffs), lower flow rate in B1, lower liquid consumption, and lower mouth-level nicotine exposure. Increasing nicotine flux from 14 to 35µg/sec was associated with lower total puff duration in both bouts, as well as lower liquid consumption. Increasing nicotine flux was associated with higher mouth-level nicotine exposure in B1 only. CONCLUSION: ENDS with protonated nicotine may enhance nicotine exposure by promoting longer puffing and thus greater dose delivered. This work highlights the importance of accounting for interactions between nicotine form and flux when considering nicotine regulation for ENDS.

Effects of Aftermarket Electronic Cigarette Pods on Device Power Output and Nicotine, Carbonyl, and ROS Emissions.

Aftermarket pods designed to operate with prevalent electronic nicotine delivery system (ENDS) products such as JUUL are marketed as low-cost alternatives that allow the use of banned flavored liquids. Subtle differences in the design or construction of aftermarket pods may intrinsically modify the performance of the ENDS device and the resulting nicotine and toxicant emissions relative to the original equipment manufacturer's product. In this study, we examined the electrical output of a JUUL battery and the aerosol emissions when four different brands of aftermarket pods filled with an analytical-grade mixture of propylene glycol, glycerol, and nicotine were attached to it and puffed by machine. The aerosol emissions examined included total particulate matter (TPM), nicotine, carbonyl compounds (CCs), and reactive oxygen species (ROS). We also compared the puff-resolved power and TPM outputs of JUUL and aftermarket pods. We found that all aftermarket pods drew significantly greater electrical power from the JUUL battery during puffing and had different electrical resistances and resistivity. In addition, unlike the case with the original pods, we found that with the aftermarket pods, the power provided by the battery did not vary greatly with flow rate or puff number, suggesting impairment of the temperature control circuitry of the JUUL device when used with the aftermarket pods. The greater power output with the aftermarket pods resulted in up to three times greater aerosol and nicotine output than the original product. ROS and CC emissions varied widely across brands. These results highlight that the use of aftermarket pods can greatly modify the performance and emissions of ENDS. Consumers and public health authorities should be made aware of the potential increase in the level of toxicant exposure when aftermarket pods are employed.

Comparing emergency department visits 10-year apart at a tertiary care center in Lebanon.

Presentations to the emergency department (ED) are growing worldwide. With the increasing risk factors of non-communicable disease (NCD) and communicable diseases (CD) in low- and middle-income countries, it is crucial to understand how ED presentations are changing with time to meet patients' needs and allocate acute care resources. The aim of this study is to compare the changes in patient and diseases characteristics over 2 time periods 10 year apart at the largest tertiary care center in Lebanon. This was a retrospective descriptive study of patients presenting to the ED at a large tertiary care center in 2009/2010 and 2018/2019. The discharge diagnoses were coded into Clinical Classification Software codes. We used descriptive statistics, odds ratios (OR), and non-parametric test to compare the different diagnoses. The total number of ED visits increased by 33% from 2009/2010 to 2018/2019. The highest increase rate was among patients older than 65 years (2.6%), whereas the percentage of pediatric patients decreased from 30.8% to 25.3%. ED presentations shifted from NCD to CD. A shift in the discharge diagnoses was also noted within age groups, specifically a shift in cardiovascular diseases to a younger age. Our study suggests that the role of the ED is changing and moving towards treating the aging population and CD. There is a need to invest and mitigate CD, better allocate resources to accommodate the aging population, focus on awareness campaigns targeting early detection of cardiovascular diseases and modifying its risk factors.

A Quick Method for the Determination of the Fraction of Freebase Nicotine in Electronic Cigarettes.

