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Term 4 Science Quiz 2019
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Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty DesirĂ©e Nieuwenhuis | NatĂ lia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. 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Ann Epidemiol. 2017;27(3):187-93.e2. 16. Glass NA, Torner JC, Letuchy EM, et al. The relationship between greater prepubertal adiposity, subsequent age of maturation, and bone strength during adolescence. Journal of bone and mineral research: the official journal of the American Society for Bone and Min- eral Research. 2016;31(7):1455-1465. 17. Holmgren A, Niklasson A, Nierop AF, et al. Pubertal height gain is inversely related to peak BMI in childhood. Pediatr Res. 2017;81(3): 448-454. 18. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman- Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347-353. 19. Kelly Y, Zilanawala A, Sacker A, Hiatt R, Viner R. Early puberty in 11-year-old girls: Millennium Cohort Study findings. Arch Dis Child. 2017;102(3):232-237. 20. Lazzeri G, Tosti C, Pammolli A, et al. Overweight and lower age at menarche: evidence from the Italian HBSC cross-sectional survey. BMC Womens Health. 2018;18(1):168-174. thereby an early onset of obesity. leptin can inhibit the production of testosterone in boys and subse- quently inhibit the development of secondary sex characteristics affecting spermatogenesis. for other adipokines, like resistin and omentin, are present in the testes and ovaries suggesting a role in puberty or reproduction; 58, 71 however, their plausible function is still unknown. that adipokines may be key regulators in an early onset of puberty in both girls and boys with obesity, specifically by affecting the HPG axis during gonadarche. Future research should focus on assessing puberty onset by measuring consistent puberty markers and determine the percentage of body fat and its distribution and adipokines and hormone serum levels particularly involved in the HPG axis. CONFLICTS OF INTEREST The authors declare no conflict of interest. FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including âonset of puberty and adiposity/obesityâ, âonset of pubertyâ, âchildren with obesityâ, âadipose tissueâ, âchildhood obesityâ, âadiposityâ, âobesityâ, âadipokine(s)â, âHPG axisâ, âadipokines ovary/ova- riesâ, or âadipokines testesâ, either alone or in combination. Selection criteria used were English language, longitudinal or cross-sectional studies assessing the onset of puberty, including menarche, thelarche, spermarche, or voice break, combined with high BMI or obesity/adiposity, and articles assessing or reviewing adipokines and its effects on the reproductive system. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 9 of 10 21. Lian Q, Mao Y, Luo S, et al. Puberty timing associated with obesity and central obesity in Chinese Han girls. BMC Pediatr. 2019; 19(1):1-7. 22. Deng Y, Liang J, Zong Y, et al. Timing of spermarche and menarche among urban students in Guangzhou, China: trends from 2005 to 2012 and association with Obesity. Sci Rep. 2018;8(1):263-270. 23. Li W, Liu Q. Association of prepubertal obesity with pubertal devel- opment in Chinese girls and boys: a longitudinal study. 2018;30: e23195. 24. Mendle J, Beltz AM, Carter R, Dorn LD. Understanding puberty and its measurement: ideas for research in a new generation. Journal of research on adolescence: the official journal of the Society for Research on Adolescence. 2019;29(1):82-95. 25. Pagani S, Meazza C, Gertosio C, Bozzola E, Bozzola M. Growth hor- mone receptor gene expression in puberty. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;47:581-584. 26. Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254-264. 27. Aguirre RS, Eugster EA. Central precocious puberty: from genetics to treatment. Best Pract Res Clin Endocrinol Metab. 2018;32(4): 343-354. 28. Sultan C, Gaspari L, Maimoun L, Kalfa N, Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gynaecol. 2018;48:62-89. 29. Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH path- way in human reproductive health and disease. Hum Reprod Update. 2014;20(4):485-500. 30. Dahl SK, Amstalden M, Coolen L, Fitzgerald M, Lehman M. Dynorphin immunoreactive fibers contact GnRH neurons in the human hypothal- amus. Reprod Sci. 2009;16(8):781-787. 31. Navarro VM, Gottsch ML, Chavkin C, Okamura H, Clifton DK, Steiner RA. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. J Neurosci. 2009;29(38):11859-11866. 32. Zhai L, Liu J, Zhao J, et al. Association of obesity with onset of puberty and sex hormones in chinese girls: a 4-year longitudinal study. PLoS ONE. 2015;10(8):1-12, e0134656. 33. Cizza G, Dorn LD, Lotsikas A, Sereika S, Rotenstein D, Chrousos GP. Circulating plasma leptin and IGF-1 levels in girls with premature adrenarche: potential implications of a preliminary study. Horm Metab Res. 2001;33(3):138-143. 34. Cousminer DL, WidĂ©n E, Palmert MR. The genetics of pubertal timing in the general population: recent advances and evidence for sex-spec- ificity. Curr Opin Endocrinol Diabetes Obes. 2016;23(1):57-65. 35. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291-303. 36. Lacroix AE, Whitten R. Physiology. Treasure Island (FL): Menarche. StatPearls. StatPearls Publishing; 2018. 37. McDowell MA, Brody DJ, Hughes JP. Has Age at Menarche Chan- ged? Results from the National Health and Nutrition Examination Sur- vey (NHANES) 1999â2004. J Adolesc Health. 2007;40(3):227-231. 38. de Muinich Keizer SM, Mul D. Trends in pubertal development in Europe. Hum Reprod Update. 2001;7(3):287-291. 