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Dentistry Journal
  • Editor’s Choice
  • Systematic Review
  • Open Access

8 June 2022

Periodontal and Peri-Implant Health Status in Traditional vs. Heat-Not-Burn Tobacco and Electronic Cigarettes Smokers: A Systematic Review

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Department of Medicine, Surgery and Dentistry “Schola Medica Salernitana”, University of Salerno, Via S. Allende, 84081 Baronissi, Italy
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Author to whom correspondence should be addressed.
This article belongs to the Section Oral Hygiene, Periodontology and Peri-implant Diseases

Abstract

The aim of the present systematic review was to evaluate and possibly differentiate the effects of traditional cigarettes, heat-not-burn tobacco, and electronic cigarettes on periodontal and peri-implant health status. Electronic cigarettes and heat-not-burn tobacco have become very popular in recent years and have been proposed to consumers as a safer alternative to conventional tobacco smoke, although their effect on periodontal and peri-implant health remains unclear. The study protocol was developed according to PRISMA guidelines, and the focus question was formulated according to the PICO strategy. A literature search was conducted across PubMed/MEDLINE and the COCHRANE library from 2003 to April 2022. From the 1935 titles initially identified, 18 articles were finally included in the study and extracted data were qualitatively synthesized. It may be carefully concluded that e-cigarettes may cause attenuated clinical inflammatory signs of periodontitis and, hypothetically, of peri-implantitis when compared to conventional tobacco smoke. Both alternative smoking products, containing nicotine, may likewise exert negative effects on periodontal and peri-implant health, as demonstrated by in vitro studies. Further investigations are needed to assess the impact of electronic cigarettes and heat-not-burn tobacco products on periodontal and peri-implant health status.

1. Introduction

Periodontitis is a chronic inflammatory disease of bacterial etiology, affecting and progressively destroying the tissues supporting the teeth and eventually leading to bone and tooth loss [1,2,3,4,5]. Analogously, peri-implantitis is an inflammatory lesion of the soft tissues surrounding an endosseous implant, leading to progressive peri-implant bone loss until implant failure [1,2,3,4,5]. Both periodontal and peri-implant diseases most frequently occur in adulthood and have been found or proposed to be associated, mainly through systemic inflammation, to a variety of systemic inflammatory disorders, including cardiovascular and pulmonary ones, diabetes, obesity, preterm birth, Alzheimer disease, and benign and solid malignant tumors [6,7,8,9,10,11].
Although periodontitis and peri-implantitis are both bacterial infections involving dental biofilm, suspected periodontal pathogens, individual age at disease onset, periodontitis severity, and rate of progression are all crucially influenced by well-known systemic factors, including inflammatory disorders—most importantly diabetes [6,7,8,9,10]—and neoplasms [11], as well as unhealthy habits [12], especially smoking [13,14].
Electronic cigarettes (E-Cigs) were introduced in the United States of America in 2006 and, since 2014, have become the most widespread tobacco product among young people between 18 and 25 years of age as a pastime [15], as well as among adults as an alternative to regular tobacco cigarettes and to quit smoking [16], similarly to the heat-not-burn (HNB) tobacco products that are becoming a new global trend [17].
E-cigarettes are small handheld devices containing a battery heating a solution and producing an aerosol. Usually, the liquid contains a mixture of substances such as nicotine, humectants, and flavoring chemical agents [18,19]. However, traces of heavy metals, such as aluminum, arsenic, nickel, and other contaminants very dangerous for human health have been found [20].Accordingly, Gaur and Agnihotri demonstrated that E-Cig use, also referred to as “vaping”, is not a safe alternative to normal tobacco cigarettes because the vaping liquid itself contains elements and toxic heavy metals predisposing the user to chronic pathological conditions [21].
Moreover, Moreover, Rahlo et al. and Yang et al. concluded that although electronic cigarette users may somehow be considered healthier than conventional cigarette smokers, they are still predisposed to the development of oral mucosal lesions and to dental and periodontal damage compared to non-smokers [22]. Figueredo et al., based on limited data available, reported that e-cigarettes have an unhealthy effect on periodontal health [23]. Similarly, Jeong et al., evaluating periodontal health status in 13,551 conventional and E-Cig smokers, concluded that electronic cigarette vaping and conventional cigarette smoking were both risk factors for periodontal diseases [24].
Furthermore, results from in vitro studies showed that E-Cig use is capable of altering myofibroblasts differentiation, causing DNA damage, inducing oxidative stress, and increasing inflammatory cytokines in human gingiva and periodontal ligament fibroblasts [25]. A recent study has also shown that the concentrations of both albumin and uric acid detectable in the whole saliva differ between smokers and non-smokers, being reduced in non-smokers [26].
Tobacco heating systems instead employ a particular heating method, reaching lower temperatures (240–350 °C) compared to traditional tobacco (>600 °C) [26], thus avoiding combustion. To our knowledge, only one study, not considering self-reported periodontitis, has presented provisional results describing more favorable periodontal treatment outcomes in HNB compared to conventional tobacco smokers [27]; however, it has been reported that HNB tobacco may potentially enhance oral epithelial cell proliferation [28].
Considering that both E-Cigs and HNB tobacco are proposed to consumers as less harmful compared to traditional cigarettes and as a safer alternative to conventional tobacco [26], a comparison of their effect on periodontal and peri-implant health status, while also evaluating former or current traditional tobacco smokers, may be especially relevant, both in the prevention and treatment planning of periodontal and peri-implant diseases. Therefore, the aim of the present systematic review was to evaluate and possibly differentiate the effects of conventional cigarettes, electronic cigarettes, and heat-not-burn tobacco products on periodontal and peri-implant status.

