Different Influence Pattern of Conventional and Alternative Sources of Smoking on Adhesion Molecules and Cytokine Secretion in THP-1 Monocytes.

BACKGROUND/AIM: Tobacco is a carcinogen that is closely associated with the occurrence of lung cancer and head and neck squamous cell carcinoma (HNSCC). The consumption of tobacco is also leading to alterations in different immune cell subtypes. However, the impact of different conventional and alternative smoking sources on human monocytes remains elusive. MATERIALS AND METHODS: In this study, we investigated the influence of aqueous extracts of different sources of smoking (cigarettes; heated tobacco product IQOS; e-cigarettes with and without nicotine; nicotine pouches) on different monocytic adhesion molecules, chemokine receptors and checkpoint molecule PD-L1 by flow cytometry. Cytokine expression patterns were evaluated using human cytokine arrays and the human monocyte leukemia cell line THP-1 as a model. RESULTS: Data revealed differential effects of the analyzed conventional and alternative smoking devices on monocyte adhesion molecules and cytokine secretion. The examined smoking devices can be assigned to two differential monocyte activation patterns. Monocytes stimulated with aqueous extracts of cigarettes, e-cigarette without nicotine, and heat not burn product IQOS revealed distinct alterations of surface markers and cytokines compared to the monocyte activation pattern in response to aqueous extracts of nicotine, nicotine pouches, and e-cigarette with nicotine. CONCLUSION: Our data indicate differential immunological consequences of different conventional and alternative smoking sources with and without nicotine. Further comprehensive analysis as well as in vivo investigations on peripheral blood monocyte subsets from smoking individuals using different smoking sources are required to better understand the impact on monocyte characteristics, especially with regard to the development of cancer.

Impact of Heated Tobacco Products, E-Cigarettes, and Combustible Cigarettes on Small Airways and Arterial Stiffness.

Smoking cessation is difficult but maintaining smoke-free without nicotine replacement therapy is even harder. During the last few years, several different alternative products, including heated tobacco products (HTP), have been introduced to the market. In this study, we investigated the acute effects of IQOSTM and gloTM (two HTP) consumption on small airway function and arterial stiffness in a head-to-head design, comparing them to combustible cigarettes, nicotine-free e-cigarettes and a sham smoking group. Seventeen healthy occasional smokers were included in a single-center, five-arm, crossover study. The parameters of small airway function and hemodynamics were collected at several time points before and after consumption using Mobil-O-Graph™ (I.E.M., Stolberg, Germany) and TremoFlo® c-100 (THORASYS Thoracic Medical Systems Inc., Montreal, QC, Canada). Small airway obstruction and resistance were both significantly increased after the consumption of cigarettes and substitute products. All products containing nicotine led to similar significant increases in blood pressure and arterial stiffness. Hemodynamic parameters were also increased after the consumption of e-cigarettes without nicotine, but compared to nicotine-containing products, the increase was shorter and weaker. We conclude that, although it has yet to be determined why, HTP have acute harmful effects on small airway function, possibly even exceeding the effects of combustible cigarettes. Like other nicotine-containing products, HTP leads to a nicotine-related acute increase in arterial stiffness and cardiovascular stress, similar to combustible cigarettes, which associates these products with an increased cardiovascular risk.

Effects of Physical Activity in the High School Curriculum on Cardiovascular Health, Cognitive and Physical Performance.

Cardiovascular health at a young age has implications for preventing cardiovascular disease, and it is associated with improved physical and cognitive performance during the aging process. Sports are well known to prevent cardiovascular disease; however, school-based interventions have mostly been neglected. This cross-sectional study aimed to compare groups of high school students, stratified by the amount of physical activity in their high school curriculum and downtime. Comparisons concerning physical and cognitive performance and arterial stiffness were made. A total of 63 senior-year students were investigated. Arterial stiffness was assessed using the oscillometric technique with ArteriographTM detection. Three-kilometer and pendulum runs were conducted as typical training loads. Cognitive performance was evaluated via the visual and verbal memory and number connection tests. Regarding cognitive skills, extracurricular physical activity improved the number connection test in male participants (p = 0.004). For physical performance, female students with a sports-focused curriculum were faster in the 3 km run (p < 0.001). Concerning arterial stiffness, the measurements yielded a lower mean arterial pressure (p = 0.015) and aortic pulse wave velocity (p = 0.04) in male students with a sports-focused curriculum. In summary, extracurricular physical activity and enrollment in a sports-focused curriculum may be associated with lower cardiovascular risk due to lower arterial stiffness and better physical and cognitive abilities.

