Energy Trade-off and 4 Extreme Human Body Types.

BACKGROUND: Resource trade-off theory suggests that increased performance on a given trait comes at the cost of decreased performance on other traits. METHODS: Growth data from 1889 subjects (996 girls) were used from the GrowUp1974 Gothenburg study. Energy Trade-Off (ETO) between height and weight for individuals with extreme body types was characterized using a novel ETO-Score (ETOS). Four extreme body types were defined based on height and ETOI at early adulthood: tall-slender, short-stout, short-slender, and tall-stout; their growth trajectories assessed from ages 0.5-17.5 years.A GWAS using UK BioBank data was conducted to identify gene variants associated with height, BMI, and for the first time with ETOS. RESULTS: Height and ETOS trajectories show a two-hit pattern with profound changes during early infancy and at puberty for tall-slender and short-stout body types. Several loci (including FTO, ADCY3, GDF5, ) and pathways were identified by GWAS as being highly associated with ETOS. The most strongly associated pathways were related to "extracellular matrix," "signal transduction," "chromatin organization," and "energy metabolism." CONCLUSIONS: ETOS represents a novel anthropometric trait with utility in describing body types. We discovered the multiple genomic loci and pathways probably involved in energy trade-off.

Family Size and the Age at Infancy-Childhood Transition Determine a Child's Compromised Growth in Large Families.

Background: Data on growth of Israeli school children show that children from Jewish ultra-orthodox Haredi and Bedouin Arab families have a higher prevalence of stature below the 3rd percentile. While these populations are usually from lower socioeconomic strata, they also have larger families. This study aimed to evaluate if family structure and the timing of a child's infancy-childhood transition (ICT) are central to variations in stature. Study Design: We analyzed the association between family size, birth order and inter-birth interval with child growth and the age at ICT in 3 groups of children, 148 high birth order children from large families (LF ≥ 6), 118 low birth order children from large families (LF ≤ 3) and 150 children from small families (SF). Results: High birth order children from large families were shorter in childhood than children from small families with a difference of 0.5 SDS in length. We found that birth length and birth order explained 35% of the total variance in infancy length whereas ICT age and infancy length explained 72% of the total variance in childhood length. Conclusion: Infancy and childhood length are compromised in children from large families. As the family grows larger the younger children tend to be shorter. Reduced length gain in the period between infancy to childhood is when growth is most affected.

Uncoupling of the Infancy Life History Stage.

BACKGROUND: The life history of Homo sapiens is unique in having a comparatively short stage of infancy which lasts for 2-3 years. Infancy is characterized by suckling of breast milk, the development of sensorimotor cognition, the acquisition of language, mini-puberty, deciduous dentition, and almost complete skull growth. Infancy ends with the infancy-childhood growth transition (ICT) and separation from the mother. In modern-day affluent societies, breastfeeding depends on the mother's decision and may happen at any age, and the characteristic traits of infancy have uncoupled. The data and theory for this contention are presented. SUMMARY: The biological traits of mini-puberty and ICT characteristic of infancy occur before age 1 along with language acquisition. The cognitive (sensorimotor) component occurs by age 2, and the social component of separation from the mother by any age from 1 to 3 years. Key Messages: Human life history is based on a coherent stage of infancy which assumes coupling between the biological, cognitive, and social maturation of a baby. This is no longer the case in industrial societies and might never be so again. The upbringing of an infant needs to consider the new biology of this dissociated infancy and a new timetable of the infant's life-history events.

Personalized approach to childhood obesity: Lessons from gut microbiota and omics studies. Narrative review and insights from the 29th European childhood obesity congress.

