medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2025-19-72-79medalphabet-4520Research ArticleСтатьиМикробиом лимфатического глоточного кольца и пробиотикиMicrobiome of the lymphatic pharyngeal ring and probioticshttps://orcid.org/0000-0002-4689-3591ОрловаС. В.OrlovaS. V.

Орлова Светлана Владимировна, д.м.н., проф., зав. кафедрой диетологии и клинической нутрициологии, главный научный сотрудник

Москва

Orlova Svetlana V., DM Sci (habil.), professor, head of Dept of Dietetics and Clinical Nutrition, chief researcher

Moscow 

orlova-sv@rudn.ruhttps://orcid.org/0000-0002-3811-9459ПрокопенкоЕ. В.ProkopenkoE. V.

Прокопенко Елена Валерьевна, руководитель отдела развития и сопровождения МИС и сервисов департамента по развитию медицинской деятельности ООО «Инвитро»

Москва

Prokopenko Elena V., head of Dept of Development and Support of MIS and Services of the Dept for the Development of Medical Activities of Invitro LLC

Moscow 

elvprokopenko@gmail.comhttps://orcid.org/0000-0003-4099-2967ПодопригораИ. В.PodoprigoraI. V.

Подопригора Ирина Викторовна, к.м.н., доцент, зав. кафедрой микробиологии им. В.С. Киктенко медицинского факультета

Москва

Podoprigora Irina V., PhD Med, associate professor, head of Dept of Microbiology named after V.S. Kiktenko of the Faculty of Medicine

Moscow 

podoprigora-iv@rudn.ruhttps://orcid.org/0000-0003-3220-0333НикитинаЕ. А.NikitinaE. A.

Никитина Елена Александровна, к.м.н., доцент кафедры диетологии и клинической нутрициологии, научный сотрудник, эксперт Методического аккредитационно-симуляционного центра

Москва

Nikitina Elena A., PhD Med, associate professor at Dept of Dietetics and Clinical Nutrition, researcher, expert of the Methodological Accreditation and Simulation Center

Moscow 

nikitina-ea1@rudn.ruhttps://orcid.org/0000-0003-3309-4683ПопадюкВ. И.PopadyukV. I.

Попадюк Валентин Иванович, д.м.н., проф., декан факультета непрерывного медицинского образования (ФНМО), зав. кафедрой оториноларингологии МИ

Москва

Popadyuk Valentin I., DM Sci (habil.), professor, dean of Faculty of Continuing Medical Education Faculty, head of Dept of Otorhinolaryngology MI

Moscow 

lorval04@mail.ruhttps://orcid.org/0000-0001-6966-8656КириченкоИ. М.KirichenkoI. M.

Кириченко Ирина Михайловна, д.м.н., проф. кафедры оториноларингологии Медицинского института, главный оториноларинголог Международного медицинского центра «Он клиник»

Москва

Kirichenko Irina M., DM Sci (habil.), professor at Dept of Otorhinolaryngology of the Medical Institute, Head of the Dept of Otorhinolaryngology of the International Medical Center On Clinics

Moscow 

loririna@yandex.ruhttps://orcid.org/0009-0007-5460-5178КузнецоваН. В.KuznetsovaN. V.

Кузнецова Надежда Владимировна, аспирант кафедры оториноларингологии Медицинского института

Москва

Kuznetsova Nadezhda V., postgraduate student at Dept of Otorhinolaryngology of the Medical Institute

Moscow 

1142230493@rudn.ruhttps://orcid.org/0009-0004-1157-8622ОрловаА. А.OrlovaA. A.

Орлова Анастасия Алексеевна, студентка Медицинского института 

Москва

Orlova Anastasia A., student at Institute of Medicine 

Moscow 

1032202909@rudn.ruФГАОУ ВО «Российский университет дружбы народов имени Патриса Лумумбы» (РУДН) ; ГБУЗ «Научно-практический центр детской психоневрологии Департамента здравоохранения г. Москвы»РоссияPeoples’ Friendship University of RussiaRussian FederationООО «ИНВИТРО»РоссияInvitro LLCRussian FederationФГАОУ ВО «Российский университет дружбы народов имени Патриса Лумумбы» (РУДН)РоссияPeoples’ Friendship University of RussiaRussian FederationФГАОУ ВО «Российский университет дружбы народов имени Патриса Лумумбы» (РУДН) ; ГБУЗ «Научно-практический центр детской психоневрологии Департамента здравоохранения г. Москвы» ; ФГБУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» Минздрава РоссииРоссияPeoples’ Friendship University of Russia ; Scientific and Practical Center for Child Psychoneurology of the Moscow City Health Department ; National Medical Research Center for Therapy and Preventive Medicine of the Russian Ministry of HealthRussian Federation202530082025119«Диетология и нутрициология»7279Copyright © Орлова С.В., Прокопенко Е.В., Подопригора И.В., Никитина Е.А., Попадюк В.И., Кириченко И.М., Кузнецова Н.В., Орлова А.А., 20252025Орлова С.В., Прокопенко Е.В., Подопригора И.В., Никитина Е.А., Попадюк В.И., Кириченко И.М., Кузнецова Н.В., Орлова А.А.Orlova S.V., Prokopenko E.V., Podoprigora I.V., Nikitina E.A., Popadyuk V.I., Kirichenko I.M., Kuznetsova N.V., Orlova A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/4520

Кольцо Пирогова – Вальдейера содержит сложный и динамичный микробиом, баланс в котором имеет ключевое значение для местного и, возможно, системного здоровья. Различные заболевания миндалин, такие как рецидивирующий нёбный тонзиллит, аденоидит, в том числе с сопутствующим средним отитом, характеризуются специфическими дисбиотическими процессами с участием бактерий, грибов и вирусов. Перорально принимаемые пробиотики, особенно такие специфические штаммы, как Streptococcus salivarius K12 и некоторые виды Lactobacillus (например, L. rhamnosus GG, L. helveticus MIMLh5), демонстрируют высокий потенциал в модулировании экосистемы лимфатического глоточного кольца. Механизмы их действия многогранны и включают прямое ингибирование патогенов с помощью бактериоцинов, конкурентное исключение путем адгезии и колонизации поверхностей ЛГК, а также сложную модуляцию местных иммунных реакций, выработку цитокинов и повышение уровня IgA. Эффективность этих вмешательств зависит от выбора оптимальных пробиотических штаммов, дозировок и способов доставки для различных заболеваний, связанных с ЛГК.