2. Materials and Methods

2.1. Protocol Development

The study protocol was developed according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines [29,30]. The research question was formulated according to the PICO (Population, Intervention, control or Comparison, Outcome) strategy [31]:
P (Population): Smokers;
I (Intervention): Electronic cigarettes and heat-not-burn tobacco systems;
C (Comparison): Non-smokers, ex-smokers, and tobacco cigarette smokers;
O (Outcome): Clinical, radiographic, and inflammatory periodontal and peri-implant tissue parameters.
The clinical question in “PICO” format was: Is there a significant difference in clinical, radiographic and inflammatory parameters of periodontal and peri-implant tissues from e-cigarette users and Heat-Not-Burn tobacco when compared to tobacco users and non-smoking subjects?

2.2. Search Strategy and Study Selection

A literature search was independently conducted by two reviewers (F.D.A., S.M.) through PubMed/MEDLINE and the COCHRANE library. Only articles published after 1st January 2003 (when the electronic cigarette was introduced) till 24th April 2022, in the English language, were included.
A combination of the following keywords was employed for the electronic search:
Periodontal disease OR periodontitis OR peri-implant disease OR peri-implantitis OR dental implant OR implant loss OR plaque index OR gingival index OR bleeding on probing OR probing depth OR tooth loss OR missing teeth OR marginal bone level OR IL-1b OR IL-8 OR IL-6 OR TNF-a OR MMP-1 OR MMP-8 OR IFN-y OR IL-4 OR IL-9 OR IL-10 OR IL-13 OR OPG OR RANK-LAND OR e-cigarette OR vaping cigarette OR electronic cigarette OR electronic nicotine delivery system OR Heat-Not-Burn Tobacco OR vape OR vaping.
Articles were included if they were published in the English language, after 1st January 2003, and described clinical trials and/or observational studies assessing clinical and/or radiographic periodontal and/or peri-implant parameters. Records were excluded if study participants were <18 years old and in case of missing data concerning clinical and/or radiographic periodontal and/or peri-implant parameters; systemic and narrative reviews and preclinical studies were also not considered in the current study.

2.3. Data Extraction and Synthesis

Extracted data concerned: author(s) and year of publication; study design; total number, mean age, gender ratio and smoking habits of participants; periodontal status, number of implants, and periodontal and peri-implant clinical, radiographic and crevicular parameters, including clinical attachment loss (CAL) probing depth (PD), bleeding on probing (BOP), plaque index (PI), gingival index (GI), marginal bone levels (MBL), cytokines profile and periodontal treatment.