The traditional approach to childhood obesity prevention and treatment should fit most patients, but misdiagnosis and treatment failure could be observed in some cases that lie away from average as part of individual variation or misclassification. Here, we reflect on the contributions that high-throughput technologies such as next-generation sequencing, mass spectrometry-based metabolomics and microbiome analysis make towards a personalized medicine approach to childhood obesity. We hypothesize that diagnosing a child as someone with obesity captures only part of the phenotype; and that metabolomics, genomics, transcriptomics and analyses of the gut microbiome, could add precision to the term "obese," providing novel corresponding biomarkers. Identifying a cluster -omic signature in a given child can thus facilitate the development of personalized prognostic, diagnostic, and therapeutic approaches. It can also be applied to the monitoring of symptoms/signs evolution, treatment choices and efficacy, predisposition to drug-related side effects and potential relapse. This article is a narrative review of the literature and summary of the main observations, conclusions and perspectives raised during the annual meeting of the European Childhood Obesity Group. Authors discuss some recent advances and future perspectives on utilizing a systems approach to understanding and managing childhood obesity in the context of the existing omics data.

Prediction of Adult Height by Machine Learning Technique.

CONTEXT: Prediction of AH is frequently undertaken in the clinical setting. The commonly used methods are based on the assessment of skeletal maturation. Predictive algorithms generated by machine learning, which can already automatically drive cars and recognize spoken language, are the keys to unlocking data that can precisely inform the pediatrician for real-time decision making. OBJECTIVE: To use machine learning (ML) to predict adult height (AH) based on growth measurements until age 6 years. METHODS: Growth data from 1596 subjects (798 boys) aged 0-20 years from the longitudinal GrowUp 1974 Gothenburg cohort were utilized to train multiple ML regressors. Of these, 100 were used for model comparison, the rest was used for 5-fold cross-validation. The winning model, random forest (RF), was first validated on 684 additional subjects from the 1974 cohort. It was additionally validated using 1890 subjects from the GrowUp 1990 Gothenburg cohort and 145 subjects from the Edinburgh Longitudinal Growth Study cohort. RESULTS: RF with 51 regression trees produced the most accurate predictions. The best predicting features were sex and height at age 3.4-6.0 years. Observed and predicted AHs were 173.9 ±â€…8.9 cm and 173.9 ±â€…7.7 cm, respectively, with prediction average error of -0.4 ±â€…4.0 cm. Validation of prediction for 684 GrowUp 1974 children showed prediction accuracy r = 0.87 between predicted and observed AH (R2 = 0.75). When validated on the 1990 Gothenburg and Edinburgh cohorts (completely unseen by the learned RF model), the prediction accuracy was r = 0.88 in both cases (R2 = 0.77). AH in short children was overpredicted and AH in tall children was underpredicted. Prediction absolute error correlated negatively with AH (P < .0001). CONCLUSION: We show successful, validated ML of AH using growth measurements before age 6 years. The most important features for prediction were sex, and height at age 3.4-6.0. Prediction errors result in over- or underestimates of AH for short and tall subjects, respectively. Prediction by ML can be generalized to other cohorts.

Sexual Dimorphism of Size Ontogeny and Life History.

Background: Ecological and physiological factors and social and economic constraints affect sex-specific body size. Here, we used the male/female (M/F) height ratio as an indicator of the combined effect of genetic and sex characteristics. We hypothesized that (1) sexual dimorphism in body size will be established during infancy and adolescence when growth velocity is maximal, (2) living standards and health are important factors which can affect sexual dimorphism in body size, (3) variations in sexual dimorphism in body size are due to the differential response of boys and girls to environmental cues, and (4) sexual dimorphism in body size will be more pronounced in those populations whose average height and weight are the greatest. Methods: To study the ontogeny of sexual dimorphism from birth until the age of 18 years, we used the 2000 CDC growth data. Data on height by country, life expectancy, and gross domestic product (GDP) per capita based on purchasing power parity were extracted from the national accounts data of NCD Risk Factor Collaboration, the World Bank, Eurostat: Demographic Statistics, Secretariat of the Pacific Community: Statistics and Demography Program, and the US Census Bureau. Results: We found that sexual dimorphism in body size starts at age 1 month, peaks at age 3 months, and diminishes by age 24 months. During childhood, there is no sexual difference in body size, and it is gradually established when the boys enter puberty. The M/F height ratio correlates positively with the average male and female height and weight by country. Conclusion: Sexual dimorphism in body size occurs when (a) the growth velocity is maximal during infancy and adolescence, (b) living standards are high, and health correlate positively with male/female height ratio. Anthropological studies and our results emphasize mostly the female resiliency hypothesis: shorter male heights in times of environmental stress lead to smaller sexual dimorphism in body size.