The Waldeyer ring contains a complex and dynamic microbiome, the balance of which is of key importance for local and, possibly, systemic health. Various diseases of tonsils, such as recurrent palatine tonsillitis, adenoiditis, including with concomitant otitis media, are characterized by specific dysbiotic processes involving bacteria, fungi and viruses. Orally administered probiotics, especially such specific strains as Streptococcus salivarius K12 and some Lactobacillus species (e.g., L. rhamnosus GG, L. helveticus MIMLh5), demonstrate high potential in modulating the ecosystem of the lymphatic pharyngeal ring. Their mechanisms of action are multifaceted and include direct inhibition of pathogens by bacteriocins, competitive exclusion by adhesion and colonization of LHG surfaces, as well as complex modulation of local immune responses, cytokine production and increased IgA levels. The effectiveness of these interventions depends on the choice of optimal probiotic strains, dosages and delivery methods for various diseases associated with LHK.

кольцо Пирогова – Вальдейерамикробиом лимфатического глоточного кольцадисбиозрецидивирующий тонзиллитаденоидитпробиотикиStreptococcus salivarius K12Lactobacillus rhamnosus GGLactobacillus helveticusPirogov – Waldeyer ringmicrobiome of the lymphatic pharyngeal ringdysbiosisrecurrent tonsillitisadenoiditisprobioticsStreptococcus salivarius K12Lactobacillus rhamnosus GGLactobacillus helveticusПубликация выполнена при поддержке Программы стратегического академического лидерства РУДН.The publication was supported by the RUDN University Strategic Academic Leadership Program.ReferencesVon Waldeyer-Hartz H.W.G. Über den lymphatischen Apparat des Pharynx. Dtsch. Med. Wochenschr. 1884; 10: 313.Von Waldeyer-Hartz H.W.G. Über den lymphatischen Apparat des Pharynx. Dtsch. Med. Wochenschr. 1884; 10: 313.Синельников Р.Д., Синельников Я.Р., Синельников А.Я. Атлас анатомии человека. Т. 3: Учение о сосудах и лимфоидных органах / 7-е изд., перераб. В 4 т. М.: Новая волна, 2009. 216 с. ISBN978‑5‑7864‑0201‑9. С. 170–171, 196.Sinelnikov R.D., Sinelnikov Ya.R., Sinelnikov A.Ya. Atlas of Human Anatomy. Vol. 3: Theory of Vessels and Lymphoid Organs / 7th ed., revised. In 4 volumes. Moscow: Novaya Volna, 2009. 216 p. (In Russ.). ISBN978‑5‑7864‑0201‑9. Pp. 170–171, 196.Анатомия человека / под ред. М.Р. Сапина. 5-е изд., переаб. и доп. В 2 т. М.: Медицина, 2001. 640 с. ISBN5‑225‑04585‑5 / ISBN5‑225‑04586‑3. С. 503–511 (т. 1), 97, 102–107 (т. 2).Human Anatomy / edited by M.R. Sapin. 5th ed., revised. and enlarged. In 2 volumes. Moscow: Meditsina, 2001. 640 p. (In Russ.). ISBN 5-225-04585-5 / ISBN 5-225-04586-3. pp. 503–511 (vol. 1), 97, 102–107 (vol. 2).Study of “Waldeyer's ring’’ in Human Anatomy and its importance -A Literature Review". International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN: 2349- 5162. 2023 Mai; 10 (5): d692-d695. Available: http://www.jetir.org/papers/JETIR2305391.pdffStudy of “Waldeyer's ring’’ in Human Anatomy and its importance -A Literature Review". International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN: 2349- 5162. 2023 Mai; 10 (5): d692-d695. Available: http://www.jetir.org/papers/JETIR2305391.pdffMasieri S., Trabattoni D., Incorvaia C., De Luca M.C., Dell’Albani I., Leo G., Frati F. (2013). A role for Waldeyer’s ring in immunological response to allergens. Current Medical Research and Opinion. 30 (2): 203–205. https://doi.org/10.1185/03007995.2013.855185Masieri S., Trabattoni D., Incorvaia C., De Luca M.C., Dell’Albani I., Leo G., Frati F. (2013). A role for Waldeyer’s ring in immunological response to allergens. Current Medical Research and Opinion. 30 (2): 203–205. https://doi.org/10.1185/03007995.2013.855185Man WH, de Steenhuijsen Piters WA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol. 2017 May; 15 (5): 259–270. DOI: 10.1038/nrmicro.2017.14. Epub 2017 Mar 20. PMID: 28316330; PMCID: PMC7097736.Man WH, de Steenhuijsen Piters WA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol. 2017 May; 15 (5): 259–270. DOI: 10.1038/nrmicro.2017.14. Epub 2017 Mar 20. PMID: 28316330; PMCID: PMC7097736.Masieri S, Trabattoni D, Incorvaia C, De Luca MC, Dell’Albani I, Leo G, Frati F. A role for Waldeyer’s ring in immunological response to allergens. Curr Med Res Opin. 2014 Feb; 30 (2): 203–5. Doi: 10.1185/03007995.2013.855185. Epub 2013 Oct 31. PMID: 24127824.Masieri S, Trabattoni D, Incorvaia C, De Luca MC, Dell’Albani I, Leo G, Frati F. A role for Waldeyer’s ring in immunological response to allergens. Curr Med Res Opin. 2014 Feb; 30 (2): 203–5. Doi: 10.1185/03007995.2013.855185. Epub 2013 Oct 31. PMID: 24127824.Man WH, de Steenhuijsen Piters