Beta-Adrenergic Receptor Polymorphism and Patho-Genetics of Trauma: A Transformational Frontier of Personalized Medicine in Neurotrauma.

Trauma is a serious public health issue, and remains a major cause of mortality and disability worldwide. The notion that genetic factors contribute to an individual's response to traumatic injury has advanced significantly. Genetic variations in severely injured patients have been linked to mortality, morbidity, and psychological outcomes. We conducted a comprehensive review of beta-adrenergic receptor polymorphisms and their impact on the pathogenetics of traumatic injuries, which could pave the way for a transformational frontier of personalized medicine in neurotrauma. It remains unclear why some individuals are vulnerable to worse outcomes, whereas others are resilient. Although genetic factors may be significant, the intricate interplay between environmental and genetic factors may be responsible for variations in the presentation and outcome after injury. Recent advancements in genetic analysis and molecular physiology have helped to shed light on the causes of such variability. Although exposure to trauma can initiate a cascade of stress-related responses, these responses alone are insufficient to explain etiopathogenesis. Therefore, gaining insights into how trauma and genetic predispositions to adrenergic variations interact at the molecular level to affect an individual's susceptibility and recuperation could provide an essential understanding of the molecular pathogenesis of traumatic injuries. Therefore, it is imperative to identify potential genetic and physiological markers to guide early management and prognosis of trauma. Such knowledge could pave the way for the discovery of novel biomarkers that can identify a transdiagnostic subgroup that is at high risk and requires early intervention. This could lead to the adoption of personalized medical approaches in neurotrauma care.

Deregulated transcription factors in the emerging cancer hallmarks.

Cancer progression is a multifaceted process that entails several stages and demands the persistent expression or activation of transcription factors (TFs) to facilitate growth and survival. TFs are a cluster of proteins with DNA-binding domains that attach to promoter or enhancer DNA strands to start the transcription of genes by collaborating with RNA polymerase and other supporting proteins. They are generally acknowledged as the major regulatory molecules that coordinate biological homeostasis and the appropriate functioning of cellular components, subsequently contributing to human physiology. TFs proteins are crucial for controlling transcription during the embryonic stage and development, and the stability of different cell types depends on how they function in different cell types. The development and progression of cancer cells and tumors might be triggered by any anomaly in transcription factor function. It has long been acknowledged that cancer development is accompanied by the dysregulated activity of TF alterations which might result in faulty gene expression. Recent studies have suggested that dysregulated transcription factors play a major role in developing various human malignancies by altering and rewiring metabolic processes, modifying the immune response, and triggering oncogenic signaling cascades. This review emphasizes the interplay between TFs involved in metabolic and epigenetic reprogramming, evading immune attacks, cellular senescence, and the maintenance of cancer stemness in cancerous cells. The insights presented herein will facilitate the development of innovative therapeutic modalities to tackle the dysregulated transcription factors underlying cancer.

Academic and healthcare efforts from Cessation to complete resumption of professional football tournaments during COVID-19 pandemic: A narrative review.

The Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus led to over 626 million infections and 6.5 million deaths worldwide and forced to cancel or postpone several sporting events. Effective control techniques are therefore urgently required to avoid COVID-19 spread at these local and global events. This narrative review addressed the healthcare and research efforts on the intersections between COVID-19 and major professional sports leagues worldwide, with special reference to the FIFA World Cup football 2022. This explained how the broader transformation of COVID-19 from being a potential risk to an urgent pandemic public health emergency, caused the world of Football to halt between February and March 2020. This review could add to the growing literature on the importance of scientific research in understanding the relationship between mass sports events and COVID-19 trajectory, concerning studies conducted globally and particularly for the recommencement of major professional football competitions. The information outlined in the article may help sports organizations understand the risks associated with sports and their settings and improve their preparedness for future events under unprecedented circumstances. There were tremendous global healthcare and research efforts to deal with this unprecedented pandemic. The successful FIFA World Cup football tournament was an indicator of the success of these efforts.

