Human Biomarker Exposure From Cigarettes Versus Novel Heat-Not-Burn Devices: A Systematic Review and Meta-Analysis.

INTRODUCTION: Novel tobacco products require independent research to assess their safety. This study assessed the current literature for trials comparing levels of biomarkers of exposure (BoE) between conventional cigarettes (CC) and heat-not-burn (HNB) devices. METHODS: Ten databases were searched using terms including: "heat not burn," "iqos," "teeps," "mrtp," "tobacco heating," and "glo" between January 1, 2010 and August 13, 2019. Randomized controlled trials (RCTs) assessing comparative BoE levels in humans using either CC or novel HNB devices were eligible. BoE were tabulated, and differences between the intervention and control groups were analyzed and combined using a random-effects meta-analysis. RESULTS: Ten nonblinded, RCTs were eligible, involving a total of 1766 participants. Studies regularly reported on 12 BoE (including nicotine). HNB devices assessed included the "IQOS" and "glo" devices and "precursor" (being developed) HNB devices. In comparison to CC, all 12 BoEs assessed were significantly lower for participants assigned to an HNB device. In comparison to smoking abstinence, HNB devices were statistically equivalent for eight BoEs and significantly elevated for four BoEs. CONCLUSIONS: This review found that the potential for harm to humans is reduced when using HNB devices compared to CC as indicated by significant reductions in BoE levels. Whilst these results support tobacco manufacturer claims of improved safety, the small number of studies included, limited range of BoE assessed, and involvement of the tobacco industry necessitate further independent research to confirm the HNB devices as being a safer alternative to CC. IMPLICATIONS: This study supports claims made by tobacco manufacturers on the improved safety of HNB tobacco devices in comparison to CC. These novel devices lead to reduced exposure to key biomarkers, which are linked to the health consequences attributed to tobacco use. This has strong implications for international public health as well as further research and policy development relating to the safety aspects and legalities of novel tobacco products.

Bronchial epithelial cells are rendered insensitive to glucocorticoid transactivation by transforming growth factor-ß1.

BACKGROUND: We have previously shown that transforming growth factor-beta (TGF-beta) impairs glucocorticoid (GC) function in pulmonary epithelial cell-lines. However, the signalling cascade leading to this impairment is unknown. In the present study, we provide the first evidence that TGF-beta impairs GC action in differentiated primary air-liquid interface (ALI) human bronchial epithelial cells (HBECs). Using the BEAS-2B bronchial epithelial cell line, we also present a systematic examination of the known pathways activated by TGF-beta, in order to ascertain the molecular mechanism through which TGF-beta impairs epithelial GC action. METHODS: GC transactivation was measured using a Glucocorticoid Response Element (GRE)-Secreted embryonic alkaline phosphatase (SEAP) reporter and measuring GC-inducible gene expression by qRT-PCR. GC transrepression was measured by examining GC regulation of pro-inflammatory mediators. TGF-beta signalling pathways were investigated using siRNA and small molecule kinase inhibitors. GRα level, phosphorylation and sub-cellular localisation were determined by western blotting, immunocytochemistry and localisation of GRα-Yellow Fluorescent Protein (YFP). Data are presented as the mean ± SEM for n independent experiments in cell lines, or for experiments on primary HBEC cells from n individual donors. All data were statistically analysed using GraphPad Prism 5.0 (Graphpad, San Diego, CA). In most cases, two-way analyses of variance (ANOVA) with Bonferroni post-hoc tests were used to analyse the data. In all cases, P <0.05 was considered to be statistically significant. RESULTS: TGF-beta impaired Glucocorticoid Response Element (GRE) activation and the GC induction of several anti-inflammatory genes, but did not broadly impair the regulation of pro-inflammatory gene expression in A549 and BEAS-2B cell lines. TGF-beta-impairment of GC transactivation was also observed in differentiated primary HBECs. The TGF-beta receptor (ALK5) inhibitor SB431541 fully prevented the GC transactivation impairment in the BEAS-2B cell line. However, neither inhibitors of the known downstream non-canonical signalling pathways, nor knocking down Smad4 by siRNA prevented the TGF-beta impairment of GC activity. CONCLUSIONS: Our results indicate that TGF-beta profoundly impairs GC transactivation in bronchial epithelial cells through activating ALK5, but not through known non-canonical pathways, nor through Smad4-dependent signalling, suggesting that TGF-beta may impair GC action through a novel non-canonical signalling mechanism.

Prevalence and Determinants of Road Traffic Accidents in Saudi Arabia: A Systematic Review.