Recently, many electronic cigarettes (ECIGs) manufacturers have begun offering e-liquids, known as "nicotine salts". These salts that have started gaining big popularity among users can be formed by adding weak acid to e-liquid mixtures consisting of propylene glycol (PG), vegetable glycerin (VG), flavors, and nicotine. The latter can exist in two forms: monoprotonated (mp) and freebase (fb) based on the pH of the matrix. Over the years, the determination of the fraction of fb was found important to policymakers as the prevalence of this form in ECIGs has been associated with the harshness sensory of inhalable aerosols. Liquid-liquid extraction (LLE), 1H NMR, and Henderson-Hasselback have been developed to deduce the fraction of fb; however, these methods were found to be time-consuming and have shown some challenges mainly due to the presence of a non-aqueous matrix consisting of PG and VG. This paper presents a quick non-aqueous pH measurement-based method that allows a quick determination of the fraction fb by just measuring the pH and the dielectric constant of the e-liquid. Then, by inputting these values into an established mathematical relationship, the fraction fb can be deduced. The relationship between pH, dielectric constant, and fb relies on knowing the values of the acidity dissociation constants of nicotine, which were determined for the first time in various PG/VG mixtures using a non-aqueous potentiometric titration. To validate the proposed method, the fraction fb was determined for commercials and lab-made nicotine salts utilizing the pH and LLE methods. The variation between the two methods was (<8.0%) for commercial e-liquids and lab-made nicotine salts containing lactic acid and salicylic acid. A larger discrepancy of up to 22% was observed for lab-made nicotine salts containing benzoic acid, which can be attributed to the stronger affinity of benzoic acid to toluene in the LLE method.

Comparison of design characteristics and toxicant emissions from Vuse Solo and Alto electronic nicotine delivery systems.

INTRODUCTION: Vuse Solo is the first electronic nicotine delivery system (ENDS) authorised by the US Food and Drug Administration for marketing in the USA. Salient features of the Vuse Solo product such as nicotine form, draw resistance, power regulation and electrical characteristics have not been reported previously, and few studies have examined the nicotine and other toxicant emissions of this product. We investigated the design characteristics and toxicant emissions of the Solo as well as Alto, another Vuse product with a greater market share than Solo. METHODS: Total/freebase nicotine, propylene glycol to vegetable glycerin ratio, carbonyl compounds (CC) and reactive oxygen species (ROS) were quantified by gas chromatography, high-performance liquid chromatography and fluorescence from aerosol emissions generated in 15 puffs of 4 s duration. The electric power control system was also analysed. RESULTS: The average power delivered was 2.1 W and 3.9 W for Solo and Alto; neither system was temperature-controlled. Vuse Solo and Alto, respectively, emitted nicotine at a rate of 38 µg/s and 115 µg/s, predominantly in the protonated form (>90%). Alto's ROS yield was similar to a combustible cigarette and one order of magnitude greater than that of Solo. Total carbonyls from both products were two orders of magnitude lower than combustible cigarettes. CONCLUSION: Vuse Solo is an above-Ohm ENDS that emits approximately one-third the nicotine flux of a Marlboro Red cigarette (129 µg/s) and considerably lower CC and ROS yields than a combustible cigarette. With its higher power, the nicotine flux and ROS yield from Alto are similar to Marlboro Red levels; Alto may thus present greater abuse liability than the lower sales-volume Solo.

Effects of Desert Dust and Sandstorms on Human Health: A Scoping Review.

Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwide. This scoping review was conducted to identify the most likely health effects of desert dust and sandstorms and the methods used to characterize desert dust exposure from the existing epidemiological literature. We systematically searched PubMed/MEDLINE, Web of Science, and Scopus to identify studies that reported the effects of desert dust and sandstorms on human health. Search terms referred to desert dust or sandstorm exposure, names of major deserts, and health outcomes. Health effects were cross-tabulated with study design variables (e.g., epidemiological design and methods to quantify dust exposure), desert dust source, health outcomes and conditions. We identified 204 studies that met the inclusion criteria for the scoping review. More than half of the studies (52.9%) used a time-series study design. However, we found a substantial variation in the methods used to identify and quantify desert dust exposure. The binary metric of dust exposure was more frequently used than the continuous metric for all desert dust source locations. Most studies (84.8%) reported significant associations between desert dust and adverse health effects, mainly for respiratory and cardiovascular mortality and morbidity causes. Although there is a large body of evidence on the health effects of desert dust and sandstorms, the existing epidemiological studies have significant limitations related to exposure measurement and statistical analysis that potentially contribute to inconsistencies in determining the effect of desert dust on human health.