39. Talma H, Schönbeck Y, van Dommelen P, Bakker B, van Buuren S, Hirasing RA. Trends in menarcheal age between 1955 and 2009 in the Netherlands. PLoS ONE. 2013;8:e60056-e60056. 40. Kaplan HS, Lancaster JB. An evolutionary and ecological analysis of human fertility, mating patterns, and parental investment. Off- spring: Human fertility behavior in biodemographic perspective. 2003;1: 170-223. 41. Mitan LA. Menstrual dysfunction in anorexia nervosa. J Pediatr Adolesc Gynecol. 2004;17(2):81-85. 42. Xu H, Li P-H, Barrow TM, et al. Obesity as an effect modifier of the association between menstrual abnormalities and hypertension in young adult women: Results from Project ELEFANT. PLoS ONE. 2018; 13(11):e0207929-e0207929. 43. Tauqeer Z, Gomez G, Stanford FC. Obesity in women: insights for the clinician. J Womens Health (Larchmt). 2018;27(4):444-457. 44. de Ridder CM, Thijssen JH, Bruning PF, Van den Brande JL, Zonderland ML, Erich WB. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. J Clin Endocrinol Metab. 1992;75(2): 442-446. 45. Lassek W, Gaulin S. Brief communication: menarche is related to fat distribution. Am J Phys Anthropol. 2007;133(4):1147-1151. 46. Loomba-Albrecht LA, Styne DM. Effect of puberty on body composi- tion. Curr Opin Endocrinol Diabetes Obes. 2009;16:10-15. 47. Simonneaux V, Bahougne T. A multi-oscillatory circadian system times female reproduction. Front Endocrinol. 2015;6:1-15. 48. Marques P, Skorupskaite K, George JT, Anderson RA. Physiology of GNRH and gonadotropin secretion. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. Endotext.org: South Dartmouth (MA); 2000. 49. Barcellos Gemelli IF, Farias EDS, Souza OF. Age at menarche and its association with excess weight and body fat percentage in girls in the Southwestern Region of the Brazilian Amazon. J Pediatr Adolesc Gynecol. 2016;29(5):482-488. 50. Aksglaede L, Juul A, Olsen LW, Sorensen TI. Age at puberty and the emerging obesity epidemic. PLoS ONE. 2009;4:1-6, e8450. 51. Ribeiro J, Santos P, Duarte J, Mota J. Association between over- weight and early sexual maturation in Portuguese boys and girls. Ann Hum Biol. 2006;33(1):55-63. 52. Budak E, Fernandez Sanchez M, Bellver J, Cervero A, Simon C, Pellicer A. Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. Fertil Steril. 2006;85(6):1563-1581. 53. Castellano JM, Tena-Sempere M. Metabolic control of female puberty: potential therapeutic targets. Expert Opin Ther Targets. 2016; 20(10):1181-1193. 54. Venancio JC, Margatho LO, Rorato R, et al. Short-term high-fat diet increases leptin activation of CART neurons and advances puberty in female mice. Endocrinology. 2017;158(11):3929-3942. 55. l'Allemand D, Schmidt S, Rousson V, Brabant G, Gasser T, Gruters A. Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche. Eur J Endocrinol. 2002;146(4):537-543. 56. Böttner A, Jr K, MĂŒller G, et al. Gender Differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metabol. 2004;89(8):4053- 4061. 57. Unanue N, Bazaes R, Iñiguez G, Cortes F, Avila A, Mericq V. Adre- narche in Prader-Willi syndrome appears not related to insulin sensi- tivity and serum adiponectin. Horm Res. 2007;67(3):152-158. 58. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and repro- ductive axis: a narrative review. Metabolism: clinical and experimental. 2013;62(4):457-478. 59. Machinal-Quelin F, Dieudonne MN, Pecquery R, Leneveu MC, Giudicelli Y. Direct in vitro effects of androgens and estrogens on ob gene expression and leptin secretion in human adipose tissue. Endo- crine. 2002;18(2):179-184. 60. Dobrzyn K, Smolinska N, Kiezun M. Adiponectin: A new regulator of female reproductive system. Int J Endocrinol. 2018;2018:1-12, 7965071. 61. Martin LJ. Implications of adiponectin in linking metabolism to testic- ular function. Endocrine. 2014;46(1):16-28. 62. Mathew H, Castracane VD, Mantzoros C. Adipose tissue and repro- ductive health. Metabolism: clinical and experimental. 2018;86:18-32. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 10 of 10 NIEUWENHUIS ET AL. 63. Sitticharoon C, Sukharomana M, Likitmaskul S, Churintaraphan M, Maikaew P. 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The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty. 2018;34:627-630. 69. Lee J, Song J, Hootman JM, et al. Obesity and other modifiable fac- tors for physical inactivity measured by accelerometer in adults with knee osteoarthritis: data from the osteoarthritis initiative (OAI). Arthritis Care Res (Hoboken). 2012;53-61. 70. Bramswig J, Dubbers A. Disorders of pubertal development. Deutsches Arzteblatt international. 2009;106:295-303. quiz 04 71. Elias CF, Purohit D. Leptin signaling and circuits in puberty and fertil- ity. Cell Mol Life Sci. 2013;70(5):841-862. 72. Riumallo J, Durnin JV. Changes in body composition in adolescent boys. Eur J Clin Nutr. 1988;42(2):107-112. 73. Siervogel RM, Demerath EW, Schubert C, et al. Puberty and body composition. Horm Res. 2003;60(Suppl 1):36-45. 74. Zhang J. Gong M. Andrologia: Review of the role of leptin in the regu- lation of male reproductive function; 2018. 75. 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The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study. BMC Pub- lic Health. 2017;17:664-673. 81. Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expres- sion of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 2007;39(1):22-27. 82. Martins AD, Moreira AC, Sa R, et al. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta. 1852;2015: 1824-1832. 83. Morash BA, Willkinson D, Ur E, Wilkinson M. Resistin expression and regulation in mouse pituitary. FEBS Lett. 2002;526(1-3):26-30. 84. Cabrera SM, Bright GM, Frane JW, Blethen SL, Lee PA. Age of thelarche and menarche in contemporary US females: a cross- sectional analysis. Journal of pediatric endocrinology & metabolism: JPEM. 2014;27(1-2):47-51. 