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A proprietary herbal extract against hair loss in androgenetic alopecia
and telogen eluvium: a placebo-controlled, single-blind, clinical-
instrumental study
Erkin Pekmezci1 ✉, Cihat Dündar2, Murat Türkoğlu2
1Department of Dermatology, Gözde Hospital, Malatya, Turkey. 2Biota Laboratories, R&D Center, Sancaktepe, Istanbul, Turkey. ✉ Corresponding author:
erkinpekmezci@gmail.com
51
2018;27:51-57
doi: 10.15570/actaapa.2018.13
Introduction
Although hair loss is not a serious problem for general health, it is
a matter of concern because it can lower self-condence and cre-
ate feelings of inferiority. In general, patients with alopecia have a
higher incidence of psychiatric disorders such as depression, anx-
iety, and social phobia compared to the rest of the population (1).
Although androgenetic alopecia (AGA) is more prevalent in
men, it is a widespread dermatological problem that also aects
women. Up to 30%, 50%, and 80% of the men aected are over
the ages of 30, 50, and 80 respectively. Androgens play an impor-
tant role that appears to be independent from genetic predisposi-
tion, which is considered the main etiologic factor in AGA (2, 3).
Testosterone is converted into its more potent form dihydrotestos-
terone (DHT) by the enzyme 5α-reductase (5α-R). The AGA-prone
scalp has high levels of DHT and augmented androgen receptor
(AR) expression (4). Inammatory processes are also increasingly
being cited as an integral part in the pathogenesis of AGA (4–8).
In AGA, scalp biopsies from both men and women revealed follic-
ular microinammation and lymphocytic folliculitis, targeting an
immunologically driven trigger (7, 8). One of the factors leading to
permanent hair loss in AGA may be this continuous inammation
and remodeling of the connective tissue of follicles (4).
Telogen euvium (TE) is another frequent cause of diuse hair
loss, but the true incidence is not well known because of insuf-
cient data, especially due to subclinical cases (9). Although TE
may be one manifestation of various chronic systemic illnesses,
an association between stress and hair loss is well accepted
among clinicians (10, 11). The sensitivity of human hair follicles to
key skin-stress mediators has been demonstrated: organ-cultured
hair follicles responded to substance P with premature catagen
development and degranulation of mast cells in the connective
tissue sheath of hair follicles, indicating a neurogenic inamma-
tion (12). Acute TE due to oxidative stress induced by ultraviolet
radiation has also been identied. Photoactivation of porphyrin
compounds produced by bacteria in the pilosebaceous duct led
to oxidative tissue injury and follicular microinammation (13).
Currently, although topical minoxidil and oral nasteride are
the only medications approved for AGA, cause-oriented treatment
is performed for TE. Considering the androgenetic and inamma-
tory factors in the pathogenesis explained above, we formulated a
herbal shampoo and solution containing a mixture of six dierent
herbal extracts (HE) with antiandrogenic, anti-inammatory, and
antioxidative features. Our hypothesis was that, if there is a high
enough concentration of relevant avonoids, vitamins, and trace
elements at the site of action (i.e., hair follicles), then inamma-
tory and aging processes can be slowed down and reversed to a
certain extent. This study was performed to assess the ecacy,
safety, and synergy of the new cosmetic herbal shampoo and so-
lution for treatment of AGA or TE.
Methods
Products tested
Herbal shampoo: aqua, sodium laureth sulfate, cocamidopropyl
betaine, sodium chloride, mixture of herbal extracts (Urtica urens
leaf extract, Urtica dioica root extract, Matricaria chamomilla ow-
er extract, Achillea millefolium aerial part extract, Ceratonia sili-
qua fruit extract, Equisetum arvense leaf extract), glycerin, benzyl
alcohol, perfume/fragrance, PEG/PPG-120/10-trimethylolpropane
trioleate, laureth-2, hydroxypropyl guar, hydroxypropyltrimonium
Abstract
Introduction: Currently there are only a limited number of drugs available for treatment of androgenetic alopecia and telogen elu-
vium. However, certain plants and their standardized extracts may provide some clinical benets against hair loss. We formulated
a herbal shampoo and a solution to evaluate their ecacy, safety, and synergy in hair loss.
