<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">problendo</journal-id><journal-title-group><journal-title xml:lang="ru">Проблемы Эндокринологии</journal-title><trans-title-group xml:lang="en"><trans-title>Problems of Endocrinology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0375-9660</issn><issn pub-type="epub">2308-1430</issn><publisher><publisher-name>Endocrinology Research Centre</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14341/probl13155</article-id><article-id custom-type="elpub" pub-id-type="custom">problendo-13155</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Детская эндокринология</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Pediatric Endocrinology</subject></subj-group></article-categories><title-group><article-title>Взаимосвязь конституционально-экзогенного ожирения и гормонально-микроэлементного статуса у мальчиков-подростков с задержкой полового развития</article-title><trans-title-group xml:lang="en"><trans-title>The relationship of constitutional-exogenous obesity and hormonalmicroelement status in adolescent boys with delayed sexual development</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1605-6354</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Друккер</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Drukker</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Друккер Нина Александровна, д.б.н., доцент</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Nina A. Drukker, BD, PhD</p><p>Rostov-on-Don</p></bio><email xlink:type="simple">n.drukker@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2278-5198</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Палиева</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Palieva</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Палиева Наталья Викторовна, д.м.н., доцент</p><p>344022, Ростов-на-Дону, пер. Нахичеванский, д. 29</p></bio><bio xml:lang="en"><p>Natalia V. Palieva, MD, PhD</p><p>29 Nakhichevanskiy street, 344022, Rostov-on-Don</p></bio><email xlink:type="simple">nat-palieva@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2348-8809</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Петров</surname><given-names>Ю. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Petrov</surname><given-names>Y. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Петров Юрий Алексеевич, д.м.н., профессор</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Yuriy A. Petrov, MD, PhD, Professor</p><p>Rostov-on-Don</p></bio><email xlink:type="simple">mr.doktorpetrov@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5329-7336</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Попова</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Рopova</surname><given-names>V. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Попова Виктория Александровна, д.м.н.</p><p>Ростов-на-Дону</p></bio><bio xml:lang="en"><p>Viktoria. A. Рopova, MD, PhD</p><p>Rostov-on-Don</p></bio><email xlink:type="simple">vait49@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Ростовский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Rostov State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>06</day><month>03</month><year>2024</year></pub-date><volume>70</volume><issue>6</issue><fpage>99</fpage><lpage>105</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Друккер Н.А., Палиева Н.В., Петров Ю.А., Попова В.А., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Друккер Н.А., Палиева Н.В., Петров Ю.А., Попова В.А.</copyright-holder><copyright-holder xml:lang="en">Drukker N.A., Palieva N.V., Petrov Y.A., Рopova V.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.probl-endojournals.ru/jour/article/view/13155">https://www.probl-endojournals.ru/jour/article/view/13155</self-uri><abstract><p>ОБОСНОВАНИЕ. Детское ожирение и темпы его распространения — серьезная угроза репродуктивному здоровью нации, особенно среди мальчиков, является фоном для задержки полового развития и в дальнейшем приводит к нарушению фертильности.ЦЕЛЬ. Изучение особенностей соотношения уровня лептина и ряда токсических и эссенциальных химических микроэлементов в биологических средах у мальчиков-подростков 13–14 лет с ожирением и задержкой полового развития.МАТЕРИАЛЫ И МЕТОДЫ. Исследованы и сформированы три группы подростков 13–14 лет: основная — с конституционально-экзогенным ожирением 1–2 степени (1 — 20 мальчиков без вторичных признаков полового созревания; 2 — 24 мальчика с 2–4 стадией полового созревания по Таннеру) и сравнения (3 — 15 мальчиков с нормальной массой тела и без отклонений в половом созревании). Определялись в утренней моче уровень свинца, цинка, селена, хрома и марганца абсорбционным методом; в сыворотке крови — лептина методом иммуноферментного анализа. Статистический анализ данных проводили в среде MeoCape 11.4.2 Statistica, непараметрический корреляционный анализ — по Спирмену и расчет t-критерия Стьюдента для независимых выборок, достоверность результатов при р&lt; 0,05.