A Systematic Review of Analytical Methods for the Separation of Nicotine Enantiomers and Evaluation of Nicotine Sources.

The introduction of synthetic nicotine by the tobacco industry, also promoted as tobacco-free nicotine, presented new challenges for analytical chemists working in tobacco regulatory science to develop and optimize new methods to assess new nicotine parameters, namely enantiomer ratio and source. We conducted a systematic literature review of the available analytical methods to detect the nicotine enantiomer ratio and the source of nicotine using PubMed and Web of Science databases. Methods to detect nicotine enantiomers included polarimetry, nuclear magnetic resonance, and gas and liquid chromatography. We also covered methods developed to detect the source of nicotine either indirectly via determining the nicotine enantiomer ratio or the detection of tobacco-specific impurities or directly using the isotope ratio enrichment analysis by nuclear magnetic resonance (site-specific natural isotope fractionation and site-specific peak intensity ratio) or accelerated mass spectrometry. This review presents an accessible summary of all these analytical methods.

Impact of smoking intensity and device cleaning on IQOS emissions: comparison with an array of cigarettes.

SIGNIFICANCE: IQOS is a heated tobacco product that has been widely advertised by Philip Morris International (PMI) as a reduced-exposure product compared with cigarettes. Reduced exposure results from reduced emission of toxicants which could be influenced by product constituents and user behaviour. This study aims to assess the influence of user behaviour, including device cleaning and puffing parameters, on toxicant emissions from IQOS. METHODS: IQOS aerosols were generated by a smoking machine using the combination of two cleaning protocols (after 1 stick vs 20 sticks) and five puffing regimes (including standard cigarette puffing regimes and IQOS-tailored regimes). The generated aerosols were analysed by targeted methods for phenol and carbonyl quantification, and by chemical screening for the identification of unknown compounds. RESULTS: Puffing parameters significantly affected phenol and carbonyl emissions while device cleaning had no effect. Harsher puffing conditions like more, longer, and larger puffs yielded higher levels for most toxicant emissions. Comparing the obtained data with data reported by PMI on 50 cigarette brands smoked under different puffing regimes showed various trends for phenol and carbonyl emissions, with IQOS emissions sometimes higher than cigarettes. Also, the chemical screening resulted in the tentative identification of ~100 compounds in the IQOS aerosols (most of limited toxicity data). CONCLUSION: This study showed that puffing parameters, but not device cleaning, have significant effects on carbonyl, phenol and other emissions. Data analysis highlighted the importance of comparing IQOS emissions with an array of commercial cigarettes tested under different puffing regimes before accepting reduced exposure claims.

Assessing toxicant emissions from e-liquids with DIY additives used in response to a potential flavour ban in e-cigarettes.

SIGNIFICANCE: Electronic cigarettes (e-cigarettes) aerosolise liquids that contain nicotine, propylene glycol, glycerol and appealing flavours. In the USA, regulations have limited the availability of flavoured e-cigarettes in pod-based systems, and further tightening is expected. In response, some e-cigarette users may attempt to make their e-liquids (do-it-yourself, DIY). This study examined toxicant emissions from several aerosolised DIY e-liquids. METHODS: DIY additives were identified by reviewing users' responses to a hypothetical flavour ban, e-cigarette internet forums and DIY mixing internet websites. They include essential oils, cannabidiol, sucralose and ethyl maltol. E-liquids with varying concentrations and combinations of additives and tobacco and menthol flavours were prepared and were used to assess reactive oxygen species (ROS), carbonyl and phenol emissions in machine-generated aerosols. RESULTS: Data showed that adding DIY additives to unflavoured, menthol-flavoured or tobacco-flavoured e-liquids increases toxicant emissions to levels comparable with those from commercial flavoured e-liquids. Varying additive concentrations in e-liquids did not have a consistently significant effect on the tested emissions, yet increasing power yielded significantly higher ROS, carbonyl and phenol emissions for the same additive concentration. Adding nicotine to DIY e-liquids with sucralose yielded increase in some emissions and decrease in others, with freebase nicotine-containing e-liquid giving higher ROS emissions than that with nicotine salt. CONCLUSION: This study showed that DIY additives can impact aerosol toxicant emissions from e-cigarettes and should be considered by policymakers when restricting commercially available flavoured e-liquids.

