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Cell Death & Disease Jun 2024Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like...
Klinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature-like Sertoli cells highly expressed XIST and had two X-chromosomes, while the mature Sertoli cells lacked XIST expression and had only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lacked XIST expression and the additional X-chromosome, while the spermatogonia expressed XIST despite having only one X-chromosome. XIST was expressed in Sertoli cells until puberty, where a gradual loss was observed. Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis.
Topics: Klinefelter Syndrome; Male; Sertoli Cells; Spermatogenesis; Animals; Humans; Mice; RNA, Long Noncoding; Chromosomes, Human, X; X Chromosome
PubMed: 38839795
DOI: 10.1038/s41419-024-06792-6 -
The American Journal of Clinical... Jun 2024The World Health Organization recommends calcium supplementation (1500-2000 mg/d) during pregnancy for women with a low-calcium intake. (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of maternal calcium supplementation on offspring blood pressure and growth in childhood and adolescence in a population with a low-calcium intake: follow-up study of a randomized controlled trial.
BACKGROUND
The World Health Organization recommends calcium supplementation (1500-2000 mg/d) during pregnancy for women with a low-calcium intake.
OBJECTIVES
The purpose of this study was to investigate whether pregnancy calcium supplementation affects offspring blood pressure and growth in The Gambia where calcium intakes are low (300-400 mg/d).
METHODS
Follow-up of offspring born during a randomized controlled trial of pregnancy calcium supplementation (ISRCTN96502494, 1996-2000) in which mothers were randomly assigned to 1500 mg Ca/d (Ca) or placebo (P) from 20 wk pregnancy to delivery. Offspring were enrolled at age 3 y in studies where blood pressure and anthropometry were measured under standardized conditions at approximately 2-yearly intervals. Mean blood pressure and growth curves were fitted for females and males separately, using the longitudinal SuperImposition by Translation and Rotation (SITAR) mixed effects model. This generates 3 individual-specific random effects: size, timing, and intensity, reflecting differences in size, age at peak velocity, and peak velocity through puberty relative to the mean curve, respectively.
RESULTS
Five hundred twenty-three singleton infants were born during the trial (maternal group assignment: Ca/P = 259/264). Four hundred ninety-one were enrolled as children (females: F-Ca/F-P = 122/129 and males: M-Ca/M-P = 119/121) and measured regularly from 3.0 y to mean age 18.4 y; 90% were measured on ≥8 occasions. SITAR revealed differences in the systolic blood pressure and height curves between pregnancy supplement groups in females, but not in males. F-Ca had lower systolic blood pressure than F-P at all ages (size = -2.1 ± SE 0.8 mmHg; P = 0.005) and lower peak height velocity (intensity = -2.9 ± SE 1.1%, P = 0.009). No significant pregnancy supplement effects were seen for other measures.
CONCLUSIONS
This study showed, in female offspring, that pregnancy calcium supplementation may lower systolic blood pressure and slow linear growth in childhood and adolescence, adding to evidence of offspring sexual dimorphism in responses to maternal supplementation. Further research is warranted on the long-term and intergenerational effects of antenatal supplementations. This trial was registered at ISRCTN Registry as ISRCTN96502494.
Topics: Humans; Female; Pregnancy; Male; Dietary Supplements; Blood Pressure; Calcium, Dietary; Follow-Up Studies; Child, Preschool; Adolescent; Gambia; Maternal Nutritional Physiological Phenomena; Adult; Child; Child Development; Prenatal Exposure Delayed Effects; Body Height
PubMed: 38839195
DOI: 10.1016/j.ajcnut.2024.02.025 -
BMC Public Health Jun 2024Adolescents frequently have emotional and behavioral difficulties as they struggle with the challenges of transition from childhood to adulthood. Many struggle...
BACKGROUND
Adolescents frequently have emotional and behavioral difficulties as they struggle with the challenges of transition from childhood to adulthood. Many struggle with issues of body image and eating distress as they deal with the difficult and frequently perplexing changes that occur with puberty. Yet there is surprisingly little research on the emotional and behavioral challenges, as well as body image and eating distress among this sizable population in Uganda. This study sought to assess attitudes and behaviors related to body image and eating distress, as well as emotional and behavioral difficulties among adolescents in Mbarara, Southwestern Uganda.
