Art-5-Gyorkos

ORAL MEDICINE                                                                                                                                             www.stomaeduj.com




THE ORAL EFFECTS OF E-CIGARETTES – A LITERATURE REVIEW




                                                                                                                                                        Review Articles
Áron Imre Györkös1a , Norbert Kulcsár2b , Péter Hermann2c , Barbara Kispélyi2d
¹Szép és Ép Fog Kft., Budapest, Hungary
²Department of Prosthodontics, Faculty of Dentistry, Semmelweis University, Szentkirályi utca 47, HU-1088 Budapest, Hungary
a
  Private Dentist; e-mail: aron.gyorkos@gmail.com; ORCiD ID: https://orcid.org/0000-0002-9657-6156
b
  Dental Student; e-mail:kulcsar.norbert@stud.semmelweis.hu; ORCiD ID: https://orcid.org/0000-0003-3070-970X
c
 DMD, MSc, PhD, Professor and Head; e-mail:hermann.peter@dent.semmelweis-univ.hu; ORCiD ID: https://orcid.org/0000-0002-9148-0139
d
  DMD, PhD, Associate Professor; e-mail:kispelyi.barbara@dent.semmelweis-univ.hu; ORCiD ID: https://orcid.org/0000-0002-0530-0905
                                                                                         https://doi.org/10.25241/stomaeduj.2022.9(3-4).art.5
ABSTRACT
Background Because of regulations made against smoking, and the rising popularity of a healthy lifestyle
there has been a visible change in the smoking habit of the population in the last 15 years. The negative
impact on the attitude toward smoking forced the industry to develop new ways to satisfy the consumer’s
nicotine need. That is how heated tobacco products and a variety of ENDS (Electronic Nicotine Delivery
System), such as electronic cigarettes) have been invented.
Objective This literature review aims to summarise the oral effects of consuming e-cigarettes which have
been proven and publicised.
Data Sources The main source of the study has been the publications found through PubMed and NBCI
(National Center for Biotechnology Information).
Study Selection Articles have been selected from the international literature if they had any information on
the oral effects of e-cigarettes.
Data Extraction The information from the articles has been categorised based on the tissue and the time
they last.
Data Synthesis Electronic cigarettes cause a change in saliva flow and its composition, a decrease in the
blood supply of soft tissues and an immunosuppressed state in the said area, therefore the incidence of
some diseases are higher among the users. Components of the e-liquid may cause damage to both soft and
hard tissues, such as cancerous lesions, inflammation, chronic periodontitis and neurodegeneration. Nicotine
may be absorbed by the surface of the teeth, causing patches, and some ingredients may be beneficial to the
bacterial flora of the oral cavity.
KEYWORDS
E-Cigarette; Electronic Nicotine Delivery Systems; Oral Health; Nicotine; Smoking
1. INTRODUCTION                                                                     smoking in the population; however, when it comes
Over the last few years, electronic cigarettes                                      to e-cigarettes, no similar action has been underway,
(e-cigarettes) have gained greater and greater                                      allowing their popularity to increase on and on. Over
popularity. According to a 2011 survey by the                                       the last years worldwide, countless research studies
WHO (World Health Organisation), 7 million people                                   have aimed to describe the health effects of electronic
used e-cigarettes regularly worldwide at the time,                                  cigarettes, which indicates that there are many
and this number increased to 41 million by 2018                                     questions without answers. For this reason, this article
[1]. Some forecasts indicate that the popularity of                                 aims to summarize present knowledge concerning
e-cigarettes will not change; furthermore, as of                                    the oral effects of using electronic cigarettes.
2021, there are an estimated 55 million daily users
[1]. Concerning the health effects of e-cigarettes,                                 2. CHANGES IN THE SALIVA FLOW AND ITS
they are thought to be a healthy alternative to                                     CONSEQUENCES
smoking, a notion rooted in the marketing strategy
and other factors of the tobacco industry. Another                                  Traditional cigarettes burn at almost 1000 degrees
problem is that these products are accessible to a                                  Celsius and produce quite toxic by-products at this
younger demographic: in 2020 alone in the USA,                                      high temperature, for instance, tar. In contrast, during
19.6% of surveyed secondary school students used                                    the use of electronic cigarettes, there is no burning;
e-cigarettes, and 22.5% used them as a daily routine                                instead, they vaporize liquid content at a much lower
[2]. The harmful effects of traditional cigarettes are                              temperature, so the exhaled vapour is assumed to
already established knowledge in people’s awareness,                                contain fewer toxic components [3]. The temperature
thanks to widespread effort to combat the habit of                                  of the vapour emitted by the e-cigarette depends on
              OPEN ACCESS This is an Open Access article under the CC BY-NC 4.0 license.
              Peer-Reviewed Article
    Citation: Györkös ÁI, Kulcsár N, Hermann P, Kispélyi B. The oral effects of e-cigarettes – a literature review. Stoma Edu J. 2022;9(3-4):109-114.
    Received: July 19, 2022; Revised: September 29, 2022; Accepted: October 21, 2022; Published: November 03, 2022.
    *Corresponding author: Norbert Kulcsar, Faculty of Dentistry, Semmelweis University, Szentkirályi utca 47, HU-1088 Budapest, Hungary
    Tel: +36 70633 3583; Fax: +36 1317 5270; e-mail: kulcsar.norbert@stud.semmelweis.hu
    Copyright: © 2022 the Editorial Council for the Stomatology Edu Journal.