85. Herman-Giddens ME, Steffes J, Harris D, et al. Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network. Pediatrics. 2012;130(5):e1058-e1068. 86. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452. 87. Akin I, Tolg R, Hochadel M, et al. No evidence of âobesity paradoxâ after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry. JACC Cardiovasc Interv. 2012;5(2): 162-169. 88. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet. 2013;106:135-141. How to cite this article: Nieuwenhuis D, Pujol-Gualdo N, Arnoldussen IAC, Kiliaan AJ. Adipokines: A gear shift in puberty. Obesity Reviews. 2020;21:e13005. https://doi.org/ 10.1111/obr.13005 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are goverQUIZ 1 TERM 1 SCIENCE 4Make mcq quiz with 4 option in which one is correct -'10 Basis of Material Science âą .....;;;";;;"~~;;,,;;,,,,;.;.,,;;,,,;,,;.;,.,------------ 6. Temporary materials: Some materials are meant to be placed in the oral cavity for a short period of time for different reasons. âą Temporary crowns: While a permanent crown is prepared in the dental laboratory, the patient must wait for few days before it can be fabricated and cemented into place. Does patient experience any problems during this time period? If the tooth is vital (the pulp is alive), the patient is likely to experience pain and sensitivity while eating and drinking, also it looks unesthetic. What can be done to solve this problem? A temporary crown is placed before the patient leaves the clinic. It is constructed and luted in the same appointment in which the crown preparation is done. Temporary crowns are not very strong or esthetic but they serve adequately till the permanent crown is ready to be cemented. âą Temporary restorations: Sometimes it is difficult to decide immediately the best line of treatment for a particular tooth. The exact condition of the pulp may not be obvious to the dentist from the patient's symptoms. A dentist removes all or part of the decay and then places a temporary restoration to have time to observe the behaviour of the pulp or to give the pilip time to heal before deciding the further treatment required. Classification based on Location of Fabrication 4,9 Materials can be classified based on the location of fabrication into: âą Direct restorative materials. âą Indirect restorative materials Direct restorative materials: They include those materials which are used to restore cavity preparations directly in the oral cavity (Box 1.5). Box 1.5: Examples of direct restorative materials Amalgam, composites, glass ionomer and other materials, which set by chemical reactions in the mouth. Indirect restorative materials: It includes those restorations which must be fabricated outside the mouth, indirectly on a cast/ model/ die, because their processing condition would harm oral tissues. Materials used in the construction of such prosthesis are called indirect restorative materials (Box 1.6). Box 1.6: Examples of indirect restorative materials Gold inlays, crowns of metal, ceramic and polymers, which are processed at elevated temperatures. Some indirect composite restorations can be processed under specific wavelength of light, e.g. Ceramage. Classification based on Longevity of Use 1. Permanent restorations: These restorations are not planned to be replaced for a particular time period. Though they are referred to as permanent, actually they are not, e.g. fillings, crowns, bridges and dentures do not last forever (Fig. 1.5). 2. Temporary restorations: These restorations are planned to be replaced in a short period of time, such as few days to weeks. For ~ Permanent C/) c c -.2 0 c- :;::; Cll co Interim ~ Q; 0 .8ll::1iJ C/) o~ Cll a:: c:=:J Temporary Time period Fig. 1.5: Diagram depicting the time period of use of a restoration. (Arrow in permanent restoration depicts that such restorations are not planned to be replaced for a long period of time.) Introducton to Dental Materials Dental materials Box 1.7: Characteristics of metals 1. High thermal and electrical conductivity 2. Ductility (pure metals are very soft and they can be bent without breaking) 3. Opacity (they do not transmit light) 4. Luster (they have a surface that strongly reflects light and appears bright and shiny) 5. They tend to dissolve to some extent in water or other aqueous solutions, producing cations. 6. All metals are white (actually gray) except for gold, which is yellow, and copper, which is reddish. 7. All metals are solid at room temperature except mercury, which is liquid at room temperature and is used with silver alloys as amalgam. 8. All metals have high melting temperatures because of high strength of the metallic bond that holds the atoms together. 3. Polymers 4. Composites Composites are mixtures of two or more of the first three classes in which the different components remain distinct from one another in the final structure. A common example is composite resin. Fig. 1.7a: Three-dimensional structure of iron (metal) Metals Metals are the oldest of the three classes of materials that have been used as dental materials. Metals are characterized by metallic bonds (Box 1.7) which will be discussed in the next chapter. Metals solidify with their atoms in a regular or crystalline arrangement (see Chapter 2), often in the form of a cube (Fig. 1.7a). example, temporary fillings done in a tooth during root canal treatment, which have to be replaced within 2-4 days during subsequent visits. They are used to protect the tooth and provide function till the final restoration is done. 3. Interim restoration: At times, dental treatment requires "long-term" definite temporary restorations or "interim" restorations. For examle, a 7-year-old child, met with trauma and fractured one of his central incisors. A large composite build- up may serve his immediate requirement until the root formation is completed and a permanent crown is placed. 