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The number of papers discussing probiotics increases tremendously that limits the possibility for primary care physicians and clinicians to stay updated. Therefore, the aim of this paper will be to summarize available evidence of probiotic use in well-defined clinical indications of importance for pediatricians. Based on currently available evidence certain probiotic strains (Lactobacillus rhamnosus GG [LGG] and Saccharomyces boulardii) have proven effect in the treatment of acute gastroenteritis and prevention of antibiotic associated diarrhea. Furthermore, LGG was proven to be effective in prevention of nosocomial diarrhea and respiratory tract infection in day care centers. In conclusion, not all probiotic strains have same efficacy for all clinical indications, therefore, only strains with proven efficacy and safety should be recommended.
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pISSN: 2234-8646 eISSN: 2234-8840
https://doi.org/10.5223/pghn.2017.20.3.1 39
Pediatr Gastroenterol Hepatol Nutr 2017 September 20(3):139-146 PGHN
Review Article
PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY & NUTRITION
Probiotics in Children: What Is the Evidence?
Iva Hojsak*,,
*Children’s Hospital Zagreb,
University of Zagreb, School of Medicine, Zagreb,
University Josip Juraj Strossmayer,
S
chool of Medicine Osijek, Osijek, Croatia
The number of papers discussing probiotics increases tremendously that limits the possibility for primary care physi-
cians and clinicians to stay updated. Therefore, the aim of this paper will be to summarize available evidence of
probiotic use in well-defined clinical indications of importance for pediatricians. Based on currently available evidence
certain probiotic strains (Lactobacillus rhamnosus GG [LGG] and Saccharomyces boulardii) have proven effect in
the treatment of acute gastroenteritis and prevention of antibiotic associated diarrhea. Furthermore, LGG was proven
to be effective in prevention of nosocomial diarrhea and respiratory tract infection in day care centers. In conclusion,
not all probiotic strains have same efficacy for all clinical indications, therefore, only strains with proven efficacy and
safety should be recommended.
Key Words: Lactobacillus, Saccharomyces, Bifidobacterium, Diarrhea, Infection
Received:July 4, 2017, Accepted:July 31, 2017
Corresponding author: Iva Hojsak, Referral Center for Pediatric Gastroenterology and Nutrition, Childrens Hospital Zagreb, Klaićeva 16, 10000
Zagreb, Croatia. Tel: +385-1-4600130 , Fax: +385-1-4600160, E-mail: ivahojsak@gmail.com
Copyright 2017 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition
T
his is an openaccess article distributed under the terms of the Creative Commons Attribution NonCommercial License (http://creativecommons.org/licenses/by-nc/4 .0/) which permits
unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
INTRODUCTION
Most widely used definition of probiotics was giv-
en by the Food and Agriculture Organization of the
United Nations and the World Health Organization
in 2002 [1]. That definition was accepted with mini-
mal change by expert panel (International Scientific
Association for Probiotics and Prebiotics) in 2014
stating that probiotics are live microorganisms that,
when administered in adequate amounts, confer a
health benefit on the host [2].
On the same document panel tried to emphasize
the probiotic action, emphasizing that some of pro-
biotics’ effect can be attributed only to specific pro-
biotic strain, but some effects can be ascribed to pro-
biotics in general or certain species of probiotics [2].
Same recognition of clinical effectiveness was also
approved and highlighted by European Society for
Pediatric Gastroenterology, Hepatology, and Nutrition
Working Group (ESPGHAN WG) on pre- and pro-
biotics. Stating that recommendations for probiotic
use should always be strain specific and aim is to rec-
ommend only the strains which have proven efficacy
by well-designed randomized controlled trials (RCTs).
There are many papers about probiotics produced
on daily basis which makes clinical up-date on their
effectiveness extremely difficult.
Therefore, the aim of this paper will be to summa-
140    Vol. 20, No. 3, September 2017
Pediatr Gastroenterol Hepatol Nutr
rize available evidence of probiotic use in well-de-
fined clinical indication including the treatment of
acute gastroenteritis, prevention of antibiotic asso-
ciated diarrhea and prevention of infections in
children.
TREATMENT OF ACUTE
GASTROENTERITIS
Acute gastroenteritis is usually defined as decrease
in the stool consistency (loose or liquid) and/or an in-
crease in the frequency (typically 3 stools/day),
with or without vomiting or fever [3]. Diarrhea typi-
cally lasts less than 7 days and not longer than 14
days [3]. The incidence of acute gastroenteritis is still
high, even in Europe, and it is estimated that the in-
cidence in small children ranges from 0.5 to 1.9 epi-
sodes/child/year [3]. Major causes are still rotavirus,
which decreases in countries with high rate of rotavi-
rus vaccination, followed by norovirus [4]. The treat-
ment strategy aims to treat and prevent dehydration,
shorten duration of diarrhea and to prevent pro-
longed diarrhea. Therefore, the mainstay of treat-
ment is rehydration which in majority of children
can be provided orally by using oral rehydration sol-
utions [3]. Yet, there is still no causal treatment. One
treatment option is racecadotril, enkephalinase in-
hibitor which was proven to be effective in short-
ening the diarrhea [5]. Other well-defined treatment
modalities include probiotics.
Recently, ESPGHAN WG on pre- and probiotic
performed systematic review and provided guide-
lines on the use of different probiotic strains for the
treatment of acute gastroenteritis [6]. Based on
available, well designed RCTs, ESPGHAN WG rec-
ommended only two probiotic strains proved to be
effective in at least two RCTs; these are Lactobacillus
rhamnosus GG (LGG) and Saccharomyces boulardii.