Globally, the frequency of road traffic accidents (RTAs) is sharply rising. It is concerning that the number of RTAs in the Kingdom of Saudi Arabia (KSA) has risen within the past ten years. As a result, laws governing things like speeding and seat belt use must be implemented to ensure driving safety. This study aims to determine the prevalence and determinants of road traffic accidents in Saudi Arabia. A thorough search was carried out in November 2023, mostly using PubMed, in compliance with PRISMA criteria. The search was limited to English-language research examining the causes of road traffic accidents and their prevalence. Certain inclusion and exclusion criteria were developed to guarantee the quality and applicability of the evaluated research. A wide spectrum of research from Saudi Arabia was included in the study without focusing on a specific gender. A discernible pattern indicated a high proportion of individuals affected by road traffic accidents. According to the findings of our investigation, there is growing evidence that Despite recent improvements in the incidence of road accidents, there is still significant variation in the incidence of accidents in Saudi Arabia. These results indicate that further study is needed to understand road accident prevention better.

Student Acceptance of Using Augmented Reality Applications for Learning in Pharmacy: A Pilot Study.

Creating engaging learning experiences that are easy to use and support the different learning requirements of university students is challenging. However, improvements in simulation technologies, such as augmented reality (AR) and virtual reality (VR), are making such changes possible. The aim of this study is to use a mobile-based AR technology to develop an interactive learning module about contraceptive devices and medicines and to measure its acceptability and usability by undergraduate pharmacy students. The learning module comprising AR images of contraceptive medicines, case studies relating to their use and a series of directed questions was completed by 33 pharmacy students. Students answered a survey to collect information about the usability and acceptability of AR for learning. The results show that the majority of students reported that AR is a useful resource for learning about medicines compared to more traditional methods, such as didactic lectures and tutorials. Students indicated that the AR application was easy to use and improved their knowledge of medicines. These findings suggest that AR technology is a useful tool to create engaging and easy to use learning experiences for university students.

Introducing Augmented Reality Technology to Enhance Learning in Pharmacy Education: A Pilot Study.

There is increasing use of augmented reality (AR) technology, which combines the virtual and real world, in the tertiary education sector. AR enables flexibility in student learning, since this technology may be used in the face to face setting and may also be accessed by students at any time outside of this setting. The purpose of this study was to develop an AR tool and investigate its effectiveness for learning about the medication naloxone using AR in a MagicBook; and determine student opinions on its acceptability and usability. Using a sequential explanatory, mixed method design, 25 undergraduate pharmacy students were recruited to participate in the study. Pre- and post-tests were used to measure changes in knowledge and a survey was used to collect information on the usability and acceptability of AR for learning. The findings of the study indicated that AR technology was able to support student learning on the chosen topic, showing 42% improvement in quiz score p < 0.0001, and that students found using AR was stimulating, interactive, engaging and easy to follow. Thus, AR technology could be an effective way to enhance student learning about medicines.

Prevalence of migraine and tension-type headache among adults in Jordan.

Here, we investigated the prevalence of headache among adults in Jordan. The study was conducted from January 2007 to November 2008. A sample of 4,836 participants were permitted to complete a self-conducted screening questionnaire. As much as 82.3% of participants complained from headache at least once per year. 36.1% were tension-type headache and 59% of the participants had other family members who suffered from headache. Headaches affected everyday activities in 51.6% of the participants; 82.7% of participants did not seek medical attention for their headaches. Among those who used analgesics (75.6%), acetaminophen was the most common (91.43%). In conclusion, headache and overuse of analgesics were prevalent in a significant part of the society. Thus, there is a need to educate the public to ensure safe practices and to make the use and selling of analgesics more stringent.

Glucocorticoid-resistant asthma and novel anti-inflammatory drugs.

Synthetic glucocorticoids are among the most commonly used prescription medicines. Nevertheless, their clinical efficacy is accompanied by dose- and indication-limiting acute and chronic adverse effects. Intrinsic or acquired resistance to glucocorticoid actions may also limit clinical efficacy. In chronic inflammatory conditions there has been a considerable focus on understanding mechanism(s) of resistance in cells with a primary immune and/or inflammatory function. However, it has become increasingly accepted that a substantial part of the efficacy of glucocorticoid treatments derives from actions on 'structural' cell types (smooth muscle, fibroblasts, epithelia). In this article we review the mechanism of action of glucocorticoids on structural cells and contrast knowledge of resistance mechanisms between structural and inflammatory cell types, using asthma as an exemplar chronic inflammatory condition associated with glucocorticoid resistance.