Methods: We conducted a randomized, placebo-controlled, single-blind, clinical and instrumental study for 6 months on 120 sub-
jects with androgenetic alopecia and telogen eluvium, conrmed by pull test and phototricogram. Each subject was examined
monthly. At the end of the study, a self-assessment test was carried out.
Results: Herbal formulations were found to be more eective in preventing and reducing hair loss than placebo at every assess-
ment point. Anagen/telogen ratios improved signicantly in the study group. In addition, concomitant use of the shampoo and
solution were found to be more eective than single product use.
Conclusion: We interpret this eutrophic eect for scalp hair as the nal outcome of the entire content of our herbal formula, which
has antiandrogenic, anti-inflammatory, antioxidative, angiogenic, and hair-stimulating features. In combination, these features
help prevent hair from falling out and reducing hair loss.
Keywords: herbal extract, hair loss, clinical study
Acta Dermatovenerologica
Alpina, Pannonica et Adriatica
Acta Dermatovenerol APA
Received: 11 December 2017 | Returned for modication: 25 January 2018 | Accepted: 26 February 2018
52
Acta Dermatovenerol APA | 2018;27:51-57E. Pekmezci et al.
chloride, polyquaternium-7, amodimethicone, tetrasodium EDTA,
menthol, mel, panthenol, C11-15 pareth-7, laureth-9, sodium PCA,
butylphenyl methylpropional, trideceth-12, coumarin, hydroxy-
isohexyl 3-cyclohexene carboxaldehyde, methylchloroisothia-
zolinone, niacinamide, Panax ginseng root extract, and methyli-
sothiazolinone.
Herbal solution: aqua, mixture of herbal extracts (Urtica urens
leaf extract, Urtica dioica root extract, Matricaria chamomilla
ower extract, Achillea millefolium aerial part extract, Ceratonia
siliqua fruit extract, Equisetum arvense leaf extract), sodium hy-
droxymethylglycinate, mel, and glycerin.
Placebo shampoo: aqua, sodium laureth sulfate, cocamido-
propyl betaine, sodium chloride, E150a (caramel color), glycerin,
benzyl alcohol, perfume/fragrance, PEG/PPG-120/10-trimethylol-
propane trioleate, laureth-2, hydroxypropyl guar, hydroxypropylt-
rimonium chloride, polyquaternium-7, amodimethicone, tetraso-
dium EDTA, menthol, mel, panthenol, C11-15 pareth-7, laureth-9,
sodium PCA, butylphenyl methylpropional, Trideceth-12, cou-
marin, hydroxyisohexyl 3-cyclohexene carboxaldehyde, methyl-
chloroisothiazolinone, niacinamide, Panax ginseng root extract,
and methylisothiazolinone.
Placebo solution: aqua, E150a (caramel color), sodium hydrox-
ymethylglycinate, mel, and glycerin. The placebo shampoo and
solution did not contain the HE. All of the products tested com-
plied with EU cosmetic regulations and the products were notied
in the Cosmetic Products Notication Portal (CPNP) system.
Phytochemical analyses of HE
Vitamin and avonoid analyses were performed with high-pres-
sure liquid chromatography (HPLC) at Phytolab, Vestenbergs-
greuth, Germany. Trace elements analyses were performed with
inductively coupled plasma optical emission spectrometry (ICP-
OES) at Saniter Lab, Istanbul, Turkey.
Clinical panel and ethical requirements
The sample consisted of otherwise healthy Caucasian subjects
(60 males and 60 females) 20 to 55 years old, suering from AGA
grades II and III in accordance with the Hamilton–Norwood scale
or TE, enrolled in the trial (54 AGA subjects, 66 TE subjects) with
written informed consent. The subjects were chosen under the
control of a dermatologist on the basis of the inclusion/exclusion
criteria: the subjects were not using any topical or systemic medi-
cations, they had no scalp or hair disease except the trial indica-
tions, they had no hypersensitivity history, and none of them were
pregnant or lactating. All of the trial procedures were performed
in line with the ethical principles laid down for medical research
(Helsinki Declaration of World Medical Association, 1964, and
amendments). In the event of any unexpected or adverse reaction,
a medical investigator was on standby for intervention.