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                    Györkös ÁI, et al.
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                    several factors such as battery voltage, resistance,          the extra quantity may be considered an indicator of
Review Articles                                                                   oral inflammation [10].
                    atomiser condition, mouthpiece size, and e-liquid
                    composition (mainly the level of propylene glycol (PG)
                    and glycerine content); furthermore, some devices             3. CHANGES CAUSED BY VACUUM
                    have adjustable voltage, so the temperature can
                    vary quite widely. Generally, it can be stated that the       During the use of an electronic cigarette, there is
                    average temperature of vaporizing is about 157 to 266         suction in the oral cavity, the size of which depends on
                    degrees Celsius [3]. The result of the extremely high-        the type of equipment, and its duration on the user’s
                    temperature vapour (mainly of PG-based liquids) may           habits. The suction power is produced by the mimic
                    be the formation of substances containing a carbonyl          muscles, and its consequence is a relative vacuum
                    group such as formaldehyde or acetaldehyde, which             in the oral cavity. In a University of California 2010
                    cause inflammation in the oral mucosa [4,5]. The most         study, the researchers ran tests on the most popular
                    common and important condition that the vapour-               e-cigarettes of that time, assessing the level of effort
                    induced temperature increase causes is xerostomia.            needed to use an e-cigarette and the health effects
                    The change in the saliva flow is assessed by measuring        of the arising vacuum. They measured the pressure
                    the resting and stimulated saliva flow. Symptoms of           by a manometer attached to a machine mimicking
                    xerostomia may be a sticky or burning sensation in            smoking and found that the user needed to generate
                    the oral cavity, increased thirst, difficulties in talking,   greater suction power with any type of e-cigarette
                    swallowing, and tasting, and halitosis. Furthermore,          than with traditional ones. In the first ten suction
                    the dried-out mucosa has a greater risk to develop            cycles, the density of the vapour did not change;
                    oral infections such as oral candidiasis, which can           after the tenth suction cycle, however, it started to
                    recur from time to time. Besides these, the user’s oral       decrease continuously. The longer the e-cigarette
                    hygiene deteriorates [6], and the saliva’s washing            had been used the greater effort was needed for the
                                                                                  same amount of vapour. The generated vacuum, the
                    effect is compromised, therefore the incidence of
                                                                                  density of the vapour and the required effort varied
                    caries rises [7]. Using an electronic cigarette changes
                                                                                  across device types [11]. There is no unified medical
                    not just the quantity of saliva but the quality as well.
                                                                                  position yet on the health effects caused by the
                    Oral pH is driven into the acidic range by nicotine;
                                                                                  vacuum; further studies are needed, but the presumed
                    however, nicotine-free liquids move oral pH into the
                                                                                  consequences are the overload of the tongue and