5 Classification based on the Chemical Nature of the Material These are the atoms that make up a material and the way they are bonded together determine the properties of that materiaLS Weak bonds make for weak materials and vice versa (Table 1.4). Materials can be classified into different categories based on their primary atomic bonds (Fig. 1.6): 1. Metals 2. Ceramics Fig. 1.6: Classification of dental materials based on chemical nature 12 Basis of Material Science Box 1.9: Benefits of ceramics in dentistry 1. Many ceramic oxides are used as pigmenting agents. These oxides produce good range of colors. Due to this characteristic, we are able to match almost any tooth color with good esthetic results. 2. They are inert, i.e. not chemically reactive. This quality provides ceramics with good bio- compatibility. 3. Ceramic materials are translucent, like natural teeth. This translucency gives the ceramic crown a more natural appearance than any other dental material. Fig. 1.7b: Internal arrangement of tetrahedral structure of ceramic (silica) four large oxygen atoms surround smaller silicon atom Ceramics A ceramic is a compound formed by the union of a metallic and a non-metallic element (Box 1.8). Most of these materials are oxides, formed by the union of oxygen with metals such as silicon, aluminum, calcium and magnesium (Fig.1.7b). Ceramics may be simple or complex. Examples of simple ceramics are alumina and silica. Examples of complex ceramics are feldspar (potassium aluminum silicate) and kaolin (hydrated aluminum silicate). Ceramics may be crystalline or non- crystalline (i.e. amorphous). Porcelain is a specific type of ceramic used extensively in dentistry (Box 1.9). Box 1.8: Characteristics of ceramics 1. High melting points. 2. Brittleness, which means they cannot be bent or deformed (no sliding) to any extent without actually cracking and breaking. 3. They are poor conductor of heat and electricity. 4. They are chemically inert. 5. They have excellent esthetic result in terms of matching natural teeth. Fig. 1.8: Stucture of synthetic polymer Polymers They are the latest addition (early to mid- 1900s) to dental materials. Most of the polymers are nowadays synthesized by humans. Polymers are giant, long-chain organic molecules (Fig. 1.8). Polymers are characterized by covalent bonds within each molecule, giving them tremendous strength in a single direction. Try to break a nylon rope by pulling it! They are poor conductors of heat and electri- city. Most polymers have a structure containing thousands of carbon atoms linked together like beads on a string. Others, such as silicone polymers are formed with silicon-oxygen bonds. Introducton to Dental Materials Table 1.4: Characteristics of different materials 13 Characteristics Bond Properties Crystal structure Metals Metallic bonding High strength and hardness, high electrical and thermal conductivity BCC, FCC, or HCP unit cells Ceramics Ionic or covalent bonding, or both High hardness and stiffness, electrically insulating, refractory, and chemically inert Crystalline or amorphous Polymers Covalent bonding Low sensitivity, high electrical resistivity, and low thermal conductivity, strength and stiffness vary widely Amorphous and crystalline Composites Composites are combinations of any of the basic ceramic, metallic and polymeric materials (Box 1.10). Each material that makes up composites is called a phase. Their properties tend to be somewhere between those of their basic constituents and are used to enhance their performance, longevity and handling chracterstics. Box 1.10: Types of composites in dentistry 1. Ceramic - metallic composite: Tungsten carbide bur. 2. Metal - polymer composite: Die materials in dental laboratory. 3. Ceramic - polymer composite: Enamel, dentin, bone and restorative composites. A composite is a kind of "combination" of materials, which compliment each other. The properties lacking in one material are compensated by those of the other material. For example, restorative composite has two phases, namely resin and fillers. Teeth and bones are examples of natural composites. Enamel is a composite of hydroxyapatite (which is a ceramic material) and protein (which is a polymer). EVALUATION OF DENTAL MATERIALS Most manufacturers of dental materials maintain a quality assurance programme (As per international standard like ADA specifications) and materials are thoroughly tested before being released into the market for dental practitioner (Fig. 1.9). Laboratory Evaluations Most ADA/ ANSI specifications involve laboratory tests. The tests performed as per these specifications are useful but they all are performed in vitro, (carried out in the laboratory away from the clinical conditions) which have a lot of limitations in clinical practice.lO Clinical Notes 1. For example, most of the direct restorative materials are tested for their compressive strength but ultimately the material is subjected to a combination of compressive, tensile and shear stresses, which may decide the final success or failure of the material under masticatory load. 2. Similarly upper dentures mostly fracture along the midline because of bending. Hence a bending or transverse strength ~B-a-s-is-o-f-M-a-t-e-ria-I-S~c-ie-n-c-e-------------- ---------. test is far more meaningful for denture base materials than a compression test. Clinical Trials The majority of new materials are subjected to extensive clinical trials normally