Based on the Cochrane review from 2010 [7], LGG
was investigated in 11 RCTs (n=2,072) and this
meta-analysis found that use of LGG reduced the du-
ration of diarrhea for mean of 27 hours (95% con-
fidence interval [CI], 41 to 13). Subsequent sys-
tematic review performed by Szajewska et al. [8] in
2013 identified 15 RCTs (n=2,963). This review con-
firmed superiority of LGG in significantly decreasing
duration of diarrhea comparing to placebo (mean
difference [MD], 1.05 days; 95% CI, 1.7 to 0.4;
based on 11 RCTs). However, there was no influence
on stool volume (MD, 8.97 mL/g; 95% CI, 86.26 to
104.2; based on 2 RCTs). Regarding the dose, 1010
colony-forming units (CFU) was more effective than
1010 CFU [8].
Other strain with well-proven effect is S. boulardii.
The above-mentioned Cochrane review found 6
RCTs (n=606) and reported reduced risk of diarrhea
lasting 4 days (risk ratio [RR], 0.37; 95% CI, 0.2 to
0.65) if S. boulardii was used [7]. More recent system-
atic review analyzing 11 RCTs (n=1,306) showed
that S. boulardii significantly reduced diarrhea dura-
tion (MD, 0.99 days; 95% CI, 1.4 to 0.6) [9].
None of the studies evaluated the influence on stool
volume.
Finally, strain Lactobacillus reuteri ATCC 55730 had
proven moderate clinical effect in treating acute gas-
troenteritis in children; however, this strain was
found to carry transferable resistance trait for anti-
biotic resistance and was replaced by a new strain, L.
reuteri DSM 17938 [10]. This, new strain L. reuteri
DSM 17938 was investigated by 3 RCTs; two RCTs
(n=196) were analyzed in systematic review from
2014 and showed significantly reduced diarrhea du-
ration (MD, 32 hours; 95% CI, 41 to 24) [11].
Subsequently, one more RCT was published includ-
ing 64 infants and children, showing similar results
in the reduction of diarrhea duration [12].
Generally, after reviewing these results ESPGHAN
WG on pre- and probiotics recommended the use of
the following probiotic strains as an adjunct to rehy-
dration therapy: LGG (quality of evidence: low; rec-
ommendation: strong), S. boulardii (quality of evi-
dence: low; recommendation: strong) and L. reuteri
DSM 17938 (quality of evidence: very low; recom-
mendation: weak) [6].
It should be emphasized once again that system-
atic review of the literature did not found enough
evidence (or evidence was negative) to recommend
other probiotic strains.
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Iva Hojsak:Probiotics in Children: What Is the Evidence?
For clinicians, it is of importance to know that pro-
biotics have been proven mostly in watery (mainly
viral) diarrhea and that their efficacy is more pro-
nounced on the duration of diarrhea (study showed
ability to shorten diarrhea for 1 day) than in stool
volume [3,6]. Furthermore, when recommended
they should be recommended only as an adjunct to
rehydration and it is better to use them in the early
course of disease [6].
PREVENTION OF ANTIBIOTIC
ASSOCIATED DIARRHEA
Antibiotic-associated diarrhea (AAD) is a com-
mon complication of antibiotic therapy, defined as
diarrhea that occurs in relation to antibiotic treat-
ment with the exclusion of other etiologies [13]. It is
more commonly caused by antibiotics that target
anaerobic bacteria (e.g. clindamycin, penicillin, amoxi-
cillin and clavulanic acid etc.) which cause significant
disruption of the enteric microbiome [14,15]. Clini-
cally, AAD may present as mild diarrhea, but it can
also present as fulminant pseudomembranous colitis
caused by Clostridium difficile [13]. Measures which
can prevent AAD are limited mainly to reduction in
antibiotic use, type of antibiotic prescribed and the
use of probiotics.
Due to large number of studies and different rec-
ommendations available ESPGHAN WG on pre- and
probiotics preformed systematic review with meta-ana-
lysis with aim to provide evidence based guidelines
for every specific probiotic strain in the prevention of
AAD [13]. This systematic review found only two
probiotic strains with enough evidence (efficacy pro-
ven in more than 2 well-designed RCTs); these
strains are LGG and S. boulardii [13].
LGG was investigated in 5 RCTs (n=445) and ad-
ministration in children reduced the risk of AAD
from 23% to 9.6% (RR, 0.48; 95% CI, 0.26 to 0.89), re-
gardless of the reason for which antibiotics and pro-
biotics were used [13]. However, only one trial [16]
evaluated the effect of LGG in the prevention of C. dif-
ficile-associated diarrhea in children and found no
effect.
Similarly, S. boulardii used in children reduced the
risk of AAD based on 6 RCTs (n=1,653) from 20.9%
to 8.8% (RR, 0.43; 95% CI, 0.30 to 0.60) [13]. Further-
more, the administration of S. boulardii reduced the
risk of C. difficile-associated diarrhea in children (2
RCTs, n=579; RR, 0.25; 95% CI, 0.08 to 0.73) [13].
However, there is a constant discussion whether
probiotics should be used every time antibiotic is
prescribed. The reasons for their routine use are the
proven effect and the fact that AAD can be serious ill-
ness [13,17]. On contrary, reasons not to use them is
usually related to their costs and fact that AAD is
usually self-limited mild disease. There are certain
groups of patients that would benefit the most from
probiotic use including children of younger age, hos-
pitalized children and children who experienced
AAD (especially C. difficile-associated diarrhea) be-
fore [17]. Once again, the recent review identified
only two strains to be effective in prevention of AAD;
these are LGG (quality of evidence: moderate, rec-
ommendation: strong) and S. boulardii (quality of
evidence: moderate, recommendation: strong) [13].
For prevention of C. difficile-associated diarrhea only
S. boulardii showed efficacy (quality of evidence:
moderate, recommendation: conditional) [13].