Group formation
The products’ allocations were randomized in accordance with
a randomization list. The randomization list was created using
Wei’s urn algorithm, which is designed to generate balanced ran-
dom samples throughout the course of an experiment. The follow-
ing groups were formed: Group A: 30 subjects that used herbal
(active) shampoo, Group B: 30 subjects that used herbal (active)
solution, Group C: 30 subjects that used herbal (active) shampoo
and herbal (active) solution, and Group D: 30 subjects that used
placebo shampoo and placebo solution. In addition to the mean/
median ages of the subjects, the gender and clinical distribution
in each group are presented in Table 1. There were no dierences
in the demographic features among the groups.
Product use
Shampoo: Every other day, three times a week, apply 5 ml on wet
hair, wait for 3 to 4 minutes aer foaming, and then rinse well.
Solution: Every day in the morning and in the evening, apply
3 ml on dry hair and massage all over the scalp. Let it stand for at
least 4 to 6 hours.
Study design
Aer the enrollment and the evaluation of the physiological scalp
and hair conditions by the dermatologist (T), the subjects were
informed about the principles of the study. At the end of each
month, the subjects were evaluated based on the criteria present-
ed in Table 2.
Pull test
The pull test was used to assess diuse hair loss. Mild traction was
performed on a bunch of hair (approximately 60 bers) and the
number of hairs extracted was counted. Operatively, the derma-
tologist took a few strands between his thumb and forenger and
pulled them gently. Anagen (growing) hair should remain rooted
in place, and telogen (non-growing) hair should come out easily.
If the number of lost hairs was greater than six, the pull test was
considered positive. Subjects were requested not to wash their
hair in the 24 hours before the pull test.
Phototricogram
A targeted area of 1.8 cm² was chosen for clipping. This was a zone
of transition between normal hair and the balding area in male
subjects with AGA, and the middle part of the vertex in TE and fe-
male AGA subjects. The shaved hair zone was dyed gray, and pho-
tos were taken with a digital close-up camera immediately and 2
days later. By comparing these two consecutive photographs with
a soware system identifying individual hair bers, growing (ana-
gen phase) or non-growing (telogen phase) bers were determined.
Table | Sex and clinical distributions, means ± standard deviations (SD), and
medians of the ages for each group and all subjects.
Group
Male
Female
AGA
TE
Age (mean ± SD)
Age (median)
A
. ± .
.
B
. ± .
.
C
. ± .
.
D
. ± .
.
Total
. ± .
.
AGA = androgenetic alopecia, TE = telogen eluvium.
Table | Summary of the study outline (T = Time of evaluation in months).
Component
T
T
T
T
T
T
T
Enrollment
X
Inclusion criteria
X
X
X
X
X
X
X
Subject compliance
X
X
X
X
X
X
X
Pull test
X
X
X
X
X
X
X
Phototricogram
X
X
X
X
Dermatological evaluations
X
X
X
X
X
X
X
Self-assessment
X
53
Acta Dermatovenerol APA | 2018;27:51-57 A herbal extract against hair loss
Dermatological evaluation
The dermatologist clinically evaluated the presence of dandru,
excess sebum, scalp redness, or the onset of an itching sensation.
Self-assessment
At the end of the study, in month 6, the subjects were given a
10-point questionnaire on which 1 was the lowest and 10 was the
highest score in order to rate the benet of the treatments on cer-
tain hair properties. The questionnaire is presented in Table 3.
Statistical analyses
In intragroup evaluation (time course), the Wilcoxon signed-rank
test for non-parametric pull test data and repeated measured
analysis of variance followed by Student’s t-test for parametric
phototricogram data were used. In intergroup evaluation (ac-
tive vs. active vs. placebo), the Wilcoxon Kruskal–Wallis one-way
analysis of variance on ranks for non-parametric pull test and self-
assessment data, and multivariate analysis of variance followed
by Student’s t-test for parametric phototricogram data were used.
Results
Phytochemical analyses of HE
The vitamins, avonoids, and trace elements found in phyto-
chemical analyses of HE are presented in Table 4. The quantities
of all of them are expressed as mg/100 g dry extract.