in co-operation with a dental college or hospital departments prior to their release. CONCLUSION As the number of available materials is going up, it is important that the dentist remains more aware about new products so that their judgement about the selection of material remains successful. Materials which have not been thoroughly evaluated should be avoided, specially with clinical dentistry falling under Consumer Protection Act (CPA). I Research and development I iI Manufacturer/analysis Ideal requirements for clinical use: Thermal, optical, mechanical, chemical, biological Available materials and their properties are evaluated Launch of new I product Choice and selection of material by the dentist Critical assessment based on clinical performance I I H feedback to IScience Term 4Revision 4 grade 6 Science Term 2âThereâs No Such Thing as Sound Scienceâ by By Christie Aschwanden was a lead science writer for FiveThirtyEight. FiveThirtyEight, Science, Dec. 6, 2017 Science is being turned against itself. For decades, its twin ideals of transparency and rigor have been weaponized by those who disagree with results produced by the scientific method. Under the Trump administration, that fight has ramped up again. In a move ostensibly meant to reduce conflicts of interest, Environmental Protection Agency Administrator Scott Pruitt has removed a number of scientists from advisory panels and replaced some of them with representatives from industries that the agency regulates. Like many in the Trump administration, Pruitt has also cast doubt on the reliability of climate science. For instance, in an interview with CNBC, Pruitt said that âmeasuring with precision human activity on the climate is something very challenging to do.â Similarly, Trumpâs pick to head NASA, an agency that oversees a large portion the nationâs climate research, has insisted that research into human influence on climate lacks certainty, and he falsely claimed that âglobal temperatures stopped rising 10 years ago.â Kathleen Hartnett White, Trumpâs nominee to head the White House Council on Environmental Quality, said in a Senate hearing last month that she thinks we âneed to have more precise explanations of the human role and the natural roleâ in climate change. The same entreaties crop up again and again: We need to root out conflicts. We need more precise evidence. What makes these arguments so powerful is that they sound quite similar to the points raised by proponents of a very different call for change thatâs coming from within science. This other movement strives to produce more robust, reproducible findings. Despite having dissimilar goals, the two forces espouse principles that look surprisingly alike: Science needs to be transparent. Results and methods should be openly shared so that outside researchers can independently reproduce and validate them. The methods used to collect and analyze data should be rigorous and clear, and conclusions must be supported by evidence. These are the arguments underlying an âopen scienceâ reform movement that was created, in part, as a response to a âreproducibility crisisâ that has struck some fields of science.1 But theyâre also used as talking points by politicians who are working to make it more difficult for the EPA and other federal agencies to use science in their regulatory decision-making, under the guise of basing policy on âsound science.â Scienceâs virtues are being wielded against it. What distinguishes the two calls for transparency is intent: Whereas the âopen scienceâ movement aims to make science more reliable, reproducible and robust, proponents of âsound scienceâ have historically worked to amplify uncertainty, create doubt and undermine scientific discoveries that threaten their interests. âOur criticisms are founded in a confidence in science,â said Steven Goodman, co-director of the Meta-Research Innovation Center at Stanford and a proponent of open science. âThatâs a fundamental difference â weâre critiquing science to make it better. Others are critiquing it to devalue the approach itself.â Calls to base public policy on âsound scienceâ seem unassailable if you donât know the termâs history. The phrase was adopted by the tobacco industry in the 1990s to counteract mounting evidence linking secondhand smoke to cancer. A 1992 Environmental Protection Agency report identified secondhand smoke as a human carcinogen, and Philip Morris responded by launching an initiative to promote what it called âsound science.â In an internal memo, Philip Morris vice president of corporate affairs Ellen Merlo wrote that the program was designed to âdiscredit the EPA report,â âprevent states and cities, as well as businesses from passing smoking bansâ and âproactivelyâ pass legislation to help their cause. The sound science tactic exploits a fundamental feature of the scientific process: Science does not produce absolute certainty. Contrary to how itâs sometimes represented to the public, science is not a magic wand that turns everything it touches to truth. Instead, itâs a process of uncertainty reduction, much like a game of 20 Questions. Any given study can rarely answer more than one question at a time, and each study usually raises a bunch of new questions in the process of answering old ones. âScience is a process rather than an answer,â said psychologist Alison Ledgerwood of the University of California, Davis. Every answer is provisional and subject to change in the face of new evidence. Itâs not entirely correct to say that âthis study proves this fact,â Ledgerwood said. âWe should be talking instead about how science increases or decreases our confidence in something.