2.4. Risk of Bias Assessment

The risk of bias of the non-randomized clinical trials was evaluated through the ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions) tool, considering biases due to confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, selection of the reported result and biases in the measurement of outcomes and biases due to [32].
Risk assessment was conducted according to the following criteria [32]:
  • Low risk of bias: The study is judged to be at low risk of bias for all domains;
  • Moderate risk of bias: The study is judged to be at low or moderate risk of bias for all domains;
  • Serious risk of bias: The study is judged to be at serious risk of bias in at least one domain, but not at critical risk of bias in any domain;
  • Critical risk of bias: The study is judged to be at critical risk of bias in at least one domain.

3. Results

3.1. Search Strategy and Study Selection

Electronic search and study selection were independently conducted by two reviewers (F.D.A., S.M.) and disagreements were discussed and solved.
Titles obtained through the electronic search were screened to eliminate duplicates. Abstracts of the pertinent records were screened according to eligibility criteria and related full texts were examined. In total, 1935 records were retrieved from PubMed/MEDLINE (1793 articles) and the COCHRANE library (142 articles). A total of 98 titles were removed because duplicates and 1796 titles were excluded as they were not pertinent to the topic of the present review; therefore, 41 articles were considered eligible and full texts were obtained. After the full-text evaluation according to the selection criteria, 23 studies were excluded (Table 1), specifically because: 11 did not describe clinical/radiographic parameters nor cytokine profile (11); 2 exclusively investigated the relationship between e-cigarettes and oral microbiome and 1 between e-cigarettes and alcohol, respectively; 2 studies involved former tobacco smokers who started using E-Cigs; 1 study assessed the effect of antimicrobial photodynamic therapy (aPDT) in E-Cigs smokers; and 6 articles were systematic reviews of the literature.
Table 1. Excluded studies and reason for exclusion.
Finally, 18 articles were included in the present systematic review (Figure 1).
Figure 1. Study selection flowchart.

3.2. Study Characteristics

Table 2 illustrates the characteristics of the 18 included studies, concerning source, study design, aim(s), participants, periodontal and peri-implant parameters considered, main results and conclusions.
Table 2. Characteristics of the studies included in the present systematic review: author(s) and year of publication; study design; total number, mean age, gender ratio and smoking habits of participants; periodontal status, number of implants, and periodontal and peri-implant clinical, radiographic and crevicular parameters, including clinical attachment loss (CAL) probing depth (PD), bleeding on probing (BoP), plaque index (PI), gingival index (GI), marginal bone levels (MBL), cytokines profile and periodontal treatment. Electronic devices intended for “vaping” were heterogeneously defined by the authors of the included studies and are currently named as “electronic cigarettes”.
All included studies evaluated periodontal parameters and in 7 out of 18 peri-implants were also assessed. Extracted and analyzed periodontal and peri-implant parameters concerned traditional and electronic cigarettes smokers, whilst no study analyzed findings from HNB tobacco smokers; results from waterpipe smokers were also reported in the synthesis of the results and briefly discussed, although not relevant for the present study, since they could not be extrapolated from data comparison among study groups.
Due to the heterogeneity of the included studies and to the lack of randomized controlled trials, it was not possible to conduct a meta-analysis.

3.3. Data Extraction and Synthesis

Detailed findings related to periodontal clinical and radiographic, as well as inflammatory parameters, are synthesized in Table 3 and in Table 4, respectively; Table 5 describes peri-implant clinical and radiographic parameters Table 6 reports inflammatory ones.
Table 3. Reported results on clinical and radiographic periodontal and peri-implant parameters.
Table 4. Reported results on crevicular inflammatory periodontal parameters.
Table 5. Reported results on clinical and radiographic peri-implant parameters.
Table 6. Reported results on crevicular inflammatory peri-implant parameters.

3.4. Quality Assessment of the Included Studies

The risk of bias of the studies included in the present systematic review is detailed in Table 7.
Table 7. Risk of bias of the studies included in the systematic review. Response options were: Yes (Y), Probably yes (PY), Probably no (PN), No (N) and No information (NI); “Y” indicates low risk of bias, “PY” indicates a moderate risk of bias; “PN” indicates a serious risk, “N” indicates a critical risk of bias and “NI” indicates no information, as per the ROBINS-I tool.