METHODS
This was a cross-sectional study among 788 adolescents aged 13 to 19 years in secondary schools in Mbarara city and Mbarara district in south-western Uganda. The study employed the Body Image and Eating Distress scale to assess attitudes and behaviors about dieting and body shape and the extended version of the Strengths and Difficulties Questionnaire (SDQ) to assess for perceived emotional and behavioral difficulties. Logistic regression was used to identify the association between body image and eating distress and perceived difficulties.
RESULTS
The prevalence of high body image and eating distress was 10.8% while that of perceived emotional and behavioral difficulties was 45.8%. Some of the adolescents (16.1%) were dissatisfied with their body shape, 24.6% exercised a lot to avoid gaining weight, 15.0% were terrified to gain even a little weight, and 12.1% could not control their eating. More males reported eating large amounts of food at one time (p = < 0.001). Having emotional and behavioral difficulties (aOR: 1.89; 95% CI: 1.18 - 3.02; p = 0.019) and coming from a two-parent household (aOR: 1.79; 95% CI: 1.10 - 2.92; p = 0.019) increased the odds of high body image and eating distress.
CONCLUSION
High levels of body image and eating distress are linked to behavioral and emotional problems and adolescent's family structure. Clinicians who treat adolescents should use a holistic care strategy and be aware of the high prevalence and close association between emotional and behavioral difficulties, concerns about weight, and dieting. It is important to encourage parental involvement and support in providing information about mental health issues among adolescents.
Topics: Humans; Adolescent; Male; Uganda; Female; Body Image; Cross-Sectional Studies; Young Adult; Feeding and Eating Disorders; Psychological Distress; Adolescent Behavior; Surveys and Questionnaires; Prevalence; Feeding Behavior
PubMed: 38835004
DOI: 10.1186/s12889-024-18973-1 -
Annals of Medicine Dec 2024Injury rates in competitive alpine skiing are high. With current methods, identifying people at risk is expensive and thus often not feasible at the youth level. The...
INTRODUCTION
Injury rates in competitive alpine skiing are high. With current methods, identifying people at risk is expensive and thus often not feasible at the youth level. The aims of this study were (1) to describe the jump performance and movement quality of youth competitive alpine skiers according to age and sex, (2) to compare the jump distance among skiers of different sexes and movement quality grades, and (3) to assess the inter-rater grading reliability of the qualitative visual movement quality classification of such jumps and the agreement between live and video-based post-exercise grading.
MATERIALS AND METHODS
This cross-sectional study is based on an anonymized dataset of 301 7- to 15-year-old competitive alpine skiers. The skiers performed two-legged forward triple jumps, whereby the jump distance was measured, and grades were assigned by experienced raters from the frontal and sagittal perspectives depending on the execution quality of the jumps. Furthermore, jumps were filmed and ultimately rated post-exercise. Differences in jump distance between various groups were assessed by multivariate analyses of variance (MANOVAs). Reliability was determined using Kendall's coefficient of concordance.
RESULTS
The jump distance was significantly greater in U16 skiers than in U11 skiers of both sexes and in skiers with execution quality than in those with or execution quality. Overall, jump distance in U16 skiers significantly differed between female (5.37 m with 95% CI [5.21, 5.53]) and male skiers (5.90 m with 95%CI [5.69, 6.10]). Slightly better inter-rater grading reliability was observed for video-based post-exercise ( agreement) ratings than for live ratings ( agreement).
CONCLUSION
In competitive alpine skiers aged 7 to 15 years, jump performance increases with age, and around puberty, sex differences start to manifest. Our results highlight the importance of evaluating both jump distance and movement quality in youth skiers. To improve test-retest reliability, however, a video-based post-exercise evaluation is recommended.
Topics: Humans; Skiing; Cross-Sectional Studies; Adolescent; Female; Male; Child; Athletic Performance; Movement; Reproducibility of Results; Sex Factors; Age Factors
PubMed: 38833367
DOI: 10.1080/07853890.2024.2361254 -
Journal of Clinical Research in... Jun 2024Central precocious puberty is treated with long-acting GnRH analogues. Some adult patients undergoing GnRHa treatment experienced prolonged QT syndrome, which is...