Trauma Quality Improvement Program: A Retrospective Analysis from A Middle Eastern National Trauma Center.

BACKGROUND: The Trauma Quality Improvement Program (American College of Surgery (ACS-TQIP)) uses the existing infrastructure of the Committee on Trauma programs and provides feedback to participating hospitals on risk-adjusted outcomes. This study aimed to analyze and compare the performance of the Level I Hamad Trauma Centre (HTC) with other TQIP participating centers by comparing TQIP aggregate database reports. The primary goal was to pinpoint the variations in adult trauma outcomes and quality measures, identify areas that need improvement, and leverage existing resources to facilitate quality improvement. METHODS: A retrospective analysis was performed for the TQIP data from April 2019-March 2020 to April 2020-March 2021. We used the TQIP methodology, inclusion and exclusion criteria, and outcomes. RESULTS: There were 915 patients from Fall 2020 and 884 patients from Fall 2021 that qualified for the TQIP database. The HTC patients' demographics differed from the TQIP's aggregate data; they were younger, more predominantly male, and had significantly different mechanisms of injury (MOI) with more traffic-related blunt trauma. Penetrating injuries were more severe in the other centers. During the TQIP Fall 2020 report, the HTC was a low outlier (good performer) in one cohort (all patients) and an average performer in the remaining cohorts. However, during Fall 2021, the HTC showed an improvement and was a low outlier in two cohorts (all patients and severe TBI patients). Overall, the HTC remained an average performer during the report cycles. CONCLUSIONS: There was an improvement over time in the risk-adjusted mortality, which reflects the continuous and demanding effort put together by the trauma team. The ACS-TQIP for the external benchmarking of quality improvement could be a contributor to better monitored patient care. Evaluating the TQIP data with emphases on appropriate methodologies, quality measurements, corrective measures, and accurate reporting is warranted.

Exosome nanovesicles as potential biomarkers and immune checkpoint signaling modulators in lung cancer microenvironment: recent advances and emerging concepts.

Lung cancer remains the leading cause of cancer-related deaths globally, and the survival rate remains low despite advances in diagnosis and treatment. The progression of lung cancer is a multifaceted and dynamic phenomenon that encompasses interplays among cancerous cells and their microenvironment, which incorporates immune cells. Exosomes, which are small membrane-bound vesicles, are released by numerous cell types in normal and stressful situations to allow communication between cells. Tumor-derived exosomes (TEXs) possess diverse neo-antigens and cargoes such as proteins, RNA, and DNA and have a unique molecular makeup reflecting tumor genetic complexity. TEXs contain both immunosuppressive and immunostimulatory factors and may play a role in immunomodulation by influencing innate and adaptive immune components. Moreover, they transmit signals that contribute to the progression of lung cancer by promoting metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and immunosuppression. This makes them a valuable resource for investigating the immune environment of tumors, which could pave the way for the development of non-invasive biomarkers that could aid in the prognosis, diagnosis, and immunotherapy of lung cancer. While immune checkpoint inhibitor (ICI) immunotherapy has shown promising results in treating initial-stage cancers, most patients eventually develop adaptive resistance over time. Emerging evidence demonstrates that TEXs could serve as a prognostic biomarker for immunotherapeutic response and have a significant impact on both systemic immune suppression and tumor advancement. Therefore, understanding TEXs and their role in lung cancer tumorigenesis and their response to immunotherapies is an exciting research area and needs further investigation. This review highlights the role of TEXs as key contributors to the advancement of lung cancer and their clinical significance in lung immune-oncology, including their possible use as biomarkers for monitoring disease progression and prognosis, as well as emerging shreds of evidence regarding the possibility of using exosomes as targets to improve lung cancer therapy.

Pushing the Boundaries of Scientific Research with the use of Artificial Intelligence tools: Navigating Risks and Unleashing Possibilities.