There is always a question when to administer
probiotic in order not to be killed by antibiotic; there
are no scientific evidence for that. However, some
probiotic strains (like S. boulardii) are resistant to an-
tibiotics used for bacterial infections. On the other
hand, other strains (like LGG) were effective in RCTs
when used for AAD, therefore their administration
should follow the same scheme like in RCTs.
PREVENTION OF INFECTIONS
Infectious diseases are the most important cause
of morbidity in children where respiratory and gas-
trointestinal (GI) infections encounter for majority
of them [18]. Recurrent respiratory tract infections
are common problem in preschool age, mainly due to
the presence of unfavorable environmental con-
ditions including early socialization in daycare cen-
ters and the physiologic immaturity of the immune
142    Vol. 20, No. 3, September 2017
Pediatr Gastroenterol Hepatol Nutr
system [19]. There are two major settings where
children acquire respiratory and GI infections and
those are hospital and day care centers.
Prevention of infections in day care centers
Children who attend daycare centers have 2-3
times more infections than children who stay at
home, they have more outpatient doctor and emer-
gency room visits and increased usage of prescribed
antibiotics [20]. Furthermore, they cause a sub-
stantial economic burden not only for child’s family,
but healthcare in general; their costs are estimated to
be $1.8 billion per year in the United States [21].
Taking all that into account, together with possible
complications, respiratory tract and GI infections are
important health care problem for pediatricians who
are facing a real task to discriminate the children
who are at higher risk and try to offer preventive
measures. These preventive measures usually in-
clude good hand hygiene, absenteeism of ill child
from daycare center in order to prevent spreading of
infection and vaccination for influenza and rotavirus
[22]. However, all those measures often are in-
effective leaving a place for possible new modalities,
like probiotics. In the last two decades, there have
been an increasing number of trials investigating the
role of probiotics on the prevention of common in-
fections in children.
As presented in Table 1, there are several trials
which evaluated probiotics in the prevention of res-
piratory tract infection in children attending daycare
centers [23-34]. Interestingly, majority of studies be-
yond infancy found positive effect on the lowering of
respiratory tract infections [23,24,26-29,31]. Recent
meta-analysis reviewed available literature and
found that probiotics (in general) reduce the risk of
respiratory tract infections (RR, 0.89; 95% CI, 0.82 to
0.96) [35]. Unfortunately, this meta-analysis in-
cluded all age groups, was not strain specific and was
not stratified based on the type of facility where pro-
biotics were used. However, it was reported that al-
though there was no effect on the duration of illness,
absenteeism from the kindergarten was decreased
[35].
Based on the presented results in Table 1, it can be
concluded that probiotics could have a place in the
prevention of upper respiratory tract infections.
However, questions that remain are what strain to
use, in which dose and when. Based on well-de-
signed RCTs in children (Table 1), LGG was exam-
ined in 3 studies [24,26,27] involving all together
1,375 children and all studies reported positive effect
on the lowering the incidence of respiratory tract
infections. Other strain Bifidobacterium animalis
subsp. lactis was evaluated in 4 RCTs [25,30,32,34]
from which all found negative results.
The question is whether to recommend probiotic
use routinely in all children who are at increased risk
for respiratory infection. Based on currently avail-
able evidence, it seems prudent to use strains with
proven efficacy in more than 2 RCT (which is LGG).
However, there are no cost-effective analyses. Regres-
sion analysis determined that children who would
benefit the most from the LGG use were children of
younger age and with recurrent respiratory in-
fections during winter months [26].
Majority of studies which investigated probiotic
use in the prevention of respiratory tract infections
also investigated the risk of acquiring GI infection
(Table 1). Results from those studies are weak. There
is no meta-analysis which assessed overall effect,
however, based on literature search there are no 2
RCTs which investigated same probiotic strain and
yielding positive results. Of note is that both studies
investigating LGG found no effect [24,26], similarly
is for B. animalis subsp. lactis investigated by other
two studies [30,32].
All these results, however, should be interpreted
with caution because most of them were performed
in the winter period when the incidence of GI in-
fections is much lower, and therefore someone can
argue that the sample size was not powered enough
to assess GI risk.
Nosocomial infections
Nosocomial, hospital-acquired or healthcare-asso-
ciated infections, develop during a hospital stay and
they are not present or incubating at the admission;
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Iva Hojsak:Probiotics in Children: What Is the Evidence?
Table 1.
Probiotics in Prevention of Respiratory and Gastrointestinal Infections in Children Attending Day Care Centers
Author n (age) Probiotic (dose) Effect on respiratory infection
Effect on
gastrointestinal
infection
Hatakka et al.
[24] (2001)
571 (1-6 y) LGG (1-2×108 CFU/day) Lower number of upper respiratory
tract infections
Lower number of prescribed
antibiotics
NS
Saavedra et al.
[33] (2004)
118 (3-24 mo) Bifidobacterium animalis
subsp. lactis (Bb12)
(107 CFU)+Streptococcus
thermophilus (106 CFU)
Not significant difference in the
incidence of upper respiratory
tract infection
Lower number of prescribed
antibiotics
NS
Weizman et al.
[34] (2005)
210 (4-10 mo) Bifidobacterium animalis subsp.
lactis (Bb12) or Lactobacillus
reuteri 55730 (minimum 107
CFU)
Not significant difference in the
incidence of upper respiratory
tract infection
L. reuteri group-lower number of
prescribed antibiotics
Not assessed
Lin et al.
[29] (2009)
1,062
(preschool
children)
Lactobacillus casei rhamnosus
(108 CFU), Lactobacillus
rhamnosus T cell-1 (1010 CFU),
multiple probiotic strains
Reduction in respiratory infection
in the L. casei rhamnosus group
Not significant for other strains
Multiple strain
group showed
reduction in
gastrointestinal
illness
Leyer et al.