WA, Bogaert D. Микробиота дыхательных путей: привратник здоровья дыхательных путей. Nat Rev Microbiol. май 2017; 15 (5): 259–270. DOI: 10.1038/nrmicro.2017.14. Epub 2017 20 марта. PMID: 28316330; PMCID: PMC7097736.Man WH, de Steenhuijsen Piters WA, Bogaert D. Микробиота дыхательных путей: привратник здоровья дыхательных путей. Nat Rev Microbiol. май 2017; 15 (5): 259–270. DOI: 10.1038/nrmicro.2017.14. Epub 2017 20 марта. PMID: 28316330; PMCID: PMC7097736.Del Chierico F, Piazzesi A, Fiscarelli EV, Ristori MV, Pirona I, Russo A, Citerà N, Macari G, Santarsiero S, Bianco F, Antenucci V, Damiani V, Mercuri L, De Vincentis GC, Putignani L. 2024. Changes in the pharyngeal and nasal microbiota in pediatric patients with adenotonsillar hypertrophy. Microbiol Spectr 12: e00728–24. https://doi.org/10.1128/spectrum.00728–24Del Chierico F, Piazzesi A, Fiscarelli EV, Ristori MV, Pirona I, Russo A, Citerà N, Macari G, Santarsiero S, Bianco F, Antenucci V, Damiani V, Mercuri L, De Vincentis GC, Putignani L. 2024. Changes in the pharyngeal and nasal microbiota in pediatric patients with adenotonsillar hypertrophy. Microbiol Spectr 12: e00728–24. https://doi.org/10.1128/spectrum.00728–24Johnston JJ, Douglas R. Adenotonsillar microbiome: an update. Postgrad Med J. 2018 Jul; 94 (1113): 398–403. DOI: 10.1136/postgradmedj‑2018-135602. Epub 2018 Jun 8. PMID: 29884749.Johnston JJ, Douglas R. Adenotonsillar microbiome: an update. Postgrad Med J. 2018 Jul; 94 (1113): 398–403. DOI: 10.1136/postgradmedj‑2018-135602. Epub 2018 Jun 8. PMID: 29884749.Lim Y, Totsika M, Morrison M, Punyadeera C. Oral microbiome: A New biomarker reservoir for oral and oropharyngeal cancers. Theranostics. 2017; 7: 4313–21. DOI: 10.7150/thno.21804Lim Y, Totsika M, Morrison M, Punyadeera C. Oral microbiome: A New biomarker reservoir for oral and oropharyngeal cancers. Theranostics. 2017; 7: 4313–21. DOI: 10.7150/thno.21804Belvoncikova P, Splichalova P, Videnska P, Gardlik R. The Human Mycobiome: Colonization, Composition and the Role in Health and Disease. Journal of Fungi. 2022; 8 (10): 1046. https://doi.org/10.3390/jof8101046Belvoncikova P, Splichalova P, Videnska P, Gardlik R. The Human Mycobiome: Colonization, Composition and the Role in Health and Disease. Journal of Fungi. 2022; 8 (10): 1046. https://doi.org/10.3390/jof8101046Deo PN, Deshmukh R. Oral microbiome: Unveiling the fundamentals. J Oral Maxillofac Pathol. 2019 Jan-Apr; 23 (1): 122–128. DOI: 10.4103/jomfp.JOMFP_304_18. PMID: 31110428; PMCID: PMC6503789.Deo PN, Deshmukh R. Oral microbiome: Unveiling the fundamentals. J Oral Maxillofac Pathol. 2019 Jan-Apr; 23 (1): 122–128. DOI: 10.4103/jomfp.JOMFP_304_18. PMID: 31110428; PMCID: PMC6503789.Sharma N, Bhatia S, Sodhi AS, Batra N. Oral microbiome and health. AIMS Microbiol. 2018; 4: 42–66. DOI: 10.3934/microbiol.2018.1.42Sharma N, Bhatia S, Sodhi AS, Batra N. Oral microbiome and health. AIMS Microbiol. 2018; 4: 42–66. DOI: 10.3934/microbiol.2018.1.42Wang L, Xu D, Huang Q, Yang G, Zhang M, Bi J, Shan J, Li E, He S. Characterization of Tonsil Microbiota and Their Effect on Adenovirus Reactivation in Tonsillectomy Samples. Microbiol Spectr. 2021 Oct 31; 9 (2): e0124621. DOI: 10.1128/Spectrum.01246-21. Epub 2021 Oct 20. PMID: 34668748; PMCID: PMC8528100.Wang L, Xu D, Huang Q, Yang G, Zhang M, Bi J, Shan J, Li E, He S. Characterization of Tonsil Microbiota and Their Effect on Adenovirus Reactivation in Tonsillectomy Samples. Microbiol Spectr. 2021 Oct 31; 9 (2): e0124621. DOI: 10.1128/Spectrum.01246-21. Epub 2021 Oct 20. PMID: 34668748; PMCID: PMC8528100.Sato M, Li H, Ikizler MR, Werkhaven JA, Williams JV, Chappell JD, Tang YW, Wright PF. Detection of viruses in human adenoid tissues by use of multiplex PCR. J Clin Microbiol. 2009 Mar; 47 (3): 771–3. DOI: 10.1128/JCM.02331-08. Epub 2008 Dec 30. PMID: 19116356; PMCID: PMC2650959.Sato M, Li H, Ikizler MR, Werkhaven JA, Williams JV, Chappell JD, Tang YW, Wright PF. Detection of viruses in human adenoid tissues by use of multiplex PCR. J Clin Microbiol. 2009 Mar; 47 (3): 771–3. DOI: 10.1128/JCM.02331-08. Epub 2008 Dec 30. PMID: 19116356; PMCID: PMC2650959.Johnston JJ, Douglas R. Adenotonsillar microbiome: an update. Postgrad Med J. 2018 Jul; 94 (1113): 398–403. DOI: 10.1136/postgradmedj‑2018-135602. Epub 2018 Jun 8. PMID: 29884749.Johnston JJ, Douglas R. Adenotonsillar microbiome: an update. Postgrad Med J. 2018 Jul; 94 (1113): 398–403. DOI: 10.1136/postgradmedj‑2018-135602. Epub 2018 Jun 8. PMID: 29884749.Wang Q, Du J, Jie C, Ouyang H, Luo R, Li W. Bacteriology and antibiotic sensitivity of tonsillar diseases in Chinese children. Eur Arch Otorhinolaryngol 2017; 274: 3153–3159. DOI: 10.1007/s00405-017-4603-yWang Q, Du J, Jie C, Ouyang H, Luo R, Li W. Bacteriology and antibiotic sensitivity of tonsillar diseases in Chinese children. Eur Arch Otorhinolaryngol 2017; 274: 3153–3159. DOI: 10.1007/s00405-017-4603-yPontin IPO, Sanchez DCJ, Di Francesco R. Asymptomatic group A streptococcus carriage in children with recurrent tonsillitis and tonsillar hypertrophy. Int J Pediatr Otorhinolaryngol. 