People Are Taller in Countries With Better Environmental Conditions.

Background: Height is considered an indicator of health and well-being of an individual and population. Height variation results from a complex interaction of genetic, environmental, socioeconomic, and cultural influences. In order to understand the contribution of environmental stress associated with the child's growth, we correlated indicators of a stressful environment with adult height. Methods: We utilized seven equally weighted indicators of a stressful environment: homicide rates, GDP per capita, income inequality (GINI index), corruption perception index (CPI), unemployment rate, urban air pollution, and life expectancy (LE). Data on male and female height by country from 1992 to 1996 were obtained from the NCD Risk Factor Collaboration dataset. We assessed separately data from the 31 member countries of the Organization for Economic Co-operation and Development (OECD). In order to establish whether the indicators reflected a single conceptual dimension, we conducted an exploratory analysis and principal component analysis (PCA) with orthogonal transformation of the original variables. The relationships between male and female heights and the z-transformed principal components: Quality of life (QoL) and the Social factor (SF) that were derived after the PCA was assessed. Results: Male and female heights strongly correlated (p < 0.0001) with each of the seven indicators. In the PCA, the indicators clustered into "Quality of Life" factors (QoL), which comprised the CPI, GDP, air pollution, LE, and "Social factors" (SF), which comprised homicide rate and GINI index. For males and females, the average height by country strongly correlated with QoL (p < 0.0001) and SF (p < 0.0001). Within OECD countries, male and female height strongly and negatively correlated with the SF, but not with QoL. Conclusion: Growth attenuation is a tradeoff adaptive response: a calorie used for growth cannot be used for fighting stress. Here we show that: (1) Adult height, when used as a measure of child's growth, is an indicator of a stressful environment in context with the genetic background and spatial factors; (2) Stressful QoL factors and the SF exert a greater effect on men's height than women's height; and (3) The ranking of the indicators of short stature are income inequality > air pollution > GDP > CPI > homicide rate > LE > unemployment.

Steroid Metabolomic Signature of Insulin Resistance in Childhood Obesity.

OBJECTIVE: On the basis of urinary steroidal gas chromatography-mass spectrometry (GC-MS), we previously defined a novel concept of a disease-specific "steroid metabolomic signature" and reclassified childhood obesity into five groups with distinctive signatures. The objective of the current study was to delineate the steroidal signature of insulin resistance (IR) in obese children. RESEARCH DESIGN AND METHODS: Urinary samples of 87 children (44 girls) aged 8.5-17.9 years with obesity (BMI >97th percentile) were quantified for 31 steroid metabolites by GC-MS. Defined as HOMA-IR >95th percentile and fasting glucose-to-insulin ratio >0.3, IR was diagnosed in 20 (of 87 [23%]) of the examined patients. The steroidal fingerprints of subjects with IR were compared with those of obese children without IR (non-IR). The steroidal signature of IR was created from the product of IR - non-IR for each of the 31 steroids. RESULTS: IR and non-IR groups of children had comparable mean age (13.7 ± 1.9 and 14.6 ± 2.4 years, respectively) and z score BMI (2.7 ± 0.5 and 2.7 ± 0.5, respectively). The steroidal signature of IR was characterized by high adrenal androgens, glucocorticoids, and mineralocorticoid metabolites; higher 5α-reductase (An/Et) (P = 0.007) and 21-hydroxylase [(THE + THF + αTHF)/PT] activity (P = 0.006); and lower 11ßHSD1 [(THF + αTHF)/THE] activity (P = 0.012). CONCLUSIONS: The steroidal metabolomic signature of IR in obese children is characterized by enhanced secretion of steroids from all three adrenal pathways. As only the fasciculata and reticularis are stimulated by ACTH, these findings suggest that IR directly affects the adrenals. We suggest a vicious cycle model, whereby glucocorticoids induce IR, which could further stimulate steroidogenesis, even directly. We do not know whether obese children with IR and the new signature may benefit from amelioration of their hyperadrenalism.