Differential Effects of Anti-PD-1/PD-L1 Checkpoint Inhibitors on Adhesion Molecules and Cytokine Secretion by THP-1 Monocytes.

BACKGROUND/AIM: Immune checkpoint inhibitors have improved the treatment regimen for human cancers in recent years. Particularly, inhibitors of the checkpoint molecules PD-1/PD-L1 have emerged as promising therapeutic treatments by preventing T-cell anergy and exhaustion. However, the impact of different anti-PD-1/PD-L1 checkpoint inhibitors on human monocytes remains elusive. MATERIALS AND METHODS: In this study, using the human monocyte leukemia cell line THP-1 as a model, we investigated the influence of different therapeutic anti-PD-1/PD-L1 checkpoint inhibitors on monocytic adhesion molecule expression and cytokine secretion. THP-1 monocytes were treated with the anti-PD-1 checkpoint inhibitors Nivolumab and Pembrolizumab and anti-PD-L1 checkpoint inhibitors Atezolizumab and Durvalumab. Cytokine expression patterns were evaluated using cytokine arrays and enzyme-linked immunosorbent assays (ELISA) and analysis of adhesion molecules was addressed using flow cytometry. RESULTS: Our data show an overall moderate apoptosis induction upon checkpoint inhibitor treatment and significantly reduced expression levels of adhesion molecules CD29, CD49d, and CX3CR1 in response to anti-PD-1 treatment. Cytokine screening revealed overall decreased secretion levels of insulin-like growth factor binding protein 2 (IGFBP2), CD147 (basigin) and CD31 (PECAM-1) as well as elevated levels of interleukin 5 (IL-5) and interferon gamma (IFNγ) in response to checkpoint inhibitor treatment. CONCLUSION: Our data indicate differential effects of anti-PD-1/PD-L1 checkpoint inhibitors on THP-1 monocytes, both by specific anti-PD-1/PD-L1 binding and unspecific antibody IgG isotype recognition. Further investigations on peripheral blood monocyte subsets in terms of their expansion and function upon checkpoint inhibitor therapy are required to better understand the individual immunological balances in cancer patients in long-term observational studies.

Smoking Behavior and Smoking Cessation Because of and during the COVID-19 Pandemic: A Brief Online Survey 12 Months into the Pandemic and during the Second Wave in Europe.

Smoking is considered a major preventable cause of cardiovascular and lung diseases, as well as cancer. During the COVID-19 pandemic, there was extensive discussion about the influence of nicotine use; ultimately, smoking was considered a major risk factor for poor disease progression. Therefore, in April 2021, we conducted an anonymous cross-sectional online survey on smoking and vaping behavior, as well as smoking cessation, in four different countries in Europe (the United Kingdom, Germany, Spain, and Italy). A total of 3605 participants completed a questionnaire on their smoking and vaping behaviors and smoking cessation because of and during the COVID-19 pandemic. Fear of COVID-19 infection, a high percentage of quarantine stays (44.9% Italy and 52.1% Spain), and high infection (75.5% Italy and 52.4% Spain) and death (42% Italy) rates in respondents' personal circles were observed mostly in the surveyed populations of Italy and Spain. Smoking cessation attempts and success were mainly seen in the Italian population and were linked to psychological distress, while the same effects were shown for vaping in Spain. In summary, health anxiety was detected in all cohorts. Despite these findings, smoking as a risk factor for severe outcomes of COVID-19 infection did not lead to a higher rate of smoking cessation attempts.

Negative Impact of the UEFA European Soccer Championship on Central Hemodynamics and Arterial Stiffness: A Multicenter Study.

(1) Background: watching sporting events may trigger cardiovascular events by elevating emotional stress levels. The underlying reasons and specific populations at risk are not well defined. (2) Methods: we conducted a multicenter prospective trial at three German sites during the UEFA Soccer EC 2012 and 2021 comprising 52 healthy participants (noCVD) and 18 patients hospitalized with cardiovascular disease (CVD). Subjects were studied during matches of the German national team (GP) as well as corresponding matches without German participation (noGP). Peripheral and central blood pressure (BP) and parameters of arterial stiffness were measured (Mobil-O-Graph™, I.E.M., Stolberg, Germany) before, during, and after the matches. (3) Results: in terms of CVD, peripheral as well as central BP and heart rate increased significantly during GP as well as noGP matches and remained elevated beyond the end of the matches. Likewise, arterial stiffness parameters and vascular resistance were higher during the matches and remained elevated after the matches. No consistent significant differences were found between GP and noGP matches. (4) Conclusions: this is the first study on real-life changes in hemodynamics during sport-associated emotional stress, with comparison between noCVD and CVD. We found that alterations were profound in CVD and remained elevated even after the matches.