â The tobacco industryâs brilliant tactic was to turn this baked-in uncertainty against the scientific enterprise itself. While insisting that they merely wanted to ensure that public policy was based on sound science, tobacco companies defined the term in a way that ensured that no science could ever be sound enough. The only sound science was certain science, which is an impossible standard to achieve. âDoubt is our product,â wrote one employee of the Brown & Williamson tobacco company in a 1969 internal memo. The note went on to say that doubt âis the best means of competing with the âbody of factââ and âestablishing a controversy.â These strategies for undermining inconvenient science were so effective that theyâve served as a sort of playbook for industry interests ever since, said Stanford University science historian Robert Proctor. The sound science push is no longer just Philip Morris sowing doubt about the links between cigarettes and cancer. Itâs also a 1998 action plan by the American Petroleum Institute, Chevron and Exxon Mobil to âinstall uncertaintyâ about the link between greenhouse gas emissions and climate change. Itâs industry-funded groupsâ late-1990s effort to question the science the EPA was using to set fine-particle-pollution air-quality standards that the industry didnât want. And then there was the more recent effort by Dow Chemical to insist on more scientific certainty before banning a pesticide that the EPAâs scientists had deemed risky to children. Now comes a move by the Trump administrationâs EPA to repeal a 2015 rule on wetlands protection by disregarding particular studies. (To name just a few examples.) Doubt merchants arenât pushing for knowledge, theyâre practicing what Proctor has dubbed âagnogenesisâ â the intentional manufacture of ignorance. This ignorance isnât simply the absence of knowing something; itâs a lack of comprehension deliberately created by agents who donât want you to know, Proctor said.2 In the hands of doubt-makers, transparency becomes a rhetorical move. âItâs really difficult as a scientist or policy maker to make a stand against transparency and openness, because well, who would be against it?â said Karen Levy, researcher on information science at Cornell University. But at the same time, âyou can couch everything in the language of transparency and it becomes a powerful weapon.â For instance, when the EPA was preparing to set new limits on particulate pollution in the 1990s, industry groups pushed back against the research and demanded access to primary data (including records that researchers had promised participants would remain confidential) and a reanalysis of the evidence. Their calls succeeded and a new analysis was performed. The reanalysis essentially confirmed the original conclusions, but the process of conducting it delayed the implementation of regulations and cost researchers time and money. Delay is a time-tested strategy. âGridlock is the greatest friend a global warming skeptic has,â said Marc Morano, a prominent critic of global warming research and the executive director of ClimateDepot.com, in the documentary âMerchants of Doubtâ (based on the book by the same name). Moranoâs site is a project of the Committee for a Constructive Tomorrow, which has received funding from the oil and gas industry. âWeâre the negative force. Weâre just trying to stop stuff.â Some of these ploys are getting a fresh boost from Congress. The Data Quality Act (also known as the Information Quality Act) was reportedly written by an industry lobbyist and quietly passed as part of an appropriations bill in 2000. The rule mandates that federal agencies ensure the âquality, objectivity, utility, and integrity of informationâ that they disseminate, though it does little to define what these terms mean. The law also provides a mechanism for citizens and groups to challenge information that they deem inaccurate, including science that they disagree with. âIt was passed in this very quiet way with no explicit debate about it â that should tell you a lot about the real goals,â Levy said. But whatâs most telling about the Data Quality Act is how itâs been used, Levy said. A 2004 Washington Post analysis found that in the 20 months following its implementation, the act was repeatedly used by industry groups to push back against proposed regulations and bog down the decision-making process. Instead of deploying transparency as a fundamental principle that applies to all science, these interests have used transparency as a weapon to attack very particular findings that they would like to eradicate. Now Congress is considering another way to legislate how science is used. The Honest Act, a bill sponsored by Rep. Lamar Smith of Texas,3 is another example of what Levy calls a âTrojan horseâ law that uses the language of transparency as a cover to achieve other political goals. Smithâs legislation would severely limit the kind of evidence the EPA could use for decision-making. Only studies whose raw data and computer codes were publicly available would be allowed for consideration. That might sound perfectly reasonable, and in many cases it is, Goodman said. But sometimes there are good reasons why researchers canât conform to these rules, like when the data contains confidential or sensitive medical information.4 Critics, which include more than a dozen scientific organizations, argue that, in practice, the rules would prevent many studies from being considered in EPA reviews.5 It might seem like an easy task to sort good science from bad, but in reality itâs not so simple. âThereâs a misplaced idea that we can definitively distinguish the good from the not-good science, but itâs all a matter of degree,â said Brian Nosek, executive director of the Center for Open Science. âThere is no perfect study.