Pull test
The comparison between Group A / shampoo (active) vs. Group B
/ solution (active) vs. Group C / shampoo (active) + solution (ac-
tive) vs. Group D / shampoo (placebo) + solution (placebo) are
presented in Fig. 1, and the graph reports the mean (%) decrease
obtained for each product tested. The data are reported as mean
(%) variation of hair loss during the pull test for each month (T1–
T6) compared to the beginning of the trial (T). Although the in-
tragroup statistical analyses revealed signicant improvement in
all groups for all months compared to T, the intergroup analyses
showed that Group C (active shampoo + solution) had the best
clinical outcomes and Group D (placebo shampoo + solution) had
the worst. The p values of the intergroup analyses are presented
in Table 5. Fig. 1 also shows that longer usage of products corre-
sponds to better clinical outcomes.
Phototrichogram
Whereas there was no increase in group D (placebo shampoo +
solution) during the study, the number of total hairs in groups A
(active shampoo), B (active solution), and C (active shampoo +
solution) increased signicantly in month 4 (T4) and month 6 (T6)
compared to the beginning of the trial (T, Fig. 2).
Table | Questionnaire given to the subjects at the end of the study.
Questions
Scores
Have you noticed a decrease in hair loss?
Have you noticed the growth of new hair?
Have you noticed an increase in hair thickness?
Has your hair grown faster?
Has the treatment reinforced your hair?
Table | Vitamins, flavonoids, and trace elements found in phytochemical ana-
lyses of HE.
Component
(mg/ g dry extract)
Vitamins
Thiamin (B
) .
Riboflavin (B
) .
Pyridoxin (B
) .
Ascorbic acid (C)
< .
Flavonoids
Myricetin
,
Quercetin
Kaempferol
Trace elements
Iron
.
Copper
.
Zinc
.
Figure | Summary of pull test results. (%) decrease in hair loss for each month
(T–T) compared to the beginning of the trial (T). Group A / shampoo (active)
vs. Group B / solution (active) vs. Group C / shampoo (active) + solution (active)
vs. Group D / shampoo (placebo) + solution (placebo).
Table | The p values of Group C / shampoo (active) + solution (active) vs. Group A / shampoo (active), Group B / solution (active), and Group D / shampoo
(placebo) + solution (placebo) for months through , each month (T–T) compared to the beginning of the trial (T).
Group
T
T
T
T
T
T
Sha(A) + Sol(A) vs. Sha(A)
.
.
.
.
.
.
Sha(A) + Sol(A) vs. Sol(A)
.
.
.
.
.
.
Sha(A) + Sol(A) vs. Sha(P) + Sol(P)
.
.
< .
< .
< .
< .
Sha = shampoo, Sol = solution, (A) = active, (P) = placebo.
Figure | Increase in number of total hairs from the beginning of the trial (T) to
the month (T) for every months. The p values of Group A / shampoo (active),
Group B / solution (active) and Group C / shampoo (active) + solution (active) in
T and T were < .; whereas T was > . compared to T. All of the values
(i.e., T–T) of Group D / shampoo (placebo) + solution (placebo) were > .
compared to T.
54
Acta Dermatovenerol APA | 2018;27:51-57E. Pekmezci et al.
Figure | Telogen-anagen (%) changes for Group A / shampoo (active) for every
months. The p values for both telogen and anagen changes in T–T were
< . compared to T.
Figure | Telogen-anagen (%) changes for Group B / solution (active) for every
months. The p values for both telogen and anagen changes in T–T were < .
compared to T.
Figure | Telogen-anagen (%) changes for Group C / shampoo (active) + solution
(active) for every months. The p values for both telogen and anagen changes in
T–T were < . compared to T.
Figure | Telogen-anagen (%) changes for Group D / shampoo (placebo) + so-
lution (placebo) for every months. The p values for both telogen and anagen
changes in T–T were > . compared to T.
The decrease in telogen hairs and increase in anagen hairs were
also signicant in groups A, B, and C in T4 and T6 compared to T
(Figs. 3–5). The (%) changes in telogen and anagen hairs through
T2–T6 in group D were not signicant (Fig. 6).
Self-assessment
Fig. 7 presents the mean scores of self-assessment questions. The
highest scores are from Group C (active shampoo + solution), and
the lowest scores are from Group D (placebo shampoo + solution).
In statistical evaluation of the self-assessment data, all of the
questions showed statistically signicant results based on the dif-
ference from placebo. Here Group C also has the best clinical out-
comes and Group D the worst. The p values of intergroup analyses
for each question are presented in Table 6.