Did JUUL alter the content of menthol pods in response to US FDA flavour enforcement policy?

BACKGROUND: The JUUL electronic cigarette (e-cigarette) remains popular in the USA and has a big prevalence among youth. In response to the popularity of JUUL and similar devices among youth, the US Food and Drug Administration issued in February 2020 an enforcement policy to remove all flavoured cartridge/pod-based e-cigarettes from the market except for tobacco and menthol. Subsequent studies showed that some users of the now-removed flavoured JUUL pods (especially cool mint) switched to menthol-flavoured JUUL pods with similar satisfaction. METHODS: We quantified menthol, nicotine, propylene glycol (PG) and vegetable glycerol (VG) in JUUL pod samples (Menthol, Classic Menthol and Cool Mint) that were purchased in 2017, 2018 and 2020 (only Menthol) to evaluate composition differences before and after the enforcement policy. We also analysed the samples to detect other cooling agents using a screening gas chromatography-mass spectrometry headspace method that we developed for this purpose. RESULTS: Menthol concentration was significantly higher in 2020 products than in products from prior years. Moreover, other cooling agents varied across pods. The PG/VG volume ratio was 27/63 in all pods examined. CONCLUSION: This study highlights how regulations intended to reduce e-cigarette prevalence among youth may influence changes in tobacco product characteristics in ways that regulators may not have foreseen.

Lessons learned from the discovery and development of the sesquiterpene lactones in cancer therapy and prevention.

INTRODUCTION: Sesquiterpene lactones (SLs) are one of the most diverse bioactive secondary metabolites found in plants and exhibit a broad range of therapeutic properties . SLs have been showing promising potential in cancer clinical trials, and the molecular mechanisms underlying their anticancer potential are being uncovered. Recent evidence also points to a potential utility of SLs in cancer prevention. AREAS COVERED: This work evaluates SLs with promising anticancer potential based on cell, animal, and clinical models: Artemisinin, micheliolide, thapsigargin dehydrocostuslactone, arglabin, parthenolide, costunolide, deoxyelephantopin, alantolactone, isoalantolactone, atractylenolide 1, and xanthatin as well as their synthetic derivatives. We highlight actionable molecular targets and biological mechanisms underlying the anticancer therapeutic properties of SLs. This is complemented by a unique assessment of SL mechanisms of action that can be exploited in cancer prevention. We also provide insights into structure-activity and pharmacokinetic properties of SLs and their potential use in combination therapies. EXPERT OPINION: We extract seven major lessons learned and present evidence-based solutions that can circumvent some scientific limitations or logistic impediments in SL anticancer research. SLs continue to be at the forefront of cancer drug discovery and are worth a joint interdisciplinary effort in order to leverage their potential in cancer therapy and prevention.

A Survey on the Knowledge, Attitudes, and Practices of Lebanese Physicians Regarding Air Pollution.