                    basic range and the saliva’s buffer capacity is not
                                                                                  mimic muscles. The result of the greater suction
                    affected [8]. Changes to the saliva’s composition are
                                                                                  power is that the vapour travels to the distal parts of
                    also notable: the amount of secretory IgA, lysozyme,
                                                                                  the lung, reaching deeper regions, with all associated
                    and lactoferrin is different from the physiologic level.
                                                                                  disadvantageous consequences [12].
                    Secretory IgA is a specialized antibody for the oral
                    cavity containing saliva. The lysozyme content of saliva      4. EFFECTS ON DIFFERENT ORAL TISSUES
                    is detrimental to the immune processes: because of
                    its proteolytic function, it breaks down antibodies.          4.1 Soft Tissues: Acute Changes
                    B-lymphocytes that have met antibodies migrate                As an effect of e-cigarette vapour, the blood supply of
                    to one of the salivary glands and transform into              the soft tissues decreases, which can be traced back
                    plasma cells. In addition to monomer IgA, these cells         to two reasons. On the one hand, the chronic nicotine
                    produce a protein called J-protein, which connects            supply has a vasoconstrictor effect; on the other, the
                    IgA molecules by their Fc regions to form a dimer; this       use of nicotine-free e-cigarettes decreases the blood
                    way, the lysozyme recognising the Fc regions becomes          supply as well. This is explained by glycerine and
                    ineffective against these IgA dimers [9]. After the use       propylene-glycol inducing endothelial inflammation,
                    of an electronic cigarette, it is proved by ELISA testing     which decreases the ability of veins to dilate so they
                    that the amount of IgA is decreased, which leads to           stay constricted [13]. A decrease in blood flow can
                    a weakened oral immune response [10]. Lysozyme                have numerous consequences such as decreased
                    is responsible for breaking the bond between                  tissue defence and a hypoxic milieu, which can
                    N-Acetylglucosamine and N-Acetylmuramic acid;                 cause changes in the bacterial microbiome, leading
                    these being the components of the bacterial cell walls,       to the proliferation of anaerobic species. Periodontal
                    the action causes the lysis of bacteria. The substance        index values become higher, and the tendency to
                    also has antiviral and antifungal functions. As an            regenerate decreases, which leads to slow or failed
                    effect of using e-cigarettes, the amount of lysozyme          wound healing [8].
                    decreases, causing a downturn in oral protection              Propionaldehyde, which appears in the aerosol
                    [10]. Lactoferrin is an iron-binding glycoprotein, a          during the decomposition of propylene-glycol, leads
                    multifunctional molecule participating in numerous            to the irritation of the oral cavity and the throat,
                    physiological processes. Concerning the oral cavity, it is    with sensitivity, redness, and dry cough [14]. The
                    produced by the serous cells of the salivary glands; like     symptoms of irritation tend to alleviate with continued
                    lysozyme, it has antibacterial, antiviral, and antifungal     use. Nicotine can cause a burning sensation by the
                    effects, and is also an important immunomodulator.            activation of the TRPA1 (transient receptor potential
                    As an effect of using e-cigarettes, its level increases;      ankyrin) channel [15].