The language of science is communicated through various modes, such as lectures, informal discussions, conferences, and peer-reviewed publications. Artificial Intelligence (AI) based writing tools, like ChatGPT, have recently become increasingly popular due to natural language processing technology advancements. ChatGPT is an AI language model that can generate text close to human writing, making it suitable for tasks such as summarizing literature, composing essays, and producing statistical studies. This technology has the potential to transform scientific communication, but concerns have been raised about its impact on the integrity of research and the role of human researchers. While this technology has advantages such as accelerating the innovation process and enhancing diversity in scientific viewpoints, it is important for the scientific community to debate and envision the consequences of its use. Publishers are working to develop guidelines for its application, which may be capable of future activities such as experiment design and peer review. As we enter the early stages of the AI revolution, it is imperative that the scientific community engages in discourse and contemplate the potential outcomes of this potentially transformative technology. With this in mind, we have outlined relevant topics as a starting point for discussion.

Bio-secure bubble during the COVID-19 pandemic to host the Asian Football Confederation (AFC) Champions League: A retrospective observational study.

Background and Aims: To describe the COVID-19 positivity rate among football players, team staff, and local organizing committee members participated in the Asian Football Confederation (AFC) Champions League (West) tournament organized with the Bio-secure bubble protocol in place. Methods: A retrospective observational study was carried out to include a total of 2184 participants during the AFC-West tournament in Qatar, which was a 3-week event (September 14-October 3, 2020). This event was undertaken under the Bio-secure bubble protocol, which was developed and implemented for sports events in Qatar during the pandemic. Within 72 h of departure and upon arrival in Qatar, all participants underwent reverse-transcriptase polymerase chain reaction testing (RT-PCR) to diagnose COVID-19. The test was considered positive based on the cycle threshold (cT) value which was <30, whereas, reactive if cT value was ≥30 and <40, and negative (cT > 40). Results: Of the 2184 participants (528 players, 388 team staff, and 1268 local staff), 916 international participants were tested for COVID-19 PCR upon arrival at the Hamad International Airport, whereas the local staff (n = 1268) were tested 2 days before entering the bubble. The mean age of the players was 27.5 ± 9.8. Fifteen teams participated and as many as 60 matches were played over 3 weeks. Most participants tested negative (95.3%) and 3.9% tests were inconclusive. During the entire tournament, the positivity rate was 2.7% among all participants. Of the total positive cases, 0.8% were positive before entering the bubble system. The remaining (1.9%) tested positive during the tournament phase (19 players, 16 team officials, and 8 organizing committee staff). Conclusion: Bio-secure bubble protocol operated in a controlled environment presents a minimal risk of COVID-19 infection for hosting international football events. This framework could be benchmarked to resume professional football competitions under unprecedented pandemic situations.

FIFA Arab Cup tournament with full capacity of spectators during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: We sought to assess the risk of COVID-19 and seasonal flu including respiratory syncytial (RSV) and influenza viruses during the FIFA Arab Cup 2021 in Qatar with full capacity of spectators. We also, evaluated the post-event attitude toward resumption of mass football events. METHODS: This was a cross-sectional study in which spectators (age ≥ 18 years) were invited for reverse-transcription PCR testing for COVID-19 and seasonal flu. At the same time, between 7 and 14 days after the event, the participants completed a self-administered questionnaire regarding their concerns during the tournament. RESULTS: The tournament included 16 international football teams from the Arab countries. As per the study protocol, 10,000 spectators were approached and 6,475 participated. Among the participants, 4,195 (65.1%), 2,253 (34.9%) and 27 (0.4%) were vaccinated with 2 doses, vaccinated with 3 doses, and recovered from SARS-Cov-2 infection, respectively. There were 61 (0.9%), 41(0.6%) and 11(0.2%) participants who tested positive for COVID-19, RSV and influenza (A/B), respectively. The average cycle threshold (Ct) value for COVID-19 positive cases was 26.1±7.3. Among those who were electronically approached, 6,102 completed the survey whereas 373 had incomplete survey. Overall, 2069 (33.9%) participants reported symptoms that theoretically could be related to COVID-19, of them 39 had positive PCR test (1.9%). Spectators (94.3%) were optimistic about returning sport events to the pre-pandemic status. CONCLUSIONS: There was no significant increase in the daily COVID-19 cases during FIFA Arab Cup 2021 with a full capacity of spectators. Therefore, upcoming mass football events can be held safely.