Evolutionary Perspective in Rickets and Vitamin D.

Modern lifestyle limits our exposure to sunlight, which photosynthesizes vitamin D in the skin, and the incidence of nutritional rickets has been resurging. Vitamin D is one of the first hormones; it is photosynthesized in all organism from the phytoplankton to mammals. A selective sweep of the promoter of the vitamin D receptor (VDR) happened as soon as Homo sapiens migrated out of Africa; it co-adapted with skin color genes to provide adaptation to latitudes and the levels of exposure to ultraviolet (UV)B radiation along the route out of Africa. Exposure to UVB radiation balances the need for vitamin D photosynthesis and degradation of folic acid by UVB radiation. Skin color follows a latitude distribution: the darkest populations dwell in the tropical belt; and the fair-skinned populations inhabit the northern countries. Due to their greater need for calcium during their reproductive life, the skin color of women is lighter- than that of men. Vitamin D is essential for mineral homeostasis and has a wide variety of non-skeletal functions, of which the most important for natural selection is a regulatory function in the innate immune system. In the human fossil record, vitamin D deficiency coincided with bone tuberculosis. About 6,000 years ago, a diet which included cow's milk provided Neolithic humans with twice as much calcium and was more alkaline than that of its Paleolithic predecessors. Adiposity is negatively associated with the vitamin D status and obese individuals require 2-3 times more vitamin D than non-obese individuals to normalize circulating 25OHD levels. In an era of an obesity epidemic, we need more research to determine whether adiposity should be considered when determining the dietary requirements for vitamin D and calcium and the optimal serum 25OHD levels.

Steroid metabolomic signature of liver disease in nonsyndromic childhood obesity.

OBJECTIVE: Analysis of steroids by gas chromatography-mass spectrometry (GC-MS) defines a subject's steroidal fingerprint. Here, we compare the steroidal fingerprints of obese children with or without liver disease to identify the 'steroid metabolomic signature' of childhood nonalcoholic fatty liver disease. METHODS: Urinary samples of 85 children aged 8.5-18.0 years with BMI >97% were quantified for 31 steroid metabolites by GC-MS. The fingerprints of 21 children with liver disease (L1) as assessed by sonographic steatosis (L1L), elevated alanine aminotransferases (L1A) or both (L1AL), were compared to 64 children without markers of liver disease (L0). The steroidal signature of the liver disease was generated as the difference in profiles of L1 against L0 groups. RESULTS: L1 comparing to L0 presented higher fasting triglycerides (P = 0.004), insulin (P = 0.002), INS/GLU (P = 0.003), HOMA-IR (P = 0.002), GGTP (P = 0.006), AST/SGOT (P = 0.002), postprandial glucose (P = 0.001) and insulin (P = 0.011). L1AL showed highest level of T-cholesterol and triglycerides (P = 0.029; P = 0.044). Fasting insulin, postprandial glucose, INS/GLU and HOMA-IR were highest in L1L and L1AL (P = 0.001; P = 0.017; P = 0.001; P = 0.001). The liver disease steroidal signature was marked by lower DHEA and its metabolites, higher glucocorticoids (mostly tetrahydrocortisone) and lower mineralocorticoid metabolites than L0. L1 patients showed higher 5α-reductase and 21-hydroxylase activity (the highest in L1A and L1AL) and lower activity of 11ßHSD1 than L0 (P = 0.041, P = 0.009, P = 0.019). CONCLUSIONS: The 'steroid metabolomic signature' of liver disease in childhood obesity provides a new approach to the diagnosis and further understanding of its metabolic consequences. It reflects the derangements of steroid metabolism in NAFLD that includes enhanced glucocorticoids and deranged androgens and mineralocorticoids.

Effect of weaning age on the small intestine mucosa of rats.