INTRODUCTION: Air pollution imposes a significant burden on public health. It is emerging as a modifiable risk factor for cancer, diabetes, and respiratory and cardiovascular diseases. This study aims to assess the knowledge, attitudes, and practices of Lebanese physicians regarding air pollution. METHODS: This observational study uses a descriptive cross-sectional correlational design. The data were collected using a self-administered online survey that was sent to 874 potential respondents who are members of the Lebanese Order of Physicians. Data analysis was done using descriptive statistics and a chi-square test. RESULTS: The results show a deficiency in the knowledge of physicians regarding many sources of air pollution, including dust, the smell of perfume, candles, vacuum cleaners, air fresheners, electronic cigarettes, etc. The majority of physicians agree that air pollution increases the risk of several health problems. Only 38% of physicians routinely ask their patients about exposure to air pollution, and 75% of them believe that they have a role as physicians in reducing air pollution levels. Over half of the sample are confident in counseling their patients on sources of air pollution, and two thirds of them are in support of including assessment of air pollution exposure during regular medical visits. CONCLUSION: Air pollution levels are progressively increasing over time. Given the health impact of exposure to air pollution, healthcare professionals need to stay up to date on this topic. The results of this study suggest the need for continuing education about air pollution for physicians and developing guidelines for what exactly to ask patients in assessing their exposure.

Low cost air quality sensors "PurpleAir" calibration and inter-calibration dataset in the context of Beirut, Lebanon.

The PurpleAir PA-II-SD is a low-cost particulate matter (PM2.5 and PM10) sensor that is currently available on the market. It is one of many such low-cost and commercially available particulate matter sensors which are being adopted by individuals and researchers worldwide. With growing use of these sensors, there is an interest in better understanding the performance and characteristics of these devices. Data was collected from twelve of these low-cost PurpleAir PA-II-SD sensors and two high fidelity Met One E-BAM PLUS instruments installed at a single location, on the campus of the American University of Beirut, in Beirut, Lebanon over a period of time from June 28, 2020 to September 30, 2020. The data was collected with the aim of assessing inter-sensor variability for the PurpleAir sensors and the sensor accuracy of the PurpleAir when compared to a high fidelity Met One E-BAM PLUS instrument.

Updated national emission inventory and comparison with the Emissions Database for Global Atmospheric Research (EDGAR): case of Lebanon.

Physically based computational modeling is an effective tool for estimating and predicting the spatial distribution of pollutant concentrations in complex environments. A detailed and up-to-date emission inventory is one of the most important components of atmospheric modeling and a prerequisite for achieving high model performance. Lebanon lacks an accurate inventory of anthropogenic emission fluxes. In the absence of a clear emission standard and standardized activity datasets in Lebanon, this work serves to fill this gap by presenting the first national effort to develop a national emission inventory by exhaustively quantifying detailed multisector, multi-species pollutant emissions in Lebanon for atmospheric pollutants that are internationally monitored and regulated as relevant to air quality. Following the classification of the Emissions Database for Global Atmospheric Research (EDGAR), we present the methodology followed for each subsector based on its characteristics and types of fuels consumed. The estimated emissions encompass gaseous species (CO, NOx, SO2), and particulate matter (PM2.5 and PM10). We compare totals per sector obtained from the newly developed national inventory with the international EDGAR inventory and previously published emission inventories for the country for base year 2010 presenting current discrepancies and analyzing their causes. The observed discrepancies highlight the fact that emission inventories, especially for data-scarce settings, are highly sensitive to the activity data and their underlying assumptions, and to the methodology used to estimate the emissions.

Electrical features, liquid composition and toxicant emissions from 'pod-mod'-like disposable electronic cigarettes.