â Requiring regulators to wait until they have (nonexistent) perfect evidence is essentially âa way of saying, âWe donât want to use evidence for our decision-making,ââ Nosek said. Most scientific controversies arenât about science at all, and once the sides are drawn, more data is unlikely to bring opponents into agreement. Michael Carolan, who researches the sociology of technology and scientific knowledge at Colorado State University, wrote in a 2008 paper about why objective knowledge is not enough to resolve environmental controversies. âWhile these controversies may appear on the surface to rest on disputed questions of fact, beneath often reside differing positions of value; values that can give shape to differing understandings of what âthe factsâ are.â Whatâs needed in these cases isnât more or better science, but mechanisms to bring those hidden values to the forefront of the discussion so that they can be debated transparently. âAs long as we continue down this unabashedly naive road about what science is, and what it is capable of doing, we will continue to fail to reach any sort of meaningful consensus on these matters,â Carolan writes. The dispute over tobacco was never about the science of cigarettesâ link to cancer. It was about whether companies have the right to sell dangerous products and, if so, what obligations they have to the consumers who purchased them. Similarly, the debate over climate change isnât about whether our planet is heating, but about how much responsibility each country and person bears for stopping it. While researching her book âMerchants of Doubt,â science historian Naomi Oreskes found that some of the same people who were defending the tobacco industry as scientific experts were also receiving industry money to deny the role of human activity in global warming. What these issues had in common, she realized, was that they all involved the need for government action. âNone of this is about the science. All of this is a political debate about the role of government,â she said in the documentary. These controversies are really about values, not scientific facts, and acknowledging that would allow us to have more truthful and productive debates. What would that look like in practice? Instead of cherry-picking evidence to support a particular view (and insisting that the science points to a desired action), the various sides could lay out the values they are using to assess the evidence. For instance, in Europe, many decisions are guided by the precautionary principle â a system that values caution in the face of uncertainty and says that when the risks are unclear, it should be up to industries to show that their products and processes are not harmful, rather than requiring the government to prove that they are harmful before they can be regulated. By contrast, U.S. agencies tend to wait for strong evidence of harm before issuing regulations. Both approaches have critics, but the difference between them comes down to priorities: Is it better to exercise caution at the risk of burdening companies and perhaps the economy, or is it more important to avoid potential economic downsides even if it means that sometimes a harmful product or industrial process goes unregulated? In other words, under what circumstances do we agree to act on a risk? How certain do we need to be that the risk is real, and how many people would need to be at risk, and how costly is it to reduce that risk? Those are moral questions, not scientific ones, and openly discussing and identifying these kinds of judgment calls would lead to a more honest debate. Science matters, and we need to do it as rigorously as possible. But science canât tell us how risky is too risky to allow products like cigarettes or potentially harmful pesticides to be sold â those are value judgements that only humans can make.Q1. Tick the properties of water. a. Water is transparent and colourless. b. Water has no smell or taste. c. One litre of water has a mass of one kilogram. d. Water supports life. e. Water has no weight. Q2. List the properties of air. --------------------------------------------------------------------- --------------------------------------------------------------------- ---------------------------------------------------------------------- ----------------------------------------------------------------------- Q3. "Which gases are the most abundant in air?" The most common gas ----------------------------------------- The second most common gas ----------------------------- 8 | Page AZ-Y5-Science- Second Mid-Term Revision2024/2025 Q4. Look at the pie chart of the components of the air and identify P, Q and R. Nitrogen 71% Oxygen 21% Other gases 1% P ------------------------------- Q ------------------------------- R -------------------------------- Q5. Identify the gas for each of these descriptions. Use the name of each gas twice. Oxygen-nitrogen-carbon dioxide. a. The gas we need to breathe. --------------------------------- b. The most common gas in the air. ---------------------------- c. The gas that gives drinks their fizz. ---------------------------- d. The gas that supports burning. -------------------------------- e. A gas used to make fertilizer. ---------------------------------- f. A gas used in fire extinguishers. ------------------------------- 9 | Page AZ-Y5-Science- Second Mid-Term Revision2024/2025 Q6. Draw and label the stages of the water cycle. Use arrows to show how water moves through the cycle." 