РЕЗУЛЬТАТЫ. Установлено, что для подростков с ожирением характерен определенный сдвиг в содержании токсических и эссенциальных микроэлементов, вектор которого смещен в сторону преобладания уровней токсических химических элементов, в частности свинца, и снижение эссенциальных элементов, таких как цинк, селен, хром и марганец. Однако более выраженное смещение значений в дисбалансе микроэлементов уже нарушает не только обменные процессы в организме детей-подростков, но и приводит к нарушению пубертата — к задержке полового развития.ЗАКЛЮЧЕНИЕ. В организме мальчиков-подростков с ожирением и задержкой полового развития прогрессируют процессы окислительного стресса, тканевой гипоксии на фоне избытка лептина, накопления тяжелых металлов и дефицита эссенциальных микроэлементов. Менее выраженные сдвиги в содержании лептина и микроэлементов у мальчиков-подростков определяют сбой в нейроэндокринной регуляции, но не затрагивают уровень полового созревания. Гомеостаз гормонально-микроэлементного состава обеспечивает гармоничное развитие мальчиков-подростков.</p></abstract><trans-abstract xml:lang="en"><p>BACKGROUND: Childhood obesity and the rate of its spread is a serious threat to the reproductive health of the nation, especially among boys, being a background for delaying sexual development and further disrupting fertility.AIM: To study the peculiarities of the ratio of the level of leptin and a number of toxic and essential chemical trace elements in biological environments in adolescent boys aged 13–14 years with obesity and delayed sexual development.MATERIALS AND METHODS: Three groups of adolescents aged 13–14 years were studied and formed: the main ones — with constitutional exogenous obesity of 1–2 degrees (1–20 boys without secondary signs of puberty; 2 — 24 boys with 2–4 stages of puberty according to Tanner) and comparisons (3 — 15 boys with normal body weight and without deviations in puberty). The level of lead, zinc, selenium, chromium and manganese in the morning urine was determined by the absorption method; in the blood serum — leptin, by the method of enzyme immunoassay. Statistical analysis of the data was carried out in the MeoCape 11.4.2 Statistica environment, nonparametric Spearman correlation analysis and calculation of the Student’s t-test for independent samples, the reliability of the results at p&lt; 0.05.RESULTS: It was found that adolescents with obesity are characterized by a certain shift in the content of toxic and essential trace elements, the vector of which is shifted towards the predominance of levels of toxic chemical elements, in particular, ead, and a decrease in essential toxic elements, such as zinc, selenium, chromium and manganese. However, a more pronounced shift in the values in the imbalance of trace elements already violates not only the metabolic processes in the body of adolescent children, but also leads to a violation of puberty - to a delay in sexual development. CONCLUSION: In the body of adolescent boys with obesity and delayed sexual development, the processes of oxidative stress, tissue hypoxia are progressing against the background of excess leptin, accumulation of heavy metals and deficiency of essential trace elements. Less pronounced shifts in the content of leptin and trace elements in adolescent boys are determined by a failure in neuroendocrine regulation, but does not affect the level of puberty. The homeostasis of the hormonal-microelement composition ensures the harmonious development of adolescent boys.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>лептин</kwd><kwd>токсические химические элементы</kwd><kwd>эссенциальные химические элементы</kwd><kwd>мальчики-подростки</kwd><kwd>пубертат</kwd><kwd>задержка полового развития</kwd><kwd>детское ожирение</kwd></kwd-group><kwd-group xml:lang="en"><kwd>leptin</kwd><kwd>toxic chemical elements</kwd><kwd>essential chemical elements</kwd><kwd>adolescent boys</kwd><kwd>puberty</kwd><kwd>delayed sexual development</kwd><kwd>childhood obesity</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование проведено в рамках выполнения государственного задания.