INTRODUCTION: Use of flavoured pod-mod-like disposable electronic cigarettes (e-cigarettes) has grown rapidly, particularly among cost-sensitive youth and young adults. To date, little is known about their design characteristics and toxicant emissions. In this study, we analysed the electrical and chemical characteristics and nicotine and pulmonary toxicant emission profiles of five commonly available flavoured disposable e-cigarettes and compared these data with those of a JUUL, a cartridge-based e-cigarette device that pod-mod-like disposables emulate in size and shape. METHODS: Device construction, electrical power and liquid composition were determined. Machine-generated aerosol emissions including particulate matter, nicotine, carbonyl compounds and heavy metals were also measured. Liquid and aerosol composition were measured by high-performance liquid chromatography, gas chromatography-mass spectrometry/flame ionisation detection, and inductively coupled plasma mass spectrometry. RESULTS: We found that unlike JUUL, disposable devices did not incorporate a microcontroller to regulate electrical power to the heating coil. Quality of construction varied widely. Disposable e-cigarette power ranged between 5 and 9 W and liquid nicotine concentration ranged between 53 and 85 mg/mL (~95% in the protonated form). In 15 puffs, total nicotine yield for the disposables ranged between 1.6 and 6.7 mg, total carbonyls ranged between 28 and 138 µg, and total metals ranged between 1084 and 5804 ng. JUUL emissions were near the floors of all of these ranges. CONCLUSIONS: Disposable e-cigarettes are designed with high nicotine concentration liquids and are capable of emitting much higher nicotine and carbonyl species relative to rechargeable look-alike e-cigarettes. These differences are likely due to the lower quality in construction, unreliable labelling and lack of temperature control regulation that limits the power during operation. From a public health perspective, regulating these devices is important to limit user exposure to carbonyls and nicotine, particularly because these devices are popular with youth and young adults.

Poor regulation implications in a low and middle income country based on PAH source apportionment and cancer risk assessment.

Ambient particle-bound polycyclic aromatic hydrocarbons (PAHs) were collected for one year at an urban background site, and spatially and temporally compared to yearly averages in three coastal cities in Lebanon. The samples were quantified using gas chromatography-mass spectrometry (GC-MS) and source apportioned with an optimized robust method using positive matrix factorization (PMF). Three major sources were found to contribute to PAH emissions at the urban background site, namely, traffic (48%), diesel generators (23%), and incineration (29%). The cancer risk was found higher than what was measured at the same site in previous years with an increase of 35%. Improper regulations of the sources (incineration, power plant, diesel generators and traffic) identified in the different sites resulted in PAH intraurban variability. It is essential to study the chemical components of particulate matter (PM) in order to assess toxicity. In particular, particle-bound PAHs and their oxidation products are known for their carcinogenicity as well as their persistence in the atmosphere, which facilitate their transport to new locations. In the absence of law enforcement, unregulated sources and their total contribution to ambient PAHs present a major health risk. This calls for the attention of development funding agencies and their need to implement sustainable "carbon-free" funding strategies in support of urban development of low and middle-income countries (LMICs).

The Effect of Different Ester Chain Modifications of Two Guaianolides for Inhibition of Colorectal Cancer Cell Growth.

Several sesquiterpene lactones (STLs) have been tested as lead drugs in cancer clinical trials. Salograviolide-A (Sal-A) and salograviolide-B (Sal-B) are two STLs that have been isolated from Centaurea ainetensis, an indigenous medicinal plant of the Middle Eastern region. The parent compounds Sal-A and Sal-B were modified and successfully prepared into eight novel guaianolide-type STLs (compounds 1-8) bearing ester groups of different geometries. Sal-A, Sal-B, and compounds 1-8 were tested against a human colorectal cancer cell line model with differing p53 status; HCT116 with wild-type p53 and HCT116 p53-/- null for p53, and the normal-like human colon mucosa cells with wild-type p53, NCM460. IC50 values indicated that derivatization of Sal-A and Sal-B resulted in potentiation of HCT116 cell growth inhibition by 97% and 66%, respectively. The effects of the different molecules on cancer cell growth were independent of p53 status. Interestingly, the derivatization of Sal-A and Sal-B molecules enhanced their anti-growth properties versus 5-Fluorouracil (5-FU), which is the drug of choice in colorectal cancer. Structure-activity analysis revealed that the enhanced molecule potencies were mainly attributed to the position and number of the hydroxy groups, the lipophilicity, and the superiority of ester groups over hydroxy substituents in terms of their branching and chain lengths. The favorable cytotoxicity and selectivity of the potent molecules, to cancer cells versus their normal counterparts, pointed them out as promising leads for anti-cancer drug design.