Cardiovascular functions and arterial stiffness after JUUL use.

INTRODUCTION: The rapid growth in the e-cigarette market after the launch of JUUL e-cigarettes led to much discussion on the potential benefits and risks of pods, JUUL devices, and conventional e-cigarettes compared with combustible cigarettes. Independent data are required to assess the effects of these products on cardiovascular surrogate parameters and cardiovascular risk. METHODS: We conducted a single-center three-arm study comparing combustible cigarettes with JUUL e-cigarettes with the old and new technology. We recruited 32 participants who were active smokers (n=15) or vapers (n=17) and performed a total of 39 measurements before and 5, 15, and 30 minutes, after participants smoked a combustible cigarette or vaped a JUUL e-cigarette with the new or old technology. Measurements included peripheral and central blood pressures and parameters of arterial stiffness, including pulse wave velocity and augmentation index. RESULTS: Peripheral systolic blood pressure, central blood pressure, and peripheral pulse rate increased significantly in all three groups (each p<0.05). Heart rate (HR) changes lasted significantly longer than blood pressure changes. The augmentation index and pulse wave velocity increased in all three groups, and a multivariate analysis of variance showed that the increases were independent of systolic blood pressure, sex, age, device, and HR. CONCLUSIONS: Changes in blood pressure and arterial stiffness are similar after cigarette smoking and JUUL use. These changes may be associated with an increased cardiovascular risk compared with no product use. However, a long-term follow-up evaluation of JUUL use and a head-to-head comparison with conventional e-cigarettes are still needed.

JUUL™ing and Heating Lead to a Worsening of Arterial Stiffness.

Background: The widespread use of the JUUL™ device ignited a discussion about the effects these products have on harm reduction. Therefore, we conducted a study directly comparing the JUUL™ device with a cigarette, a heated tobacco product, and a nicotine-free e-cigarette to examine the acute effects on arterial stiffness. Methods: This crossover-designed study examines 20 occasional smokers (age 25.2 ± 2.5 years). Study participants used each of the four smoking devices for a duration of 5 min following a protocol. Peripheral blood pressure and parameters of arterial stiffness and endothelial vasodilator function such as the reactive hyperemia index and the augmentation index were measured using the EndoPAT™2000 before and after. Results: In addition to significant peripheral hemodynamic changes after 5 and 10 min (p < 0.05), the reactive hyperemia index showed a significant decrease for all devices 15 min after consumption and remained significantly decreased after 60 min (p < 0.01). The augmentation index adjusted for a heart rate of 75 bpm increased significantly for all devices 15 and 60 min after consumption (p < 0.01). Conclusions: In conclusion, the increases in blood pressure and arterial stiffness are similar after smoking, JUUL™ing, heating, and vaping. These changes may be associated with an increase in cardiovascular risks; however, an evaluation of the long-term effects of JUUL™ing, vaping and heating is needed.

Differential Effects of Angiotensin-II Compared to Phenylephrine on Arterial Stiffness and Hemodynamics: A Placebo-Controlled Study in Healthy Humans.

The α1-adrenoceptor agonist phenylephrine (PE) and Angiotensin II (Ang II) are both potent vasoconstrictors at peripheral resistance arteries. PE has pure vasoconstrictive properties. Ang II, additionally, modulates central nervous blood pressure (BP) control via sympathetic baroreflex resetting. However, it is unknown whether Ang II vs. PE mediated vasoconstriction at equipressor dose uniformly or specifically modifies arterial stiffness. We conducted a three-arm randomized placebo-controlled cross-over trial in 30 healthy volunteers (15 female) investigating the effects of Ang II compared to PE at equal systolic pressor dose on pulse wave velocity (PWV), pulse wave reflection (augmentation index normalized to heart rate 75/min, AIx) and non-invasive hemodynamics by Mobil-O-Graph™ and circulating core markers of endothelial (dys-)function. PE but not Ang II-mediated hypertension induced a strong reflex-decrease in cardiac output. Increases in PWV, AIx, total peripheral resistance and pulse pressure, in contrast, were stronger during PE compared to Ang II at equal mean aortic BP. This was accompanied by minute changes in circulating markers of endothelial function. Moreover, we observed differential hemodynamic changes after stopping either vasoactive infusion. Ang II- and PE-mediated BP increase specifically modifies arterial stiffness and hemodynamics with aftereffects lasting beyond mere vasoconstriction. This appears attributable in part to different interactions with central nervous BP control including modified baroreflex function.