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As a result of the immunosuppressed state in the oral      include the lack of long-term experiments and




                                                                                                                        Review Articles
cavity, the incidence of infectious mucosal diseases,      participant recruitment challenges since the ideal
mainly candidiasis caused by Candida albicans,             subject would be a person who has never smoked and
increases among e-cigarette users. It has been proved      does not have any risk factors. Despite the shortage
by in vitro experiments that in candida cells exposed      of clinical proof, current medical opinion states that
to e-cigarette vapour, the expression of chitin and        because there are carcinogenic components and
SAP-2,3,9 (secreted aspartic protease) increases, and      adverse changes induced in cells, using an e-cigarette
a change takes place in the phenotype: the hyphae          could have a carcinogenic effect [20].
become longer. These changes help the adhesion of
candida to the oral mucosa [16].                           4.3 Hard Tissues: Teeth
Upon exposure to some components of the vapour             Nicotine can be absorbed by the surface of the teeth,
such as carbonyls, reactive oxygen radicals, and           causing yellowish-brown patches [21]. During the
different types of aldehydes, the cytokine secretion of    degradation of propylene-glycol, which is one of
epithelial cells increases, which causes inflammation      the components of the e-liquid, acidic substances
[17]. The components of e-liquid may cause an allergic     such as acetic acid or lactic acid are produced, which
reaction depending on one’s immune system.                 can directly damage the enamel [22]. Furthermore,
The prevalence of some mucosal diseases is higher          propylene-glycol is a quite hygroscopic substance: it
among e-cigarette users. One such disease is               binds the water from saliva and soft tissues, further
stomatitis nicotina palati; induced by nicotine, the       increasing the rate of xerostomia already developed,
lesion mainly occurs on the hard palate, appearing         along with all the adverse consequences [22]. During
as hyperkeratotic patches. Another disease occurring       a 2018 research, enamel was incubated in flavoured
more often is lingua villosa nigra (black hairy tongue),   and non-flavoured e-cigarette vapour; measuring
causing the enlargement of the tongue’s papillae and       their hardness, the researchers found that the enamel
a change in colour to black. The risk of the disease       treated with flavoured vapour was 27% softer than the
cheilitis angularis also increases; this is a state        other preparation. Considering these results, flavours
associated with the bilateral drying and cracking of       may promote the demineralisation of enamel. The
the anguli oris, which can be superinfected by some        pathomechanism of this process is that triacetin
candida species [18].                                      (traditional tobacco flavour), hexyl acetate (apple
                                                           flavour), and ethyl butyrate (pineapple flavour) are
4.2 Soft Tissues: Chronic Changes                          all esters, sources of nutrients for cariogenic bacteria,
Several components of e-liquids may damage the             manly for Streptococcus mutans. They facilitate the
epithelial cells, which can cause the death of these       extracellular polymer formation of bacteria, which
cells, leading to ulcerative areas and wounds. During      is the main process of biofilm generation, and they
the use of an e-cigarette, metal particles may get into    promote bacterial growth. During the degradation
the aerosol from the atomiser or the cotton wool,          of carbohydrates, acids are generated, mainly lactic
including cadmium, nickel, and arsenic. Metal particles    acid, decreasing pH and causing the demineralisation
cause cancerous lesions, inflammation, chronic             of teeth [23].
periodontitis, and neurodegeneration. As a result of       The metal content of e-cigarette vapour is beneficial
heat and atomizing, flavouring substances decompose        for the bacteria as well because it contains iron,
to carbonyls such as diacetyl. The main ingredients        copper, and magnesium ions, which are the cofactors
(propylene glycol and glycerine) decompose because         of some of the essential enzymes in Streptococcus
of the heat, and among the decomposition products          mutans, and help the bacteria survive the attacks
there are molecules containing a carbonyl group            of the immune system. Researchers think e-liquid
(formaldehyde, acetaldehyde) and reactive oxygen           flavours are like fizzy drinks considering all things
species (ROS). These molecules are cytotoxic               above, because of their cariogenic potency [23].
regardless of the nicotine content; they induce DNA        E-liquids usually contain glycerine as well, which is a
damage in the oral epithelium. They decrease the           desiccant like propylene-glycol. In the food industry,
cells’ defence via antioxidants, which would protect       it is used as a sweetener, but cariogenic bacteria
the cell against the reactive radicals; apoptosis and      cannot break it down, meaning it does not facilitate
inflammation are induced. Carbonyl compounds               the development of caries this way. On the other hand,
cause protein carbonylation and oxidative stress.          through its viscosity, it helps bacterial adhesion to
The consequence of all the above is a decrease in          the surface of teeth; with the flavours in the e-liquid,
proliferative capacity and viability [15].                 it quadruples microbial adhesion to enamel, and the
The volatile organic compounds with the potential          bacterial biofilm’s size becomes twice as large [23]. The
for carcinogenicity in the e-cigarettes’ vapour have       result of dental tissue weakening may be the fracture
a genotoxic effect [19]. Compared to traditional           of enamel or fracture of an entire tooth. During a 2016
cigarettes, e-cigarettes have fewer carcinogenic           cross-sectional study, 11.4% of young respondents
substances at lower levels, but further studies are        reported such damage to their teeth, proving the
needed to find out if e-cigarettes can cause malignant     scientific position that with the use of e-cigarettes, the
transformations. The difficulties to judge the situation   number of cracks and fractures of teeth increases [24].