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">WHO.int [internet]. World Health Organization Fact sheet №311. Obesity and overweight [cited 2021 Jul 6]. Available from: http://www.who.int/mediacentre/factsheets/fs311/en</mixed-citation><mixed-citation xml:lang="en">WHO.int [internet]. World Health Organization Fact sheet №311. Obesity and overweight [cited 2021 Jul 6]. Available from: http://www.who.int/mediacentre/factsheets/ fs311/en</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Гончаров Н.П., Дедов И.И., Гависова А.А., Сухих Г.Т. Эндокринная система человека в различные периоды его жизни. — М.: «АДАМАНТЪ»; 2020. 556 с.</mixed-citation><mixed-citation xml:lang="en">Goncharov NP, Dedov II, Gavisova AA, Suhih GT. Jendokrinnaja sistema cheloveka v razlichnye periody ego zhizni. Moscow: «ADAMANT»; 2020. 556 s. (in Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">El Salam MAA. Obesity, an enemy of male fertility: a mini review. Oman Med J. 2018;33(1):3-6. doi: https://doi.org/10.5001/omj.2018.02</mixed-citation><mixed-citation xml:lang="en">El Salam MAA. Obesity, an enemy of male fertility: a mini review. Oman Med J. 2018;33(1):3-6. doi: https://doi.org/10.5001/omj.2018.02</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">He Y, Tian J, Oddy WH, Dwyer T, Venn AJ. Association of childhood obesity with female infertility in adulthood: a 25-year follow-up study. Fertil Steril. 2018;110(4):596-604.e1. doi: https://doi.org/10.1016/j.fertnstert.2018.05.011</mixed-citation><mixed-citation xml:lang="en">He Y, Tian J, Oddy WH, Dwyer T, Venn AJ. Association of childhood obesity with female infertility in adulthood: a 25-year follow-up study. Fertil Steril. 2018;110(4):596-604.e1. doi: https://doi.org/10.1016/j.fertnstert.2018.05.011</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Манунова Э.А., Петров Ю.А., Палиева Н.В. Ожирение и репродуктивное здоровье // Главный врач Юга России. — 2021. — Т. 79. — № 4. — С. 29-32.</mixed-citation><mixed-citation xml:lang="en">Manunova JeA, Petrov JuA, Palieva NV. Ozhirenie i reproduktivnoe zdorov’e. Glavnyj vrach Juga Rossii. 2021;4(79):29-32. (in Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Tomova A, Robeva R, Kumanov P. Influence of the body weight on the onset and progression of puberty in boys. J. Pediatr. Endocrinol. Metab. 2015;28(7-8):859-865.doi: https://doi.org/10.1515/jpem.2014-0363</mixed-citation><mixed-citation xml:lang="en">Tomova A, Robeva R, Kumanov P. Influence of the body weight on the onset and progression of puberty in boys. J. Pediatr. Endocrinol. Metab. 2015;28(7-8):859-865.doi: https://doi.org/10.1515/jpem.2014-0363</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Lee JM, Wasserman R, Kaciroti N, et al. Timing of puberty in overweight versus obese boys. Pediatrics. 2016;137(2). doi: https://doi.org/10.1542/peds.2015-0164</mixed-citation><mixed-citation xml:lang="en">Lee JM, Wasserman R, Kaciroti N, et al. Timing of puberty in overweight versus obese boys. Pediatrics. 2016;137(2). doi: https://doi.org/10.1542/peds.2015-0164</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Cao Y, Li Z, Jiang W, et al. Reproductive functions of Kisspeptin/KISS1R Systems in the Periphery. Reprod Biol Endocrinol. 2019;17(1):65. doi: https://doi.org/10.1186/s12958-019-0511-x</mixed-citation><mixed-citation xml:lang="en">Cao Y, Li Z, Jiang W, et al. Reproductive functions of Kisspeptin/KISS1R Systems in the Periphery. Reprod Biol Endocrinol. 2019;17(1):65. doi: https://doi.org/10.1186/s12958-019-0511-x</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254-264. doi: https://doi.org/10.1016/S2213-8587(15)00418-0</mixed-citation><mixed-citation xml:lang="en">Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254-264. doi: https://doi.org/10.1016/S2213-8587(15)00418-0</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Оберлис Д., Харланд Б., Скальный А. Биологическая роль макро- и микроэлементов у человека и животных / Под ред. Скального А.В. — М.: Изд-во Российского университета дружбы народов; 2018. 657 с.</mixed-citation><mixed-citation xml:lang="en">Oberlis D, Harland B, Skal’nyj A. Biologicheskaja rol’ makro- i mikrojelementov u cheloveka i zhivotnyh. Ed by A.V. Skal’nogo. Moscow: Izdatel’stvo Rossijskogo universiteta druzhby narodov; 2018. 657 s. (in Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Li L, Yang X. The essential element manganese, oxidative stress, and metabolic diseases: links and interactions. Oxid Med Cell Longev. 2018;2018:7580707. doi: https://doi.org/10.1155/2018/7580707</mixed-citation><mixed-citation xml:lang="en">Li L, Yang X. The essential element manganese, oxidative stress, and metabolic diseases: links and interactions. Oxid Med Cell Longev. 2018;2018:7580707. doi: https://doi.org/10.1155/2018/7580707</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Попова В.А., Кожин А.А., Пузикова О.