2016; 86: 57–59. DOI: 10.1016/j.ijporl.2016.03.044Pontin IPO, Sanchez DCJ, Di Francesco R. Asymptomatic group A streptococcus carriage in children with recurrent tonsillitis and tonsillar hypertrophy. Int J Pediatr Otorhinolaryngol. 2016; 86: 57–59. DOI: 10.1016/j.ijporl.2016.03.044Prates M, Tamashiro E, Proenca-Modena JL, Criado MF, Saturno TH, Oliveira AS, Buzatto GP, Jesus BLS, Jacob MG, Carenzi LR, Demarco RC, Massuda ET, Aragon D, Valera FCP, Arruda E, Anselmo-Lima WT. 2018. The relationship between colonization by Moraxella catarrhalis and tonsillar hypertrophy. Can J Infect Dis Med Microbiol. 2018: 5406467. DOI: 10.1155/2018/5406467Prates M, Tamashiro E, Proenca-Modena JL, Criado MF, Saturno TH, Oliveira AS, Buzatto GP, Jesus BLS, Jacob MG, Carenzi LR, Demarco RC, Massuda ET, Aragon D, Valera FCP, Arruda E, Anselmo-Lima WT. 2018. The relationship between colonization by Moraxella catarrhalis and tonsillar hypertrophy. Can J Infect Dis Med Microbiol. 2018: 5406467. DOI: 10.1155/2018/5406467Jensen A, Fagö-Olsen H, Sørensen CH, Kilian M. Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis. PLoS One. 2013; 8: e56418. DOI: 10.1371/journal.pone.0056418Jensen A, Fagö-Olsen H, Sørensen CH, Kilian M. Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis. PLoS One. 2013; 8: e56418. DOI: 10.1371/journal.pone.0056418Wu S, Hammarstedt-Nordenvall L, Jangard M, Cheng L, Radu SA, Angelidou P, Zha Y, Hamsten M, Engstrand L, Du J, Ternhag A. Tonsillar Microbiota: a Cross-Sectional Study of Patients with Chronic Tonsillitis or Tonsillar Hypertrophy. mSystems. 2021 Mar 9; 6 (2): e01302–20. DOI: 10.1128/mSystems.01302–20. PMID: 33688019; PMCID: PMC8547005.Wu S, Hammarstedt-Nordenvall L, Jangard M, Cheng L, Radu SA, Angelidou P, Zha Y, Hamsten M, Engstrand L, Du J, Ternhag A. Tonsillar Microbiota: a Cross-Sectional Study of Patients with Chronic Tonsillitis or Tonsillar Hypertrophy. mSystems. 2021 Mar 9; 6 (2): e01302–20. DOI: 10.1128/mSystems.01302–20. PMID: 33688019; PMCID: PMC8547005.Jeong JH, Lee DW, Ryu RA, Lee YS, Lee SH, Kang JO, Tae K. Bacteriologic comparison of tonsil core in recurrent tonsillitis and tonsillar hypertrophy. Laryngoscope. 2007; 117: 2146–2151. DOI: 10.1097/MLG.0b013e31814543c8Jeong JH, Lee DW, Ryu RA, Lee YS, Lee SH, Kang JO, Tae K. Bacteriologic comparison of tonsil core in recurrent tonsillitis and tonsillar hypertrophy. Laryngoscope. 2007; 117: 2146–2151. DOI: 10.1097/MLG.0b013e31814543c8Kim K.S., Min H.J. Correlations Between the Adenotonsillar Microbiome and Clinical Characteristics of Pediatric Patients with Snoring. Clin. Exp. Otorhinolaryngol. 2021; 14: 295–302. DOI: 10.21053/ceo.2020.01634Kim K.S., Min H.J. Correlations Between the Adenotonsillar Microbiome and Clinical Characteristics of Pediatric Patients with Snoring. Clin. Exp. Otorhinolaryngol. 2021; 14: 295–302. DOI: 10.21053/ceo.2020.01634Jensen A, Fagö-Olsen H, Sørensen CH, Kilian M. Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis. PLoS One. 2013; 8 (2): e56418. DOI: 10.1371/journal.pone.0056418. Epub 2013 Feb 21. PMID: 23437130; PMCID: PMC3578847.Jensen A, Fagö-Olsen H, Sørensen CH, Kilian M. Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis. PLoS One. 2013; 8 (2): e56418. DOI: 10.1371/journal.pone.0056418. Epub 2013 Feb 21. PMID: 23437130; PMCID: PMC3578847.Kostić M., Ivanov M., Babić S.S., Tepavčević Z., Radanović O., Soković M., Ćirić A. Analysis of tonsil tissues from patients diagnosed with chronic tonsillitis-microbiological profile, biofilm-forming capacity and histology. Antibiotics. 2022; 11: 1747. DOI: 10.3390/antibiotics11121747Kostić M., Ivanov M., Babić S.S., Tepavčević Z., Radanović O., Soković M., Ćirić A. Analysis of tonsil tissues from patients diagnosed with chronic tonsillitis-microbiological profile, biofilm-forming capacity and histology. Antibiotics. 2022; 11: 1747. DOI: 10.3390/antibiotics11121747Denton O, Wan Y, Beattie L, Jack T, McGoldrick P, McAllister H, Mullan C, Douglas CM, Shu W. Understanding the Role of Biofilms in Acute Recurrent Tonsillitis through 3D Bioprinting of a Novel Gelatin-PEGDA Hydrogel. Bioengineering. 2024; 11 (3): 202. https://doi.org/10.3390/bioengineering11030202Denton O, Wan Y, Beattie L, Jack T, McGoldrick P, McAllister H, Mullan C, Douglas CM, Shu W. Understanding the Role of Biofilms in Acute Recurrent Tonsillitis through 3D Bioprinting of a Novel Gelatin-PEGDA Hydrogel. Bioengineering. 