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                    4.4 Hard Tissues: Bone                                           gingivitis, and periodontitis may develop [4]. The
Review Articles
                    Some ingredients of e-liquids are harmful to bone cells,         symptoms of such gingivitis include pain, redness and
                    affecting the cells’ viability, differentiation, proliferative   bleeding-while-brushing of the gingiva [17].
                    capacity, and matrix production. Cadmium found in                It is quite interesting that according to research on the
                    e-liquid causes a decrease in the lifetime of osteoblasts        microbiome of the saliva, done on 119 participants,
                    even at a small concentration; furthermore, it increases         some gram-negative bacteria such as periodonto-
                    the risk of certain musculoskeletal diseases such as             pathogenic Porphyromonas and Veillonella occur in a
                    rheumatoid arthritis and osteoarthritis [25,26].                 greater quantity in e-cigarette users’ saliva than in that
                    In a 2019 experiment series, the effect of different             of traditional smokers, showing e-cigarettes’ potential
                    flavouring substances of e-liquids on bone cells was             harm leading to periodontitis [29].
                    assessed: osteoblasts were exposed to the most                   Furthermore, nicotine is antiproliferative to
                    popular flavoured e-liquids, both nicotine-containing            fibroblasts: as a result of prostaglandins and matrix
                    and nicotine-free, for 48 hours, then the cells’ viability       metalloproteases released upon exposure to
                    and their main osteoblast markers were evaluated.                nicotine, myofibroblast and mesenchymal stem cell
                    Results showed an increase in the expression of type             differentiation are blocked, holding back wound
                    I collagen, and the conclusion was that e-cigarettes             healing. Osteoblast functions and new vessel growth
                    are osteotoxic: all e-liquids decreased the viability of         are similarly suppressed, negatively impacting the
                    the cells, which was explained by oxidative stress and           success rate of implant dentures, osteointegration,
                    a higher level of reactive oxygen radicals. The rate             and the regeneration of papillae. Decreased
                    of osteotoxicity was determined by the dosage and                osseointegration has been confirmed by animal
                    the flavour but was unrelated to nicotine content.               experiments: around implants in rats getting a nicotine
                    Considering these findings, flavourless e-liquid is the          injection, the size of BIC (Bone Implant Contact), i.e.,
                    least harmful, and cinnamon flavoured is the most                the contact surface between bones and implants, was
                    cytotoxic [25].                                                  lower than in the control group [27].
                    The negative effects of e-cigarettes cause a change              The components of the periodontium – gingival
                    in the bone’s features, and a decrease in its density            fibroblasts, periodontal ligaments, and epithelial cells
                    and mineral content, which is dangerous mainly in                – develop and maintain inflammation as a response to
                    childhood because this period is crucial in proper               specific stimuli or stress caused mainly by cytokines.
                    bone growth and development, this being the time                 Some components of the vapour of e-cigarettes
                    when 90% of the bone mass develops. A long-time                  such as reactive oxygen substances, aldehydes
                    consequence of the change in the bones’ condition                and compounds containing a carbonyl group, are
                    might be osteoporosis [25], thus bone fractures                  among the triggers of inflammation. The potential
                    might occur more frequently; furthermore, as an                  inflammatory effects of carbonyl compounds include
                    effect of nicotine, the regeneration of bone fractures           carbonylation of proteins, leading to autoantibody
                    is disturbed as well [27]. The changes in the bone’s             production and periodontal destruction [30].
                    condition start in about two months of e-cigarette               Furthermore, the stress caused by these compounds
                    use; upon quitting, the alveolar bone recovers to its            gives rise to DNA damage, which translates to early
                    original, healthy state [28].                                    cell ageing. In vitro experiments have proved that
                                                                                     gingival fibroblasts exposed to e-cigarette vapour
                    4.5 Effects on the Periodontium                                  face a greater risk of necrosis and apoptosis [30].
                    The duty of the periodontium is anchoring, and fixing            Periodontitis is a multifactorial disease where the
                    the teeth in the tooth ridge. The inflammation of                presence of bacteria is a necessary but not sufficient
                    periodontal tissues may lead to losing all the teeth,            condition; the effects of e-cigarette vapour provide
                    meaning that a healthy periodontium is necessary to              a favourable medium for the development of this
                    keep and maintain one’s teeth. Traditional cigarettes            disease. The depth of an e-cigarette user’s periodontal
                    are well known for leading to periodontitis; the                 sac increases, the developed gingivitis may cause
                    question here is if e-cigarettes have this consequence,          sensitivity and bleeding, and the plaque index
                    too. Because of the vasoconstrictor effect of nicotine,          increases.[17] The risk of periodontitis increases, which
                    the gingiva’s oxygen and nutrition supply decrease.              leads to tissue and bone destruction, tooth mobility
                    The consequence is a decrease in local white blood               and, in the worst case, tooth loss.
                    cell count, followed by these cells’ inability to fulfil
                    their defensive role, reinforced by low levels of                5. CONCLUSION
                    lysozyme as a result of reduced saliva flow. On the
                    other hand, there are consequential changes to                   The main purpose of inventing e-cigarettes was to
                    the microbiome of the oral cavity, creating perfect              find a less harmful alternative to traditional cigarettes;
                    circumstances for anaerobic periodonto-pathogenic                it is therefore useful to compare the health effects
                    bacteria to multiply, such as Porphyromonas                      of these two harmful habits. In numerous cases, the
                    gingivalis, Aggregatibacter actinomycetemcomitans                e-cigarettes’ harmful effects on the oral cavity are
                    and Prevotella intermedia. As a result of weakened               milder than those of traditional cigarettes; however,
                    defence and bacterial colonisation, inflammation,                they have several adverse effects and may cause