З., Друккер Н.А. Микроэлементны дисбаланс как фактор, потенцирующи задержку полового развития у мальчиков подростков с конституционально-экзогенным ожирением // Педиатрия. — 2019. — №1. — с. 223–227. doi: https://doi.org/10.24110/0031-403X-2019-98-1-223-227</mixed-citation><mixed-citation xml:lang="en">Popova VA, Kozhin AA, Puzikova OZ, Drukker NA. Mikrojelementnyj disbalans kak faktor, potencirujushhij zaderzhku polovogo razvitija u mal’chikov podrostkov s konstitucional’no-jekzogennym ozhireniem. Pediatrija. 2019;1:223–27. (in Russ.)] doi: https://doi.org/10.24110/0031-403X-2019-98-1-223-227</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Błażewicz A, Klatka M, Astel A, et al. Serum and urinary selenium levels in obese children: a cross-sectional study. J Trace Elem Med Biol. 2015;29:116-122. doi: https://doi.org/10.1016/j.jtemb.2014.07.016</mixed-citation><mixed-citation xml:lang="en">Błażewicz A, Klatka M, Astel A, et al. Serum and urinary selenium levels in obese children: a cross-sectional study. J Trace Elem Med Biol. 2015;29:116-122. doi: https://doi.org/10.1016/j.jtemb.2014.07.016</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Cayir Y, Cayir A, Turan MI, et al. Antioxidant status in blood of obese children: the relation between trace elements, paraoxonase, and arylesterase values. Biol Trace Elem Res. 2014;160(2):155-160. doi: https://doi.org/10.1007/s12011-014-0038-0</mixed-citation><mixed-citation xml:lang="en">Cayir Y, Cayir A, Turan MI, et al. Antioxidant status in blood of obese children: the relation between trace elements, paraoxonase, and arylesterase values. Biol Trace Elem Res. 2014;160(2):155-160. doi: https://doi.org/10.1007/s12011-014-0038-0</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Wan H, Wang B, Cui Yu, et al. Low-level lead exposure promotes hepatic gluconeogenesis and contributes to the elevation of fasting glucose level. Chemosphere. 2021;276:130111. doi: https://doi.org/10.1016/j.chemosphere.2021.130111</mixed-citation><mixed-citation xml:lang="en">Wan H, Wang B, Cui Yu, et al. Low-level lead exposure promotes hepatic gluconeogenesis and contributes to the elevation of fasting glucose level. Chemosphere. 2021;276:130111. doi: https://doi.org/10.1016/j.chemosphere.2021.130111</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Tyrrell JB, Hafida S, Stemmer P, Adhami A, Leff T. Lead (Pb) exposure promotes diabetes in obese rodents. J Trace Elem Med Biol. 2017;39:221-226. doi: https://doi.org/10.1016/j.jtemb.2016.10.007</mixed-citation><mixed-citation xml:lang="en">Tyrrell JB, Hafida S, Stemmer P, Adhami A, Leff T. Lead (Pb) exposure promotes diabetes in obese rodents. J Trace Elem Med Biol. 2017;39:221-226. doi: https://doi.org/10.1016/j.jtemb.2016.10.007</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Wen WL, Wang CW, Wu DW, et al. Associations of heavy metals with metabolic syndrome and anthropometric indices. Nutrients. 2020;12(9):2666. doi: https://doi.org/10.3390/nu12092666</mixed-citation><mixed-citation xml:lang="en">Wen WL, Wang CW, Wu DW, et al. Associations of heavy metals with metabolic syndrome and anthropometric indices. Nutrients. 2020;12(9):2666. doi: https://doi.org/10.3390/nu12092666</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Fan Y, Zhang C, Bu J. Relationship between Selected Serum Metallic Elements and Obesity in Children and Adolescent in the U.S. Nutrients. 2017;9(2):104. doi: https://doi.org/10.3390/nu9020104</mixed-citation><mixed-citation xml:lang="en">Fan Y, Zhang C, Bu J. Relationship between Selected Serum Metallic Elements and Obesity in Children and Adolescent in the U.S. Nutrients. 2017;9(2):104. doi: https://doi.org/10.3390/nu9020104</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Olechnowicz J, Tinkov A, Skalny A, Suliburska J. Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci. 2018;68(1):19-31. doi: https://doi.org/10.1007/s12576-017-0571-7</mixed-citation><mixed-citation xml:lang="en">Olechnowicz J, Tinkov A, Skalny A, Suliburska J. Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci. 2018;68(1):19-31. doi: https://doi.org/10.1007/s12576-017-0571-7</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Lapik IA, Galchenko AV, Gapparova KM. Micronutrient status in obese patients: a narrative review. Obesity Medicine. 2020;18(1):100224. doi: https://doi.org/10.1016/j.obmed.2020.100224</mixed-citation><mixed-citation xml:lang="en">Lapik IA, Galchenko AV, Gapparova KM. Micronutrient status in obese patients: a narrative review. Obesity Medicine. 2020;18(1):100224. doi: https://doi.org/10.1016/j.obmed.2020.100224</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