The evolving role of extracellular vesicles (exosomes) as biomarkers in traumatic brain injury: Clinical perspectives and therapeutic implications.

Developing effective disease-modifying therapies for neurodegenerative diseases (NDs) requires reliable diagnostic, disease activity, and progression indicators. While desirable, identifying biomarkers for NDs can be difficult because of the complex cytoarchitecture of the brain and the distinct cell subsets seen in different parts of the central nervous system (CNS). Extracellular vesicles (EVs) are heterogeneous, cell-derived, membrane-bound vesicles involved in the intercellular communication and transport of cell-specific cargos, such as proteins, Ribonucleic acid (RNA), and lipids. The types of EVs include exosomes, microvesicles, and apoptotic bodies based on their size and origin of biogenesis. A growing body of evidence suggests that intercellular communication mediated through EVs is responsible for disseminating important proteins implicated in the progression of traumatic brain injury (TBI) and other NDs. Some studies showed that TBI is a risk factor for different NDs. In terms of therapeutic potential, EVs outperform the alternative synthetic drug delivery methods because they can transverse the blood-brain barrier (BBB) without inducing immunogenicity, impacting neuroinflammation, immunological responses, and prolonged bio-distribution. Furthermore, EV production varies across different cell types and represents intracellular processes. Moreover, proteomic markers, which can represent a variety of pathological processes, such as cellular damage or neuroinflammation, have been frequently studied in neurotrauma research. However, proteomic blood-based biomarkers have short half-lives as they are easily susceptible to degradation. EV-based biomarkers for TBI may represent the complex genetic and neurometabolic abnormalities that occur post-TBI. These biomarkers are not caught by proteomics, less susceptible to degradation and hence more reflective of these modifications (cellular damage and neuroinflammation). In the current narrative and comprehensive review, we sought to discuss the contemporary knowledge and better understanding the EV-based research in TBI, and thus its applications in modern medicine. These applications include the utilization of circulating EVs as biomarkers for diagnosis, developments of EV-based therapies, and managing their associated challenges and opportunities.

A quick scoping review of the first year of vaccination against the COVID-19 pandemic: Do we need more shots or time?

BACKGROUND: The emergence of new severe acute respiratory syndrome coronavirus 2 variants, along with the waning of vaccine-induced immunity, has increased breakthrough infections and urged booster jabs and debates. In the short term, the administration of booster doses has been reported to be safe and enhance severe acute respiratory syndrome coronavirus 2-specific neutralizing antibody levels. However, the effects of these doses on the pandemic trajectory and herd immunity are unclear. There is insufficient evidence that a third booster shot of the coronavirus disease 2019 (COVID-19) vaccine maintains longer immunity and covers new viral variants. The lack of sufficient evidence, combined with the fact that millions of people have not yet received 1 or 2 jabs of the COVID-19 vaccine, has raised concerns regarding the call for booster vaccinations. METHODS: We conducted a quick scoping review to explore the literature on the need for a booster COVID-19 vaccination from January 1, 2021, to April 30, 2022. RESULTS: Sixty-one relevant publications were identified, of which 17 were related to waning immunity after 2 doses of the vaccine among the general population or healthcare workers, 19 were related to the third or booster dose of vaccination after the second dose among the general population or healthcare workers, and 25 were related to booster dose among immunocompromised patient. CONCLUSIONS: Initially, the need for a booster dose was equivocal; however, several studies demonstrated the benefit of the booster dose over time. Adequate scientific information is required regarding the administration of booster doses to the general population as well as the high-risk individuals.

Recommencement of football competition with spectators during the active phase of the COVID-19 pandemic in a Middle Eastern country.