Weaning of mammalian progeny is associated with a change in food composition and mother-offspring separation. Weaning results in a critical period of low voluntary feed intake, during which the animal is adapting to the starter diet. To evaluate the effects of weaning age on morphological changes that occur in the intestines of rats, we assessed intestinal histomorphometry and somatic growth in 21-days-old pups and 90-days-old mature rats that had been weaned early (day 16), normally (day 21), or late (day 26). Early weaning resulted in deeper crypts, lower villous/crypt ratio, and a smaller villous area on day 21. Crown-tail length correlated positively with the crypt depth and negatively with the villous/crypt ratio. At age 90 days, early weaned animals had shallower crypts, a greater villous/crypt ratio, and a smaller villous area compared with their normally weaned counterparts. The rats' crown-tail length correlated negatively with the crypt depth and positively with the villous/crypt ratio. Early weaning significantly affects the intestinal mucosa, which may impact food absorption and lead to differences in somatic growth compared with late weaning. Over time there may be a phase of compensation with increased villus height and crypt depth.

Emerging Adulthood, a Pre-adult Life-History Stage.

The duration of human maturation has been underestimated; an additional 4-6-year pre-adult period of "emerging adulthood," should be included in models of human maturation. It is a period of brain maturation, learning about intimacy and mutual support, intensification of pre-existing friendships, family-oriented socialization, and the attainment of those social skills that are needed for mating and reproduction. We propose that emerging adulthood is a life-history stage that is a foundation of the high reproductive success of human beings. The period of emerging adulthood has an evolutionary context and developmental markers, and we present evidence that supports the idea that emerging adults require protection because they are still learning and maturing.

Increased symptoms of anxiety and depression in prepubertal girls, but not boys, with premature adrenarche: associations with serum DHEAS and daily salivary cortisol concentrations.

Concerns over anxiety and depressive symptoms in children with premature adrenarche (PA) have been recently raised. However, to date, most relevant studies are on a small number of girls. In this cross-sectional study, 82 pre-pubertal children (66 girls and 16 boys) diagnosed with PA, were compared to 63 control children regarding their psychological characteristics and hypothalamic-pituitary-adrenal (HPA) axis function, as assessed by salivary cortisol measurement. Symptoms of anxiety and depression were assessed by child self-report (Spence Children's Anxiety Scale (SCAS) and Depression self-rating scale for Children (DSRS)) and parent-report (Child Behaviour Checklist (CBCL)) tests validated for the Greek population. Salivary cortisol levels were determined directly after awakening (approximately 7am) and evening (8pm) of the same day. Morning serum DHEAS levels were assessed in PA children. Girls with PA scored significantly higher on anxiety (p = .016) and depression (p =.039) scales than controls. No group differences were noted for parent reports and children's salivary cortisol concentrations. Boys with PA did not demonstrate significant differences in any of the aforementioned parameters. Our findings suggest that girls with PA may be at higher risk for reporting symptoms of anxiety and depression than their non-PA peers. HPA axis dysregulation in this population was not documented.

Normal Performance in Non-Visual Social Cognition Tasks in Women with Turner Syndrome.

Turner syndrome (TS) is a chromosomal disorder in women resulting from a partial or complete absence of the X chromosome. In addition to physical and hormonal dysfunctions, along with a unique neurocognitive profile, women with TS are reported to suffer from social functioning difficulties. Yet, it is unclear whether these difficulties stem from impairments in social cognition per se or from other deficits that characterize TS but are not specific to social cognition. Previous research that has probed social functioning in TS is equivocal regarding the source of these psychosocial problems since they have mainly used tasks that were dependent on visual-spatial skills, which are known to be compromised in TS. In the present study, we tested 26 women with TS and 26 matched participants on three social cognition tasks that did not require any visual-spatial capacities but rather relied on auditory-verbal skills. The results revealed that in all three tasks the TS participants did not differ from their control counterparts. The same TS cohort was found, in an earlier study, to be impaired, relative to controls, in other social cognition tasks that were dependent on visual-spatial skills. Taken together these findings suggest that the social problems, documented in TS, may be related to non-specific spatial-visual factors that affect their social cognition skills.

Early Adiposity Rebound and Premature Adrenarche.