INTRODUCTION
Central precocious puberty is treated with long-acting GnRH analogues. Some adult patients undergoing GnRHa treatment experienced prolonged QT syndrome, which is associated with an increased risk of serious cardiac events such as myocardial infarction, stroke, arrhythmias, and sudden cardiac death.
METHOD
Seventy-four patients, aged between 5 and 11 years and diagnosed with central precocious puberty but with no other concomitant disease or medication use, underwent electrocardiogram assessment. They had been receiving 3.75 mg leuprolide acetate (Lucrin® Depot) injections every 28 days for at least three months.
RESULTS
The electrocardiograms of all patients showed a QTc interval within normal limits, consistent with the data of healthy Turkish children of the same age and gender. No other pathological physical examination or ECG findings were observed. Furthermore, there was no significant difference in QTc interval in relation to age, anthropometric data, or the duration or cumulative dose of the treatment.
CONCLUSION
The study found no correlation between QTc interval values and age, treatment duration, total cumulative dose, and anthropometric data. The findings suggest that cardiovascular adverse events associated with GnRHa may be related to age and other underlying physiopathological conditions rather than the drug.
PubMed: 38828891
DOI: 10.4274/jcrpe.galenos.2024.2024-2-8 -
Journal of Clinical Research in... May 2024A rarely reported phenomenon of rapid-tempo puberty in which the physical changes of puberty and testosterone levels increase very rapidly has not been reported outside...
A rarely reported phenomenon of rapid-tempo puberty in which the physical changes of puberty and testosterone levels increase very rapidly has not been reported outside apart from in two reviews. The resulting rapid advancement of skeletal age causes early completion of growth with shorter adult stature than expected. This appears to be genetic given its occurrence in the present report in two families, one with three brothers, one with two. We also describe potential treatments and found for the youngest that early initiation of standard therapy preserved or reclaimed adult height (AH) potential. The foreshortened AH in this situation involves rapidly advancing puberty resulting from high circulating testosterone levels leading to rapid advance in skeletal age. This was recognized earlier among younger brothers and treatment with gonadotropin-releasing analogues, growth hormone (GH) and/or aromatase inhibitor therapy (AIT) was tried. Two brothers in family A and family B were treated. Case 5 started treatment early enough so his AH was within target height (mid-parental height) range. Cases 2, 3, 4 were tried on GH and/or AIT with outcomes suggesting benefit. The prevalence and mechanism of rapid-tempo puberty requires further study. Furthermore, as illustrated by two of the current cases, this phenomenon may have a heightened prevalence, or at least may occur, in children previously diagnosed with constitutional delay of growth, underscoring the need to be cautious in assurance of a normal AH outcomes in this population, based on data from a single assessment.
Topics: Humans; Male; Body Height; Child; Puberty; Growth Disorders; Adolescent; Female; Human Growth Hormone; Adult; Aromatase Inhibitors; Puberty, Precocious; Gonadotropin-Releasing Hormone; Testosterone
PubMed: 38828521
DOI: 10.4274/jcrpe.galenos.2024.2024-1-13 -
Fertility and Sterility May 2024To assess whether the use of assisted reproductive technology for conception is associated with imprinting disorders in children and the impact of parental factors...
OBJECTIVE
To assess whether the use of assisted reproductive technology for conception is associated with imprinting disorders in children and the impact of parental factors related to infertility.
DESIGN
A nationwide register-based cohort study.
SUBJECTS
All liveborn singletons in Sweden (N = 2 084 127) between 1997-2017 with follow-up to December 31, 2018.
EXPOSURE
The use of specific methods implemented in the assisted reproductive technology MAIN OUTCOME MEASURES: The International Classification of Diseases version 10 was used to identify three distinct imprinting disorder groups: Prader-Willi/Silver-Russell syndrome, Beckwith-Wiedemann syndrome, and central precocious puberty. The Cox model combined with inverse probability treatment weights were used to estimate weighted hazard ratio (wHR) with 95% confidence interval (CI), accounting for multiple confounders.