[28] (2009)
326 (3-5 y) Lactobacillus acidophilus NCFM
(1010 CFU) vs. Lactobacillus
acidophilus NCFM+Bifidobacterium
animalis subsp. lactis Bi-07
(1010 CFU)
Lower fiver and coughing episodes,
lower antibiotic use in single and
combination group
Not assessed
Hojsak et al.
[26] (2010)
281 (1-7 y) LGG (109 CFU) Lower number of upper respiratory
tract infections
No difference in prescribed antibiotics
NS
Merenstein et al.
[31] (2010)
638 (3-6 y) Lactobacillus casei DN-114
001/CNCM I-1518 (108 CFU)
(in yoghurt with Streptococcus
thermophilus and Lactobacillus
bulgaricus)
Lower number of upper respiratory
tract infections
Lower number of prescribed
antibiotics
NS
Merenstein et al.
[32] (2010)
182 (13 y) Bifidobacterium animalis subsp.
lactis (Bb12) (1010 CFU)
(yoghurt containing also
Streptococcus thermophilus
and Lactobacillus bulgaricus)
NS NS
Merenstein et al.
[30] (2011)
172 (2-4 y) Bifidobacterium animalis subsp.
lactis (Bb12) (1010 CFU)
(yoghurt containing also
Streptococcus thermophilus
and Lactobacillus bulgaricus)
NS NS
Kumpu et al.
[27] (2012)
523 (2-6 y) LGG (6.7×105 to 1.9×106
CFU/mL)
Lower risk of respiratory infection
in completed cases subgroup
(recovery of LGG in fecal samples)
Not assessed
Gutierrez-Castrellon
et al. [23] (2014)
336 (0.5-3 y) Lactobacillus reuteri DSM 17938
(108 CFU)
Lower risk of respiratory tract
infections
Lower risk of
diarrhea
Hojsak et al.
[25] (2016)
210 (1-7 y) Bifidobacterium animalis subsp.
lactis (Bb12) (109 CFU)
NS NS
LGG: Lactobacillus rhamnosus GG, CFU: colony-forming units, NS: not significant.
144    Vol. 20, No. 3, September 2017
Pediatr Gastroenterol Hepatol Nutr
infections that occur more than 48 hours after the
admission are usually considered as nosocomial
[36]. The incidence of nosocomial infections on pe-
diatric wards even in developed countries is still
high, ranging from 5% to 10% and GI and respiratory
tract infections account for the majority of them
[37]. Nosocomial infections have several negative
impacts; they worsen the treatment outcome, could
prolong the hospitalization, and significantly increase
hospital costs [38]. Standard preventive measures,
mainly hand hygiene, isolation of sick children and
reduction in the number of hospitalized patients de-
creases infection spreading, but cannot successfully
prevent them [39,40]. Therefore, there is a place for
new strategies, one of which is the use of probiotics.
Recently, ESPGHAN WG on pre- and probiotics
performed systematic review on the role of different
probiotic strains in the prevention of nosocomial di-
arrhea [41]. This meta-analysis identified 8 RCTs out
of which 3 investigated LGG. The administration of
LGG reduced the risk of nosocomial diarrhea from
13.9% to 5.2% (2 RCTs, n=1823; RR, 0.35; 95% CI,
0.19 to 0.65) [41]. On contrary, L. reuteri DSM 17938
was investigated by two studies (same probiotic
strain but different doses: 108 CFU/day [42] and 109
CFU/day [43]) and had negative results (RR, 1.11;
95% CI, 0.68 to 1.81) [41]. Based on the evidence
ESPGHAN WG concludes that if probiotics for pre-
venting nosocomial diarrhea in children are consid-
ered, LGG (at least 109 CFU/day, for the duration of
hospital stay) should be used (quality of evidence:
moderate, recommendation: strong) [41].
Due to lack of cost effectiveness, currently there is
a need for identifying children in risk for acquiring
nosocomial diarrhea. Based on regression analysis
published in one of the RCTs [38] children who stay
longer in hospital are especially prone to nosocomial
infection, therefore this group of children would
benefit the most.
On contrary to role of probiotics in the prevention
of nosocomial diarrhea, we have only limited evi-
dence of the role of probiotics in the prevention of
nosocomial respiratory tract infection outside of in-
tensive care unit. There are only two (although big)
RCTs. One RCT investigated LGG (n=742) at the
dose of 109 CFU and found reduction in risk of upper
respiratory tract infection [41]. Other study, per-
formed at the same center used different probiotic
strain, B. animalis subsp. lactis (Chr Hansen,
Denmark) at the same dose, was not able to prove
positive effect [44]. Authors also identified that chil-
dren who stayed longer in the hospital and who were
younger had higher chance of acquiring upper respi-
ratory tract infections [41]. Although there is an evi-
dence that some probiotic strain could have effect in
the prevention of infection, still there is no enough
evidence to recommend probiotics for the prevention
of nosocomial respiratory tract infections.
CONCLUSION
Above mentioned evidence further demonstrates
that not all probiotics have the same efficacy for ev-
ery specific clinical indication. Based on currently
available evidence certain probiotic strains (LGG and
S. boulardii) have proven effect in the treatment of
acute gastroenteritis and prevention of AAD. Fur-
thermore, LGG was proven to be effective in pre-
vention of nosocomial diarrhea and respiratory tract
infection in day care centers.
Field of probiotics increases tremendously, thus it
is hard for clinicians to follow the literature. Therefore,
it is of utmost importance to recognize scientific au-
thorities and to follow up their guidelines.
ACKNOWLEDGEMENTS
Iva Hojsak has participated as a clinical inves-
tigator for Biogaia and Chr Hansen and speaker for
Biogaia and Medis Adria.
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... The decision regarding the duration of probiotic usage should be customized, taking into account factors such as the intended purpose of using probiotics, the specific type or product of probiotics being used, and the underlying health conditions. Probiotics are used for shortterm relief of acute digestive issues, such as diarrhea and antibiotic-associated diarrhea [33], as well as for long-term management of chronic digestive ailments, such as irritable bowel syndrome and inflammatory bowel disease [34]. ...