General considerations for clinical-instrumental results
The products were well tolerated and no side eects were recorded
during the study. The herbal/active shampoo and solution helped
ameliorate the baseline conditions of subjects suering from
AGA or TE. In this 6-month study, the regular use of the herbal
shampoo and/or solution decreased hair loss and increased the
number of anagen hairs. These eects, clinically or instrumen-
tally conrmed, were also perceived by the subjects participating
in the study and signicantly delineated in the statistical analy-
ses of self-assessment results. The results obtained in the group
that used both active products (shampoo and solution) were sig-
Figure | Results of self-assessment questions for the treatments and placebo.
Table | The p values of Group C / shampoo (active) + solution (active) vs. Group A / shampoo (active), Group B / solution (active), and Group D / shampoo
(placebo) + solution (placebo) for each self-assessment question. All of the values are statistically signicant.
Group
Q
Q
Q
Q
Q
Sha(A) + Sol(A) vs. Sha(A)
.
.
.
.
.
Sha(A) + Sol(A) vs. Sol(A)
.
.
.
.
.
Sha(A) + Sol(A) vs. Sha(P) + Sol(P)
< .
< .
< .
< .
< .
Sha = shampoo, Sol = solution, (A) = active, (P) = placebo.
55
Acta Dermatovenerol APA | 2018;27:51-57 A herbal extract against hair loss
nicantly better than those obtained in the groups that used only
one active product (shampoo or solution). The concomitant use
of herbal shampoo and herbal solution had a synergistic eect in
improving the parameters measured.
Discussion
The causes for the clear signicant positive results of the products
tested should be sought in the interaction between the properties
of the plants in our HE and etiopathogenetic factors in the hair
loss types included in this study.
Among the plants used in the formulation, Urtica dioica (Ud)
is the most widely studied. The use of Ud root extract in sympto-
matic benign prostate hyperplasia (BPH) and lower urinary tract
symptoms has been investigated in numerous clinical trials and
found eective (14–17). This indication is mainly due to its 5α-R
inhibition activity (18, 19). Inhibition of 5α-R hampers the forma-
tion of DHT from testosterone. An excess amount of DHT is related
to BPH (17). The same pathogenesis is also true for AGA (4, 5), and
this mechanism of action may be the main cause of the success of
our formulation in patients with AGA. Although Ud leaves have
traditionally been used for hair loss, conrmatory clinical trials
are still lacking (17). In a study performed with a combination of
herbal extracts including Ud, it was shown that the combination
enhanced human dermal papilla cell proliferation at concentra-
tions between 1.5% and 4.5% (20).
As stated in the introduction to this report, apart from the
pathogenesis of AGA related to androgen metabolism, inamma-
tory and oxidative processes are the basic common pathways in
the etiopathogenesis of both AGA and TE (4–13). Polysaccharides
and caeic malic acid (CMA) both exist to some extent in every
part of Ud. Urtica polysaccharides and CMA present anti-inam-
matory activity by inhibiting cyclooxigenase and lipoxygenase
(21, 22). β sitosterol, also a component of Ud, stimulates angio-
genesis by increasing vascular endothelial growth factor (VEGF)
synthesis and supports new hair growth (23). This molecule also
suppresses testosterone synthesis and contributes to decreased
DHT levels (24).
The proximate analysis results showed that leaf extract of
Urtica urens (Uu) contains a high amount of total phenolics, a-
vonoids, tannins, ortho-diphenols, and avonols (25, 26). It has
been shown to decrease paw edema aer carrageenin administra-
tion in rats and to improve the activities of catalase, superoxide
dismutase, glutathione peroxidase, and malondialdehyde, exhib-
iting powerful antioxidant and anti-inammatory activity (26).