2024; 11 (3): 202. https://doi.org/10.3390/bioengineering11030202Klagisa R, Racenis K, Broks R, Balode AO, Kise L, Kroica J. Analysis of Microorganism Colonization, Biofilm Production, and Antibacterial Susceptibility in Recurrent Tonsillitis and Peritonsillar Abscess Patients. Int J Mol Sci. 2022 Sep 7; 23 (18): 10273. DOI: 10.3390/ijms231810273. PMID: 36142185; PMCID: PMC9499404.Klagisa R, Racenis K, Broks R, Balode AO, Kise L, Kroica J. Analysis of Microorganism Colonization, Biofilm Production, and Antibacterial Susceptibility in Recurrent Tonsillitis and Peritonsillar Abscess Patients. Int J Mol Sci. 2022 Sep 7; 23 (18): 10273. DOI: 10.3390/ijms231810273. PMID: 36142185; PMCID: PMC9499404.Klagisa R, Racenis K, Broks R, Balode AO, Kise L, Kroica J. Analysis of Microorganism Colonization, Biofilm Production, and Antibacterial Susceptibility in Recurrent Tonsillitis and Peritonsillar Abscess Patients. Int J Mol Sci. 2022 Sep 7; 23 (18): 10273. DOI: 10.3390/ijms231810273. PMID: 36142185; PMCID: PMC9499404.Klagisa R, Racenis K, Broks R, Balode AO, Kise L, Kroica J. Analysis of Microorganism Colonization, Biofilm Production, and Antibacterial Susceptibility in Recurrent Tonsillitis and Peritonsillar Abscess Patients. Int J Mol Sci. 2022 Sep 7; 23 (18): 10273. DOI: 10.3390/ijms231810273. PMID: 36142185; PMCID: PMC9499404.Sokolovs-Karijs O, Brīvība M, Saksis R, Rozenberga M, Bunka L, Girotto F, Osīte J, Reinis A, Sumeraga G, Krūmiņa A. Comparing the Microbiome of the Adenoids in Children with Secretory Otitis Media and Children without Middle Ear Effusion. Microorganisms. 2024; 12 (8): 1523. https://doi.org/10.3390/microorganisms12081523Sokolovs-Karijs O, Brīvība M, Saksis R, Rozenberga M, Bunka L, Girotto F, Osīte J, Reinis A, Sumeraga G, Krūmiņa A. Comparing the Microbiome of the Adenoids in Children with Secretory Otitis Media and Children without Middle Ear Effusion. Microorganisms. 2024; 12 (8): 1523. https://doi.org/10.3390/microorganisms12081523Xu J, Dai W, Liang Q, Ren D. The microbiomes of adenoid and middle ear in children with otitis media with effusion and hypertrophy from a tertiary hospital in China. Int J Pediatr Otorhinolaryngol. 2020 Jul; 134: 110058. DOI: 10.1016/j.ijporl.2020.110058. Epub 2020 Apr 21. PMID: 32388082.Xu J, Dai W, Liang Q, Ren D. The microbiomes of adenoid and middle ear in children with otitis media with effusion and hypertrophy from a tertiary hospital in China. Int J Pediatr Otorhinolaryngol. 2020 Jul; 134: 110058. DOI: 10.1016/j.ijporl.2020.110058. Epub 2020 Apr 21. PMID: 32388082.Pettigrew MM, Gent JF, Pyles RB, Miller AL, Nokso-Koivisto J, Chonmaitree T. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection. J Clin Microbiol. 2011 Nov; 49 (11): 3750–5. DOI: 10.1128/JCM.01186-11. Epub 2011 Sep 7. PMID: 21900518; PMCID: PMC3209086.Pettigrew MM, Gent JF, Pyles RB, Miller AL, Nokso-Koivisto J, Chonmaitree T. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection. J Clin Microbiol. 2011 Nov; 49 (11): 3750–5. DOI: 10.1128/JCM.01186-11. Epub 2011 Sep 7. PMID: 21900518; PMCID: PMC3209086.Miura C.S., Lima T.M., Martins R.B., Jorge D.M.M., Tamashiro E., Anselmo-Lima W.T., Arruda E., Valerab F.C.P. Asymptomatic SARS-COV‑2 infection in children’s tonsils. Braz. J. Otorhinolaryngol. 2022; 88: 9. DOI: 10.1016/j.bjorl.2022.10.016Miura C.S., Lima T.M., Martins R.B., Jorge D.M.M., Tamashiro E., Anselmo-Lima W.T., Arruda E., Valerab F.C.P. Asymptomatic SARS-COV‑2 infection in children’s tonsils. Braz. J. Otorhinolaryngol. 2022; 88: 9. DOI: 10.1016/j.bjorl.2022.10.016Bezega M., Zachepylo S., Polianska V., Podovzhnii O.: Current views on the functional status of the palatine tonsils in chronic tonsillitis and alternatives in treatment strategies (literature review); Pol Otorhino Rev. 2023; 12 (1): 26–34. DOI: 10.5604/01.3001.0016.3166Bezega M., Zachepylo S., Polianska V., Podovzhnii O.: Current views on the functional status of the palatine tonsils in chronic tonsillitis and alternatives in treatment strategies (literature review); Pol Otorhino Rev. 2023; 12 (1): 26–34. DOI: 10.5604/01.3001.0016.3166Zhou X, Wu Y, Zhu Z, Lu C, Zhang C, Zeng L, Xie F, Zhang L, Zhou F. Mucosal immune response in biology, disease prevention and treatment. Signal Transduct Target Ther. 2025 Jan 8; 10 (1): 7. DOI: 10.1038/s41392‑024‑02043‑4. PMID: 39774607; PMCID: PMC11707400.Zhou X, Wu Y, Zhu Z, Lu C, Zhang C, Zeng L, Xie F, Zhang L, Zhou F. Mucosal immune response in biology, disease prevention and treatment. Signal Transduct Target Ther. 2025 Jan 8; 10 (1): 7. DOI: 10.1038/s41392‑024‑02043‑4. PMID: 39774607; PMCID: PMC11707400.Bourgeois Denis, Orsini Giovanna, Carrouel Florence. Editorial: Exploring oral microbiota dysbiosis as a risk factor for oral and non-communicable diseases. Frontiers in Oral Health. 