BACKGROUND: With the global spread of COVID-19 infection caused by the severe acute respiratory syndrome coronavirus-2 virus (SARS-CoV-2), all the national and international sports events were ceased early in 2020. The sport activities have been reinstated since then, albeit without spectators. However, several governments have established a variety of risk-mitigation measures to gradually reintroduce the spectators to stadiums. OBJECTIVES: We aimed to evaluate the implementation of a strict health protocol to ensure the resumption of professional football with spectators and to access its effectiveness in limiting the spread of COVID-19 infections within the community. METHODS: This was a retrospective, observational study involving football players, match officials, local organizing committee members, working in close coordination, and over 16,000 spectators in the state of Qatar. We examined data from the Amir Cup final (December 18th, 2020), which was played under a strict protocol that included extensive reverse transcription-Polymerase chain reaction (RT-PCR) testing for players and match officials, as well as the utility of COVID-19 rapid antigen and antibody testings as screening tools for spectators to ensure their safe return to the stadiums. In addition, we reviewed the guidelines and protocols that were put in place to organize Qatar's Amir Cup Football Final, which drew over 16,000 spectators in the stadium. RESULTS: A total of 16,171 spectators undertook rapid antigen and antibody tests for the Amir cup final (from December16-December18, 2020). Fifteen Spectators (n = 15) returned with a positive result for COVID-19 infection during the final event (positivity rate = 0.12%). All players underwent RT-PCR testing 48 h before the match. None of the players tested positive for COVID-19 infections. 1311 individuals reported having symptoms related to COVID-19 post final of Amir Cup. These spectators were tested for COVID-19 RT-PCR with an overall positivity rate (positive/reactive) to be 0.42% (69/16171). CONCLUSION: This report shows a meagre incidence rate of COVID-19 infections during and post-Amir Cup football final. Based on the low infectivity rate reported during and post the Amir Cup, we propose that supervised and controlled resumption of football matches with spectators can be carried out safely following a strict testing and tracing protocol. Similar infection control policies can be replicated with a higher number of spectators.

All-terrain vehicle (ATV)-related injuries among different age groups: insights from a 9-year observational study.

PURPOSE: To describe the epidemiology, patterns, seasonality and outcome of all-terrain vehicle-related injuries (ATVRIs) among different age groups in Qatar. METHODS: A retrospective analysis of all patients hospitalized with ATVRI from 2010 to 2018 was conducted. Data were analyzed by age, gender, seasonality, and Injury severity Score  (ISS). Chi-square, Student t and ANOVA tests were used for analysis. Multivariate regression analysis was performed to find out predictors of head injury and severe injury among ATV users. RESULTS: Out of 15,000 trauma admissions, 521 had ATVRI (4%) with a mean age of 23.3 ± 12.3. The male-to-female ratio was 4:1 and the pediatric population represented 40%. The compliance with helmet use was 3.6%. The most injured regions were chest (29.8%), upper extremities (28.8%) and the head (25.9%). The mean ISS was 10.6 ± 7.7. Fracture fixation was the most operative intervention. Among hospitalized patients, 7.7% were transferred to rehabilitation . ATVRIs occurred more frequently between October and April and a large proportion (57.8%) occurred during weekends. The overall ATV-related hospital mortality rate was 2.1%. Young and older ATV users were more likely to suffer spine injuries than the pediatric population (p = 0.001). The mean ISS was greater in the older groups (p = 0.03). There were no statistically significant differences regarding the use of protective devices, mortality, or length of hospital stay between the different age groups. On multivariate analysis, young age and ISS were predictors of head injury among ATV users after adjusting for gender and helmet use. CONCLUSION: This is a nationwide study looking at all age groups who sustained ATVRI in Qatar. ATVRIs were observed in all age groups following leisure and recreational use. It follows a seasonal pattern with poor protective measures compliance. There is a need to reinforce helmet use and raise public awareness.

The nature and consequences of camel-related injuries: A scoping review with special reference to Arab Middle Eastern countries.