RESULTS
A total of 1044 children were diagnosed with the disorders of interest, and 52 of them were conceived with assisted reproductive technology. The overall risk of being diagnosed with any of the studied imprinting disorders was elevated in children conceived with ART compared to all other children (HR 1.84, 95% CI: 1.38-2.45). After adjusting for parental background factors, the association was partially attenuated (wHR 1.50, 95% CI: 0.97-2.32), but remained also in the weighted comparison restricted to children of couples with known infertility (wHR 1.52, 95% CI: 1.05-2.21). For the specific diagnoses of Prader-Willi/Silver-Russell syndrome and Beckwith-Wiedemann syndrome, compared to children of couples with known infertility, children conceived with assisted reproductive technology showed a small excess risk, which could not be distinguished from the null (wHR 1.56 [95% CI: 0.93-2.62] and 1.80 [95% CI: 0.99-3.28], respectively). Further subgroup analysis showed that the combined use of intra-cytoplasmic sperm injection and cryopreserved embryos was associated with higher risk of both Prader-Willi/Silver-Russell syndrome (wHR 4.60, 95% CI: 1.72-12.28) and Beckwith-Wiedemann syndrome (wHR 6.69, 95% CI: 2.09-21.45). The number of central precocious puberty cases in children conceived with assisted reproductive technology was too small (N=3) to make any meaningful inference.
CONCLUSION
The combined use of intra-cytoplasmic sperm injection and cryopreserved embryos was associated with small elevated risks of Prader-Willi/Silver-Russell syndrome and Beckwith-Wiedemann syndrome in children, independent of parental factors related to infertlity.
PubMed: 38825304
DOI: 10.1016/j.fertnstert.2024.05.168 -
Gynecological Endocrinology : the... Dec 2024To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis.
METHODS
The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents.
RESULTS
Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 - 0.595; = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD - 0.027; CI95% -0.227 - 0.172; = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS.
CONCLUSIONS
The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.
Topics: Humans; Polycystic Ovary Syndrome; Female; Adolescent; Menarche; Hypothalamo-Hypophyseal System; Body Mass Index; Ovary; Menstrual Cycle
PubMed: 38818646
DOI: 10.1080/09513590.2024.2360077 -
Neurology. Genetics Jun 2024Multiple sclerosis (MS) age at onset (AAO) is a clinical predictor of long-term disease outcomes, independent of disease duration. Little is known about the genetic and...
BACKGROUND AND OBJECTIVES
Multiple sclerosis (MS) age at onset (AAO) is a clinical predictor of long-term disease outcomes, independent of disease duration. Little is known about the genetic and biological mechanisms underlying age of first symptoms. We conducted a genome-wide association study (GWAS) to investigate associations between individual genetic variation and the MS AAO phenotype.
METHODS
The study population was comprised participants with MS in 6 clinical trials: ADVANCE (N = 655; relapsing-remitting [RR] MS), ASCEND (N = 555; secondary-progressive [SP] MS), DECIDE (N = 1,017; RRMS), OPERA1 (N = 581; RRMS), OPERA2 (N = 577; RRMS), and ORATORIO (N = 529; primary-progressive [PP] MS). Altogether, 3,905 persons with MS of European ancestry were analyzed. GWAS were conducted for MS AAO in each trial using linear additive models controlling for sex and 10 principal components. Resultant summary statistics across the 6 trials were then meta-analyzed, for a total of 8.3 × 10 single nucleotide polymorphisms (SNPs) across all trials after quality control and filtering for heterogeneity. Gene-based tests of associations, pathway enrichment analyses, and Mendelian randomization analyses for select exposures were also performed.
RESULTS
Four lead SNPs within 2 loci were identified ( < 5 × 10), including a) 3 SNPs in the major histocompatibility complex and their effects were independent of and b) a variant on chromosome 7. At the gene level, the top association was ( = 1.2 × 10), which plays an important role in antiviral immunity. Functional annotation revealed the enrichment of pathways related to T-cell receptor signaling, autoimmunity, and the complement cascade. Mendelian randomization analyses suggested a link between both earlier age at puberty and shorter telomere length and earlier AAO, while there was no evidence for a role for either body mass index or vitamin D levels.
DISCUSSION
Two genetic loci associated with MS AAO were identified, and functional annotation demonstrated an enrichment of genes involved in adaptive and complement immunity. There was also evidence supporting a link with age at puberty and telomere length. The findings suggest that AAO in MS is multifactorial, and the factors driving onset of symptoms overlap with those influencing MS risk.
PubMed: 38817245
DOI: 10.1212/NXG.0000000000200159