2025; 6. DOI: 10.3389/froh.2025.1611120Bourgeois Denis, Orsini Giovanna, Carrouel Florence. Editorial: Exploring oral microbiota dysbiosis as a risk factor for oral and non-communicable diseases. Frontiers in Oral Health. 2025; 6. DOI: 10.3389/froh.2025.1611120Hrncir T. Gut Microbiota Dysbiosis: Triggers, Consequences, Diagnostic and Therapeutic Options. Microorganisms. 2022 Mar 7; 10 (3): 578. DOI: 10.3390/microorganisms10030578. PMID: 35336153; PMCID: PMC8954387.Hrncir T. Gut Microbiota Dysbiosis: Triggers, Consequences, Diagnostic and Therapeutic Options. Microorganisms. 2022 Mar 7; 10 (3): 578. DOI: 10.3390/microorganisms10030578. PMID: 35336153; PMCID: PMC8954387.Li J, Li S, Jin J, Guo R, Jin Y, Cao L, Cai X, Rao P, Zhong Y, Xiang X, Sun X, Guo J, Hu F, Ye H, Jia Y, Xiao W, An Y, Zhang X, Xia B, Yang R, Zhou Y, Wu L, Qin J, He J, Wang J, Li Z. The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis. JCI Insight. 2024 Aug 20; 9 (18): e175916. DOI: 10.1172/jci.insight.175916. PMID: 39163137; PMCID: PMC11457857.Li J, Li S, Jin J, Guo R, Jin Y, Cao L, Cai X, Rao P, Zhong Y, Xiang X, Sun X, Guo J, Hu F, Ye H, Jia Y, Xiao W, An Y, Zhang X, Xia B, Yang R, Zhou Y, Wu L, Qin J, He J, Wang J, Li Z. The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis. JCI Insight. 2024 Aug 20; 9 (18): e175916. DOI: 10.1172/jci.insight.175916. PMID: 39163137; PMCID: PMC11457857.Hirofumi Watanabe, Shin Goto, Hiroshi Mori, Koichi Higashi, Kazuyoshi Hosomichi, Naotaka Aizawa, Nao Takahashi, Masafumi Tsuchida, Yusuke Suzuki, Takuji Yamada, Arata Horii, Ituro Inoue, Ken Kurokawa, Ichiei Narita, Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy. Nephrology Dialysis Transplantation. Volume 32, Issue 12, Dec 2017; 32 (12): 2072–2079. https://doi.org/10.1093/ndt/gfw343Hirofumi Watanabe, Shin Goto, Hiroshi Mori, Koichi Higashi, Kazuyoshi Hosomichi, Naotaka Aizawa, Nao Takahashi, Masafumi Tsuchida, Yusuke Suzuki, Takuji Yamada, Arata Horii, Ituro Inoue, Ken Kurokawa, Ichiei Narita, Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy. Nephrology Dialysis Transplantation. Volume 32, Issue 12, Dec 2017; 32 (12): 2072–2079. https://doi.org/10.1093/ndt/gfw343Li J, Li S, Jin J, Guo R, Jin Y, Cao L, Cai X, Rao P, Zhong Y, Xiang X, Sun X, Guo J, Hu F, Ye H, Jia Y, Xiao W, An Y, Zhang X, Xia B, Yang R, Zhou Y, Wu L, Qin J, He J, Wang J, Li Z. The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis. JCI Insight. 2024 Aug 20; 9 (18): e175916. DOI: 10.1172/jci.insight.175916. PMID: 39163137; PMCID: PMC11457857.Li J, Li S, Jin J, Guo R, Jin Y, Cao L, Cai X, Rao P, Zhong Y, Xiang X, Sun X, Guo J, Hu F, Ye H, Jia Y, Xiao W, An Y, Zhang X, Xia B, Yang R, Zhou Y, Wu L, Qin J, He J, Wang J, Li Z. The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis. JCI Insight. 2024 Aug 20; 9 (18): e175916. DOI: 10.1172/jci.insight.175916. PMID: 39163137; PMCID: PMC11457857.Jiaoling Chen, Xuan Liu, Yaxing Bai, Xin Tang, Ke Xue, Zhenlai Zhu, Wanting Liu, Jiaqi Wang, Caiyu Wang, Hongjiang Qiao, Erle Dang, Wen Yin, Gang Wang, Shuai Shao. Tonsillar microbiota alterations contribute to immune responses in psoriasis by skewing aged neutrophils. British Journal of Dermatology. 2025; ljaf134. https://doi.org/10.1093/bjd/ljaf134Jiaoling Chen, Xuan Liu, Yaxing Bai, Xin Tang, Ke Xue, Zhenlai Zhu, Wanting Liu, Jiaqi Wang, Caiyu Wang, Hongjiang Qiao, Erle Dang, Wen Yin, Gang Wang, Shuai Shao. Tonsillar microbiota alterations contribute to immune responses in psoriasis by skewing aged neutrophils. British Journal of Dermatology. 2025; ljaf134. https://doi.org/10.1093/bjd/ljaf134Masieri S, Trabattoni D, Incorvaia C, De Luca MC, Dell’Albani I, Leo G, Frati F. A role for Waldeyer’s ring in immunological response to allergens. Curr Med Res Opin. 2014 Feb; 30 (2): 203–5. DOI: 10.1185/03007995.2013.855185. Epub 2013 Oct 31. PMID: 24127824.Masieri S, Trabattoni D, Incorvaia C, De Luca MC, Dell’Albani I, Leo G, Frati F. A role for Waldeyer’s ring in immunological response to allergens. Curr Med Res Opin. 2014 Feb; 30 (2): 203–5. DOI: 10.1185/03007995.2013.855185. Epub 2013 Oct 31. PMID: 24127824.Tagg JR, Harold LK, Hale JDF. Review of Streptococcus salivarius BLIS K12 in the Prevention and Modulation of Viral Infections. Applied Microbiology. 2025; 5 (1): 7. https://doi.org/10.3390/applmicrobiol5010007Tagg JR, Harold LK, Hale JDF. Review of Streptococcus salivarius BLIS K12 in the Prevention and Modulation of Viral Infections. Applied Microbiology. 