OBJECTIVES: To examine differences in the growth pattern and the age at adiposity rebound (AR) between children with premature adrenarche (PA) and their healthy peers (controls). STUDY DESIGN: In this cross-sectional study of 82 prepubertal children with PA and 63 controls, the main outcome measures were height and body mass index SDS progression, from birth to presentation at the clinic, baseline biochemical and hormonal evaluation, bone age determination, and age at AR. RESULTS: Children with PA were significantly taller and more adipose than controls from the first years of life. 33% of children with PA presented the growth pattern of constitutional advancement of growth (ie, early growth acceleration) vs 19% of controls (P = .045). Children with PA had an earlier AR compared with controls; mean age at AR in girls with PA was 3.73 (1.03) years vs 4.93 (1.36) years for control girls (P = .001) and in boys with PA was 3.45 (0.73) vs 5.10 (1.50) years in control boys (P = .048). Both obese and nonobese girls with PA were taller and had earlier age at AR compared with nonobese controls. CONCLUSIONS: Early AR and constitutional advancement of growth may be triggering factors for adrenal androgen production and PA.

Face perception in women with Turner syndrome and its underlying factors.

Turner syndrome (TS) is a chromosomal condition that affects development in females. It is characterized by short stature, ovarian failure and other congenital malformations, due to a partial or complete absence of the sex chromosome. Women with TS frequently suffer from various physical and hormonal dysfunctions, along with impairments in visual-spatial processing and social cognition difficulties. Previous research has also shown difficulties in face and emotion perception. In the current study we examined two questions: First, whether women with TS, that are impaired in face perception, also suffer from deficits in face-specific processes. The second question was whether these face impairments in TS are related to visual-spatial perceptual dysfunctions exhibited by TS individuals, or to impaired social cognition skills. Twenty-six women with TS and 26 control participants were tested on various cognitive and psychological tests to assess visual-spatial perception, face and facial expression perception, and social cognition skills. Results show that women with TS were less accurate in face perception and facial expression processing, yet they exhibited normal face-specific processes (configural and holistic processing). They also showed difficulties in spatial perception and social cognition capacities. Additional analyses revealed that their face perception impairments were related to their deficits in visual-spatial processing. Thus, our results do not support the claim that the impairments in face processing observed in TS are related to difficulties in social cognition. Rather, our data point to the possibility that face perception difficulties in TS stem from visual-spatial impairments and may not be specific to faces.

Steroid Metabolomic Disease Signature of Nonsyndromic Childhood Obesity.

CONTEXT: The profile of urinary steroids as measured by gas chromatography-mass spectrometry defines a subject's "steroidal fingerprint." OBJECTIVE: Here, we clustered steroidal fingerprints to characterize patients with nonsyndromic childhood obesity by "steroid metabolomic signatures." HYPOTHESIS: Nonsyndromic obesity is a symptom of different diseases and conditions, some of them will have their own signature. DESIGN: A total of 31 steroid metabolites were quantified by gas chromatography-mass spectrometry, and their excretion rates were z-transformed. Using MetaboAnalyst 3.0, we divided the subjects into 5 distinctive groups by k-means clustering. Steroidal fingerprints and clinical/biochemical data of patients in each cluster were analyzed. PATIENTS: A total of 87 obese children (44 females), aged 8.5-17.9 years, were clinically characterized, and their 24-hour urine was collected. RESULTS: Cluster 1 (n = 39, 21 females) had normal steroid profile. Cluster 2 (n = 20, 11 females) showed mild, nonspecific elevation of C19 and C21 steroids, females' resistance to polycystic ovary morphology, and hirsutism. Cluster 3 (n = 7 female), with relative 21-hydroxylase insufficiency, was characterized by partial or full polycystic ovary syndrome. Cluster 4 (n = 4 males), showed markedly elevated C21 steroids and imbalance in the 11ß-hydroxysteroid dehydrogenase system, higher insulin, increased frequency of glucose/insulin index more than 0.3, γ-glutamyl transpeptidase activity, systolic blood pressure, and tendency to liver steatosis. Cluster 5 (n = 17, 5 females) had elevated dehydroepiandrosterone and 17-OH-pregnenolone metabolites, suggesting 3ß-hydroxysteroid dehydrogenase insufficiency but no clinically unique phenotype. Z-score body mass index values were not significantly different between the clusters. CONCLUSIONS: We defined a novel concept of disease-specific steroid metabolomic signature based on urinary steroidal gas chromatography-mass spectrometry. Clustering by software designed for metabolic data analysis reclassified childhood obesity into 5 groups with distinctive signatures; groups require further definition and may require cluster-specific therapeutic strategies.