4. Discussion

Electronic cigarettes and Heat-Not-Burn tobacco products are becoming very popular among the population, especially as many people think they are less harmful than conventional tobacco; therefore, the aim of the present systematic review was to evaluate the effects of electronic cigarettes and heat-not-burn tobacco products on periodontal and peri-implant status compared to traditional tobacco use. Unfortunately, data from clinical studies on Heat-Not-Burn tobacco systems were lacking and retrieved data on electronic cigarettes were heterogeneous, thus precluding the possibility of conducting a meta-analysis and, therefore, representing the main limitation of the study. Analyzed and qualitatively synthesized data are discussed below.

4.1. Clinical Periodontal and Peri-Implant Parameters in Traditional vs. HNB and E-Cigs Smokers

Jeong et al. suggested that vaping may not be a safe alternative to cigarette smoke; indeed, periodontitis was more prevalent in E-Cigs and CS than NS [26]; this finding may be considered especially relevant since this study, based on community periodontal status (CPI), included more participants (5715 males and 7836 females) than other studies included in this review [26].
A typical feature of periodontal disease associated with tobacco smoking is a greater destruction of the supporting tissues of the teeth with clinical attachment loss [67]. Many studies, reported in this review, agreed with this; in fact, Mokeem et al., BinShabaib et al., Ibraheem et al. and Fangxi Xu et al. described that CS had the worst CAL values compared to NS [50,54,58,65]. Aldakheel et al. also came to the same conclusion, reporting higher CAL values in CS, E-Cigs and NS with periodontitis compared to NS without periodontitis [57]. Nevertheless, Ibraheem et al. found similar CAL values between CS and E-Cigs [58]; consistently, Vohra et al. and Javed et al. found no difference in CAL values between CS, E-Cigs and NS [55,56]. Mokeem et al. and BinShabaib et al. found no statistically significant differences in CAL between NS and E-Cigs [50,54]. Similar results were also reported by Al-Hamoudi before and after SRP [61].
Regarding Bleeding on Probing, which is a clinical sign of periodontal and peri-implant tissues inflammation [1,2,8,9,10], several studies included in the present systematic review [50,53,54,56,59,60,62,64] showed an increased BoP in NS compared to CS and E-Cigs, with no differences, instead, between CS and E-Cigs [50,54]. These findings suggest that nicotine-containing e-cigarettes may cause vasoconstriction within both outer periodontal and peri-implant tissues, similarly to traditional tobacco products [68], although such an effect may not be as strong as that that related to tobacco products. Tatullo et al. found that BoP decreased over a 4-month period in e-cigarette smokers who were former smokers, even if they had been smoking for more than 10 years [47]; nonetheless, a few authors did not find statistically significantly differences between smokers and those who had never smoked [51,58,64].
Regarding plaque accumulation, many authors reported higher PI values in CS and E-Cigs compared to NS [53,58,59,64]. In more detail, Vohra et al. reported that CS had the worst PI values compared to E-Cigs and NS [55]; conversely, AlJasser et al. found that NS had worse plaque conditions than E-Cigs and CS [65]. Mokeem et al. also found higher, although not significantly different, PI values around natural teeth in CS than E-Cigs and in E-Cigs than in, otherwise ArRejaie et al. did not find any differences in PI around dental implants between CS and E-Cigs [50,60]. Aldakeel et al. instead found that CS, E-Cigs and NS with periodontitis had a statistically significantly higher PI compared to NS, CS and E-Cigs without periodontitis [57]. However, nicotine appears to induce proliferation of suspected periodontal pathogens, as A. actinomycetemcomitans and P. gingivalis, which were more frequently detected in CS and E-Cigs gingival biofilm compared to NS smokers with periodontitis plaque [57]. Al-Aali et al., Sinha et al., BinShabaib et al. and Karaaslan et al. found no statistically significant differences in PI values between E-Cigs and NS [51,52,54,64]. Al-Hamoudi et al. also found no differences among PI in E-Cigs and NS at baseline, but after a 3-month follow-up, significant reductions in PI in NS were described [61].
Regarding the Probing Depth, several authors described overall worse PD in Cs and E-Cigs compared to NS [51,53,54,55,56,58,60,62,63], despite the fact that E-Cigs showed less clinical signs related to periodontal and peri-implant inflammation and disruption to CS [55]. Al Qahtani et al. found significantly lower PD values in E-Cigs compared to CS and WS [53], supporting the hypothesis that cigarette smoke may be responsible for periodontal tissue destruction and cell death and may increase the production of matrix metalloproteinases involved in the inflammatory process [55]. Karaslaan et al. [52], as well as AlDakheel et al. [57], did not find significant differences in PD values among CS, E-Cigs and NS with and without periodontitis [57]. Although many authors found no differences in PD values among NS and E-Cigs [50,54,59], Alhamoudi et al. [61], who similarly reported similar findings at baseline between NS and E-Cigs, described, following mechanical periodontal treatment, a significant PD reduction in NS but not in E-Cigs.
As for GI, it was found to be significantly higher in E-Cigs compared to CS [52] and in CS, E-Cigs, and NS with periodontitis compared to NS without periodontitis (p < 0.001); no statistically significant difference among CS, E-Cigs, and NS with periodontitis was observed, but instead for GI [57]. Noteworthy, GI was reported to be significantly higher in NS than E-Cigs at baseline, but at the 3-month follow-up, a statistically significant improvement was observed in NS [61] but not in E-Cigs.
Many authors did not find statistically significant differences for MT among CS, E-Cigs and NS, probably because the follow–up period considered in the studies was too short [54,55,56,59,60].