2025; 5 (1): 7. https://doi.org/10.3390/applmicrobiol5010007Swanljung E, Tapiovaara L, Lehtoranta L, Mäkivuokko H, Roivainen M, Korpela R, Pitkäranta A. Lactobacillus rhamnosus GG in adenoid tissue: Double-blind, placebo-controlled, randomized clinical trial. Acta Otolaryngol. 2015 Aug; 135 (8): 824–30. DOI: 10.3109/00016489.2015.1027412. Epub 2015 Mar 26. PMID: 25813240.Swanljung E, Tapiovaara L, Lehtoranta L, Mäkivuokko H, Roivainen M, Korpela R, Pitkäranta A. Lactobacillus rhamnosus GG in adenoid tissue: Double-blind, placebo-controlled, randomized clinical trial. Acta Otolaryngol. 2015 Aug; 135 (8): 824–30. DOI: 10.3109/00016489.2015.1027412. Epub 2015 Mar 26. PMID: 25813240.Tagg JR, Harold LK, Hale JDF. Review of Streptococcus salivarius BLIS K12 in the Prevention and Modulation of Viral Infections. Applied Microbiology. 2025; 5 (1): 7. https://doi.org/10.3390/applmicrobiol5010007Tagg JR, Harold LK, Hale JDF. Review of Streptococcus salivarius BLIS K12 in the Prevention and Modulation of Viral Infections. Applied Microbiology. 2025; 5 (1): 7. https://doi.org/10.3390/applmicrobiol5010007Power D.A., Burton J.P., Chilcott C.N., Dawes P.J., Tagg J.R. Preliminary investigations of the colonisa tion of upper respiratorytract tissues of infants using a paediatric formulation of the oralprobiotic Streptococcus salivarius K12. Eur J Clin Microbiol Infect Dis. 2008; 27: 1261–1263. DOI: 10.1007/s10096‑008‑0569‑4Power D.A., Burton J.P., Chilcott C.N., Dawes P.J., Tagg J.R. Preliminary investigations of the colonisa tion of upper respiratorytract tissues of infants using a paediatric formulation of the oralprobiotic Streptococcus salivarius K12. Eur J Clin Microbiol Infect Dis. 2008; 27: 1261–1263. DOI: 10.1007/s10096‑008‑0569‑4Alexander Bertuccioli, Marco Rocchi, Ilaria Morganti, Giorgia Vici, Marco Gervasi, Stefano Amatori, Davide Sisti. Streptococcus salivarius K12 in pharyngotonsillitis and acute otitis media – a meta-analysis. Nutrafoods. 2019; 2: 80–88. DOI: 10.17470/NF‑019-0011Alexander Bertuccioli, Marco Rocchi, Ilaria Morganti, Giorgia Vici, Marco Gervasi, Stefano Amatori, Davide Sisti. Streptococcus salivarius K12 in pharyngotonsillitis and acute otitis media – a meta-analysis. Nutrafoods. 2019; 2: 80–88. DOI: 10.17470/NF‑019-0011Swanljung E, Tapiovaara L, Lehtoranta L, Mäkivuokko H, Roivainen M, Korpela R, Pitkäranta A. Lactobacillus rhamnosus GG in adenoid tissue: Double-blind, placebo-controlled, randomized clinical trial. Acta Otolaryngol. 2015 Aug; 135 (8): 824–30. DOI: 10.3109/00016489.2015.1027412. Epub 2015 Mar 26. PMID: 25813240.Swanljung E, Tapiovaara L, Lehtoranta L, Mäkivuokko H, Roivainen M, Korpela R, Pitkäranta A. Lactobacillus rhamnosus GG in adenoid tissue: Double-blind, placebo-controlled, randomized clinical trial. Acta Otolaryngol. 2015 Aug; 135 (8): 824–30. DOI: 10.3109/00016489.2015.1027412. Epub 2015 Mar 26. PMID: 25813240.Lucio Capurso, MD. Thirty Years of Lactobacillus rhamnosus GG. A Review. J Clin Gastroenterol. March 2019; 53: 1.Lucio Capurso, MD. Thirty Years of Lactobacillus rhamnosus GG. A Review. J Clin Gastroenterol. March 2019; 53: 1.Harini Priya Vishnu (2012). Probiotics and Oral Health, Oral Health Care – Pediatric, Research, Epidemiology and Clinical Practices, Prof. Mandeep Virdi (Ed.), ISBN: 978‑953‑51‑0133‑8, InTech, Available from: http://www.intechopen.com/books/oral-health-care-pediatric-research-epidemiology-and-clinicalpractices/probiotics-oral-health.Harini Priya Vishnu (2012). Probiotics and Oral Health, Oral Health Care – Pediatric, Research, Epidemiology and Clinical Practices, Prof. Mandeep Virdi (Ed.), ISBN: 978‑953‑51‑0133‑8, InTech, Available from: http://www.intechopen.com/books/oral-health-care-pediatric-research-epidemiology-and-clinicalpractices/probiotics-oral-health.Tagg JR, Harold LK, Hale JDF. Review of Streptococcus salivarius BLIS K12 in the Prevention and Modulation of Viral Infections. Applied Microbiology. 2025; 5 (1): 7. https://doi.org/10.3390/applmicrobiol5010007Tagg JR, Harold LK, Hale JDF. Review of Streptococcus salivarius BLIS K12 in the Prevention and Modulation of Viral Infections. Applied Microbiology. 