10 | Page AZ-Y5-Science- Second Mid-Term Revision2024/2025 Q7. The diagram shows how gases in the upper atmosphere trap heat. a. What does the diagram refer to? _____________________________________________________________ b. Give two reasons why the amount of greenhouse gases in the atmosphere is increasing. _____________________________________________________________ _____________________________________________________________ c. If more heat is trapped, how will the earth's temperature change? 1. It will rise. 2. It will fall. d. "Which of the following is a greenhouse gas?" 1. Argon 2. Nitrogen 3. Carbon dioxide 11 | Page AZ-Y5-Science- Second Mid-Term Revision2024/2025 Q8. Write (T) for True or (F) for False. 1. Global warming leads to rising sea levels and more droughts. ( ) 2. Water exists in only one state: liquid. ( ) 3. It is not safe to drink untreated water from lakes and rivers. ( ) 4. Air pollution does not affect the environment. ( ) 5. Nitrogen is the most common gas in the atmosphere. ( ) Q9. Fill in the blanks: a. Air is a mixture of gases, and the most abundant gas in the air is __________. b. The water cycle includes four stages: __________, __________, __________, and __________. c. __________ is a gas used in the production of fertilizers. d. __________ is a harmful gas that contributes to global warming by trapping heat in the atmosphere. Q10. Answer the following questions: 1. What are the four main stages of the water cycle? -------------------------------------------------------------------------------- 2. Name one way to help reduce air pollution. ----------------------------------------------------------------------------------- 12 | Page AZ-Y5-Science- Second Mid-Term Revision2024/2025 3. State one use of oxygen gas. ------------------------------------------------------------------------------------ 4. What is one consequence of global warming? -------------------------------------------------Of the 7 billion people on Earth roughly 0:02 6 billion own a cell phone which is 0:05 pretty shocking given that only 4 and2 0:07 billion have access to a working toilet 0:09 so how are these popular gadgets 0:11 changing your body and brain If you're 0:13 looking down at your phone right now 0:15 your spine angle is equivalent to that 0:17 of an 8-year-old child sitting on your 0:19 neck which is fairly significant 0:21 considering people spend an average of 0:23 4.7 hours a day looking at their phone 0:26 this combined with the length of time 0:28 spent in front of computers has led to 0:30 an increase in the prevalence of myopia 0:32 or nearsightedness in North America in 0:34 the 1970s about one quar of the 0:36 population had myopia where today nearly 0:39 half do and in some parts of Asia 80 to 0:41 90% of the population is now nearsighted 0:44 and it can be hard to put your phone 0:46 down take for example the game Candy 0:48 Crush as you play the game you achieve 0:50 small goals causing your brain to be 0:52 rewarded with little bursts of dopamine 0:54 and eventually you're rewarded in the 0:56 game with new content this novelty also 0:58 gives little bursts of dopamine and 1:00 together create what is known as a 1:01 compulsion Loop which just happens to be 1:04 the same Loop responsible for the 1:05 behaviors associated with nicotine or 1:07 cocaine our brains are hardwired to make 1:10 us novelty seeking and this is why apps 1:12 on our phones are designed to constantly 1:14 provide us with new content making them 1:16 hard to put down as a result 93% of 1:19 young people aged 18 to 29 report using 1:21 their smartphone as a tool to avoid 1:23 boredom as opposed to other activities 1:26 like reading a book or engaging with 1:27 people around them this has created a 1:29 new term nomophobia the fear or anxiety 1:32 of being without your phone we also see 1:35 a change in brain patterns Alpha rhythms 1:37 are commonly associated with wakeful 1:39 relaxation like when your mind wanders 1:41 off whereas gamma waves are associated 1:44 with conscious attentiveness and 1:46 experiments have shown that when a cell 1:47 phone is transmitting say during a phone 1:49 call the power of these Alpha Waves is 1:52 significantly boosted meaning phone 1:54 Transmissions can literally change the 1:56 way your brain functions your smartphone 1:58 can also disrupt your sleep the screen 2:00 emits a blue light which has been shown 2:02 to alter our circadian rhythms 2:03 diminishing the time spent in deep Sleep 2:06 which is linked to the development of 2:07 diabetes cancer and obesity Studies have 2:10 shown that people who read on their 2:11 smartphone at night have a harder time 2:13 falling asleep and produce less 2:15 melatonin a hormone responsible for the 2:17 regulation of sleep wake Cycles Harvard 2:20 medical school advises the last 2 to 3 2:22 hours before bed be technology free so 2:24 pick up a book before bed instead of 2:26 course smartphones also completely 2:28 change our ability to access information 2:30 most notably in poor and minority 2:32 populations 7% of Americans are entirely 2:35 dependent on smartphones for their 2:37 access to the internet a 2014 study 2:40 found that the majority of smartphone 2:41 owners use their phone for online 2:43 banking to look up medical information 2:45 and searching for jobs so while phones 2:47 are in no way exclusively bad and have 2:50 been part of a positive change in the 2:51 world there's no denying that they are 2:53 changing us but many successful people 2:56 have now decided to take smartphone 2:58 vacations in order to increase 3:00 productivity in our new ASAP thought 3:01 video we break down the top six reasons 3:04 you should take a smartphone vacation 3:06 and how it could benefit your life right 3:08 now and subscribe for more weekly 3:09 science videos