This manuscript combined two studies that assessed the effects of cannabidiol (CBD) exposure in distinct organ-on-a-chip models. Hesperos, Inc.'s Human-on-a-Chip® (HoaC) technology utilizes custom-designed human-based, serum-free, and pumpless microphysiological systems (MPS). The first study, study 1, assessed the level of off-target toxicity for CBD and its associated metabolites, 7-carboxy cannabidiol and 7-hydroxy cannabidiol, using a multi-organ heart-liver system. In study 1, CBD was delivered to systems with and without the inclusion of a liver organ module to evaluate metabolic contributions to corresponding cardiac toxicity. The results suggested that metabolism of the parent compound into its metabolites resulted in significant effects when compared to exposure to the parent compound only. Interestingly, significant distinctions in cardiac function, such as beat frequency and contractile force, were detected even though no significant cytotoxic effects were noted. The second study, study 2, utilized the same HoaC technology and employed a central nervous system (CNS) model using human induced-pluripotent stem cell derived cortical neurons. This model assessed CBD efficacy in alleviating stress-induced neural dysfunction in a single-organ model of the CNS, mimicking neuromodulation through a CBD administration route that does not involve first-pass metabolism. The results indicated a concentration-dependent rescue of CBD on cortisol-induced deficits in long-term potentiation (LTP) in this model, which was mirrored by associated changes in anandamide levels. Overall, these studies highlight the potential of human-based in vitro systems to evaluate drug toxicity and efficacy profiles specific to target mechanisms for toxicity and efficacy.
Associations between cigarette smoking and increased risk of cardiovascular disease are well established. However, it is unclear whether the association is mediated by exposure to nicotine and/or to other constituents in cigarette smoke. The objective of this systematic review and meta-analysis of randomized control trials (RCTs) was to identify any potential associations between exposure to nicotine and the risk of clinically diagnosed adverse cardiovascular events in adult current users and nonusers of tobacco products. Among 1,996 results, 42 studies, comparing nicotine and non-nicotine groups, were included and were both qualitatively and quantitatively synthesized across the outcomes of arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. The majority of studies evaluating nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death reported no events that occurred in either the nicotine or non-nicotine control groups. Among the studies that reported events, rates of adverse events were similarly low between both groups. Consistent with findings from previous systematic reviews and meta-analyses, pooled data showed that rates for arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death were not significantly different between nicotine and non-nicotine groups. The overall quality of the body of evidence for each of the four outcomes of interest was graded as "moderate," limited only by the imprecision of results. The findings of this systematic review and meta-analysis indicate that, with moderate certainty, there are no significant associations between the use of nicotine and the risk of clinically diagnosed adverse cardiovascular events-specifically, arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death.
Better understanding of indoor air quality (IAQ) and parameters affecting it, can improve the management of indoor environment quality (IEQ), reduce health risks, and enhance the occupant's well-being. The energy divisions, health and economy sectors are highly correlated to the concept of IAQ in terms of air ventilation, public health, and productivity. We performed a worldwide scoping review in accordance with the PRISMA extension (PRISMA-ScR) on IAQ indexes with different definitions and indicators, for various aims and applications (from indoor climate to indoor pollutants; for different indoor environments and ventilation setups). Correspondingly, IAQ-related issues were reviewed, including health effects, energy efficiency, and economic impacts. Information on different IAQ indexes was obtained from 110 studies from 23 countries. The use and type of ventilation systems as well as the duration and location of studies are reviewed. Also, the variability of the studied parameters in the literature were investigated. Finally, a novel detailed scoping classification based on different approaches for IAQ index development is presented for the first time. The “objective” approach, has become prevalent over the “subjective” approach, in design, development, and application of IAQ indexes. In addition, consideration of mechanical and natural ventilation was observed in 57 and 18% of the studies, respectively. This scoping review can aid as a first step, to better understand different expressions of IAQ by mean of an index, and their applications for future research and developments.
Due to the novel nature of oral nicotine pouches, limited studies have been conducted on the usage of these products in real-world settings. Consumption patterns and use behaviour of current nicotine pouch users need to be investigated to monitor the use and support the assessment of reduced risk products. Here we report the findings of an online survey completed by 550 participants across Sweden, Denmark, Germany and Switzerland who were current nicotine pouch users. The key areas of research were oral nicotine use history, mouth hold duration, nicotine strength, average daily consumption (ADC) and flavour preferences. Across all countries, most participants used oral nicotine pouches for 12 months or less. Longer use of nicotine pouches was reported in Sweden. Pouches containing 6‒15 mg nicotine were used most frequently in all countries, and particularly 11‒15 mg pouches in Sweden and Denmark. Average ADC across all countries was 1-5 pouches, closely followed by 6-10 pouches in Sweden and Denmark. Menthol was the most preferred flavour in all countries, followed by fruity and other food flavours. These findings reflect the differing product use patterns across nascent and mature markets as well as the need to investigate how different experience of product types can affect the use of new categories. Further research is required with a larger sample over time to understand product use patterns more clearly, including transition from and into other product categories.
E-cigarettes have the potential to reduce the harm caused by cigarette smoking; however, product likeability and product satisfaction are important in encouraging smokers to switch to less harmful products. Actual use studies play a key part in evaluating the reduced risk potential of tobacco and nicotine products. User’s puffing behaviour, including puff duration and sensory effects were evaluated for two types of e-cigarette device: a coil-and-wick ‘pen-type’ device (Vype ePen3), and a ceramic block-and-plate ‘pod-type’ device (Vype ePod) with 18 mg/ml nicotine e-liquid. Puffing topography was recorded for these devices with two groups (n=52 each) of adult regular vapers (age 21-64 years) following a fixed 10 puffs protocol where subjects vaped through a special holder attached to a puffing analyser. The sensory characteristics of the aerosol were evaluated using a questionnaire. Mean puff volume was significantly greater (p≤0.0001) for ePen3 than for ePod (79.8 vs 49.4 ml), while puff duration and puff interval were similar (2.13 vs 2.29 s and 8.9 vs 10.3 s, respectively). Notably, MLE to aerosol and nicotine from ePen3 and ePod were similar (3.89 vs 4.80 mg and 0.06 vs 0.07 mg respectively) despite of very different designs of the devices. Participants reported similar overall likeability and other sensory scores for ePen3 and ePod. In summary, the puffing topography attributes support the CORESTA recommended method no. 81, (CRM81) puffing regime, used for in vitro and chemical analysis. The MLE to nicotine per session from both the products were lower than a typical 6 mg cigarette.