4.2. Radiographic Periodontal and Peri-Implant Parameters in Traditional vs. HNB and E-Cigs Smokers

Marginal bone loss was generally higher in CS compared to NS [50,53,54,58,60].
Conversely, Vohra et al. and Javed et al. found no differences in MBL among NS, E-Cigs and CS, although Javed et al. found significantly higher MBL in older (>65 years) smokers and nonsmokers compared to younger (<45 years) ones [55,56]. No statistically significant difference in MBL among CS, E-Cigs and NS with periodontitis was found by Aldakeel et al., revealing, however, a greater MBL in periodontal smokers (CS and E-Cigs) and nonsmokers compared to NS without periodontitis, as expected [57]. No differences in MBL were found by Binshabib et al. and Mokeem et al. between NS and E-Cigs and by Al Hamoudi et al., both at baseline and after periodontal treatment [50], although opposite results were reported instead by other authors [51,58,63].

4.3. Crevicular Inflammatory Periodontal and Peri-Implant Parameters in Traditional vs. HNB and E-Cigs Smokers

Pro-inflammatory biomarkers have also been analyzed by many authors. In particular, Interleukin IL-1 β and Tumor Necrosis Factor-alpha (TNF-α), detectable in PISF (peri-implant sulcular fluid), may be considered as biomarkers for both periodontal and peri-implant diseases diagnosis and prognosis [51,62]. PISF levels were generally higher in smokers compared to nonsmokers [53,60,62,64] and in E-Cigs compared to NS [51,63]. Pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, secreted by activated macrophages in response to bacterial lipopolysaccharide [69,70], may potentially play a crucial role in periodontal and peri-implant tissue inflammation and destruction [53,60,62], stimulating osteoclastogenesis, osteoclasts activation with subsequent bone resorption, and inducing fibroblasts apoptosis [71,72], and have been found increased in saliva and in GCF of CS and WS and E-Cigs compared to NS [50,51,55,56,73]. Al-Hamoudi et al. found, after mechanical periodontal treatment, higher crevicular IL-4, IL-10, IL-11 and IL-13 levels in E-Cigs with moderate chronic periodontitis compared to NS with moderate chronic periodontitis, assuming that nicotine may compromise periodontal healing [61]. Bin Shabaib et al. and Mokeem et al. reported significantly higher IL-1β, IL-6 and TNF-a levels in CS compared to E-Cigs and NS, while no differences were found among E-Cigs and NS, probably because, in this study, E-Cigs participants were vaping for a relatively short duration [50,54]. Additionally, ArRejaie et al. obtained similar results comparing CS, E-Cigs and NS, but he also found statistically significant differences between E-Cigs and NS for IL-1b, where IL-b levels were higher in E-Cigs than NS [60]; accordingly, Al–Ali et al. and Sinha et al. obtained the same results between E-Cigs and NS [51,63]. Al Quatani et al. found similar IL-1b, IL-6 and TNF-a levels among CS, WS and E-Cigs, all significantly higher than those from NS [53]. Similar findings were also reported for crevicular TNF-a values by other authors with a general reduction after periodontal treatment [64].
RANKL (receptor activator of nuclear factor-kappaB ligand), RANK (receptor activator for nuclear factor-kappaB) and OPG (osteoprotegerin) mainly regulate osteoclast activity [72,74]. Coherently, Bostanci et al. described periodontal subjects who showed a significantly higher RANKL/OPG ratio compared to periodontally healthy ones [6,71,72,75,76]. Ibraham et al. demonstrated that crevicular RANKL and OPG levels were higher in CS and E-Cigs compared to NS [58].