2025; 5 (1): 7. https://doi.org/10.3390/applmicrobiol5010007Masieri S, Trabattoni D, Incorvaia C, De Luca MC, Dell’Albani I, Leo G, Frati F. A role for Waldeyer’s ring in immunological response to allergens. Curr Med Res Opin. 2014 Feb; 30 (2): 203–5. DOI: 10.1185/03007995.2013.855185. Epub 2013 Oct 31. PMID: 24127824.Masieri S, Trabattoni D, Incorvaia C, De Luca MC, Dell’Albani I, Leo G, Frati F. A role for Waldeyer’s ring in immunological response to allergens. Curr Med Res Opin. 2014 Feb; 30 (2): 203–5. DOI: 10.1185/03007995.2013.855185. Epub 2013 Oct 31. PMID: 24127824.Harini Priya Vishnu (2012). Probiotics and Oral Health, Oral Health Care – Pediatric, Research, Epidemiology and Clinical Practices, Prof. Mandeep Virdi (Ed.). ISBN: 978‑953‑51‑0133‑8, InTech, Available from: http://www.intechopen.com/books/oral-health-care-pediatric-research-epidemiology-and-clinicalpractices/probiotics-oral-health.Harini Priya Vishnu (2012). Probiotics and Oral Health, Oral Health Care – Pediatric, Research, Epidemiology and Clinical Practices, Prof. Mandeep Virdi (Ed.). ISBN: 978‑953‑51‑0133‑8, InTech, Available from: http://www.intechopen.com/books/oral-health-care-pediatric-research-epidemiology-and-clinicalpractices/probiotics-oral-health.Mosquera FEC, de la Rosa Caldas M, Naranjo Rojas A, Perlaza CL, Liscano Y. Probiotic, Prebiotic, and Synbiotic Supplementation for the Prevention and Treatment of Acute Otitis Media: A Systematic Review and Meta-Analysis. Children. 2025; 12 (5): 591. https://doi.org/10.3390/children12050591Mosquera FEC, de la Rosa Caldas M, Naranjo Rojas A, Perlaza CL, Liscano Y. Probiotic, Prebiotic, and Synbiotic Supplementation for the Prevention and Treatment of Acute Otitis Media: A Systematic Review and Meta-Analysis. Children. 2025; 12 (5): 591. https://doi.org/10.3390/children12050591Federica Del Chierico, Antonia Piazzesi, Ersilia Vita Fiscarelli et al. Changes in the pharyngeal and nasal microbiota in pediatric patients with adenotonsillar hypertrophy. Microbiology Spectrum. Sept 2024; 12 (10): e0072824. DOI: 10.1128/spectrum.00728-24Federica Del Chierico, Antonia Piazzesi, Ersilia Vita Fiscarelli et al. Changes in the pharyngeal and nasal microbiota in pediatric patients with adenotonsillar hypertrophy. Microbiology Spectrum. Sept 2024; 12 (10): e0072824. DOI: 10.1128/spectrum.00728-24Del Chierico F, Piazzesi A, Fiscarelli EV, Ristori MV, Pirona I, Russo A, Citerà N, Macari G, Santarsiero S, Bianco F, Antenucci V, Damiani V, Mercuri L, De Vincentis GC, Putignani L. Changes in the pharyngeal and nasal microbiota in pediatric patients with adenotonsillar hypertrophy. Microbiol Spectr. 2024; 12: e00728–24. https://doi.org/10.1128/spectrum.00728-24Del Chierico F, Piazzesi A, Fiscarelli EV, Ristori MV, Pirona I, Russo A, Citerà N, Macari G, Santarsiero S, Bianco F, Antenucci V, Damiani V, Mercuri L, De Vincentis GC, Putignani L. Changes in the pharyngeal and nasal microbiota in pediatric patients with adenotonsillar hypertrophy. Microbiol Spectr. 2024; 12: e00728–24. https://doi.org/10.1128/spectrum.00728-24Baljošević I, Šubarević V, Stanković K, Bajec Opančina A, Novković M, Petrovic M. The Efficacy of Paraprobiotic Lozenges (Lactobacillus helveticus MIMLh5) for the Prevention of Acute and Chronic Nose and Throat Infections in Children. Medicina (Kaunas). 2024 Jul 30; 60 (8): 1235. DOI: 10.3390/medicina60081235. PMID: 39202516; PMCID: PMC11356307.Baljošević I, Šubarević V, Stanković K, Bajec Opančina A, Novković M, Petrovic M. The Efficacy of Paraprobiotic Lozenges (Lactobacillus helveticus MIMLh5) for the Prevention of Acute and Chronic Nose and Throat Infections in Children. Medicina (Kaunas). 2024 Jul 30; 60 (8): 1235. DOI: 10.3390/medicina60081235. PMID: 39202516; PMCID: PMC11356307.Latvala S, Lehtinen MJ, Mäkelä SM, Nedveck D, Zabel B, Ahonen I, Lehtoranta L, Turner RB, Liljavirta J. The effect of probiotic Bifidobacterium lactis Bl‑04 on innate antiviral responses invitro. Heliyon. 2024 Apr 15; 10 (8): e29588. DOI: 10.1016/j.heliyon.2024.e29588. PMID: 38665561; PMCID: PMC11043947.Latvala S, Lehtinen MJ, Mäkelä SM, Nedveck D, Zabel B, Ahonen I, Lehtoranta L, Turner RB, Liljavirta J. The effect of probiotic Bifidobacterium lactis Bl‑04 on innate antiviral responses invitro. Heliyon. 2024 Apr 15; 10 (8): e29588. DOI: 10.1016/j.heliyon.2024.e29588. PMID: 38665561; PMCID: PMC11043947.Wan Z, Zheng J, Zhu Z, Sang L, Zhu J, Luo S, Zhao Y, Wang R, Zhang Y, Hao K, Chen L, Du J, Kan J and He H. Intermediate role of gut microbiota in vitamin B nutrition and its influences on human health. Front. Nutr. 2022; 9: 1031502. DOI: 10.3389/fnut.2022.1031502Wan Z, Zheng J, Zhu Z, Sang L, Zhu J, Luo S, Zhao Y, Wang R, Zhang Y, Hao K, Chen L, Du J, Kan J and He H. Intermediate role of gut microbiota in vitamin B nutrition and its influences on human health. Front. Nutr. 2022; 9: 1031502. DOI: 10.3389/fnut.2022.1031502Осадчук А.М., Осадчук М.М. Перспективные направления применения пробиотической терапии в гастроэнтерологии. Поликлиника. 2025; 3: 18–22.Osadchuk A.M., Osadchuk M.M. Promising directions for the use of probiotic therapy in gastroenterology. Clinic. 2025; 3:18–22. (In Russ.).

The authors declare that there are no conflicts of interest present.