Animal-related injuries are a substantial but under-reported, emerging public health problem contributing considerably to worldwide morbidity and death. Understanding the behavior of big animals may help in injury prevention. Camels are large long-neck ungulates of the genus Camelus that have been domesticated for millennia as a mode of transportation, race, and food source. Camel-related injuries are not well studied when compared with other animals' injuries. Camels can occasionally be very hostile to humans, inflicting serious injuries. These injuries can be caused by camel bites, falls from their backs, kicks, or collisions with motor vehicles. The relative magnitude of each mechanism has never been extensively studied in the literature. Furthermore, the incidence of camel-related injuries is not well reported worldwide. Camels remain a potential cause of serious injuries and a public health problem for some countries in the Middle East. There are gaps in the incidence, risk factors and mechanism, distribution of camel-related injuries. We aimed to summarize the data and draw conclusions pertaining not just to the most common mechanism of injury but to demographics, incidence, severity, and appropriate methods of prevention of camel-related injuries. This scoping review findings will help for better understanding of the nature and consequences of camel-related injuries, and to improve the existing preventive and management strategies.

Role of Cytokines and Chemokines in NSCLC Immune Navigation and Proliferation.

With over a million deaths every year around the world, lung cancer is found to be the most recurrent cancer among all types. Nonsmall cell lung carcinoma (NSCLC) amounts to about 85% of the entire cases. The other 15% owes it to small cell lung carcinoma (SCLC). Despite decades of research, the prognosis for NSCLC patients is poorly understood with treatment options limited. First, this article emphasises on the part that tumour microenvironment (TME) and its constituents play in lung cancer progression. This review also highlights the inflammatory (pro- or anti-) roles of different cytokines (ILs, TGF-ß, and TNF-α) and chemokine (CC, CXC, C, and CX3C) families in the lung TME, provoking tumour growth and subsequent metastasis. The write-up also pinpoints recent developments in the field of chemokine biology. Additionally, it covers the role of extracellular vesicles (EVs), as alternate carriers of cytokines and chemokines. This allows the cytokines/chemokines to modulate the EVs for their secretion, trafficking, and aid in cancer proliferation. In the end, this review also stresses on the role of these factors as prognostic biomarkers for lung immunotherapy, apart from focusing on inflammatory actions of these chemoattractants.

The Patterns and Impact of Off-Working Hours, Weekends and Seasonal Admissions of Patients with Major Trauma in a Level 1 Trauma Center.

BACKGROUND: The trauma incidence follows specific patterns in different societies and is expected to increase over the weekend and nighttime. We aimed to explore and analyze the incidence, pattern, and severity of trauma at different times (working hours vs. out off-working hours, weekdays vs. weekends and season). METHODS: A retrospective analysis was conducted at a level 1 trauma facility in Qatar. All injured patients admitted between June 2017 and May 2018 were included. The data were analyzed to determine whether outcomes and care parameters of these patients differed between regular working hours and off-working hours, weekdays vs. weekends, and between season intervals. RESULTS: During the study period, 2477 patients were admitted. A total of 816 (32.9%) patients presented during working hours and 1500 (60.6%) during off-working hours. Off-working hours presentations differed significantly with the injury severity score (ISS) (p < 0.001), ICU length of stay (p = 0.001), blood transfusions (p = 0.001), intubations (p = 0.001), mortality rate (9.7% vs. 0.7%; p < 0.001), and disposition to rehabilitation centers. Weekend presentations were significantly associated with a higher ISS (p = 0.01), Priority 1 trauma activation (19.1% vs. 14.7%; p = 0005), and need for intubation (21% vs. 16%; p = 0.002). The length of stay (ICU and hospital), mortality, and disposition to rehabilitation centers and other clinical parameters did not show any significant differences. No significant seasonal variation was observed in terms of admissions at the trauma center. CONCLUSIONS: The off-working hours admission showed an apparent demographic effect in involved mechanisms, injury severity, and trauma activations, while outcomes, especially the mortality rate, were significantly different during nights but not during the weekends. The only observed seasonal effect was a decrease in the number of admissions during the summer break.