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This research study aimed to investigate the impact of probiotic mouthwash and kefir on the surface characteristics, specifically surface roughness and microhardness, of different restorative materials, as well as permanent and deciduous tooth enamels. Thirty disc-shaped specimens were prepared from composite resin (G-aenial Posterior (GP)), polyacid-modified composite resin (compomer) (Dyract-XP (DXP)), and resin-modified glass ionomer cement (Ionoseal (IS)). Additionally, thirty specimens of enamel were obtained from permanent teeth (PT) and thirty from deciduous teeth (DT) by embedding buccal and lingual sections, acquired through vertical sectioning of 15 permanent and 15 deciduous human tooth crowns in the mesiodistal orientation within acrylic resin blocks. The specimens were then categorized into three distinct groups and immersed for 14 days in one of the following solutions: distilled water, kefir or probiotic mouthwash. The mean surface roughness values of all specimens were assessed using an atomic force microscope, while the mean surface microhardness was measured using a Vickers hardness measuring instrument. The results revealed a statistically significant difference in mean surface roughness among the various restorative materials (p < 0.001). Among the restorative materials, the IS material exhibited notably higher mean surface roughness values than other restorative materials and tooth enamel, while no significant differences were observed between the PT and DT groups. Importantly, the main effect of the solutions under investigation was not statistically significant (p = 0.208). No significant difference was found between the surface roughness values of specimens subjected to the different solutions. When evaluating the effects of materials and solutions on microhardness, the main effects of material and solution variables and the influence of material-solution interactions were statistically significant (p < 0.001). Taken together, these results indicate that consistent use of kefir or probiotic mouthwashes may impact the surface properties of various restorative materials and tooth enamel.
... The word probiotic was derived from a Greek word in which pro means promoting and biotic means life [1]. The term probiotic was also defined by World Health Organization as live microorganisms which, when taken in appropriate quantity, provide a health benefit to the host [2]. ...
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ackground: Exploration of beneficial bacteria as probiotics inputs are drawing interest in dairy industry but their long-term survival and viability is an important consideration. Methods: The current work focused on the exploration of probiotic potential of indigenously isolated Lactobacillus strains from dairy products and their encapsulation and utilization in yogurt formation. Results: These Lactobacillus strains were identified as Lactobacillus fermentum MGA23-1 and Lactobacillus fermentum LMEM19 and found resistant to inhibitory substances like phenol (0.2%), bile salts (0.3%), pancreatin (0.5%) and pepsin (0.3%). The highest antibacterial activity was observed by Lactobacillus fermentum MGA23-1 against Pseudomonas aeruginosa (13mm). Encapsulation experiment showed that the number of bacterial CFU/g increased significantly (p < 0.05) in beads during storage up to 7 days. Chemical characterization of microcapsules was assessed using FTIR and showed characteristics wavelength major at 1541-1716 cm-1 and 3336 cm-1. Yogurt was prepared using a single probiotic strain, in a consortium of Lactobacillus fermentum MGA23-1 and Lactobacillus fermentum LMEM19 and in the form of beads. Best results were observed in the case of microencapsulation. Conclusion: It was concluded that both strains had the potential to be used as a probiotic in the dairy industry. B Abstract www.als-journal.com/ ISSN 2310-5380/ July 2021
... It is well known that, especially in monogastrics, bacterial probiotics can modify the permeability of the intestinal mucosa, activate immune cells and prevent adhesion of pathogens to the intestinal mucosa [16,17]. For antibioticassociated diarrhea, probiotics have been shown to be useful as a preventative treatment, and potentially, they can be used to alleviate signs and symptoms once antibiotic-induced diarrhea has occurred [18,19,20]. ...
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Aims: This research aims to isolate and characterize from dairy products, in particular yogurts, cultivated Lactobacillus strains with potential for use as probiotics in poultry farming. Study Design: This research consists of four parts, an introduction with literature review, a description of the materials and methods used, finally the results obtained and their discussion. Place and Duration of Study: Central Veterinary Laboratory of Kinshasa, specifically in the Bacteriology and Animal Services departments, between April and September 2022. Methodology: A yogurt was cultured in order to observe the presence of Lactobacilli in the MRS (Mans, Rogosa and Sharp) Agar culture medium; this culture revealed the growth of Lactobacilli. It was even proceeded to the serial dilution of these strains, the results had also revealed the growth of Lactobacilli in the 6 test tubes used. Results: The results obtained showed a significant increase in weight (positive effect on the immune system) in the poultry of the experimental group and an absence of pathogenicity after an incubation period (inhibitory effect of strains of Lactobacilli on those of Escherichia coli and Streptococcus sp.) whereas in the control group, the poultry showed a lower weight gain compared to the experimental group and developed colibacillosis associated with other effects such as weakness, fever and angina after an incubation period. Conclusion: The positive results of Lactobacilli strains obtained in poultry in the experimental group show the potential of these strains to be used as probiotics in poultry farming to improve poultry health through the inhibitory effect of these strains on pathogenic Escherichia coli and Streptococcus sp. This opens up safe alternatives to the use of these strains to fight the misuse of antibiotics by reducing their use in human and animal care.
... These studies were different in some aspects, including the sample size, type of probiotics, probiotic doses, type of the studied infections, wards where patients were admitted (ICU or non-ICU), and type of infant feeding (breastfeeding or formula), which can cause conflicting findings. In a review study published in 2017, 73 Hojsak discussed the effect of probiotics on children and suggested that L. rhamnosus GG is efficacious for preventing hospital-acquired diarrhea and respiratory tract infections in daycare centers. It is important to note that the influences of probiotics are speciesspecific, and not all types of probiotics are suitable for fighting different infections. ...