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The Oral Effects of E-cigarettes
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severe diseases. A further danger of e-cigarettes is                   on e-cigarettes’ health effects are clear: they may be




                                                                                                                                               Review Articles
that there are various types of devices and e-liquids,                 a useful assistive device while quitting traditional
making the uniformity of regulations and medical                       cigarettes, but they are unadvised to use in other cases
research more difficult. Even though much research                     due to their negative effects on oral tissues.
has been done in this area, there are still numerous                   AUTHOR CONTRIBUTIONS
unanswered questions and statements awaiting
proof. Despite our lack of knowledge, the opinion                      All authors agree to be accountable for the content of the work.




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                                                                                                    Áron Imre GYÖRKÖS
                                                                                                             DMD, Clinical Doctor
                                                                                                              Szép és Ép fog Kft.
                                                                                                                   Érd, Hungary

                    CV
                    Dr. Áron Imre Györkös, DMD, graduated from the Faculty of Dentistry, Semmelweis University, Budapest, Hungary in 2021. He is
                    currently working as a dentist in Érd, next to Budapest, both in the public and private sector. The title of his research is The oral
                    effects of e-cigarettes - a literature review. He started exploring this topic as his thesis and tried to summarise today's knowledge
                    of e-cigarette health effects. He is currently working on something similar with IQOS and other heated tobacco products.




                    Questions
                    1. Generally, what temperature range do e-cigarettes vaporise the e-liquid?
                    qa. 57 to 66 degrees Celsius;
                    qb. 157 to 266 degrees Celsius;
                    qc. 200 to 400 degrees Celsius;
                    qd. 800 to 1000 degrees Celsius.

                    2. Which statement is true about the changes on the saliva because of e-cigarette usage?
                    qa. The pH of the saliva rises by the usage of nicotine-free liquids;
                    qb. The pH of the saliva decreases by the usage of nicotine-free liquids;
                    qc. The pH of the saliva rises by the usage of nicotine containing liquids;
                    qd. The vapour-inducted temperature rise causes more saliva secretion.

                    3. According to a 2011 survey by the WHO, how many people used e-cigarettes regularly
                    worldwide at the time?
                    qa. 1 million;
                    qb. 34 million;
                    qc. 7 million;
                    qd. 1 billion.

                    4. Which component of the e-liquid can cause yellowish-brownish patches on the surface
                    of the teeth?
                    qa. Propylene-glycol;
                    qb. Glycerine;
                    qc. Sweeteners;
                    qd. Nicotine.




 114                Stoma Edu J. 2022;9(3-4):109-114                                                      pISSN 2360-2406; eISSN 2502-0285