CS and E-Cigs had the same adverse effects on oxidative stress markers and inflammatory cytokines, as demonstrated by significantly higher Glutathione peroxidase (GSH-Px) levels detected in NS was compared to CS and E-Cigs; however, no significant difference between CS and E-Cigs was found [52,77]. Higher levels of GSH-Px, protecting tissues from oxidative stress, has also been found in subjects with periodontitis [52].
Moreover, nicotine increases the accumulation in periodontal and peri-implant tissues of Advanced Glycation and Products (AGEs), along with their receptors (RAGEs), which have been associated with the formation of ROS (reactive oxygen species), inducing, in turn, oxidative stress and metabolic changes [27,28] within tissues. Currently analyzed data on MMP-8 and MMP-9, specifically activated by ROS [78], revealed significantly higher levels in CS and E-Cigs compared to NS, once more supporting the contributing role of nicotine to periodontal and peri-implant tissues destruction [54,60,64].
Furthermore, cotinine, which is a nicotinic metabolite that remains in saliva and crevicular fluid for up to 1 week after using nicotine-containing products, has been found in higher concentrations in CS, WS and E-Cigs PISF compared to NS [62], as expected, although no significant differences were found by Alquantani et al. and Mookem et al. among individuals using nicotinic products [50,62]. Conversely, Fangxi Xu et al. described higher crevicular cotinine levels in CS compared to E-Cigs.
Further studies are needed to highlight the impact of electronic cigarettes and Heat-Not-Burn tobacco products on periodontal and peri-implant health status. Indeed, a better comprehension of the role of these alternative smoking habits, which may affect periodontitis and peri-implantitis onset differently from traditional tobacco use, may pave the way for multi-disciplinary personalized prevention strategies, especially in subjects considered at higher risk, such as those who are diabetic [79,80,81,82]. Moreover, the indirect effect of both E-Cigs and HNB tobacco products on periodontitis and peri-implant treatment outcomes may encourage the use of adjunctive therapies, also comprising antibiotics and oral antiseptics administration in non-conventional smokers [80,83,84,85,86].

5. Conclusions

The presented results carefully support the hypothesis that e-cigarettes may cause attenuated clinical inflammatory signs of periodontitis, and, hypothetically, of peri-implantitis, when compared to conventional tobacco smoke. However, both electronic cigarettes and Heat-Not-Burn tobacco, considered as alternative smoking products, containing nicotine, may have negative effects on periodontal and peri-implant health, as demonstrated in vitro by the toxic effects at the cellular level detected.
Furthermore, a deeper insight into the existence and extent of the effect putatively exerted by E-Cigs and HNB tobacco products on periodontitis progression rate, as already estimated for traditional tobacco use, may guide in the optimal planning of active periodontal treatment sessions and, above all, of maintenance phase recall intervals.

Author Contributions

Conceptualization, F.D. and A.I.; methodology, S.M. and A.A.; validation, A.I. and M.P.; investigation, F.D. and M.C.; data curation, S.M. and A.I.; writing—original draft preparation, F.D. and M.C.; writing—review and editing, M.P., A.I., A.A. and S.M.; supervision, S.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Medline/PubMed and Cochrane databases.

Conflicts of Interest

The authors declare no conflict of interest.

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