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Background and Aims The present study aimed to review probiotics' clinical efficacy in preventing infectious diseases among hospitalized patients in ICU and non‐ICU wards. Methods A search of Medline, EMBASE, The Cochrane Library, Science Direct, Open Grey, and Google Scholar was conducted for eligible publications from 2002 to 2020 following the requirements outlined in the PRISMA guideline. The search strategy was based on the combination of the following terms: “probiotics,” “prebiotics,” “synbiotics,” and “cross‐infection.” The logical operators “AND” (or the equivalent operator for the databases) and “OR” (e.g., probiotics OR prebiotics OR synbiotics) were used. Results The results indicated that the probiotic consumption caused a significant reduction in antibiotic‐associated diarrhea (AAD) and Clostridioides difficile infection (CDI) in 2/8 randomized clinical trials (RCTs) investigating AAD/CDI. Also, 5/12 clinical trials highlighted the considerable effects of probiotics on the reduction or prevention of ventilator associated pneumoniae (VAP), so the mean prevalence of VAP was lower in the probiotic group than in the placebo group. The total rate of nosocomial infections among preterm infants was nonsignificantly higher in the probiotic group compared to the control group. Conclusion This systematic review shows that the administration of probiotics has moderate preventive or mitigating effects on the occurrence of VAP in ICU patients, CDI, AAD, and nosocomial infections among children. Consequently, applying antibiotics along with the proper probiotic species can be advantageous.
... These outcomes include death, severe dehydration, etc. In contrast, Hojsak [8], a Croatian researcher, argued that "not all probiotic strains have the same efficacy for all clinical indications, therefore, only strains with proven efficacy and safety should be recommended". This contradictory finding indicates a need for further investigation into the issue of probiotic use in treating gastroenteritis in children. ...
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Acute infectious diarrhea (AID) is one of the most common diseases in pediatric age with relevant burden both in high and in low-income countries. Thanks to their direct action on enterocyte functions and indirect actions on the mucosal and systemic immune system and on intestinal microbiome, probiotics are an ideal intervention to treat AID in childhood. However, their efficacy is strictly related to strains and indications, and practitioners should take this information into account in clinical practice. This chapter summarizes the main mechanisms of action of probiotics in AID, with a focus on proof of efficacy supporting their use in prevention and treatment of childhood AID. The use of selected strains in appropriate doses is strongly recommended by guidelines of AID, based on compelling proofs of efficacy and safety. At present, therapy with probiotics of AID is probably the strongest indication for probiotic use in medicine. Their role in prevention of AID is however questionable in healthy population, whereas it should be considered in at-risk population. Evidence for prevention of diarrhea in day-care centers and communities is lacking, but consistent evidence supports efficacy in prevention of hospital acquired diarrhea. Finally, this chapter presents novelties on this topic, in particular the role of rotavirus immunization on probiotics effectiveness and the effect of probiotics and postbiotics on Covid-associated diarrhea. Overall: AID is the most convincing area for probiotic use in children with gastrointestinal disorders, and effective strains should be used early on after onset of symptoms.
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Introduction An appendectomy is the most common urgent surgical intra-abdominal procedure performed on children. Approximately one third of the population ends up having complicated appendicitis requiring the use of intravenous antibiotics and a prolonged hospital stay. Antibiotic-associated diarrhea (AAD) is a common obstacle seen in both outpatient and inpatient settings. Use of probiotics in a pediatric population exposed to antibiotics and gastrointestinal surgery such as an appendectomy may provide a protective effect and prevent AAD. Methods This study was a prospective randomized controlled trial conducted at a large freestanding pediatric hospital. Patients in the treatment group received a standard dose of Lactobacillus rhamnosus GG capsule twice a day until discharge, and those in the control group received a placebo twice a day until discharge. In this study, we hypothesize that patients given probiotics will decrease the overall length of stay (LOS) by 25% versus the LOS in those patients who do not receive probiotics. Results Ninety-eight patients were randomized, with 93 included in the data analysis, into the probiotic group ( n = 57) and the placebo group ( n = 41). The LOS for the probiotic group ( n = 53; M = 121.55, SD = 59.51) was lower than that for the placebo group ( n = 40; M = 131.69, SD = 74.27) but was not found to be statistically different ( t (91) = 0.731, p = .467). The average total number of diarrhea counts was higher in the probiotic group ( M = 13, SD = 16) than in the placebo group ( M = 10, SD = 11) but was not found to be statistically different ( t (91) = −1.017, p = .312). Discussion Use of probiotics to reduce AAD has been found to be effective in other patient populations. Because of the small sample size, we were unable to determine if the use of L. rhamnosus in patients with complicated appendicitis was effective in reducing the LOS or average diarrhea counts.
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This document provides recommendations developed by the ESPGHAN Working Group (WG) on Probiotics and Prebiotics on the role of probiotics in the prevention of nosocomial diarrhea in children based on a systematic review of previously completed systematic reviews and of subsequently published randomized controlled trials (RCTs). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Recommendations were given only if at least 2 RCTs examined the same probiotic strain. Based on currently available evidence the WG recommends using Lactobacillus rhamnosus GG if the use of probiotics for preventing nosocomial diarrhea in children is considered.