Systemic biomarkers of inflammation, oxidative stress and tissue injury and repair among waterpipe, cigarette and dual tobacco smokers.

BACKGROUND: Waterpipe tobacco (WPT) smoking is associated with deleterious effects on cardio-pulmonary systems which may have adverse repercussions in pathophysiology and progression of chronic lung and cardiovascular diseases. We compared the biomarkers of systemic inflammation, lipid mediators, injury/repair and oxidative stress between groups of non-smokers (NS), exclusive WPT smokers (WPS), exclusive cigarette smokers (CS) and dual WPS and CS (DS). METHODS: Two cohorts were recruited. Cohort I consisted of WPS (n=12), CS (n=26), DS (n=10) and NS (n=25). Cohort II consisted of WPS (n=33) and NS (n=24). Plasma and urine samples were collected and analysed for various systemic biomarkers. RESULTS: Compared with NS, plasma levels of inflammatory mediators (interleukin (IL)-6, IL-8, IL1ß and tumor necrosis factor-α) were significantly higher in WPS and CS, and were further augmented in DS. Endothelial biomarkers (intracellular adhesion molecule-1, prostaglandin E-2 and metalloproteinase-9) were significantly higher in CS. Most notably, pro-resolving lipid mediator (resolvin E1) and biomarkers of immunity, tissue injury, and repair were significantly lower in WPS and CS. Urinary levels of 8-isoprostane were significantly higher in all smoking groups in cohort I, while 8-isoprostane, myeloperoxidase, receptor for advanced glycation end products (RAGE), En-RAGE and matrix metalloproteinase-9 were significantly higher in all smoking groups in cohort II. CONCLUSIONS: Biomarkers of inflammation, oxidative stress, immunity, tissue injury and repair were elevated in WPS and CS groups. Furthermore, concurrent use of WPT and cigarettes is more harmful than cigarette or WPT smoking alone. These data may help inform the public and policy-makers about the dangers of WPT smoking and dual use of tobacco products.

Dysregulated repair and inflammatory responses by e-cigarette-derived inhaled nicotine and humectant propylene glycol in a sex-dependent manner in mouse lung.

Nicotine inhalation via electronic cigarettes (e-cigs) is an emerging concern. However, little is known about the acute toxicity in the lungs following inhalation of nicotine-containing e-cig aerosols. We hypothesized that acute exposure to aerosolized nicotine causes lung toxicity by eliciting inflammatory and dysregulated repair responses. Adult C57BL/6J mice were exposed 2 h daily for 3 days to e-cig aerosols containing propylene glycol (PG) with or without nicotine. Acute exposure to nicotine-containing e-cig aerosols induced inflammatory cell influx (neutrophils and CD8a+ T-lymphocytes), and release of pro-inflammatory cytokines in bronchoalveolar lavage fluid in a sex-dependent manner. Inhalation of e-cig aerosol containing PG alone significantly augmented the lung levels of various homeostasis/repair mediators (PPARγ, ADRP, ACTA2, CTNNB1, LEF1, ß-catenin, E-cadherin, and MMP2) in a sex-dependent manner when compared to air controls. These findings were accompanied by an increase in protein abundance and altered gene expression of lipogenic markers (PPARγ, ADRP) and myogenic markers (fibronectin, α-smooth muscle actin and ß-catenin), suggesting a dysregulated repair response in mouse lungs. Furthermore, exposure to nicotine containing e-cig aerosols or PG alone differentially affected the release of pro-inflammatory cytokines in healthy and COPD human 3D EpiAirway tissues. Overall, acute exposure to nicotine containing e-cig aerosols was sufficient to elicit a pro-inflammatory response and altered mRNA and protein levels of myogenic, lipogenic, and extracellular matrix markers in mouse lung in a sex-dependent manner. Thus, acute exposure to inhaled nicotine via e-cig leads to dysregulated repair and inflammatory responses, which may lead to airway remodeling in the lungs.