Cortisol-Metabolizing Enzymes in Polycystic Ovary Syndrome.

OBJECTIVE: The aim of this study was to assess the activity of cortisol-metabolizing enzymes in women with polycystic ovary syndrome (PCOS), using a fully quantitative gas chromatography/mass spectrometry (GCMS) method. DESIGN: We investigated the glucocorticoid degradation pathways that include 11ß-hydroxysteroid dehydrogenase (11ß-HSD) type 1, 5α-reductase (5α-R) and 5ß-reductase (5ß-R), 3α-hydroxysteroid dehydrogenase, and 20α- and 20ß-hydroxysteroid dehydrogenase (20α-HSD and 20ß-HSD, respectively) in young nonobese women with PCOS, using a fully quantitative GCMS method. SETTING: This study was conducted in a tertiary referral hospital in Israel. PATIENTS: This study group consisted of 13 young women, aged 20.1 ± 2.8 years (mean ± SD), with the body mass index (BMI) of 22.6 ± 3.7 kg/m(2), diagnosed with PCOS according to the Rotterdam criteria. The control group consisted of 14 healthy young women matched for weight, height, and BMI. INTERVENTIONS: Urine samples were analyzed using GCMS. We measured urinary steroid metabolites that represent the products and substrates of the study enzymes and calculated the product/substrate ratios to represent enzyme activity. MAIN OUTCOME MEASURES: The calculation of enzymatic activity, based on glucocorticoid degradation metabolites, was done by GCMS in PCOS vs. controls. RESULTS: All glucocorticoid degradation metabolites were higher in the PCOS group than in controls. Of the adrenal enzymes, the activities of 21-hydroxylase and 17α-hydroxylase were reduced, whereas the activity of 17,20-lyase was enhanced in PCOS. Of the degradation enzymes, the activity of 11ß-HSD type 1 was reduced in women with PCOS only when calculated from cortoles and cortolones ratios. The activities of 5α-R/5ß-R were increased only when calculating the 11-hydroxy metabolites of androgens. The activity of 20α-HSD was elevated in the patients with PCOS and its relation with the substrate levels was lost. CONCLUSIONS: We confirm PCOS association with low 21-hydroxylase activity. PCOS is associated with dysregulation in glucocorticoid degradation. The activity of 5α-R is enhanced only through the backdoor pathway. Marked increase in the activity of 20α-HSD suggests a hitherto unknown derangement in PCOS.

DIAGNOSIS OF ENDOCRINE DISEASE: On the need for national-, racial-, or ethnic-specific standards for the assessment of bone maturation.

In an attempt to overcome ethnic and racial differences in skeletal maturation, the use of ethnic-specific standards has been suggested. Do we need such standards? Based on a fundamental understanding of phenotypic plasticity and an individual's ability to respond to environmental cues, the author argues that we do not need ethnic-specific standards for bone maturity. I suggest that we use a unified international standard of bone maturity for comparing the health, nutrition, and quality of life of all children, regardless of their race, nationality, and ethnicity.

Evo-devo of Child Growth: The Role of Weaning in the Transition from Infancy to Childhood.

Homo sapiens are unique in having a life history phase of childhood, which follows infancy, as defined by breastfeeding. This review uses evolutionary life history theory in understanding child growth in a broad evolutionary perspective, using the data and theory of evolutionary predictive adaptive growth-related strategies for transition from infancy to childhood. We have previously shown that a delayed infancy-childhood transition has a lifelong impact on stature. Feeding practices during infancy are fundamental elements of nutrition as they program for future growth and body composition. A relationship between the duration of breastfeeding and the nature of weaning has been suggested as a possible cause for later obesity and growth patterns. This review highlights the role that breast milk feeding and variations in the weaning age have on transition to childhood, growth, and body composition.