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BACKGROUND: Probiotics may offer a safe intervention in acute infectious diarrhoea to reduce the duration and severity of the illness. OBJECTIVES: To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's trials register (July 2010), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2010), MEDLINE (1966 to July 2010), EMBASE (1988 to July 2010), and reference lists from studies and reviews. We also contacted organizations and individuals working in the field, and pharmaceutical companies manufacturing probiotic agents. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of the trial and extracted data. Primary outcomes were the mean duration of diarrhoea, stool frequency on day 2 after intervention and ongoing diarrhoea on day 4. A random-effects model was used. MAIN RESULTS: Sixty-three studies met the inclusion criteria with a total of 8014 participants. Of these, 56 trials recruited infants and young children. The trials varied in the definition used for acute diarrhoea and the end of the diarrhoeal illness, as well as in the risk of bias. The trials were undertaken in a wide range of different settings and also varied greatly in organisms tested, dosage, and participants' characteristics. No adverse events were attributed to the probiotic intervention. Probiotics reduced the duration of diarrhoea, although the size of the effect varied considerably between studies. The average of the effect was significant for mean duration of diarrhoea (mean difference 24.76 hours; 95% confidence interval 15.9 to 33.6 hours; n = 4555, trials = 35) diarrhoea lasting > 4 days (risk ratio 0.41; 0.32 to 0.53; n = 2853, trials = 29) and stool frequency on day 2 (mean difference 0.80; 0.45 to 1.14; n = 2751, trials = 20). The differences in effect size between studies was not explained by study quality, probiotic strain, the number of different strains, the viability of the organisms, dosage of organisms, the causes of diarrhoea, or the severity of the diarrhoea, or whether the studies were done in developed or developing countries. AUTHORS' CONCLUSIONS: Used alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea. However, more research is needed to guide the use of particular probiotic regimens in specific patient groups. This is the abstract of a Cochrane Review published in the Cochrane Database of Systematic Reviews (CDSR) 2010, Issue 11, DOI: 10.1002/14651858.CD003048.pub3. (www.thecochranelibrary.com). For full citation and authors details see reference 1
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Recent studies have highlighted the fact that the enteric microbiome, the trillions of microbes that inhabit the human digestive tract, has a significant effect on health and disease. Methods for manipulating the enteric microbiome, particularly through probiotics and microbial ecosystem transplantation, have undergone some study in clinical trials. We review some of the evidence for microbiome alteration in relation to childhood disease and discuss the clinical trials that have examined the manipulation of the microbiome in an effort to prevent or treat childhood disease with a primary focus on probiotics, prebiotics, and/or synbiotics (ie, probiotics + prebiotics). Studies show that alterations in the microbiome may be a consequence of events occurring during infancy and/or childhood such as prematurity, C-sections, and nosocomial infections. In addition, certain childhood diseases have been associated with microbiome alterations, namely necrotizing enterocolitis, infantile colic, asthma, atopic disease, gastrointestinal disease, diabetes, malnutrition, mood/anxiety disorders, and autism spectrum disorders. Treatment studies suggest that probiotics are potentially protective against the development of some of these diseases. Timing and duration of treatment, the optimal probiotic strain(s), and factors that may alter the composition and function of the microbiome are still in need of further research. Other treatments such as prebiotics, fecal microbial transplantation, and antibiotics have limited evidence. Future translational work, in vitro models, long-term and follow-up studies, and guidelines for the composition and viability of probiotic and microbial therapies need to be developed. Overall, there is promising evidence that manipulating the microbiome with probiotics early in life can help prevent or reduce the severity of some childhood diseases, but further research is needed to elucidate biological mechanisms and determine optimal treatments.
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Background: Respiratory tract infections (RTIs) represent one of the main health problems in children. Probiotics are viable bacteria that colonize the intestine and affect the host intestinal microbial balance. Accumulating evidence suggests that probiotic consumption may decrease the incidence of or modify RTIs. The authors systematically reviewed data from randomized controlled trials (RCTs) to investigate the effect of probiotic consumption on RTIs in children. Methods: MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for RCTs regarding the effect of probiotics on RTIs in children. The outcomes included number of children experienced with at least 1 RTI episode, duration of illness episodes, days of illness per subject, and school/day care absenteeism due to infection. A random-effects model was used to calculate pooled relative risks, or mean difference (MD) with the corresponding 95% confidence interval (CI). Results: A total of 23 trials involving 6269 children were eligible for inclusion in the systematic review. None of the trials showed a high risk of bias. The quality of the evidence of outcomes was moderate. The age range of subjects was from newborn to 18 years. The results of meta-analysis showed that probiotic consumption significantly decreased the number of subjects having at least 1 RTI episode (17 RCTs, 4513 children, relative risk 0.89, 95% CI 0.82–0.96, P = 0.004). Children supplemented with probiotics had fewer numbers of days of RTIs per person compared with children who had taken a placebo (6 RCTs, 2067 children, MD −0.16, 95% CI −0.29 to 0.02, P = 0.03), and had fewer numbers of days absent from day care/school (8 RCTs, 1499 children, MD −0.94, 95% CI −1.72 to −0.15, P = 0.02). However, there was no statistically significant difference of illness episode duration between probiotic intervention group and placebo group (9 RCTs, 2817 children, MD −0.60, 95% CI −1.49 to 0.30, P = 0.19). Conclusion: Based on the available data and taking into account the safety profile of RCTs, probiotic consumption appears to be a feasible way to decrease the incidence of RTIs in children.
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Background: Multiple studies of probiotics used to prevent nosocomial diarrhea have provided conflicting results. The effects likely depend on the probiotic strain and/or dosage. The aim of this study was to assess the effectiveness of Lactobacillus reuteri DSM 17938 (L reuteri) [daily dose of 1 x 10 colony forming units (CFU)] for preventing nosocomial diarrhea in children. Methods: We conducted a multicenter, randomized, double- blind, placebo-controlled trial in 184 children, 1 to 48 month of age , admitted to the hospital for reasons other than diarrhea. A computer-generated randomization scheme was used to allocate participants to receive either L reuteri (n=91) at a daily dose of 1 x 10 CFU, for the duration of hospitalization, or an identical appearing placebo (n=93). Patients, study personnel, and data analysts were blinded to assignment. The primary outcome was the occurrence of nosocomial diarrhea (≥3 loose or watery stools in 24 h that occurred >72 h after admission). Analysis was by intention-to-treat. Results: Baseline characteristics were similar in the 2 groups. Nosocomial diarrhea occurred in 13 (7.1%) children. No difference was found between the L reuteri and the placebo groups (7/91 versus 6/93, respectively, relative risk; 1.19; 95% confidence interval 0.43 to 3.27). There was also no difference between the L reuteri and placebo groups for any of the secondary outcomes, including adverse effects. Rotavirus vaccination status had no effect on the results. Conclusion: L reuteri in the dosage regimen used was not effective in preventing nosocomial diarrhea in children.