In a study performed with Equisetum arvense (Ea) alone and
with a combination of some other plants, Ea suppressed super-
oxide anion levels in the xanthine/xanthine oxidase system and
eliminated the hydroxyl radical. Ea also reduced reactive oxygen
species (ROS) in neutrophils that were stimulated by phorbol
myristate acetate. In the same study, although carrageenin-in-
duced paw swelling in rats was signicantly inhibited by the plant
mixture, this inhibition could not be achieved by the components
on an individual basis (27). This phenomenon could explain why
our plant mixture also had a synergistic eect in obtaining the
good outcomes in the study. In addition to various studies depict-
ing its antioxidative features (28–30), Ea exhibited signicant
diabetic wound healing by showing higher epidermal and dermal
regeneration, angiogenesis, and granulation tissue thickness in
diabetic rats (31). Ea is one of the highest silicon accumulators
among plant species. Silicon penetrates the hair follicles, enters
in the hair matrix, and makes the hair bers thicker. Therefore,
the higher the silicon quantity in the hair, the lower the extent of
hair loss (32, 33).
Leaves and owers of Achillea millefolium (Am) have been used
for centuries for their anti-inammatory eect in conditions such
as rheumatism, wound healing, and skin inammation (34). In an
in vivo study performed with Am oil extract on articially irritated
skin, the parameters tested (i.e., pH, capacitance, and erythema
index) were restored to basal values aer 3 to 7 days of treatment
(35). Am extract showed an augmentation in cytokeratin-10,
transglutaminase-1, and laggrin expressions, together with an
increase in the thickness of epidermis in cultured skin biopsies.
In addition, a 2-month topical application of 2% Am extract signif-
icantly improved the outlook of wrinkles and pores in vivo when
compared with placebo (36).
Historically, oil of Matricaria chamomilla (Mc, German chamo-
mile) has been used in the treatment of some inammatory der-
matoses. It contains three major sesquiterpene compounds (i.e.,
azulene, bisabolol, and farnesene) with anti-inammatory or
antihistamine eects. Among them, α-bisabolol has the strongest
anti-inammatory eect (37, 38). In a study performed with 3%
Mc oil topically on the skin of mice showing its immunoregula-
tory potential, it alleviated atopic dermatitis through inuencing
helper T cell 2 (Th2) activation (39). Mc extract applied topically
also showed wound healing potential in a linear incisional model
in rats (40). A pharmacologically active avonoid apigenin that is
contained by both Mc and Am supports hair growth by suppress-
ing transforming growth factor-β1 (TGF-β1), which stimulates the
catagen phase in the hair growth cycle (41, 42).
Ceratonia siliqua (Cs) pod extract presents antioxidant features
due to its catechin, epicatechin, epigallocatechin, epigallocate-
chin gallate, and epicatechin gallate contents, along with simpler
phenolics, such as phloroglucinol, pyrogallol, catechol, and gal-
lic acid (43–45). In addition, Cs bers exhibit higher antioxidant
capacity than many edible products rich in polyphenols, such as
blueberries, grapes, or red wine (46, 47).
On the other hand, the avonoids, vitamins, and trace ele-
ments we found in the phytochemical analyses of our formulation
may oer more specic support for the wellbeing of hair physi-
ology. Myricetin, quercetin, kaempferol, and copper keep the
hair follicle in the anagen phase longer by inhibiting 5α-R type 2
and preventing DHT formation (48, 49). Vitamin B complex and
vitamin C (ascorbic acid) enhance blood vessel formation and
increase blood ow in the scalp by stimulating the synthesis of
VEGF (50). It was reported that mice that were exposed to high
amounts of environmental cigarette smoke developed alopecia,
and this was precluded by administration of l-cystine and vitamin
B6 (pyridoxine) combination (51). B-group vitamins and l-cystine
mixtures are also customarily used in OTC products for hair loss
(52). Vitamin B2 (riboavin) is known to enhance the metabolism
of vitamin B6 (53, 54). Vitamin C might improve the ecacy of
therapeutic angiogenesis by cell transplantation (55). Some deriv-
atives of vitamin C were also found to be promising in treating and
preventing DHT-induced balding (56). Iron is a crucial cofactor for
the enzymes implicated in energy metabolism and DNA synthesis.
It is a fundamental element for healthy skin, mucous membranes,
hair, and nails. In the case of scalp hair, iron deciency leads to
dryness and fragility (57). Zinc is found in the enzyme systems af-
fecting hair formation, and local zinc ions stimulate scalp cellular
formation (50). Zinc metabolism disturbances play a key role in
hair loss, especially in AGA and TE (58).
56
Acta Dermatovenerol APA | 2018;27:51-57E. Pekmezci et al.
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57
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