Synonyms and Symptoms of COVID-19 and Individual and Official Actions against the Disease-A Brief Online Survey 6 Months into the Pandemic and on the Threshold of the Second Wave in Germany.

To control the ongoing global pandemic due to SARS-CoV-2, we need to influence people's behavior. To do so, we require information on people's knowledge and perception of the disease and their opinions about the importance of containment measures. Therefore, in August 2020, we conducted an anonymous cross-sectional online survey on these topics in 913 participants in Germany. Participants completed a questionnaire on various synonyms and symptoms of corona virus and specified the importance they attributed to individual and regulatory measures. The virus was linked more closely with most synonyms and the discovery in China than with the places of the first larger European outbreaks. General (cold-like) symptoms, such as "cough" and "fever," were more widely known than COVID-19-specific ones, e.g., "loss of taste and smell." The widely promoted individual measures "distancing," "hygiene," and "(facial) mask wearing" were rated as highly important, as were the corresponding official measures, e.g., the "distancing rule" and "mask mandate." However, the "corona warning app" and a "vaccine mandate" were rated as less important. A subgroup analysis showed broad agreement between the subgroups on nearly all issues. In conclusion, the survey provided information about the German population's perception and knowledge of the coronavirus five months into the pandemic; however, participants were younger and more educated than a representative sample. To learn from the beginning and still ongoing pandemic and develop concepts for the future, we need more conclusive studies, especially on the acceptance of further specified lockdowns, the population's willingness to be vaccinated, and the influence of misinformation on public opinion.

GHRH-mediated GH release is associated with sympathoactivation and baroreflex resetting: a microneurographic study in healthy humans.

Previous research suggested substantial interactions of growth hormone (GH) and sympathetic nervous activity. This cross talk can be presumed both during physiological (e.g., slow-wave sleep) and pathological conditions of GH release. However, microneurographic studies of muscle sympathetic nerve activity (MSNA) and assessment of baroreflex function during acute GH-releasing hormone (GHRH)-mediated GH release were not conducted so far. In a balanced, double-blind crossover design, GHRH or placebo (normal saline) were intravenously administered to 11 healthy male volunteers. MSNA was assessed microneurographically and correlated with blood pressure (BP) and heart rate (HR) at rest before (pre-) and 30-45 (post-I) and 105-120 min (post-II) after respective injections. Additionally, baroreflex function was assessed via graded infusion of vasoactive drugs. GHRH increased GH serum levels as intended. Resting MSNA showed significant net increases of both burst rate and total activity from pre- to post-I and post-II following GHRH injections compared with placebo (ANOVA for treatment and time, burst rate: P = 0.028; total activity: P = 0.045), whereas BP and HR were not altered. ANCOVA revealed that the dependent variable MSNA was not affected by the independent variables mean arterial BP (MAP) or HR (MAP: P = 0.006; HR: P = 0.003). Baroreflex sensitivity at baroreflex challenge was not altered. GHRH-mediated GH release is associated with a significant sympathoactivation at central nervous sites superordinate to the simple baroreflex feedback loop because GH induced a baroreflex resetting without altering baroreflex sensitivity.

Renal denervation improves 24-hour central and peripheral blood pressures, arterial stiffness, and peripheral resistance.

Ambulatory blood pressure (BP) and central BP are better predictors for overall cardiovascular risk and mortality than brachial BP. Renal denervation (RDN) has been shown to reduce office brachial and central BP as well as brachial ambulatory BP, but data on central ambulatory BP are limited. Patients (N = 94) with treatment resistant hypertension (TRH) who underwent RDN were included. Ambulatory BP, including central pressures, hemodynamics, and arterial stiffness were measured at baseline and 3, 6, 12 months after RDN by an oscillometric device (MobiloGraph™ ). At 3, 6, and 12-month follow-ups, brachial ambulatory BP was reduced (P for all < .001). Consistently, central ambulatory BP was reduced (P for all < .001). Ambulatory assessed averaged daytime pulse wave velocity improved after RDN (P < .05). Total vascular resistance decreased (P for all < .01). In patients with TRH, RDN improves brachial and central ambulatory BP, arterial stiffness, and total vascular resistance, indicating an improvement of cardiovascular outcome.