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Background: Diarrhoea accounts for 1.8 million deaths in children in low- and middle-income countries (LMICs). One of the identified strategies to prevent diarrhoea is hand washing. Objectives: To assess the effects of hand washing promotion interventions on diarrhoeal episodes in children and adults. Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register (27 May 2015); CENTRAL (published in the Cochrane Library 2015, Issue 5); MEDLINE (1966 to 27 May 2015); EMBASE (1974 to 27 May 2015); LILACS (1982 to 27 May 2015); PsycINFO (1967 to 27 May 2015); Science Citation Index and Social Science Citation Index (1981 to 27 May 2015); ERIC (1966 to 27 May 2015); SPECTR (2000 to 27 May 2015); Bibliomap (1990 to 27 May 2015); RoRe, The Grey Literature (2002 to 27 May 2015); World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), metaRegister of Controlled Trials (mRCT), and reference lists of articles up to 27 May 2015. We also contacted researchers and organizations in the field. Selection criteria: Individually randomized controlled trials (RCTs) and cluster-RCTs that compared the effects of hand washing interventions on diarrhoea episodes in children and adults with no intervention. Data collection and analysis: Three review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. We stratified the analyses for child day-care centres or schools, community, and hospital-based settings. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CIs). We used the GRADE approach to assess the quality of evidence. Main results: We included 22 RCTs: 12 trials from child day-care centres or schools in mainly high-income countries (54,006 participants), nine community-based trials in LMICs (15,303 participants), and one hospital-based trial among people with acquired immune deficiency syndrome (AIDS) (148 participants).Hand washing promotion (education activities, sometimes with provision of soap) at child day-care facilities or schools prevents around one-third of diarrhoea episodes in high income countries (rate ratio 0.70; 95% CI 0.58 to 0.85; nine trials, 4664 participants, high quality evidence), and may prevent a similar proportion in LMICs but only two trials from urban Egypt and Kenya have evaluated this (rate ratio 0.66, 95% CI 0.43 to 0.99; two trials, 45,380 participants, low quality evidence). Only three trials reported measures of behaviour change and the methods of data collection were susceptible to bias. In one trial from the USA hand washing behaviour was reported to improve; and in the trial from Kenya that provided free soap, hand washing did not increase, but soap use did (data not pooled; three trials, 1845 participants, low quality evidence).Hand washing promotion among communities in LMICs probably prevents around one-quarter of diarrhoea episodes (rate ratio 0.72, 95% CI 0.62 to 0.83; eight trials, 14,726 participants, moderate quality evidence). However, six of these eight trials were from Asian settings, with only single trials from South America and sub-Saharan Africa. In six trials, soap was provided free alongside hand washing education, and the overall average effect size was larger than in the two trials which did not provide soap (soap provided: rate ratio 0.66, 95% CI 0.56 to 0.78; six trials, 11,422 participants; education only: rate ratio: 0.84, 95% CI 0.67 to 1.05; two trials, 3304 participants). There was increased hand washing at major prompts (before eating/cooking, after visiting the toilet or cleaning the baby's bottom), and increased compliance to hand hygiene procedure (behavioural outcome) in the intervention groups than the control in community trials (data not pooled: three trials, 3490 participants, high quality evidence).Hand washing promotion for the one trial conducted in a hospital among high-risk population showed significant reduction in mean episodes of diarrhoea (1.68 fewer) in the intervention group (Mean difference 1.68, 95% CI 1.93 to 1.43; one trial, 148 participants, moderate quality evidence). There was increase in hand washing frequency, seven times per day in the intervention group versus three times in the control in this hospital trial (one trial, 148 participants, moderate quality evidence).We found no trials evaluating or reporting the effects of hand washing promotions on diarrhoea-related deaths, all-cause-under five mortality, or costs. Authors' conclusions: Hand washing promotion probably reduces diarrhoea episodes in both child day-care centres in high-income countries and among communities living in LMICs by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term.
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Two randomized controlled clinical trials have shown that Lactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea. This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1×10(8)CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded. The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15h, 60.4±24.5h [95% CI: 51.0-69.7h] vs. 74.3±15.3h [95% CI: 68.7-79.9h], p<0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79, p<0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted. L. reuteri DSM 17938 is effective, safe, and well-tolerated in outpatient children with acute infectious diarrhea. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
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This paper provides recommendations, developed by the Working Group (WG) on Probiotics of the ESPGHAN, for the use of probiotics for the prevention of antibiotic-associated diarrhea (AAD) in children based on a systematic review of previously completed systematic reviews and of randomized controlled trials (RCTs) published subsequently to these reviews. The use of probiotics for the treatment of AAD is not covered. The recommendations were formulated only if at least 2 RCTs that used a given probiotic (with strain specification) were available. The quality of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. If the use of probiotics for preventing AAD is considered because of the existence of risk factors such as class of antibiotic(s), duration of antibiotic treatment, age, need for hospitalization, comorbidities, or previous episodes of AAD diarrhea, the WG recommends using Lactobacillus rhamnosus GG (moderate QoE, strong recommendation) or Saccharomyces boulardii (moderate QoE, strong recommendation). If the use of probiotics for preventing C. difficile-associated diarrhea is considered, the WG suggests using S. boulardii (low QoE, conditional recommendation). Other strains or combinations of strains have been tested, but sufficient evidence is still lacking.
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